Synthesis of 2-Sulfonyl Indenes and Indanes

Subscriber access provided by Macquarie University

Article

Synthesis of 2-Sulfonyl Indenes and Indanes Meng-Yang Chang, Yan-Shin Wu, Yu-Lin Tsai, and Hsing-Yin Chen J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01606 • Publication Date (Web): 29 Aug 2019 Downloaded from pubs.acs.org on August 30, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry

Synthesis of 2-Sulfonyl Indenes and Indanes Meng-Yang Chang,*a,b Yan-Shin Wu,a Yu-Lin Tsaia and Hsing-Yin Chen*a a

Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan bDepartment of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan *Email: [email protected]; [email protected] R O

S

Ar'

O

O

+

Amberlyst 15 Ar

O

R O

S

R

O NaBH4 then Ar

Ar'

O

Amberlyst 15

O

O S 2

Ar'

Ar

R'MgBr R O

S

Ar'

O R'

Amberlyst 15 Ar

O

R O

O S 2

Ar'

R'

Ar

ABSTRACT: In this paper, we developed facile and high-yield synthetic routes for the preparation of 2-sulfonyl indenes and indanes, including: (i) Amberlyst 15-promoted Knoevenagel reaction of β-ketosulfones and arylaldehydes in refluxing toluene; (ii) Grignard reagent (R’MgBr) or reducing reagent (NaBH4) promoted regio- and/or stereocontrolled 1,4-addition or 1,4-/1,2-reduction of the resulting sulfonyl chalcones in THF or MeOH/THF at 25 °C; then, (iii) Amberlyst 15 mediated intramolecular Friedel-Crafts annulation of the corresponding -ketosulfones or -hydroxysulfones in toluene at reflux. This present method describes a highly efficient (3+2) annulation via the formation of two carbon-carbon (C-C) bonds. The DFT calculations were utilized to rationalize the regioselectivity of the addition reaction.

Introduction Indane and indene ring structures with a benzofused bicyclic ring system are important skeleton units in diversified natural products, functionalized building blocks, biological active molecules, and drug candidates.1-3 The development of new methodologies to provide access to these diversified indane and indene derivatives has steadily increased according to recent reports. Many considerable attempts have been evaluated to determine versatile synthetic routes, including: (1) Brønsted (TfOH, Tf2NH)4 or Lewis acid (Ph3CB(C6F5)4, BF3·OEt2, Ca(NTf2)2, In(OTf)3)5 mediated inter- or intramolecular Friedel-Crafts type ring-closure and (2) metal complex (Al,6 Pd,7 Rh,8 Rh/Ag,9 Rh,10 Rh/Mn,11 Cu,12 Fe,13 or Ni14) catalysed inter- or intramolecular carboannulation. There are various methods described in the literature for the efficient synthesis of substituted indanes or indenes via tandem coupling/annulation modes, but there are only limited reports for the synthesis of sulfonyl indanes or indenes.15-20 The sulfonyl group represents one of the most important organic functionalities and is found in many biologically active compounds and synthetic intermediates. Therefore, the incorporation of the sulfonyl group into organic molecules is an important task.21-27 In Scheme 1, the typical routes for the synthesis of 2sulfonyl indanes and indenes include: (i) oxidation of 2-indanyl phenyl sulfide,15 (ii) Ir+ catalysed [2+2+2] cycloaddition of sulfonyl diyne and monoyne,16 (iii) base-mediated conjugation of tosylmethyl isocyanide (TosMIC) and 2-bromobenzyl bro-

mide,17 (iv) Cu+ promoted sulfonylation of indene with dimethyl sulfoxide in the presence of an oxygen atmosphere, 18 (v) Pd2+ promoted remote ortho C-H alkenylation of arylethyl 2pyridyl sulfone followed by base mediated intramolecular ringclosure19 and (vi) electrooxidative tandem cyclization of activated alkynes with sulfinic acid.20 Although diversified routes have been described to construct sulfonyl indanes or indenes, it still remains challenging to explore a facile and high-yield method in the formation of this core system. Scheme 1. Typical Routes of 2-Sulfonyl Indanes and Indenes electrooxidative cycliztion (ref 20)

condensation / ring-closure (this work) O O R S O + Ar Ar' O

Ph

O

O S OH + Ph

Pt (+) / Pt (_)

Amberlyst 15

N Ph

S

R O

O

R

S 2

O

O

O S Pd(II) O

S 2

then base

Ar

Ar oxidation (ref 15) Me S O MeO2C

Ir(I)

O

t-BuLi Tol

+

Ph

O

S

Cu(I), O2

O Br

Et N

+

o-alkenylation/ annulation (ref 19)

O Me S Me

+

Br [2+2+2] cycloaddition (ref 16)

ACS Paragon Plus Environment

isocyanide-cyanide rearrangement (ref 17)

SO2Ph

+

sulfonylation (ref 18)

The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Herein, we describe easy-operational and high-yield synthetic routes for Amberlyst 15-promoted syntheses of 2sulfonyl arylindenes and arylindanes.28 To the best of our knowledge, there have been no reports for an acidic solid support mediated synthesis of indenes and indanes via (3+2) annulation fashion via the recyclable heterogeneous catalytic procedure. Commercially available Amberlyst-15 (abbreviated as A15, an ion exchange resin with a strongly acidic sulfonic group) is now routinely applied in organic synthesis as an environmentally benign reusable heterogeneous catalyst in functional group transformations of various molecules.29-32 Results and Discussion In continuation with our investigation efforts in the synthetic researches of β-ketosulfones,33-38 we investigated synthetic routes towards 2-sulfonyl arylindenes 1 and arylindanes 2, including (i) A-15-promoted Knoevenagel reaction of βketosulfones 5 and arylaldehydes 6 in toluene, (ii) R’MgBr or NaBH4-mediated regio- and/or stereochemical 1,4-addition of 1,4-/1,2-reduction of the resulting sulfonyl (E)-chalcones 4 in MeOH, THF or MeOH/THF and (iii) A-15 mediated sequential intramolecular Friedel-Crafts annulation of substituted βketosulfones 3 or -hydroxysulfones 7, as shown in Scheme 2. Scheme 2. Retrosynthetic Route of Indenes 1 and Indanes 2 Friedel-Crafts annulation R O

S

Ar'

O

R1 A-15 Ar

indene 1 O R S O Ar'

R

Ar

indane 2

O

S

O R'

R O

S

Ar'

Knoevenagel condensation R

Ar

Ar'

A-15

1,4-addition or 1,4- / 1,2-reduction

O 3

O

R'MgBr R O

O

S

Ar' Ar

NaBH4

O

S

O

Ar' A-15 Ar O

O 5

O

+

4

Ar

OH 7

6

The initial work began with the reaction of two model compounds, 5a (Ar’ = Ph, R = Tol, 0.5 mmol) and 6a (Ar = 3,4(MeO)2Ph, 0.6 mmol), with p-TsOH (0.5 mmol) in toluene at 25 °C and reflux for 20 h, respectively, in the presence of MgSO4 (200 mg) under an open-vessel condition. However, no reaction was observed (Table 1, entries 1-2). Using a DeanStark distillation apparatus, 4a was isolated in a 35% yield after reflux for 3 h (entry 3). After elongating the reaction (3  10 h), a similar yield (32%) of 4a was observed (entry 4). By the removal of water, the yield of 4a was slightly increased. After adjusting the solvent from toluene to CHCl3, only 21% of 4a was obtained (entry 5). In entries 6-7, other solvents (e.g., benzene and xylene) could not enhance the yield of 4a. Next, catalytic and stoichiometric amounts of p-TsOH were examined. In entries 10-13, the use of 0.1, 0.5 and 1.5 equiv of pTsOH gave 4a in 89%, 68% and 33% yields, respectively (entries 8-10). From the results, we found that catalytic amounts (0.1 equiv) provided better yields of 4a (85%) than other stoichiometric amounts. Possible reasons for this could be that excess protons triggered the intermediate of β-hydroxysulfone to cause the retro-aldol process to occur easily, thus inhibiting the dehydration pathway, and two starting materials, 5a and 6a, were recovered as major products under Brønsted acid mediated Knoevenagel condensation. Other commercially available sulfonic acids were screened next (entries 11-13). We found that the catalytic amounts of MsOH, TfOH and Tf 2NH could not enhance the yield of 4a due to the stronger acidity resulting in the formation of a complex mixture. With these considera-

Page 2 of 30

tions in mind, we turned our attention to A-15. It is a macroreticular polystyrene-based ion exchange solid support with a strongly acidic sulfonic group.39 By using A-15 (1.0 g), the yield of 4a was increased to 92% (entry 14). To decrease the weight (1.0  0.5  0.1 g), high yields were maintained by using the Dean-Stark apparatus (entries 15-16). Entry 17 showed that once recovered A-15 (0.1 g) also provided 4a in an 85% yield. Twice recovered A-15 (0.1 g) provided 4a in low yield (40%, entry 18). However, when recovered A-15 (0.1 g) was used three times, only a trace amount (5%) of 4a was observed. Therefore, we believe that A-15 is an optimal acidic promoter because it is required in catalytic amounts, is safe to operate, and is readily removed at the end of the reaction. Table 1. Reaction Conditionsa Tol O

S

O

O

OMe

+

Ph

O 5a

OMe 6a

acidic conditions

Tol O

S

Ph

O OMe O

OMe 4a

entry reagent (equiv or g) solvent time (h) temp (oC) %b 1 p-TsOH (1 equiv) toluene 20 25 ─c-e 2 p-TsOH (1 equiv) toluene 20 111 ─c-e 3 p-TsOH (1 equiv) toluene 3 111 35f 4 p-TsOH (1 equiv) toluene 20 111 32f 5 p-TsOH (1 equiv) CHCl3 3 61 21f 6 p-TsOH (1 equiv) benzene 3 80 30f 7 p-TsOH (1 equiv) xylene 3 145 32f 8 p-TsOH (0.1 equiv) toluene 3 111 85f 9 p-TsOH (0.5 equiv) toluene 3 111 68f 10 p-TsOH (1.5 equiv) toluene 3 111 33f 11 MsOH (0.1 equiv) toluene 3 111 80f 12 TfOH (0.1 equiv) toluene 3 111 46f-g 13 Tf2NH (0.1 equiv) toluene 3 111 25f-g 14 A-15 (1.0 g) toluene 3 111 92f 15 A-15 (0.5 g) toluene 3 111 92f 16 A-15 (0.1 g) toluene 3 111 92f h 17 A-15 (0.1 g) toluene 3 111 85f i 18 A-15 (0.1 g) toluene 3 111 40f a Reactions were performed using a 0.5 mmol scale with 5a, 6a (1.2 equiv), solvent (10 mL). bIsolated yields. cMgSO4 (0.2 g) was added. dNo reactions. eOpen-vessel condition. fDean-Stark apparatus. gMajor complex mixture was obtained. hRecovered A-15 was used. iTwice recovered A-15 was used. To study the substrate scope of A-15 mediated Knoevenagel condensation, substituted 5 and 6 were reacted in toluene to afford diversified 4 by the optimal conditions established (Table 1, entry 16). As shown in Table 2, the facile formation of 4a-4ai showed that the R and Ar’ substituents of 5a-5p and the Ar substituent of 6a-6y did not influence the yield (entries 141). However, 4s, having a tricyclic bulky group (Ar = 9anthracyl), was not produced (from 5a and 6s, entry 19). Among these substrates, 4ai (Ar = 2-NO2C6H4, entry 35), 4al (Ar = 2-pyridyl, entry 38) and 4am (Ar = 2-furyl, entry 39) provided lower yields (72%, 68% and 64%). For the electronic character of the Ar’ substituents of 4, electron-neutral, electron withdrawing, and electron-donating groups were suitable. For the R substituent of 4, both aliphatic and aromatic sulfonyl groups were appropriate. For the Ar substituent of 6, electron-


Page 3 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


neutral, donating and withdrawing and heterocyclic groups were also well-tolerated. For the structural framework of all isolated 4, only the (E)-isomer was observed. The structure of 4n was determined by single-crystal X-ray analysis.40 Table 2. Synthesis of 4a-b R O

S

O

O

Ar'

Ar

O 5

R

2

+ 6

5

3

Amberlyst 15

4

toluene

O

S

Ar'

O Ar O 4

entry 5, R =, Ar’ = 6, Ar = 4, %b 1 5a, Tol, Ph 6a, 3,4-(MeO)2C6H3 4a, 92 2 5a, Tol, Ph 6b, 3,4-CH2O2C6H3 4b, 95 3 5a, Tol, Ph 6c, 3-MeOC6H4 4c, 96 4 5a, Tol, Ph 6d, 4-MeOC6H4 4d, 93 5 5a, Tol, Ph 6e, 3,4,5-(MeO)3C6H2 4e, 93 6 5a, Tol, Ph 6f, Ph 4f, 94 7 5a, Tol, Ph 6g, 2-naphthyl 4g, 90 8 5a, Tol, Ph 6h, 4-ClC6H4 4h, 96 9 5a, Tol, Ph 6i, 3,4-Cl2C6H3 4i, 95 10 5a, Tol, Ph 6j, 4-FC6H4 4j, 94 11 5a, Tol, Ph 6k, 2-BrC6H4 4k, 93 12 5a, Tol, Ph 6l, 3-NO2C6H4 4l, 92 13 5a, Tol, Ph 6m, 4-HOC6H4 4m, 94 14 5a, Tol, Ph 6n, 4-PhC6H4 4n, 90 15 5a, Tol, Ph 6o, 4-MeC6H4 4o, 90 16 5a, Tol, Ph 6p, 2-allyl-3,4-(MeO)2C6H2 4p, 83 17 5a, Tol, Ph 6q, 3-pyridyl 4q, 80 18 5a, Tol, Ph 6r, 2-thienyl 4r, 84 19 5a, Tol, Ph 6s, 9-anthracyl 4s, ─c 20 5b, Tol, 4-FC6H4 6a, 3,4-(MeO)2C6H3 4t, 98 21 5c, Tol, 4-MeOC6H4 6a, 3,4-(MeO)2C6H3 4u, 97 22 5d, Tol, Tol 6a, 3,4-(MeO)2C6H3 4v, 95 23 5e, Tol, 4-CF3C6H4 6a, 3,4-(MeO)2C6H3 4w, 92 24 5f, Tol, 4-NO2C6H4 6a, 3,4-(MeO)2C6H3 4x, 90 25 5g, Tol, 4-PhC6H4 6a, 3,4-(MeO)2C6H3 4y, 90 26 5h, Tol, 2-naphthyl 6a, 3,4-(MeO)2C6H3 4z, 92 27 5i, Ph, Ph 6a, 3,4-(MeO)2C6H3 4aa, 90 28 5j, 4-FC6H4, Ph 6a, 3,4-(MeO)2C6H3 4ab, 96 29 5k, 4-MeOC6H4, Ph 6a, 3,4-(MeO)2C6H3 4ac, 96 30 5l, 4-EtC6H4, Ph 6a, 3,4-(MeO)2C6H3 4ad, 94 31 5m, 4-tBuC6H4, Ph 6a, 3,4-(MeO)2C6H3 4ae, 93 32 5n, Me, Ph 6a, 3,4-(MeO)2C6H3 4af, 96 33 5o, nBu, Ph 6a, 3,4-(MeO)2C6H3 4ag, 96 34 5p, Tol, 3,4-Cl2C6H3 6f, Ph 4ah, 96 35 5a, Tol, Ph 6t, 2-NO2C6H4 4ai, 72 36 5a, Tol, Ph 6u, 2-NBn-pyrrolyl 4aj, 80 37 5i, Ph, Ph 6r, 2-thienyl 4ak, 84 38 5a, Tol, Ph 6v, 2-pyridyl 4al, 68 39 5a, Tol, Ph 6w, 2-furyl 4am, 64 40 5a, Tol, Ph 6x, 2-benzofuryl 4an, 84 41 5a, Tol, Ph 6y, 2-benzothienyl 4ao, 78 a Reactions were performed using a 0.5 mmol scale with 5, 6 (1.2 equiv), A-15 (0.1 g), toluene (10 mL), reflux, 3 h. bIsolated yields. cNo reaction.

Furthermore, phenylacetaldehyde was examined, but no desired product was detected. We think that these abovementioned reaction conditions could make the cross-aldol coupling of aldehydes and β-ketosulfones occur easily, which could allow a complex mixture to be formed. Another attempt to adjust the carbonyl synthon from aldehyde to ketone was evaluated. However, no reaction was observed for the A-15 catalysed condensation of 5a and acetophenone. Overall, the present condition would only be suitable for the arylaldehyde group. Scheme 3. Synthesis of 3a-3an R O

S

O

R'MgBr, THF

3

Ar

Ar'

R

2

O

4

reflux, 10 h

5

O

S

O R'

3

Ar'

O

4

Tol O

S

Ph

O

2

Ar

4

5

3

Tol O

Ar

S

Ph

O

3a, Ar = Ph (86%) 3b, Ar = 4-MeOC6H4 (85%) 3c, Ar = 4-MeC6H4 (80%) 3d, Ar = 4-FC6H4 (83%) 3e, Ar = 4-PhC6H4 (79%) 3f, Ar = 2-naphthyl (78%) 3g, Ar = 3,4-(MeO)2C6H3 (80%) 3h, Ar = 3,4-CH2O2C6H3 (82%) 3i, Ar = 3,4,5-(MeO)3C6H2 (78%)

O R'

Tol OMe OMe

O

3j, R' = Ph (73%) 3k, R' = 4-FC6H4 (72%) 3l, R' = 4-MeOC6H4 (70%) 3m, R' = 4-MeC6H4 (74%) 3n, R' = 2-MeC6H4 (67%) 3o, R' = Me (63%) 3p, R' = iPr (80%) 3q, R' = cC5H9 (83%)

Tol O

S

O

O OMe

Ar'

O

OMe

3r, Ar' = 4-FC6H4 (82%) 3s, Ar' = 4-MeC6H4 (84%) 3t, Ar' = 4-MeOC6H4 (80%) 3u, Ar' = 4-CF3C6H4 (86%) 3v, Ar' = 4-PhC6H4 (85%) 3w, Ar' = 2-naphthyl (82%)

R

O R'

S

O

S

O

Ar Ph O R = Tol Ar = Ph, 3ah, Ar = 2-NBn-pyrrolyl (80%) 3ad, R' = 4-FC6H4 (74%) 3ai, Ar = 2-pyridyl (82%) Ph O OMe Ar = 2-thienyl, 3aj, Ar = 2-furyl (80%) 3ae, R' = cC6H11 (75%) R = Ph 3x, R = Ph (80%) 3af, R' = cC5H9 (78%) 3ak, Ar = 2-thienyl (86%) 3y, R = Me (78%) 3ag, R' = iPr (80%) 3z, R = 4-MeOC6H4 (74%) R = Tol 3al, R' = 2-benzofuryl (83%) 3aa, R = 4-FC6H4 (82%) 3ab, R = 4-iPrC6H4 (85%) 3am, R' = 2-benzothienyl (80%) 3an, R' = 2-allyl-3,4-(MeO)2C6H3 (72%) 3ac, R = 4-nBuC6H4 (82%) R

O

S

O

OMe

Ph

Ar

O

With the above experimental results in hand, we shifted the synthetic aim to investigate the conjugate addition of sulfonyl chalcones 4 with the use of different Grignard reagents (Scheme 3). Initially, by controlling the R and Ar’ group on 4 as the Tol and Ph, the cC6H11MgBr-mediated 1,4-addition of 4 with diversified Ar group provided 3a-3l in modest to good yields (78%-86%). For the Ar group, electron-neutral groups (Ph, Tol, biphenyl, naphthyl), an electron-withdrawing group (4-FC6H4) and electron-donating mono-, di- or tri-oxygenated groups were appropriate. Then, the R’ group was changed from cyclohexyl to different aromatic and aliphatic groups, and 3j3q were produced in lower yields (63%-83%) by the conjugate addition of 4a. For the R’ group, the aromatic groups (Ph, 4FC6H4, 4-MeOC6H4, 4-MeC6H4, 2-MeC6H4) provided slightly higher yields than the aliphatic groups (Me, iPr, cC5H9). Among them, the 2-MeC6H4 group afforded 3n at a low yield (67%) due to the steric hindrance of the ortho-methyl group. In particular, Me with a smaller group also provided a low yield (63%) of 3o. Following, when the Ar’ group was changed to other aromatic groups, 3r-3w were obtained in good yields (80%-86%) via the Grignard addition of 4t-4w and 4y-4z with cC6H11MgBr. Furthermore, adjusting the R group to methyl and other aromatic groups, 3z-3ad were isolated with yields in a range from 74%-85%. Since Ar became a heterocycle, the monocycles (2-thienyl, 2-NBn-pyrrolyl, 2-pyridyl, 2-furyl) and bicycles (2-benzofuryl and 2-benzothienyl) provided 3ae-3am in 75%-86% yields. Additionally, 3an with an allylaryl moiety was generated in a 72% yield. The results showed that treat-



ment of 4 with different Grignard reagents generated diversified Michael adducts. Among these products, no 1,2-adducts were detected. For comparison between the 1,2-addition and 1,4-addition, DFT calculations were applied to provide a reasonable explanation for the regiospecificity of the addition reaction of 4. Two conformations were found for 4a (Figure 1). One was the closed conformation in which the toluene ring on the sulfonyl group and the phenyl ring on the carbonyl group formed a -stacked arrangement; the - distance (centroid to centroid) was 3.94 Å and the torsional angle (centroid-S-C-centroid) was approximately 15. It can be clearly seen in this structure that the carbon atom of the carbonyl group is well shielded by the toluene and (MeO)2C6H3 rings; therefore, the 1,2-addition is expected to be sterically hindered. By contrast, the carbon atom of the =CH bridging group is exposed and in a less crowded environment, rendering the 1,4-addition more favourable in terms of steric consideration. The other conformation was an open form in which the toluene ring and the phenyl ring pointed in opposite directions; the torsional angle was 110. Although in this structure the carbonyl group is not protected by the toluene ring, the environment of the carbonyl group was still somewhat crowded due to the presence of the sulfonyl group (S=OC=O distance is 2.91 Å ). Furthermore, this open conformation was 2 kcal/mol higher than the closed conformation and should be the minor form. Figure 1. DFT Optimized Structures of 4a. The Relative Free Energy (in kcal/mol) is Given in Parenthesis.

Page 4 of 30

We also calculated the 1,2- and 1,4-adducts derived from the reaction of 4a and the cC5H9MgBr Grignard reagent (Figure 2). The 1,4-adduct (3q) was found to be substantially more stable than the 1,2-adduct by 15 kcal/mol, which is in line with the experimental observation that no 1,2-adduct was detected. The natural steric analysis showed that the steric repulsion in the 1,2-adduct is significantly greater than that in the 1,4-adduct; the steric exchange energies are 2468.3 and 2390.2 kcal/mol for the 1,2- and 1,4-adducts, respectively. These results suggest that the stability of these adducts; thus, the regioselectivity of the addition reaction are determined by the steric effect. Scheme 4. Synthesis of 3ao-3as Tol O

S

O

Tol Ar

Ar'

O

S

NaBH4, THF / MeOH

O

then PCC, CH2Cl2 (yields of two-steps)

Ar'

4a-4b, 4e, 4w-4x

O

2 3

Ar O

4

5

Ar' = Ph 3ao, Ar = 3,4-(MeO)2C6H3 (90%) 3ap, Ar = 3,4-CH2O2C6H3 (86%) 3aq, Ar = 3,4,5-(MeO)3C6H2 (90%) Ar = 3,4-(MeO)2C6H3 3ar, Ar' = 4-CF3C6H4 (84%) 3as, Ar' = 4-NO2C6H4 (90%)

On the other hand, by adjusting the R’ group from aliphatic and aromatic to hydride, the reduction of sulfonyl chalcones 4 was examined (Scheme 4). When R’MgBr was changed to NaBH4, we found that a sequential 1,4- and then a 1,2reduction process occurred to generate -hydroxysulfones by the use of 4a-4b, 4e and 4w-4x. The tandem reduction procedure has been described in our previous report.41 Then, oxidation of the resulting -hydroxysulfones with PCC provided 3ao-3as in 84%-90% yields of a two-step process. Overall, skeleton 3 could be prepared with good yields and was utilized as the precursor for the formation of indenes. Scheme 5. Synthesis of 1a-1z R O

S

Ar'

O R'

R Amberlyst 15

O

Ar toluene reflux, 10 h

O

S

O

S

O

1

Tol O Ar

Ph

2

Ar

Ar'

3

Tol

R'

O

S

O

R'

5

Tol O

Ph

3

4

S

O

Ar'

OMe

OMe

OMe 1a, Ar = 3,4-(MeO)2C6H2 (90%) 1b, Ar = 3,4-CH2O2C6H2 (86%) 1c, Ar = 3,4,5-(MeO)3C6H (90%)

Figure 2. DFT Optimized Structures of 1,2- and 1,4-Adducts from 4a + cC5H9MgBr Reaction (for 3q). The Relative Free Energy (in kcal/mol) is Given in Parenthesis.

R O

S

OMe

1d, R' = Ph (89%) 1e, R' = 4-FC6H4 (85%) 1f, R' = 4-MeOC6H4 (92%) 1g, R' = iPr (74%) 1h, R' = cC5H9 (86%)

O

Ph

Tol OMe

1o, R = Ph (88%) OMe 1p, R = Me (90%) 1q, R = 4-MeOC6H4 (91%) 1r, R = 4-FC6H4 (92%) 1s, R = 4-iPrC6H4 (86%) 1t, R = 4-nBuC6H4 (86%)

O

S

Tol

O

Ph 1u (80%)

1i, Ar' = 4-FC6H4 (92%) 1j, Ar' = 4-MeC6H4 (90%) 1k, Ar' = 4-MeOC6H4 (93%) 1l, Ar' = 4-CF3C6H4 (89%) 1m, Ar' = 4-PhC6H4 (85%) 1n, Ar' = 2-naphthyl (86%)

Me O OMe

O

S

Ar'

O

Ar

Ar' = Ph, 1v, Ar = 3,4-(MeO)2 (78%) 1w, Ar = 3,4-CH2O2 (74%) 1x, Ar = 3,4,5-(MeO)3 (83%) Ar = 3,4-(MeO)2C6H2 1y, Ar' = 4-CF3C6H4 (82%) 1z, Ar' = 4-NO2C6H4 (75%)

On the basis of these experimental results, we focused on the construction of sulfonyl indenes 1 by A-15 mediated intramolecular Friedel-Crafts annulation of skeleton 3. First, the reaction of 3a was treated with A-15 under the above DeanStark distillation. However, no desired indene skeleton was isolated and only starting material 3a was recovered. For the A-15 mediated reaction of 3b-3f, no reactions were observed until Ar was introduced with an oxygenated aromatic group, then intramolecular Friedel-Crafts annulation could be trig-


Page 5 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


gered (Scheme 5). The resulting phenomenon suggested that the electron-donating oxygenated group enrich the -electron density of the reaction system to trigger intramolecular ringclosure. Furthermore, 1a-1c (Ar = 3,4-(MeO)2C6H2, 3,4CH2O2C6H2, 3,4,5-(MeO)3C6H) were obtained in good yields (90%, 86%, 90%) via the A-15 mediated ring-closure of 3g-3i at reflux for 10 h. Changing the R’ group formed a cyclohexyl group to the aromatic (R’ = Ph, 4-FC6H4, 4-MeOC6H4) and aliphatic (R’ = iPr, cC5H9) groups; 1d-1h were obtained in 74%-92% yields. After adjusting the Ar’ from phenyl to other aromatic groups, 1i-1n were isolated in yields ranging from 85%-93%. Next, changing the R group to methyl and other aromatic groups, 1o-1t were isolated in yields ranging from 86%-92%. By controlling the Ar = 3,4-(MeO)C6H2 and R’ = cC6H11, different Ar’ and R substituents were well-tolerated in maintaining good yields for the formation of skeleton 1. Furthermore, when 3an was reacted with A-15, a tricyclic indenofused dihydrofuran 1u was isolated at an 80% yield via intramolecular Friedel-Crafts annulation. After replacing the R’ group with hydrogen, the A-15 mediated ring-closure of 3ao3as was examined. Under the reaction conditions, 1v-1z were produced in modest to good (74%-83%) yields. Although the Ar group on substrate 3 was limited to the oxygenated aryl group, it still provided a novel and efficient transformation from -arylketones to indenes. The molecular structures of 1a, 1e, 1h, 1q and 1z were determined by single-crystal X-ray analysis.40 As an extension of A-15 mediated Knoevenagel condensation protocol, the synthesis of indane 2 was explored. Initially, treatment of 4a with NaBH4 in THF-MeOH (1:1) at 25 °C for 3 h produced 7a (R = Tol, Ar’ = Ph) in a nearly quantitative yield (Scheme 6). The procedure possessed a regioselective 1,4reduction of 4a followed by a stereoselective 1,2-reduction of the corresponding ketone A. Because the isolated yield was high, crude 7a was reacted with A-15 without further purification. By the facile route, 2a was obtained in an 84% yield via intramolecular Friedel-Crafts type annulation. According to the Felkin-Anh model,41 the effect of steric hindrance on the sulfonyl group could inhibit the carbonyl reduction such that the hydride attacked the carbonyl with less-repulsion face to yield 7a via a possible intermediate B, which is completed by the A15-chelated complexation of a hydroxyl motif on 7a. Participation of the oxygenated arene led to 2a via one methoxy grouppromoted intramolecular stereocontrolled SN2 para-addition on intermediate C (see blue arrow). Scheme 6. Plausible Mechanism 1,4-reduction Tol O

S

O

Tol OMe

Ph

O 4a

NaBH4

less repulsion face

1,2-reduction

O

OMe THF / MeOH 25 oC, 3 h

S

O

H

OMe

H

OMe

O BH3 O S O Tol B

Ph

Ph

O

OMe

A

OMe

Felkin-Anh model Friedel-Crafts annulation Tol O

S

O

Ph 2a (84%)

Tol

O O S Ph

O H S

Tol

H

OMe

O

OH

OMe OMe

H

OMe

A-15 C

OMe

Ph

H

OH

OMe 7a

Considering these results, 4 was reacted via this approach to afford diversified 2, as shown in Table 3. In addition to 2i (Ar = 3,4-Cl2C6H3), 2l (Ar = 3-NO2C6H4), 2q (Ar = 3-pyridyl), 2w

(Ar’ = 4-CF3C6H4) and 2x (Ar’ = 4-NO2C6H4), the efficient formation of sulfonyl arylindane 2 showed that the R, Ar’ and Ar substituents did not influence the changes of yield (entries 1~34). For the R substituent of 4, both the aliphatic and aromatic sulfonyl groups were appropriate. For entries 9, 12, 17, 22 and 23, only 7i, 7l, 7q, 7w and 7x were afforded in excellent yields, and the desired skeleton 2 with the indane ring was not observed. After elongating the reaction time (3  60 h), the results were unchanged. Table 3. Synthesis of 2a R O

S

Ar'

O

2 3

Ar O

4

5

4

NaBH4 THF / MeOH (v / v = 1 / 1)

R O

S

Ar'

O

Amberlyst 15 Ar OH 7

toluene

R O

S

O

Ar

Ar' 2

entry 4, R =, Ar1 =, Ar = 2, %b 1 4a, Tol, Ph, 3,4-(MeO)2C6H3 2a, 84 2 4b, Tol, Ph, 3,4-CH2O2C6H3 2b, 86 3 4c, Tol, Ph, 3-MeOC6H4 2c, 88 4 4d, Tol, Ph, 4-MeOC6H4 2d, 86 5 4e, Tol, Ph, 3,4,5-(MeO)3C6H2 2e, 91 6 4f, Tol, Ph, Ph 2f, 84 7 4g, Tol, Ph, 2-naphthyl 2g, 86 8 4h, Tol, Ph, 4-ClC6H4 2h, 83 9 4i, Tol, Ph, 3,4-Cl2C6H3 2i, ─c 10 4j, Tol, Ph, 4-FC6H4 2j, 88 11 4k, Tol, Ph, 2-BrC6H4 2k, 87 12 4l, Tol, Ph, 3-NO2C6H4 2l, ─c 13 4m, Tol, Ph, 4-HOC6H4 2m, 86 14 4n, Tol, Ph, 4-PhC6H4 2n, 84 15 4o, Tol, Ph, 4-MeC6H4 2o, 82 16 4p, Tol, Ph, 2-allyl-3,4-(MeO)2C6H2 2p, 80 17 4q, Tol, Ph, 3-pyridinyl 2q, ─c 18 4r, Tol, Ph, 2-thienyl 2r, 80 19 4t, Tol, 4-FC6H4, 3,4-(MeO)2C6H3 2t, 82 20 4u, Tol, 4-MeOC6H4, 3,4-(MeO)2C6H3 2u, 82 21 4v, Tol, 4-MeC6H4, 3,4-(MeO)2C6H3 2v, 82 22 4w, Tol, 4-CF3C6H4, 3,4-(MeO)2C6H3 2w, ─c 23 4x, Tol, 4-NO2C6H4, 3,4-(MeO)2C6H3 2x, ─c 24 4y, Tol, 4-PhC6H4, 3,4-(MeO)2C6H3 2y, 86 25 4z, Tol, 2-naphthyl, 3,4-(MeO)2C6H3 2z, 87 26 4aa, Ph, Ph, 3,4-(MeO)2C6H3 2aa, 87 27 4ab, 4-FC6H4, Ph, 3,4-(MeO)2C6H3 2ab, 88 28 4ac, 4-MeOC6H4, Ph, 3,4-(MeO)2C6H3 2ac, 86 29 4ad, 4-EtC6H4, Ph, 3,4-(MeO)2C6H3 2ad, 84 30 4ae, 4-tBuC6H4, Ph, 3,4-(MeO)2C6H3 2ae, 86 31 4af, Me, Ph, 3,4-(MeO)2C6H3 2af, 89 32 4ag, nBu, Ph, 3,4-(MeO)2C6H3 2ag, 85 33 4ah, Tol, 3,4-Cl2C6H3, 3,4-(MeO)2C6H3 2ah, 82 a The reactions were performed using a 0.3 mmol scale with 4, NaBH4 (38 mg, 1.0 mmol), THF/MeOH (v/v = 1/1, 10 mL), 30 min, 25 oC; then A-15 (0.1 g), toluene (10 mL), reflux, 10 h. b Isolated yields. c7i (96%), 7l (96%), 7q (96%), 7w (98%), 7x (94%) were isolated.



For the annulation of 4g with a naphthyl group, angular 2g was obtained as the only product, and another linear regioisomer could be observed. In particular, 2h, having a 4chlorophenyl group, was isolated in an 83% yield; however, 2i with a 3,4-dichlorophenyl group could not be produced under A-15 mediated annulation (entries 8-9). It was considered that the 3-chloro group controlled the reaction. For the electronic nature of aryl substituents (Ar’ and Ar) of 4, stronger electronwithdrawing nitro and trifluoromethyl groups (for 4l, 4w, 4x) were inappropriate. In the comparison of heterocyclic (3pyridyl and 2-thienyl) groups (entries 17-18), 2q with a pyridyl group was not isolated because the nitrogen atom trapped the proton such that intramolecular annulation was easily inhibited. According to the above results, two adjacent stereochemical centres on skeleton 2 were assigned as the trans orientation. The structures of 2e, 2g, 2k, 2r and 7l were determined by single-crystal X-ray analysis.40 Subsequently, the construction of 2ai-2ak was furnished via the NaBH4-mediated stereochemical 1,2-reduction of 3v-3w and 3ad, which was followed by A-15-mediated intramolecular ring-closure of the corresponding -hydroxysulfones (Scheme 7). For 2ai-2ak, the isolated yields (75%, 70%, 62%, respectively) were lower than the other 2 (in Table 3) due to the steric hindrance of the R’ group that resulted. The stereochemical structure of 2ai with three contiguous trans-trans chiral centres was determined by single-crystal X-ray analysis.40 From the Xray structure of 2ai, we also indirectly determined that the relative stereochemistry of skeleton 3 between the R’ and tosyl substituents was in the trans-conformation.

(Scheme 8). Desulfonylation of 2ah with sodium amalgam (6% Na/Hg) in MeOH followed by benzylic oxidation of the corresponding product with PDC in DMF furnished the indatraline intermediate 8 in a 64% yield in two steps. Furthermore, synthesis of sulfonyl arylquinoline skeleton 9 was accomplished with a 75% yield via SnCl2-mediated reduction of 4ai in CH2Cl2 at 25 °C for 10 h.43 After NaBH4-mediated reduction of 4k, the resulting 1,5-bromoalcohol underwent an intramolecular CuI-catalysed Ullman coupling rection,44 producing tosyl chroman 10 in a 48% yield in two steps.45 Then, by the use of the abovementioned two-step route (desulfonylation and benzylic oxidation), flavanone 11 was prepared in a 52% yield.46 As an extension of the synthetic application of 1v, the isoquinoline skeleton was synthesized.47 By using a OsO4/NaIO4mediated double bond oxidative cleavage procedure, 48 the cyclopentene moiety of 1v could be converted into a 1,5dicarbonyl group. Following, by the inclusion of NH 4OAc (a nitrogen source), 12 was obtained in a 27% yield via the (5C+1N) annulation process. Scheme 9. Gram-Scale Synthesis of 8 Tol O

S

O

O

S

Tol

Ar'

O

S

OMe

1) NaBH4, THF / MeOH

O

OMe

2) Amberlyst 15, toluene

Ar'

O

R'

OMe OMe

3w, R' = cC6H11, Ar' = 2-naphthyl 3v, R' = cC6H11, Ar' = 4-PhC6H4 3ad, R' = 4-FC6H4, Ar' = Ph

2ai (75%, X-Ray) 2aj (70%) 2ak (62%)

Scheme 8. Synthesis of 8-12 Tol O

S

O

O

NHMe

1) 6% Na/Hg, MeOH 2) PDC, DMF (64% of two steps)

Cl

2ah

Cl Tol O

S

O

Tol

O 4ai

O

S

O

S

Br

Cl

Cl

indatraline

O

N 9 (75%)

Tol

O

S

Ph

1) NaBH4, THF / MeOH

4k Tol

O

NO2

O

Ph

8

Cl

SnCl2, CH2Cl2

Ph

Tol

Cl

2) CuI, KI, K3PO4, toluene, 1,10-Phen (48% of two steps)

O

S

O 1) 6% Na/Hg, MeOH

Ph

2) PDC, DMF (52% of two steps)

O 10

O

O

1) OsO4, NMO THF / H2O, then NaIO4

Ph 1v

OMe 2) NH4OAc, MeOH (27% of two steps) OMe

OMe N

OMe

Ph

O

Ph 12

11

Indatraline (Lu 19-005) is a non-selective monoamine transporter inhibitor that has been shown to block the reuptake of dopamine, norepinephrine and serotonin with effects similar to those of cocaine. Many facile and efficient synthetic methods have been developed.42 Based on the Amberlyst 15-catalysed route, the formal synthesis of indatraline was investigated

S

O

O

toluene

Cl Cl 5p (3.42 g, 10 mmol)

O

Amberlyst 15

+

Cl Cl 4ah (85%, 3.66 g)

6f (1.12 g, 11 mmol) Tol

NaBH4, THF / MeOH, then

O

S

O

O 1) 6% Na/Hg, MeOH 2) PDC, DMF

Amberlyst 15, toluene Cl

O R'

Tol

O O

Scheme 7. Synthesis of 2ai-2ak Tol

Page 6 of 30

Cl 2ah (72%, 2.55 g)

Cl

Cl 8 (59%, 995 mg)

Because of the potential application of this protocol in synthesis of indatraline intermediate 8, attempts to scale up the transformation would improve the significance of the results. Thus, the development of a gram-scale method was highly in demand. When the scale for the A-15 mediated Knoevenagel condensation of 5p and 6f increased to 10 mmol (3.42 g) and 11 mmol (1.12 g), 4ah was isolated in an 85% (3.66 g) yield in toluene at reflux. After NaBH4-mediated reduction and A-15promoted intramolecular annulation, 2ah was isolated in a 72% yield (2.55 g). Finally, the Na/Hg-mediated desulfonylation of 2ah and PDC-mediated benzylic oxidation of the resulting indane furnished 8 in a 59% yield (995 mg). For the gram scale (10 mmol) synthesis of 8, the total yield was 36%. In summary, we have developed an Amberlyst 15 (A-15) mediated synthetic route for constructing sulfonyl arylindenes 1 and indanes 2 in good to excellent yields, including (1) Knoevenagel condensation of 5 and 6, (ii) regio- and/or stereocontrolled addition or reduction of 4 and (iii) intramolecular Friedel-Crafts annulation of the resulting -ketosulfones or hydroxysulfones. DFT calculations for the regioselectivity of the addition reaction have been discussed. The process provides a facile route for the formation of two carbon-carbon (CC) bonds. The use of different sulfonic acids was studied for a novel and efficient transformation. We took the initiative to explore the synthetic applications of the developed method towards the skeletons of indanone, quinoline, chroman, flavanone and isoquinoline. Further investigations regarding the synthetic researches of β-ketosulfones are underway in our laboratory.


Page 7 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Experimental Section General. All reagents and solvents were commercial grade and were used without further purification. All reactions were routinely performed under an air atmosphere with magnetic stirring (an open-vessel condition). All products in organic solvents were dried with anhydrous MgSO4 before concentration in vacuo under reduced pressure. Melting points (mp) were measured with a SMP3 melting apparatus. 1H (400 MHz) and 13 C NMR (100 MHz) spectra were recorded on a Varian INOVA-400 spectrometer, respectively. Chemical shifts (δ) are reported in ppm and the J values are given in Hertz. Highresolution mass spectra (HRMS) were measured with a double focusing mass spectrometer by ESI using a hybrid ion-trap. Xray crystal structures were determined with a diffractometer (CAD4, Kappa CCD). For the starting substrates 5, these compounds were known and their related analytical data (e.g., mp, 1H NMR, 13C NMR and HRMS) were consistent with those in the references 34-36. For the starting substrates 6, these materials were purchased commercially and were used without further purification. General synthetic procedure of skeleton 4 is as follows: Amberlyst® 15 (A-15, 100 mg) was added to a solution of βketosulfones 5 (0.5 mmol) in toluene (20 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 10 min under DeanStark distillation apparatus. Arylaldehydes 6 (0.6 mmol) was added to the reaction mixture at 25 oC. The reaction mixture was stirred at reflux for 3 h. The reaction mixture was cooled to 25 oC. A-15 was filtered by filter paper and the A-15 was washed with toluene (3 x 5 mL). The combined toluene layers were concentrated. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product mixture under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 4. A15 was dried and recovered for the next reaction cycle of intermolecular Knoevenagel condensation. 3-(3,4-Dimethoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4a). 4a was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 92% (194 mg); Colorless solid; mp = 134-136 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23O5S 423.1266; Found 423.1266; 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.94-7.92 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.547.49 (m, 1H), 7.38-7.34 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.96 (dd, J = 2.0, 8.4 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.0 Hz, 1H), 3.79 (s, 3H), 3.49 (s, 3H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 151.5, 148.7, 144.5, 141.1, 137.1, 136.7, 135.7, 134.4, 129.7 (2x), 129.6 (2x), 128.8 (2x), 128.4 (2x), 125.5, 124.0, 112.0, 110.8, 55.8, 55.4, 21.6. 3-Benzo[1,3]dioxol-5-yl-1-phenyl-2-(toluene-4sulfonyl)propenone (4b). 4b was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6b (90 mg, 0.6 mmol). Yield = 95% (193 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H19O5S 407.0953; Found 407.0954; 1H NMR (400 MHz, CDCl3): δ 7.91-7.89 (m, 2H), 7.90 (s, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.54-

7.50 (m, 1H), 7.39-7.35 (m, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.87 (dd, J = 1.6, 8.0 Hz, 1H), 6.66 (s, 1H), 6.65 (d, J = 9.6 Hz, 1H), 5.86 (s, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.5, 150.1, 148.1, 144.6, 140.7, 137.5, 136.9, 135.6, 134.4, 129.80 (2x), 129.75 (2x), 128.8 (2x), 128.5 (2x), 126.7, 125.5, 109.1, 108.6, 101.7, 21.6. 3-(3-Methoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4c). 4c was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6c (82 mg, 0.6 mmol). Yield = 96% (188 mg); Colorless solid; mp = 115-117 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O4S 393.1161; Found 393.1163; 1H NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.92-7.89 (m, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.53-7.49 (m, 1H), 7.38-7.33 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.11 (t, J = 8.0 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.80 (ddd, J = 0.8, 2.4, 8.4 Hz, 1H), 6.75 (t, J = 2.4 Hz, 1H), 3.55 (s, 3H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 159.5, 144.8, 140.9, 139.9, 136.6, 135.5, 134.4, 132.6, 129.8, 129.7 (4x), 128.8 (2x), 128.6 (2x), 123.0, 117.7, 114.2, 55.0, 21.6. 3-(4-Methoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4d). 4d was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6d (82 mg, 0.6 mmol). Yield = 93% (182 mg); Colorless solid; mp = 131-133 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O4S 393.1161; Found 393.1160; 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H), 7.93-7.90 (m, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.53-7.49 (m, 1H), 7.37-7.33 (m, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 2.41 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.7, 161.8, 144.5, 140.8, 137.1, 136.8, 135.6, 134.3, 132.3 (2x), 129.8 (2x), 129.7 (2x), 128.7 (2x), 128.4 (2x), 123.9, 114.3 (2x), 55.2, 21.6. 1-Phenyl-2-(toluene-4-sulfonyl)-3-(3,4,5trimethoxyphenyl)propenone (4e). 4e was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6e (118 mg, 0.6 mmol). Yield = 93% (210 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H25O6S 453.1372; Found 453.1373; 1H NMR (400 MHz, CDCl3): δ 7.94 (s, 1H), 7.94-7.91 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.537.49 (m, 1H), 7.38-7.34 (m, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.48 (s, 2H), 3.74 (s, 3H), 3.56 (s, 6H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.4, 152.9 (2x), 144.6, 141.0, 140.3, 138.4, 136.7, 135.5, 134.4, 129.6 (2x), 129.5 (2x), 128.8 (2x), 128.4 (2x), 126.4, 107.7 (2x), 60.7, 55.7 (2x), 21.5. 1,3-Diphenyl-2-(toluene-4-sulfonyl)propenone (4f). 4f was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6f (64 mg, 0.6 mmol). Yield = 94% (170 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19O3S 363.1055; Found 363.1054; 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.91-7.88 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.54-7.49 (m, 1H), 7.37-7.17 (m, 9H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 144.8, 141.0, 139.9, 136.7, 135.5, 134.4, 131.5, 131.0, 130.2 (2x), 129.9 (2x), 129.8 (2x), 128.9 (2x), 128.8 (2x), 128.7 (2x), 21.7. 3-Naphthalen-2-yl-1-phenyl-2-(toluene-4sulfonyl)propenone (4g). 4g was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6g (94 mg, 0.6 mmol). Yield = 90% (185 mg); Colorless solid; mp



= 164-166 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H21O3S 413.1212; Found 413.1213; 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 7.96-7.94 (m, 2H), 7.86 (d, J = 0.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.73-7.68 (m, 2H), 7.59 (d, J = 8.8 Hz, 1H), 7.49-7.44 (m, 3H), 7.35-7.25 (m, 5H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.5, 144.8, 141.1, 139.7, 136.8, 135.7, 134.4, 134.0, 132.7, 132.0, 129.8 (3x), 128.9, 128.7 (3x), 128.6 (4x), 127.9, 127.6, 126.8, 125.5, 21.6. 3-(4-Chlorophenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4h). 4h was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6h (84 mg, 0.6 mmol). Yield = 96% (190 mg); Colorless solid; mp = 162-164 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18ClO3S 397.0665; Found 397.0668; 1H NMR (400 MHz, CDCl3): δ 7.98 (s, 1H), 7.89-7.86 (m, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.53-7.49 (m, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.33-7.30 (m, 2H), 7.20 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.0, 144.9, 140.4, 139.3, 137.0, 136.4, 135.2, 134.5, 131.2 (2x), 129.8, 129.71 (2x), 129.69 (2x), 129.1 (2x), 128.8 (2x), 128.6 (2x), 21.5. 3-(3,4-Dichlorophenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4i). 4i was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6i (104 mg, 0.6 mmol). Yield = 95% (204 mg); Colorless solid; mp = 151-153 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H17Cl2O3S 431.0276; Found 431.0278; 1H NMR (400 MHz, CDCl3): δ 7.91 (s, 1H), 7.88-7.86 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.567.52 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 7.06 (dd, J = 2.0, 8.4 Hz, 1H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.7, 145.2, 142.0, 137.8, 136.1, 135.2, 135.1, 134.8, 133.2, 131.8, 131.4, 130.8, 129.8 (2x), 129.7 (2x), 128.9 (2x), 128.7 (2x), 128.6, 21.7. 3-(4-Fluorophenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4j). 4j was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6j (74 mg, 0.6 mmol). Yield = 94% (179 mg); Colorless solid; mp = 134-136 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18FO3S 381.0961; Found 381.0960; 1H NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.89-7.87 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.52-7.48 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.32-7.25 (m, 4H), 6.89-6.84 (m, 2H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.1, 163.8 (d, J = 251.7 Hz), 144.8, 139.6 (d, J = 1.6 Hz), 139.5, 136.5, 135.3, 134.4, 132.2 (d, J = 9.1 Hz, 2x), 129.7 (4x), 128.7 (2x), 128.5 (2x), 127.6 (d, J = 3.0 Hz), 116.0 (d, J = 22.0 Hz, 2x), 21.5. 3-(2-Bromophenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4k). 4k was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6k (110 mg, 0.6 mmol). Yield = 93% (205 mg); Colorless solid; mp = 124-126 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18BrO3S 441.0160; Found 441.0163; 1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.78-7.75 (m, 2H), 7.517.48 (m, 1H), 7.46-7.42 (m, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.31-7.27 (m, 2H), 7.07-7.03 (m, 2H), 7.01-6.96 (m, 1H), 2.44

Page 8 of 30

(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.3, 145.0, 142.3, 140.5, 136.5, 135.5, 134.3, 133.0, 132.3, 131.6, 130.3, 129.8 (2x), 129.6 (2x), 128.9 (2x), 128.6 (2x), 127.4, 124.5, 21.7. 3-(3-Nitrophenyl)-1-phenyl-2-(toluene-4-sulfonyl)propenone (4l). 4l was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6l (91 mg, 0.6 mmol). Yield = 92% (187 mg); Colorless solid; mp = 160-162 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18NO5S 408.0906; Found 408.0904; 1 H NMR (400 MHz, CDCl3): δ 8.12 (t, J = 1.6 Hz, 1H), 8.06 (s, 1H), 8.05 (dd, J = 1.6, 8.0 Hz, 1H), 7.87-7.85 (m, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 1H), 7.51-7.47 (m, 1H), 7.38-7.33 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 191.4, 148.0, 145.3, 143.3, 137.7, 135.8, 135.0 (2x), 134.7, 133.0, 129.9, 129.8 (2x), 129.6 (2x), 128.8 (2x), 128.7 (2x), 125.0, 124.4, 21.5. 3-(4-Hydroxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4m). 4m was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6m (73 mg, 0.6 mmol). Yield = 94% (178 mg); Colorless solid; mp = 79-81 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19O4S 379.1004; Found 379.1005; 1H NMR (400 MHz, CDCl3): δ 9.25 (br s, 1H), 7.86 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.43-7.39 (m, 1H), 7.27-7.19 (m, 4H), 7.04 (d, J = 8.8 Hz, 2H), 6.57 (d, J = 8.8 Hz, 2H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.5, 160.2, 144.2, 141.4, 137.1, 135.4, 135.1, 134.0, 132.4 (2x), 129.5 (2x), 129.4 (2x), 128.5 (2x), 128.0 (2x), 122.2, 115.9 (2x), 21.3. 3-Biphenyl-4-yl-1-phenyl-2-(toluene-4-sulfonyl)propenone (4n). 4n was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6n (109 mg, 0.6 mmol). Yield = 90% (197 mg); Colorless solid; mp = 151-153 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H23O3S 439.1368; Found 439.1369; 1H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 7.96-7.84 (m, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.55-7.31 (m, 14H), 2.43 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.4, 144.7, 143.6, 140.5, 139.44, 139.37, 136.8, 135.6, 134.4, 130.8 (2x), 130.3, 129.9 (2x), 129.7 (2x), 128.83 (2x), 128.79 (2x), 128.6 (2x), 128.1, 127.3 (2x), 126.9 (2x), 21.6. Single-crystal X-Ray diagram: crystal of 4n was grown by slow diffusion of EtOAc into a solution of 4n in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 14.5709(16) Å , b = 8.0748(8) Å , c = 18.602(2) Å , V = 2188.3(4) Å 3, Z = 4, dcalcd = 1.331 g/cm3, F(000) = 920, 2θ range 1.760 ~26.369o, R indices (all data) R1 = 0.0575, wR2 = 0.151. 1-Phenyl-2-(toluene-4-sulfonyl)-3-p-tolylpropenone (4o). 4o was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6o (72 mg, 0.6 mmol). Yield = 90% (169 mg); Colorless solid; mp = 130-132 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O3S 377.1211; Found 377.1210; 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.92-7.90 (m, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.52-7.47 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.33-7.29 (m, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H), 2.22 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.4, 144.5, 141.7, 141.0, 138.4, 136.8, 135.5,


Page 9 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


134.2, 130.2 (2x), 129.7 (2x), 129.6 (2x), 129.5 (2x), 128.6 (2x), 128.5, 128.5 (2x), 21.5, 21.3. 3-(2-Allyl-3,4-dimethoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4p). 4p was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6p (124 mg, 0.6 mmol). Yield = 83% (192 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H27O5S 463.1579; Found 463.1580; 1H NMR (400 MHz, CDCl3): δ 8.23 (s, 1H), 7.79-7.76 (m, 4H), 7.47-7.43 (m, 1H), 7.33-7.27 (m, 4H), 6.80 (d, J = 8.8 Hz, 1H), 6.44 (d, J = 8.8 Hz, 1H), 6.01-5.93 (m, 1H), 5.19 (dq, J = 1.6, 10.0 Hz, 1H), 5.05 (dq, J = 1.6, 17.2 Hz, 1H), 3.74 (s, 3H), 3.73 (s, 3H), 3.64 (d, J = 5.6 Hz, 2H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 154.8, 147.2, 144.5, 139.9, 138.7, 137.3, 136.1, 135.8, 134.0, 129.70 (2x), 129.68 (2x), 128.6 (2x), 128.5 (3x), 126.2, 124.1, 116.4, 110.0, 60.9, 55.5, 30.7, 21.7. 1-Phenyl-3-pyridin-3-yl-2-(toluene-4-sulfonyl)propenone (4q). 4q was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6q (64 mg, 0.6 mmol). Yield = 80% (145 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18NO3S 364.1007; Found 364.1009; 1H NMR (400 MHz, CDCl3): δ 8.55 (s, 1H), 8.43 (d, J = 4.0 Hz, 1H), 7.99 (s, 1H), 7.86-7.84 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.51-7.46 (m, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.06 (dd, J = 4.8, 8.0 Hz, 1H), 2.39 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 191.5, 151.3, 150.9, 145.1, 142.4, 136.9, 136.1, 135.9, 135.0, 134.7, 129.8 (2x), 129.7 (2x), 128.8 (2x), 128.6 (2x), 127.5, 123.4, 21.5. 1-Phenyl-3-thiophen-2-yl-2-(toluene-4-sulfonyl)propenone (4r). 4r was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6r (67 mg, 0.6 mmol). Yield = 84% (155 mg); Colorless solid; mp = 142-144 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H17O3S2 369.0619; Found 369.0621; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 8.01-7.98 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.59-7.55 (m, 1H), 7.43-7.39 (m, 2H), 7.34 (dd, J = 0.8, 4.8 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.22 (dd, J = 0.8, 4.0 Hz, 1H), 6.93 (dd, J = 4.0, 4.8 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.7, 144.6, 136.7, 136.6, 135.5, 134.6, 134.4, 134.3, 133.0, 132.3, 130.0 (2x), 129.7 (2x), 128.8 (2x), 128.4 (2x), 127.9, 21.6. 3-(3,4-Dimethoxyphenyl)-1-(4-fluorophenyl)-2-(toluene-4sulfonyl)propenone (4t). 4t was synthesized according to general synthetic procedure from 5b (146 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 98% (216 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H22FO5S 441.1172; Found 441.1175; 1H NMR (400 MHz, CDCl3): δ 7.97-7.94 (m, 2H), 7.94 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.05-7.01 (m, 2H), 6.94 (dd, J = 1.6, 8.0 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.0 Hz, 1H), 3.80 (s, 3H), 3.53 (s, 3H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.1, 166.4 (d, J = 255.4 Hz), 151.6, 148.7, 144.6, 141.2, 137.0, 136.5, 132.5 (d, J = 9.8 Hz, 2x), 132.2 (d, J = 3.0 Hz), 129.7 (2x), 128.4 (2x), 125.3, 123.9, 116.1 (d, J = 22.0 Hz, 2x), 112.0, 110.9, 55.8, 55.4, 21.6. 3-(3,4-Dimethoxyphenyl)-1-(4-methoxyphenyl)-2-(toluene-4sulfonyl)propenone (4u). 4u was synthesized according to general synthetic procedure from 5c (152 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 97% (219 mg); Colorless liquid;

HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H25O6S 453.1372; Found 453.1374; 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.98 (dd, J = 2.0, 8.4 Hz, 1H), 6.83 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 1H), 6.70 (d, J = 2.0 Hz, 1H), 3.80 (s, 6H), 3.51 (s, 3H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 190.8, 164.6, 151.4, 148.6, 144.4, 140.5, 137.1, 137.0, 132.2 (2x), 129.6 (2x), 128.9, 128.4 (2x), 125.4, 124.2, 114.1 (2x), 111.9, 110.8, 55.8, 55.44, 55.39, 21.6. 3-(3,4-Dimethoxyphenyl)-2-(toluene-4-sulfonyl)-1-ptolylpropenone (4v). 4v was synthesized according to general synthetic procedure from 5d (144 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 95% (207 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H25O5S 437.1423; Found 437.1425; 1H NMR (400 MHz, CDCl3): δ 7.92 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.96 (dd, J = 2.0, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 2.0 Hz, 1H), 3.76 (s, 3H), 3.48 (s, 3H), 2.38 (s, 3H), 2.31 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.1, 151.3, 148.5, 145.6, 144.3, 140.7, 137.1, 136.8, 133.3, 129.7 (2x), 129.52 (2x), 129.48 (2x), 128.3 (2x), 125.4, 124.0, 111.9, 110.7, 55.7, 55.3, 21.6, 21.5. 3-(3,4-Dimethoxyphenyl)-2-(toluene-4-sulfonyl)-1-(4trifluoromethylphenyl)propenone (4w). 4w was synthesized according to general synthetic procedure from 5e (171 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 92% (225 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22F3O5S 491.1140; Found 491.1143; 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.4 Hz, 2H), 8.01 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.92 (dd, J = 2.0, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.0 Hz, 1H), 3.77 (s, 3H), 3.55 (s, 3H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.0, 151.8, 148.8, 144.7, 141.7, 138.2, 136.8, 136.2, 135.2 (q, J = 32.6 Hz), 129.9 (2x), 129.7 (2x), 128.4 (2x), 125.9 (q, J = 271.4 Hz), 125.8 (d, J = 3.8 Hz, 2x), 125.1, 123.6, 112.1, 111.0, 55.7, 55.4, 21.5. 3-(3,4-Dimethoxyphenyl)-1-(4-nitrophenyl)-2-(toluene-4sulfonyl)propenone (4x). 4x was synthesized according to general synthetic procedure from 5f (160 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 90% (210 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H22NO7S 468.1117; Found 468.1118; 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 9.2 Hz, 2H), 8.06 (d, J = 9.2 Hz, 2H), 8.05 (d, J = 0.8 Hz, 1H), 7.77 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 6.90 (dd, J = 2.4, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 2.4 Hz, 1H), 3.80 (s, 3H), 3.60 (s, 3H), 2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.6, 152.0, 150.8, 149.0, 145.0, 142.3, 140.0, 136.8, 136.1, 130.6 (2x), 129.9 (2x), 128.5 (2x), 125.1, 124.0 (2x), 123.6, 112.2, 111.1, 55.9, 55.6, 21.7. 1-Biphenyl-4-yl-3-(3,4-dimethoxyphenyl)-2-(toluene-4sulfonyl)propenone (4y). 4y was synthesized according to general synthetic procedure from 5g (175 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 90% (224 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H27O5S 499.1579; Found 499.1581; 1H NMR (400 MHz, CDCl3): δ 8.03 (d, J = 8.4 Hz, 2H), 7.99 (s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.56-7.53 (m, 2H), 7.44-7.34 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 7.01 (dd, J = 2.0, 8.4 Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 3.78 (s, 3H), 3.54 (s,



3H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 151.5, 148.7, 147.0, 144.5, 140.9, 139.3, 137.1, 136.8, 134.4, 130.3 (2x), 129.6 (2x), 128.8 (2x), 128.4 (3x), 127.4 (2x), 127.1 (2x), 125.4, 124.0, 112.0, 110.8, 55.7, 55.4, 21.5. 3-(3,4-Dimethoxyphenyl)-1-naphthalen-2-yl-2-(toluene-4sulfonyl)propenone (4z). 4z was synthesized according to general synthetic procedure from 5h (162 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 92% (217 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H25O5S 473.1423; Found 473.1425; 1H NMR (400 MHz, CDCl3): δ 8.40 (d, J = 1.6 Hz, 1H), 8.04 (s, 1H), 8.02 (d, J = 1.6 Hz, 1H), 7.83-7.78 (m, 5H), 7.55 (dt, J = 1.2, 8.0 Hz, 1H), 7.46 (dt, J = 1.2, 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.01 (dd, J = 2.0, 8.4 Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 3.72 (s, 3H), 3.47 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.5, 151.4, 148.6, 144.5, 141.2, 137.0, 136.9, 136.0, 133.1 (2x), 132.3, 129.8, 129.6 (2x), 129.1, 128.8, 128.4 (2x), 127.6, 126.8, 125.4, 124.0, 123.6, 111.9, 110.8, 55.6, 55.3, 21.5. 2-Benzenesulfonyl-3-(3,4-dimethoxyphenyl)-1phenylpropenone (4aa). 4aa was synthesized according to general synthetic procedure from 5i (130 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 90% (184 mg); Colorless solid; mp = 194-196 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O5S 409.1110; Found 409.1111; 1H NMR (400 MHz, CDCl3): δ 7.98 (s, 1H), 7.95-7.89 (m, 4H), 7.63-7.59 (m, 1H), 7.55-7.50 (m, 3H), 7.39-7.35 (m, 2H), 6.98 (dd, J = 2.4, 8.4 Hz, 1H), 6.72 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.0 Hz, 1H), 3.80 (s, 3H), 3.49 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.6, 151.6, 148.8, 141.6, 140.2, 136.4, 135.7, 134.5, 133.5, 129.7 (2x), 129.0 (2x), 128.9 (2x), 128.4 (2x), 125.7, 124.0, 112.1, 110.9, 55.8, 55.4. 3-(3,4-Dimethoxyphenyl)-2-(4-fluorobenzenesulfonyl)-1phenylpropenone (4ab). 4ab was synthesized according to general synthetic procedure from 5j (139 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 96% (204 mg); Colorless solid; mp = 184-186 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H20FO5S 427.1016; Found 427.1015; 1H NMR (400 MHz, CDCl3): δ 7.96 (s, 1H), 7.93-7.88 (m, 4H), 7.54-7.49 (m, 1H), 7.38-7.34 (m, 2H), 7.20-7.15 (m, 2H), 6.96 (dd, J = 2.0, 8.4 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H), 3.78 (s, 3H), 3.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.6, 165.6 (d, J = 254.7 Hz), 151.7, 148.7, 141.7, 136.2, 136.0, 135.5, 134.5, 131.2 (d, J = 9.9 Hz, 2x), 129.6 (2x), 128.9 (2x), 125.7, 123.8, 116.2 (d, J = 22.8 Hz, 2x), 112.0, 110.8, 55.7, 55.3. 3-(3,4-Dimethoxyphenyl)-2-(4-methoxybenzenesulfonyl)-1phenylpropenone (4ac). 4ac was synthesized according to general synthetic procedure from 5k (145 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 96% (210 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23O6S 439.1215; Found 439.1216; 1H NMR (400 MHz, CDCl3): δ 7.94-7.91 (m, 2H), 7.93 (s, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.527.48 (m, 1H), 7.37-7.33 (m, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.94 (dd, J = 2.0, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H), 3.82 (s, 3H), 3.77 (s, 3H), 3.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 163.6, 151.4, 148.6, 140.5, 137.0, 135.7, 134.4, 131.5, 130.6 (2x), 129.6 (2x), 128.8 (2x), 125.4, 124.0, 114.2 (2x), 111.9, 110.8, 55.7, 55.5, 55.3.

Page 10 of 30

3-(3,4-Dimethoxyphenyl)-2-(4-ethylbenzenesulfonyl)-1phenylpropenone (4ad). 4ad was synthesized according to general synthetic procedure from 5l (144 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 94% (205 mg); Colorless solid; mp = 110-112 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H25O5S 437.1423; Found 437.1425; 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.93-7.91 (m, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.527.48 (m, 1H), 7.37-7.30 (m, 4H), 6.96 (dd, J = 2.0, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.0 Hz, 1H), 3.77 (s, 3H), 3.47 (s, 3H), 2.69 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.6, 151.5, 150.5, 148.6, 141.1, 137.3, 136.7, 135.6, 134.4, 129.6 (2x), 128.8 (2x), 128.5 (2x), 128.4 (2x), 125.5, 124.0, 112.0, 110.8, 55.7, 55.3, 28.7, 14.9. 2-(4-t-Butylbenzenesulfonyl)-3-(3,4-dimethoxyphenyl)-1phenylpropenone (4ae). 4ae was synthesized according to general synthetic procedure from 5m (158 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 93% (216 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H29O5S 465.1736; Found 465.1735; 1H NMR (400 MHz, CDCl3): δ 7.94 (s, 1H), 7.92-7.90 (m, 2H), 7.81 (d, J = 8.8 Hz, 2H), 7.527.48 (m, 3H), 7.36-7.32 (m, 2H), 6.97 (dd, J = 2.0, 8.4 Hz, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 2.0 Hz, 1H), 3.78 (s, 3H), 3.48 (s, 3H), 1.31 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 152.3, 151.5, 148.7, 141.1, 137.1, 136.7, 135.7, 134.4, 129.7 (2x), 128.8 (2x), 128.2 (2x), 126.0 (2x), 125.6, 124.0, 112.0, 110.8, 55.8, 55.4, 35.1, 30.9 (3x). 3-(3,4-Dimethoxyphenyl)-2-methanesulfonyl-1phenylpropenone (4af). 4af was synthesized according to general synthetic procedure from 5n (99 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 96% (166 mg); Colorless solid; mp = 98-100 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H19O5S 347.0953; Found 347.0955; 1H NMR (400 MHz, CDCl3): δ 7.96-7.93 (m, 2H), 7.82 (s, 1H), 7.53-7.48 (m, 1H), 7.37-7.34 (m, 2H), 6.94 (dd, J = 2.4, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 2.4 Hz, 1H), 3.77 (s, 3H), 3.49 (s, 3H), 3.21 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 193.4, 151.6, 148.6, 142.1, 135.4, 135.2, 134.6, 129.7 (2x), 128.9 (2x), 125.7, 123.5, 112.1, 110.8, 55.7, 55.4, 43.4. 2-(n-Butane-1-sulfonyl)-3-(3,4-dimethoxy-phenyl)-1-phenylpropenone (4ag). 4ag was synthesized according to general synthetic procedure from 5o (120 mg, 0.5 mmol) and 6a (100 mg, 0.6 mmol). Yield = 96% (186 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H25O5S 389.1423; Found 389.1425; 1H NMR (400 MHz, CDCl3): δ 7.96-7.93 (m, 2H), 7.74 (s, 1H), 7.51-7.47 (m, 1H), 7.36-7.32 (m, 2H), 6.94 (dd, J = 2.4, 8.4 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 6.65 (d, J = 2.4 Hz, 1H), 3.76 (s, 3H), 3.48 (s, 3H), 3.223.28 (m, 2H), 1.85-1.77 (m, 2H), 1.51-1.41 (m, 2H), 0.92 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 193.5, 151.5, 148.6, 142.7, 135.4, 134.5, 133.8, 129.7 (2x), 128.8 (2x), 125.6, 123.6, 112.1, 110.8, 55.7, 55.3, 54.4, 24.3, 21.3, 13.4. 1-(3,4-Dichlorophenyl)-3-phenyl-2-(toluene-4sulfonyl)propenone (4ah). 4ah was synthesized according to general synthetic procedure from 5p (171 mg, 0.5 mmol) and 6f (64 mg, 0.6 mmol). Yield = 96% (206 mg); Colorless solid; mp = 149-151 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H17Cl2O3S


Page 11 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


431.0276; Found 431.0277; 1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.93 (dd, J = 0.4, 2.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.69 (dd, J = 2.4, 8.4 Hz, 1H), 7.43 (dd, J = 0.4, 8.4 Hz, 1H), 7.35-7.28 (m, 3H), 7.25-7.22 (m, 4H), 2.44 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 190.3, 145.1, 141.6, 139.2, 139.1, 136.3, 135.1, 133.6, 131.4, 131.2, 131.12, 130.95, 130.1 (2x), 129.9 (2x), 129.1 (2x), 128.9, 128.6 (2x), 21.7. 3-(2-Nitrophenyl)-1-phenyl-2-(toluene-4-sulfonyl)propenone (4ai). 4ai was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6t (91 mg, 0.6 mmol). Yield = 72% (147 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H18NO5S 408.0906; Found 408.0904; 1H NMR (400 MHz, CDCl3): δ 8.43 (s, 1H), 8.02 (dd, J = 2.4, 7.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.64-7.62 (m, 2H), 7.42-7.35 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 7.22-7.16 (m, 3H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 190.4, 146.7, 145.2, 142.6, 138.9, 136.1, 135.8, 134.2, 133.9, 131.0, 130.7, 129.9 (2x), 129.2 (2x), 128.8 (2x), 128.52, 128.49 (2x), 125.0, 21.6. 3-(1-Benzyl-1H-pyrrol-2-yl)-1-phenyl-2-(toluene-4sulfonyl)propenone (4aj). 4aj was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6u (111 mg, 0.6 mmol). Yield = 80% (353 mg); Colorless solid; mp = 138-140 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H24NO3S 442.1477, found 442.1483; 1H NMR (400 MHz, CDCl3): δ 7.86 (s, 1H), 7.79-7.75 (m, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.53-7.47 (m, 1H), 7.45-7.38 (m, 3H), 7.32-7.28 (m, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.10-7.08 (m, 2H), 6.89 (dd, J = 1.6, 2.8 Hz, 1H), 6.12 (dd, J = 1.6, 4.4 Hz, 1H), 5.99 (dd, J = 2.8, 4.4 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 143.9, 137.5, 137.0, 135.3, 133.9, 131.8, 129.5 (2x), 129.4 (2x), 128.9, 128.8 (2x), 128.5 (2x), 128.1, 127.9 (2x), 127.8, 126.4 (2x), 124.3, 117.5, 110.5, 51.1, 21.4. 2-Benzenesulfonyl-1-phenyl-3-thiophen-2-ylpropenone (4ak). 4ak was synthesized according to general synthetic procedure from 5i (130 mg, 0.5 mmol) and 6r (67 mg, 0.6 mmol). Yield = 84% (297 mg); Colorless solid; mp = 124-126 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H15O3S2 355.0463, found 355.0469; 1 H NMR (400 MHz, CDCl3): δ 8.10 (s, 1H), 8.00-7.97 (m, 2H), 7.88-7.85 (m, 2H), 7.63-7.56 (m, 2H), 7.53-7.48 (m, 2H), 7.447.40 (m, 2H), 7.36 (ddd, J = 0.8, 1.6, 4.8 Hz, 1H), 7.22 (ddd, J = 0.8, 1.6, 3.6 Hz, 1H), 6.95 (dd, J = 3.6, 4.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.6, 139.8, 136.2, 135.5, 134.7, 134.6, 134.4, 133.6, 133.5, 132.5, 130.0 (2x), 129.1 (2x), 128.9 (2x), 128.4 (2x), 128.0. 1-Phenyl-3-pyridin-2-yl-2-(toluene-4-sulfonyl)propenone (4al). 4al was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6v (64 mg, 0.6 mmol). Yield = 68% (247 mg); Colorless solid; mp = 221-223 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H18NO3S 364.1007, found 364.1015; 1 H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 4.0 Hz, 1H), 7.92 (s, 1H), 7.88-7.86 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.63 (dt, J = 2.0, 7.6 Hz, 1H), 7.48-7.42 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.06 (ddd, J = 0.8, 4.4, 7.6 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 190.8, 150.0,

149.4, 144.9, 143.5, 138.5, 136.9, 136.7, 136.1, 133.0, 129.7 (2x), 128.9 (2x), 128.8 (2x), 128.3 (2x), 126.3, 124.4, 21.6. 3-Furan-2-yl-1-phenyl-2-(toluene-4-sulfonyl)propenone (4am). 4am was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6w (58 mg, 0.6 mmol). Yield = 64% (225 mg); Colorless solid; mp = 170-172 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H17O4S 353.0848, found 353.0856; 1 H NMR (400 MHz, CDCl3): δ 7.93-7.91 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.72 (s, 1H), 7.56-7.52 (m, 1H), 7.42-7.37 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 2.0 Hz, 1H), 6.68 (d, J = 3.6 Hz, 1H), 6.33 (dd, J = 2.0, 3.6 Hz, 1H), 2.40 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 191.1, 147.5, 146.6, 144.6, 136.7, 136.3, 135.7, 133.9, 129.7 (2x), 129.6 (2x), 128.5 (2x), 128.4 (2x), 126.7, 118.9, 112.6, 21.6. 3-Benzofuran-2-yl-1-phenyl-2-(toluene-4sulfonyl)propenone (4an). 4an was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6x (88 mg, 0.6 mmol). Yield = 84% (338 mg); Colorless solid; mp = 168-170 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H19O4S 403.1004, found 403.1009; 1H NMR (400 MHz, CDCl3): δ 8.00-7.97 (m, 2H), 7.85 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.557.50 (m, 2H), 7.43-7.39 (m, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.22 (dt, J = 1.2, 8.0 Hz, 1H), 7.15 (dt, J = 1.2, 8.4 Hz, 1H), 7.05 (d, J = 0.4 Hz, 1H), 7.01 (dd, J = 0.4, 8.0 Hz, 1H), 2.43 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 190.9, 156.0, 148.8, 144.9, 138.9, 136.7, 136.5, 134.0, 129.8 (2x), 129.5 (2x), 128.7 (2x), 128.6 (2x), 127.5, 127.3, 127.1, 123.6, 122.1, 114.9, 111.4, 21.7. 3-Benzo[b]thiophen-2-yl-1-phenyl-2-(toluene-4sulfonyl)propenone (4ao). 4ao was synthesized according to general synthetic procedure from 5a (137 mg, 0.5 mmol) and 6y (97 mg, 0.6 mmol). Yield = 78% (326 mg); Colorless solid; mp = 183-185 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H19O3S2 419.0776, found 419.0778; 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 0.8 Hz, 1H), 8.04-8.02 (m, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.74-7.71 (m, 1H), 7.61-7.57 (m, 2H), 7.54 (s, 1H), 7.467.42 (m, 2H), 7.33-7.28 (m, 4H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.4, 144.9, 142.3, 139.0, 138.4, 136.5, 135.9, 134.7, 134.5, 133.6, 132.1, 130.2 (2x), 129.8 (2x), 128.9 (2x), 128.6 (2x), 126.7, 125.0, 124.8, 122.3, 21.7. General synthetic procedure of skeleton 3 is as follows: Grignard reagent (R’MgBr, 2 mL, 1.0 M in THF, 2.0 mmol) was added to a solution of 4 (1.0 mmol) in THF (10 mL) at 25 oC. The reaction mixture was stirred at reflux for 10 h. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product mixture under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 3. 3-Cyclohexyl-1,3-diphenyl-2-(toluene-4-sulfonyl)propan-1one (3a). 3a was synthesized according to general synthetic procedure from 4f (362 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 86% (384 mg); Colorless



solid; mp = 184-187 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H31O3S 447.1994, found 447.1996; 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.0 Hz, 2H), 7.58-7.54 (m, 2H), 7.44-7.40 (m, 1H), 7.28-7.20 (m, 4H), 7.00-6.95 (m, 3H), 6.89-6.84 (m, 2H), 5.79 (d, J = 11.2 Hz, 1H), 3.57 (dd, J = 3.2, 11.2 Hz, 1H), 2.50-2.41 (m, 1H), 2.36 (s, 3H), 2.07-2.04 (m, 1H), 1.88-1.49 (m, 4H), 1.42-1.25 (m, 2H), 0.96-0.84 (m, 2H), 0.74-0.64 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.9, 145.1, 136.8, 133.0, 129.8 (2x), 129.4 (2x), 129.0, 128.7, 128.21 (4x), 128.20 (2x), 127.5 (2x), 126.7, 70.7, 51.3, 38.4, 32.3, 27.4, 26.7, 26.3, 26.2, 21.5. 3-Cyclohexyl-3-(4-methoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3b). 3b was synthesized according to general synthetic procedure from 4d (392 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 85% (405 mg); Colorless solid; mp = 182-184 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H33O4S 477.2100, found 477.2101; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.0 Hz, 2H), 7.56 (dd, J = 0.8, 8.0 Hz, 2H), 7.43-7.39 (m, 1H), 7.28-7.24 (m, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 6.52 (d, J = 8.4 Hz, 2H), 5.74 (d, J = 11.6 Hz, 1H), 3.62 (s, 3H), 3.53 (dd, J = 3.2, 11.2 Hz, 1H), 2.45-2.37 (m, 1H), 2.34 (s, 3H), 2.04-2.01 (m, 1H), 1.75-1.49 (m, 4H), 1.42-1.25 (m, 2H), 0.99-0.84 (m, 2H), 0.740.64 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.9, 158.1, 145.1, 137.6, 135.1, 133.0, 130.7, 129.7 (2x), 129.4 (2x), 128.7 (2x), 128.2 (4x), 112.9 (2x), 70.8, 54.9, 50.4, 38.6, 32.2, 27.3, 26.6, 26.2 (2x), 21.5. 3-Cyclohexyl-1-phenyl-2-(toluene-4-sulfonyl)-3-ptolylpropan-1-one (3c). 3c was synthesized according to general synthetic procedure from 4o (376 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (368 mg); Colorless solid; mp = 219-221 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H33O3S 461.2150, found 461.2152; 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.45-7.41 (m, 1H), 7.29-7.26 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 8.4 Hz, 2H), 5.78 (d, J = 11.2 Hz, 1H), 3.55 (dd, J = 3.2, 11.2 Hz, 1H), 2.48-2.39 (m, 1H), 2.36 (s, 3H), 2.14 (s, 3H), 2.06-2.03 (m, 1H), 1.76-1.51 (m, 4H), 1.42-1.28 (m, 2H), 0.97-0.85 (m, 2H), 0.75-0.65 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.9, 145.1, 137.7, 136.2, 135.1, 133.7, 132.9, 129.8 (2x), 129.6 (2x), 129.4 (2x), 128.3 (2x), 128.24 (2x), 128.16 (2x), 70.7, 50.8, 38.5, 32.2, 27.4, 26.7, 26.3, 26.2, 21.5, 20.8. 3-Cyclohexyl-3-(4-fluorophenyl)-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3d). 3d was synthesized according to general synthetic procedure from 4j (380 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 83% (385 mg); Colorless solid; mp = 195-197 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H30FO3S 465.1900, found 465.1903; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.57-7.55 (m, 2H), 7.46-7.42 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.87-6.83 (m, 2H), 6.71-6.66 (m, 2H), 5.72 (d, J = 11.2 Hz, 1H), 3.57 (dd, J = 3.6, 11.2 Hz, 1H), 2.48-2.40 (m, 1H), 2.35 (s, 3H), 2.04-2.01 (m, 1H), 1.76-1.50 (m, 4H), 1.421.24 (m, 2H), 0.95-0.82 (m, 2H), 0.70-0.60 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 161.5 (d, J = 244.1 Hz),

Page 12 of 30

145.2, 137.5, 135.0, 133.2, 132.6 (d, J = 3.1 Hz), 131.1 (2x), 129.8 (2x), 129.4 (2x), 128.3 (2x), 128.2 (2x), 114.5 (d, J = 20.5 Hz, 2x), 70.7, 50.5, 38.4, 32.2, 27.3, 26.6, 26.23, 26.20, 21.6. 3-Biphenyl-4-yl-3-cyclohexyl-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3e). 3e was synthesized according to general synthetic procedure from 4n (438 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 79% (413 mg); Colorless solid; mp = 233-235 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H35O3S 523.2307, found 523.2305; 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.4 Hz, 2H), 7.59-7.57 (m, 3H), 7.46-7.22 (m, 11H), 6.95 (d, J = 8.0 Hz, 2H), 5.82 (d, J = 11.2 Hz, 1H), 3.63 (dd, J = 2.8, 11.2 Hz, 1H), 2.52-2.47 (m, 1H), 2.36 (s, 3H), 2.10-2.05 (m, 1H), 1.79-1.30 (m, 6H), 1.02-0.88 (m, 2H), 0.81-0.72 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 193.0, 145.2, 140.4, 139.4, 137.7, 135.9, 135.0, 133.1, 130.2 (2x), 129.8 (2x), 129.4 (2x), 128.6 (2x), 128.2 (4x), 127.1, 126.8 (2x), 126.2 (2x), 70.7, 51.0, 38.5, 32.3, 27.4, 26.7, 26.3, 16.2, 21.6. 3-Cyclohexyl-3-naphthalen-2-yl-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3f). 3f was synthesized according to general synthetic procedure from 4g (412 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 78% (387 mg); Colorless solid; mp = 213-214 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H33O3S 497.2150, found 497.2150; 1H NMR (400 MHz, CDCl3): δ 8.20-8.18 (m, 2H), 7.81-7.80 (m, 1H), 7.737.53 (m, 6H), 7.48-7.43 (m, 2H), 7.30 (br s, 1H), 7.22-7.18 (m, 1H), 7.13 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 8.0 Hz, 1H), 5.90 (d, J = 11.6 Hz, 1H), 3.77 (d, J = 11.2 Hz, 1H), 2.18 (s, 3H), 1.631.29 (m, 6H), 1.20-1.08 (m, 1H), 0.98-0.82 (m, 1H), 0.78-0.61 (m, 2H), 0.55-0.45 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 193.4, 144.3, 138.2, 133.8, 133.0, 132.6, 132.5, 129.9, 129.0 (2x), 128.8 (4x), 128.7 (4x), 127.7, 127.4, 126.8, 125.7 (2x), 72.2, 51.6, 40.7, 32.0, 27.8, 26.2, 26.1, 25.7, 21.4. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-1-phenyl-2-(toluene4-sulfonyl)propan-1-one (3g). 3g was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (405 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H35O5S 507.2205, found 507.2203; 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.0 Hz, 2H), 7.60-7.58 (m, 2H), 7.45-7.38 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.50 (d, J = 8.0 Hz, 1H), 6.42 (dd, J = 2.0, 8.4 Hz, 1H), 6.31 (d, J = 1.6 Hz, 1H), 5.74 (d, J = 11.6 Hz, 1H), 3.71 (s, 3H), 3.50-3.47 (m, 1H), 3.50 (s, 3H), 2.45-2.37 (m, 1H), 2.36 (s, 3H), 2.04-2.00 (m, 1H), 1.76-1.20 (m, 6H), 0.99-0.85 (m, 2H), 0.79-0.69 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 147.7, 147.6, 145.1, 137.8, 135.0, 133.0, 129.8 (2x), 129.4 (2x), 129.2, 128.3 (2x), 128.2 (2x), 122.3, 113.0, 110.2, 70.7, 55.6, 55.4, 50.9, 38.5, 32.3, 27.4, 26.7, 26.3, 26.2, 21.6. 3-Benzo[1,3]dioxol-5-yl-3-cyclohexyl-1-phenyl-2-(toluene4-sulfonyl)propan-1-one (3h). 3h was synthesized according to general synthetic procedure from 4b (406 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (402 mg); Colorless solid; mp = 115-117 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H31O5S 491.1892, found 491.1895; 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.4 Hz, 2H), 7.69-7.57 (m, 2H),


Page 13 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


7.45-7.41 (m, 1H), 7.29 (d, J = 7.6 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.43 (d, J = 8.0 Hz, 1H), 6.39 (d, J = 1.2 Hz, 1H), 6.33 (dd, J = 1.2, 8.0 Hz, 1H), 5.79 (d, J = 1.2 Hz, 1H), 5.75 (d, J = 0.8 Hz, 1H), 5.69 (d, J = 11.2 Hz, 1H), 3.50 (dd, J = 3.2, 11.2 Hz, 1H), 2.49-2.36 (m, 1H), 2.34 (s, 3H), 2.04-2.00 (m, 1H), 1.76-1.20 (m, 6H), 0.99-0.85 (m, 2H), 0.79-0.69 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.7, 146.9, 146.2, 145.1, 137.6, 135.0, 133.0, 130.5, 129.8 (2x), 129.4 (2x), 128.24 (2x), 128.20 (2x), 122.8, 110.3, 107.3, 100.7, 70.7, 50.9, 38.5, 32.3, 27.4, 26.6, 26.2 (2x), 21.5. 3-Cyclohexyl-1-phenyl-2-(toluene-4-sulfonyl)-3-(3,4,5trimethoxyphenyl)propan-1-one (3i). 3i was synthesized according to general synthetic procedure from 4e (452 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 78% (418 mg); Colorless solid; mp = 180-181 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H37O6S 537.2311, found 537.2312; 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.0 Hz, 2H), 7.59-7.57 (m, 2H), 7.45-7.41 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.26-7.23 (m, 2H), 5.99 (s, 2H), 5.72 (d, J = 11.2 Hz, 1H), 3.67 (s, 3H), 3.47-3.44 (m, 6H), 2.45-2.38 (m, 1H), 2.36 (s, 3H), 2.03-1.97 (m, 1H), 1.76-1.50 (m, 5H), 1.42-1.23 (m, 2H), 0.99-0.75 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 152.1, 145.2 (2x), 138.1, 136.7, 135.1, 133.0 (2x), 132.2, 129.8 (2x), 129.5 (2x), 128.3 (2x), 128.1 (2x), 107.3, 70.7, 60.7, 55.7 (2x), 51.7, 38.4, 32.4, 27.4, 26.7, 26.3, 26.2, 21.6. 3-(3,4-Dimethoxyphenyl)-1,3-diphenyl-2-(toluene-4sulfonyl)propan-1-one (3j). 3j was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and PhMgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 73% (365 mg); Colorless solid; mp = 203-205 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H29O5S 501.1736, found 501.1735; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4 Hz, 2H), 7.55-7.51 (m, 1H), 7.437.29 (m, 6H), 7.22-7.17 (m, 3H), 7.12 (d, J = 8.0 Hz, 2H), 6.66 (dd, J = 2.0, 8.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.50 (d, J = 8.4 Hz, 1H), 6.08 (d, J = 11.6 Hz, 1H), 4.79 (d, J = 12.0 Hz, 1H), 3.66 (s, 3H), 3.57 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 148.7, 147.7, 144.7, 139.5, 138.0, 135.7, 133.4, 133.2, 129.3 (2x), 129.2 (2x), 128.6 (2x), 128.5 (2x), 128.43 (2x), 128.40 (2x), 127.1, 119.9, 111.2, 111.1, 75.4, 55.7, 55.6, 51.5, 21.6. 3-(3,4-Dimethoxyphenyl)-3-(4-fluorophenyl)-1-phenyl-2(toluene-4-sulfonyl)propan-1-one (3k). 3k was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and 4-FC6H4MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 72% (373 mg); Colorless solid; mp = 199-201 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H28FO5S 519.1642, found 519.1643; 1H NMR (400 MHz, CDCl3): δ 7.83-7.81 (m, 2H), 7.55-7.51 (m, 1H), 7.42-7.38 (m, 4H), 7.30-7.26 (m, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.91-6.86 (m, 2H), 6.64 (dd, J = 2.0, 8.4 Hz, 1H), 6.55 (d, J = 2.0 Hz, 1H), 6.51 (d, J = 8.4 Hz, 1H), 6.03 (d, J = 12.0 Hz, 1H), 4.81 (d, J = 12.0 Hz, 1H), 3.67 (s, 3H), 3.57 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.1, 161.9 (d, J = 244.8 Hz), 148.7, 147.8, 144.9, 137.8, 135.7, 135.4 (d, J = 3.0 Hz), 133.5, 132.9, 130.0, 129.9, 129.3 (2x), 129.2 (2x), 128.6 (2x), 128.4 (2x), 119.7, 115.3 (d, J = 21.2 Hz, 2x), 111.1 (d, J = 21.2 Hz, 2x), 73.2, 55.7, 55.6, 50.6, 21.6.

3-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-2(toluene-4-sulfonyl)propan-1-one (3l). 3l was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and 4-MeOC6H4MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 70% (371 mg); Colorless solid; mp = 204-206 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H31O6S 531.1841, found 531.1842; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 7.2 Hz, 2H), 7.53-7.50 (m, 1H), 7.41-7.37 (m, 4H), 7.21 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.71 (d, J = 7.6 Hz, 2H), 6.64 (dd, J = 2.0, 8.4 Hz, 1H), 6.56 (d, J = 2.0 Hz, 1H), 6.50 (d, J = 8.4 Hz, 1H), 6.05 (d, J = 11.6 Hz, 1H), 4.76 (d, J = 12.0 Hz, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.56 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 158.6, 148.6, 147.6, 144.6, 137.9, 135.8, 133.5, 133.3, 131.5, 129.4 (2x), 129.2 (2x), 129.1 (2x), 128.5 (2x), 128.4 (2x), 119.6, 113.8 (2x), 111.2, 111.0, 73.2, 55.6, 55.5, 55.1, 50.7, 21.5. 3-(3,4-Dimethoxyphenyl)-1-phenyl-2-(toluene-4-sulfonyl)-3p-tolylpropan-1-one (3m). 3m was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and 4-MeC6H4MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 74% (380 mg); Colorless solid; mp = 188-190 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H31O5S 515.1892, found 515.1893; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4 Hz, 2H), 7.55-7.51 (m, 1H), 7.43-7.39 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.88 (dd, J = 2.0, 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H), 6.03 (d, J = 11.6 Hz, 1H), 4.77 (d, J = 12.0 Hz, 1H), 3.82 (s, 3H), 3.77 (s, 3H), 2.38 (s, 3H), 2.10 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.3, 148.6, 148.1, 144.5, 137.7, 136.5, 133.3, 131.8, 129.3 (2x), 129.14 (2x), 129.06 (2x), 128.52 (2x), 128.46 (2x), 124.4, 128.2, 127.4 (2x), 120.7, 111.8, 111.0, 73.4, 55.8, 55.7, 51.2, 21.5, 20.8. 3-(3,4-Dimethoxyphenyl)-1-phenyl-2-(toluene-4-sulfonyl)-3o-tolyl-propan-1-one (3n). 3n was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and 2-MeC6H4MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 67% (345 mg); Colorless solid; mp = 153-155 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H31O5S 515.1892, found 515.1896; 1H NMR (400 MHz, CDCl3): δ 7.84-7.82 (m, 2H), 7.54-7.49 (m, 1H), 7.42-7.37 (m, 4H), 7.12-7.08 (m, 3H), 6.97-6.79 (m, 4H), 6.72 (d, J = 2.0 Hz, 1H), 6.64 (d, J = 4.0 Hz, 1H), 6.07 (d, J = 10.8 Hz, 1H), 5.22 (d, J = 12.0 Hz, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 2.40 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.0, 148.6, 148.2, 144.4, 139.1, 137.7, 136.6, 135.9, 133.2, 131.0, 130.8, 129.1 (2x), 128.8 (2x), 128.5 (2x), 128.3 (2x), 126.7, 125.9, 125.6, 121.6, 112.3, 110.9, 74.0, 55.8, 55.7, 45.9, 21.5, 20.0. 3-(3,4-Dimethoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)butan-1-one (3o). 3o was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and MeMgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 63% (276 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C25H27O5S 439.1579, found 439.1580; 1H NMR (400 MHz, CDCl3): δ 7.86-7.83 (m, 2H), 7.59-7.54 (m, 1H), 7.45-7.42 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.70-6.65 (m, 2H), 6.52 (d, J = 1.6 Hz, 1H), 5.32 (d, J = 8.8 Hz, 1H), 3.89-3.75 (m, 1H), 3.83 (s, 3H), 3.71 (s, 3H), 2.35 (s, 3H), 1.20 (d, J = 7.2 Hz, 3H);



13

C{1H} NMR (100 MHz, CDCl3): δ 193.0, 148.7, 148.1, 144.5, 137.7, 136.2, 134.0, 133.7, 129.2 (2x), 128.9 (2x), 128.7 (2x), 128.6 (2x), 120.0, 111.01, 110.98, 75.4, 55.8, 55.6, 40.0, 21.5, 20.3.

3-(3,4-Dimethoxyphenyl)-4-methyl-1-phenyl-2-(toluene-4sulfonyl)pentan-1-one (3p). 3p was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and iPrMgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (373 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H31O5S 467.1892, found 467.1893; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.59-7.57 (m, 2H), 7.447.40 (m, 1H), 7.29-7.25 (m, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 2.0, 8.4 Hz, 1H), 6.33 (d, J = 1.6 Hz, 1H), 5.66 (d, J = 11.2 Hz, 1H), 3.70 (s, 3H), 3.52-3.49 (m, 1H), 3.49 (s, 3H), 2.88-2.82 (m, 1H), 2.34 (s, 3H), 0.99 (d, J = 6.8 Hz, 3H), 0.78 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 147.71, 177.67, 145.1 (2x), 137.7, 134.8, 133.0, 129.9 (2x), 129.4 (2x), 128.3 (2x), 128.2 (2x), 122.5, 113.2, 110.2, 71.6, 55.5, 55.4, 50.7, 28.1, 21.6, 21.5, 16.5. 3-Cyclopentyl-3-(3,4-dimethoxyphenyl)-1-phenyl-2-(toluene4-sulfonyl)propan-1-one (3q). 3q was synthesized according to general synthetic procedure from 4a (422 mg, 1.0 mmol) and cC5H9MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 83% (409 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H33O5S 493.2049, found 493.2048; 1H NMR (400 MHz, CDCl3): δ 7.66-7.61 (m, 4H), 7.47-7.43 (m, 1H), 7.337.27 (m, 2H), 7.18 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.4 Hz, 1H), 6.49 (dd, J = 1.2, 8.4 Hz, 1H), 6.41 (br s, 1H), 5.60 (d, J = 9.6 Hz, 1H), 3.72 (s, 3H), 3.69 (dd, J = 5.6, 9.6 Hz, 1H), 3.52 (s, 3H), 2.78-2.71 (m, 1H), 2.34 (s, 3H), 1.82-1.63 (m, 2H), 1.501.05 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 147.8, 147.7, 145.0, 137.8, 135.0, 133.1, 129.8 (2x), 129.6, 129.3 (2x), 128.4 (2x), 125.3 (2x), 122.5, 113.2, 110.2, 73.2, 55.6, 55.4, 48.2, 41.8, 30.5, 27.5, 24.6, 24.3, 21.5. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-1-(4-fluorophenyl)-2(toluene-4-sulfonyl)propan-1-one (3r). 3r was synthesized according to general synthetic procedure from 4t (440 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (430 mg); Colorless solid; mp = 166-168 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H34FO5S 525.2111, found 525.2112; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.4 Hz, 2H), 7.67-7.63 (m, 2H), 7.25 (d, J = 8.4 Hz, 2H), 6.99-6.95 (m, 2H), 6.50 (d, J = 8.0 Hz, 1H), 6.39 (dd, J = 2.0, 8.4 Hz, 1H), 6.32 (d, J = 1.6 Hz, 1H), 5.67 (d, J = 11.6 Hz, 1H), 3.72 (s, 3H), 3.56 (s, 3H), 3.46 (dd, J = 3.2, 11.2 Hz, 1H), 2.38 (s, 3H), 2.45-2.37 (m, 1H), 2.04-2.00 (m, 1H), 1.76-1.20 (m, 6H), 1.06-0.85 (m, 2H), 0.780.68 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.3, 165.6 (d, J = 254.7 Hz), 147.8, 147.7, 145.3, 134.9, 134.2, 131.0 (d, J = 9.1 Hz, 2x), 129.8 (2x), 120.5 (2x), 129.2, 122.0, 115.5 (d, J = 22.0 Hz, 2x), 113.1, 110.1, 71.0, 55.6, 55.5, 50.9, 38.5, 32.3, 27.4, 26.7, 26.3, 26.2, 21.6. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-(toluene-4sulfonyl)-1-p-tolylpropan-1-one (3s). 3s was synthesized according to general synthetic procedure from 4v (436 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 84% (437 mg); Colorless solid; mp = 118-121 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H37O5S 521.2362, found 521.2361; 1H

Page 14 of 30

NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 7.06 (d, J = 7.6 Hz, 2H), 6.49 (d, J = 8.0 Hz, 1H), 6.42 (d, J = 8.4 Hz, 1H), 6.32 (s, 1H), 5.71 (d, J = 11.2 Hz, 1H), 3.70 (s, 3H), 3.50 (s, 3H), 3.493.46 (m, 1H), 2.43-2.36 (m, 1H), 2.34 (s, 3H), 2.31 (s, 3H), 2.03-2.01 (m, 1H), 1.74-1.20 (m, 6H), 0.99-0.85 (m, 2H), 0.780.68 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 147.6, 147.5, 145.0, 144.0, 135.3, 135.1, 129.7 (2x), 129.32 (2x), 129.25, 128.9 (2x), 128.4 (2x), 122.2, 112.9, 110.1, 70.5, 55.5, 55.4, 50.8, 38.5, 32.3, 27.4, 26.6, 26.23, 26.21, 21.50, 21.48. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-1-(4-methoxyphenyl)2-(toluene-4-sulfonyl)propan-1-one (3t). 3t was synthesized according to general synthetic procedure from 4u (452 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (429 mg); Colorless solid; mp = 96-98 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H37O6S 537.2311, found 537.2310; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 9.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 6.50 (d, J = 8.1 Hz, 1H), 6.43 (dd, J = 2.0, 8.4 Hz, 1H), 6.35 (d, J = 1.6 Hz, 1H), 5.68 (d, J = 11.2 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 3.55 (s, 3H), 3.48 (dd, J = 3.2, 11.2 Hz, 1H), 2.43-2.36 (m, 1H), 2.36 (s, 3H), 2.04-2.00 (m, 1H), 1.82-1.30 (m, 6H), 1.040.85 (m, 2H), 0.79-0.69 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 190.9, 163.5, 147.6, 147.5, 145.0, 135.1, 130.9, 130.7 (2x), 129.8 (2x), 129.4, 129.3 (2x), 122.2, 113.5 (2x), 113.1, 110.1, 70.4, 55.55, 55.48, 55.46, 50.7, 38.6, 32.4, 27.5, 26.7, 26.29, 26.26, 21.6. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-(toluene-4sulfonyl)-1-(4-trifluoromethylphenyl)propan-1-one (3u). 3u was synthesized according to general synthetic procedure from 4w (490 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 86% (494 mg); Colorless solid; mp = 149151 oC (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z: [M + H]+ calcd for C31H34F3O5S 575.2079, found 575.2080; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.48 (d, J = 8.0 Hz, 1H), 6.38 (dd, J = 2.0, 8.4 Hz, 1H), 6.29 (d, J = 1.6 Hz, 1H), 5.68 (d, J = 11.2 Hz, 1H), 3.71 (s, 3H), 3.53 (s, 3H), 3.47 (d, J = 3.2, 11.2 Hz, 1H), 2.442.36 (m, 1H), 2.37 (s, 3H), 2.03-2.01 (m, 1H), 1.74-1.20 (m, 6H), 0.98-0.85 (m, 2H), 0.78-0.67 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 147.9, 147.8, 145.5, 140.4, 134.9, 134.6 (q, J = 32.6 Hz), 129.7 (2x), 129.6 (2x), 128.9, 128.5 (2x), 125.8 (q, J = 224.4 Hz), 125.3 (q, J = 3.8 Hz, 2x), 122.0, 113.2, 110.2, 71.6, 55.6, 55.5, 50.9, 38.5, 32.3, 27.3, 26.6, 26.21, 26.19, 21.5. 1-Biphenyl-4-yl-3-cyclohexyl-3-(3,4-dimethoxyphenyl)-2(toluene-4-sulfonyl)propan-1-one (3v). 3v was synthesized according to general synthetic procedure from 4y (498 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 85% (495 mg); Colorless solid; mp = 134-136 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C36H39O5S 583.2518, found 583.2517; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.56-7.37 (m, 7H), 7.24 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 8.4 Hz, 1H), 6.46 (dd, J = 1.6, 8.0 Hz, 1H), 6.36 (s, 1H), 5.78 (d, J = 11.2 Hz, 1H), 3.71 (s, 3H), 3.54-3.47 (m, 1H), 3.52 (s, 3H), 2.47-2.40 (m, 1H), 2.35 (s, 3H), 2.07-2.02 (m,


Page 15 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1H), 1.90-1.57 (m, 4H), 1.39-1.17 (m, 2H), 1.06-0.85 (m, 2H), 0.81-0.71 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 147.7, 147.6, 145.7, 145.1, 139.4, 136.5, 135.0, 129.8 (2x), 129.4 (2x), 129.3, 128.93 (2x), 128.85 (2x), 128.4, 127.1 (2x), 126.8 (2x), 122.2, 113.1, 110.2, 70.8, 55.5, 55.4, 50.8, 38.5, 32.3, 27.4, 26.7, 26.3, 26.2, 21.6. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-1-naphthalen-2-yl-2(toluene-4-sulfonyl)propan-1-one (3w). 3w was synthesized according to general synthetic procedure from 4z (472 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (456 mg); Colorless solid; mp = 92-94 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H37O5S 557.2362, found 557.2361; 1H NMR (400 MHz, CDCl3): δ 8.17 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 1H), 7.59-7.51 (m, 3H), 7.18 (d, J = 8.0 Hz, 2H), 6.45 (s, 2H), 6.38 (s, 1H), 5.89 (d, J = 11.6 Hz, 1H), 3.65 (s, 3H), 3.56 (d, J = 3.6, 11.2 Hz, 1H), 3.44 (s, 3H), 2.51-2.42 (m, 1H), 2.26 (s, 3H), 2.26-2.10 (m, 1H), 1.79-1.30 (m, 6H), 1.00-0.85 (m, 2H), 0.82-0.72 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 147.7, 147.6, 145.2, 135.3, 135.2, 135.0, 132.0, 130.1, 129.8 (2x), 129.6, 129.4 (2x), 129.3, 128.8, 128.2, 127.6, 126.9, 123.7, 122.1, 113.2, 110.1, 71.0, 55.5, 55.4, 51.0, 38.6, 32.4, 27.5, 26.7, 26.30, 26.27, 21.5. 2-Benzenesulfonyl-3-cyclohexyl-3-(3,4-dimethoxyphenyl)-1phenylpropan-1-one (3x). 3x was synthesized according to general synthetic procedure from 4aa (408 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (394 mg); Colorless solid; mp = 75-77 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H33O5S 493.2049, found 493.2047; 1H NMR (400 MHz, CDCl3): δ 7.85-7.82 (m, 2H), 7.58-7.56 (m, 2H), 7.53-7.49 (m, 1H), 7.44-7.38 (m, 3H), 7.28-7.24 (m, 2H), 6.49 (d, J = 8.4 Hz, 1H), 6.42 (dd, J = 2.0, 8.4 Hz, 1H), 6.31 (d, J = 1.6 Hz, 1H), 5.76 (d, J = 11.6 Hz, 1H), 3.69 (s, 3H), 3.54 (dd, J = 3.6, 11.6 Hz, 1H), 3.48 (s, 3H), 2.44-2.36 (m, 1H), 2.02-1.98 (m, 1H), 1.71-1.30 (m, 6H), 1.04-0.83 (m, 2H), 0.78-0.68 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.6, 147.7, 147.6, 138.1, 137.6, 134.0, 133.1, 129.7 (2x), 129.0, 128.8 (2x), 128.3 (2x), 128.1 (2x), 122.2, 112.9, 110.1, 70.6, 55.5, 55.4, 50.9, 38.6, 32.2, 27.4, 26.6, 26.21, 26.17. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-methanesulfonyl-1phenylpropan-1-one (3y). 3y was synthesized according to general synthetic procedure from 4af (346 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 78% (336 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H31O5S 431.1892, found 431.1893; 1H NMR (400 MHz, CDCl3): δ 7.80-7.78 (m, 2H), 7.55-7.51 (m, 2H), 7.427.38 (m, 1H), 6.61-6.56 (m, 2H), 6.45 (s, 1H), 5.51 (d, J = 10.4 Hz, 1H), 3.76 (s, 3H), 3.58 (s, 3H), 3.49 (dd, J = 4.8, 10.4 Hz, 1H), 2.94 (s, 3H), 2.17-2.10 (m, 1H), 1.94-1.90 (m, 1H), 1.861.48 (m, 5H), 1.28-1.23 (m, 2H), 0.95-0.79 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 194.2, 148.0, 137.9, 133.6, 128.7 (2x), 128.6, 128.4 (3x), 122.7, 112.9, 110.3, 69.6, 55.63, 55.57, 51.6, 38.8, 38.5, 32.3, 28.0, 26.4, 26.11, 26.07. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-(4methoxybenzenesulfonyl)-1-phenylpropan-1-one (3z). 3z was synthesized according to general synthetic procedure from 4ac (438 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 74% (386 mg); Colorless liquid; HRMS

(ESI-TOF) m/z: [M + H]+ calcd for C30H35O6S 523.2154, found 523.2154; 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.8 Hz, 2H), 7.59-7.57 (m, 2H), 7.43-7.39 (m, 1H), 7.29-7.25 (m, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.49 (d, J = 8.4 Hz, 1H), 6.41 (dd, J = 2.0, 8.4 Hz, 1H), 6.31 (s, 1H), 5.73 (d, J = 11.6 Hz, 1H), 3.79 (s, 3H), 3.69 (s, 3H), 3.48 (br s, 3H), 3.47 (dd, J = 4.8, 11.6 Hz, 1H), 2.44-2.37 (m, 1H), 2.08-2.01 (m, 1H), 1.79-1.49 (m, 5H), 1.41-1.32 (m, 2H), 1.09-0.83 (m, 1H), 0.79-0.68 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.9, 163.9, 147.64, 147.55, 137.8, 133.0, 132.0 (2x), 129.4, 129.2, 128.3 (2x), 128.1 (2x), 122.2, 113.9 (2x), 113.0, 110.1, 70.7, 55.6, 55.5, 55.4, 50.9, 38.5, 32.3, 27.3, 26.6, 26.3, 26.2. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-(4fluorobenzenesulfonyl)-1-phenylpropan-1-one (3aa). 3aa was synthesized according to general synthetic procedure from 4ab (426 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (418 mg); Colorless solid; mp = 145147 oC (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z: [M + H]+ calcd for C29H32FO5S 511.1955, found 511.1956; 1H NMR (400 MHz, CDCl3): δ 7.85-7.82 (m, 2H), 7.59-7.57 (m, 2H), 7.45-7.42 (m, 1H), 7.30-7.26 (m, 2H), 7.117.07 (m, 2H), 6.49 (d, J = 8.4 Hz, 1H), 6.42 (dd, J = 2.0, 8.4 Hz, 1H), 6.32 (s, 1H), 5.76 (d, J = 11.2 Hz, 1H), 3.69 (s, 3H), 3.49 (br s, 3H), 3.48 (dd, J = 4.8, 11.6 Hz, 1H), 2.41-2.34 (m, 1H), 2.08-2.02 (m, 1H), 1.77-1.49 (m, 5H), 1.40-1.22 (m, 1H), 1.010.86 (m, 2H), 0.80-0.70 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 165.9 (d, J = 256.2 Hz), 147.72, 147.68, 137.5, 133.89 (d, J = 3.0 Hz), 133.0, 132.7 (d, J = 9.8 Hz, 2x), 128.9, 128.4 (2x), 128.1 (2x), 122.2, 116.04 (d, J = 22.7 Hz, 2x), 113.0, 110.2, 70.7, 55.5, 55.4, 51.0, 38.7, 32.3, 27.4, 26.6, 26.23, 26.16. 3-Cyclohexyl-3-(3,4-dimethoxyphenyl)-2-(4isopropylbenzenesulfonyl)-1-phenylpropan-1-one (3ab). 3ab was synthesized according to general synthetic procedure from 4ap (450 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 85% (454 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H39O5S 535.2518, found 535.2519; 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.4 Hz, 2H), 7.56-7.54 (m, 2H), 7.41-7.37 (m, 1H), 7.24-7.22 (m, 4H), 6.51 (d, J = 8.4 Hz, 1H), 6.45 (dd, J = 2.0, 8.4 Hz, 1H), 6.36 (s, 1H), 5.75 (d, J = 11.2 Hz, 1H), 3.70 (s, 3H), 3.60 (dd, J = 4.8, 11.2 Hz, 1H), 3.51 (br s, 3H), 2.89-2.83 (m, 1H), 2.44-2.37 (m, 1H), 2.10-2.01 (m, 1H), 1.89-1.54 (m, 5H), 1.37-1.24 (m, 1H), 1.16 (d, J = 7.2 Hz, 6H), 0.98-0.87 (m, 2H), 0.85-0.69 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.6, 155.7, 147.7, 147.6, 137.6, 135.6, 133.0, 129.9 (2x), 129.3, 128.22 (2x), 128.15 (2x), 126.9 (2x), 122.3, 113.0, 110.2, 70.8, 55.5, 55.4, 50.8, 38.6, 34.1, 32.3, 27.4, 26.6, 26.2 (2x), 23.5, 23.4. 2-(4-n-Butylbenzenesulfonyl)-3-cyclohexyl-3-(3,4dimethoxyphenyl)-1-phenylpropan-1-one (3ac). 3ac was synthesized according to general synthetic procedure from 4aq (464 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (450 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H41O5S 549.2675, found 549.2677; 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.4 Hz, 2H), 7.58-7.55 (m, 2H), 7.43-7.39 (m, 1H), 7.28-7.24 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.51 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 2.0, 8.4 Hz, 1H), 6.34 (s, 1H), 5.75 (d, J = 11.6 Hz, 1H), 3.71 (s, 3H), 3.59 (dd, J = 4.8, 11.6 Hz, 1H), 3.51 (br s, 3H), 2.61-



2.57 (m, 2H), 2.45-2.39 (m, 1H), 2.10-2.01 (m, 1H), 1.82-1.50 (m, 6H), 1.47-1.20 (m, 4H), 0.89 (d, J = 7.2 Hz, 3H), 0.92-0.85 (m, 2H), 0.79-0.72 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 150.0, 155.7, 147.6, 137.7, 135.5, 133.1, 129.8 (2x), 129.3, 128.8 (2x), 128.3 (2x), 128.2 (2x), 122.3, 113.1, 110.2, 70.6, 55.6, 55.5, 50.9, 38.7, 35.5, 33.0, 32.3, 27.4, 26.7, 26.30, 26.28, 22.1, 13.8. 3-(4-Fluorophenyl)-1,3-diphenyl-2-(toluene-4sulfonyl)propan-1-one (3ad). 3ad was synthesized according to general synthetic procedure from 4f (362 mg, 1.0 mmol) and 4FC6H4MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Rotamer; Yield = 74% (339 mg); Colorless solid; mp = 246-250 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H24FO3S 459.1430, found 459.1432; 1H NMR (400 MHz, CDCl3): δ 7.78-7.74 (m, 2H), 7.52-7.47 (m, 1H), 7.40-7.24 (m, 6H), 7.19-7.93 (m, 7H), 6.87-6.83 (m, 1H), 6.696.64 (m, 1H), 6.03 (d, J = 12.0 Hz, 1H), 4.79 (t, J = 12.0 Hz, 1H), 2.35 (d, J = 2.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3 (1/2C), 192.1 (1/2C), 161.9 (d, J = 244.8 Hz, 1/2C), 161.44 (d, J = 244.8 Hz, 1/2C), 145.0 (1/2C), 144.9 (1/2C), 140.4 (1/2C), 138.9 (1/2C), 137.7 (1/2C), 136.5 (1/2C), 135.3 (1/2C), 135.1 (1/2C), 133.60 (1/2C), 133.55 (1/2C), 133.48 (1/2C), 133.45 (1/2C), 130.1 (J = 8.4 Hz, 1C), 129.4 (1C), 129.31 (1C), 129.28 (2C), 129.27 (1C), 129.2 (1/2C), 128.9 (1/2C), 128.8 (1/2C), 128.7 (1/2C), 128.60 (1C), 128.56 (1C), 128.5 (1C), 128.4 (2C), 127.6 (1C), 127.3 (1/2C), 127.0 (1/2C), 115.6 (d, J = 21.3 Hz, 1C), 115.4 (d, J = 19.7 Hz, 1C), 73.1 (1C), 51.2 (1/2C), 51.1 (s, 1/2C), 21.6 (1C). 3-Cyclohexyl-1-phenyl-3-thiophen-2-yl-2-(toluene-4sulfonyl)propan-1-one (3ae). 3ae was synthesized according to general synthetic procedure from 4r (368 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 75% (339 mg); Colorless solid; mp = 168-170 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H29O3S2 453.1558, found 453.1557; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.4 Hz, 2H), 7.58-7.55 (m, 2H), 7.44-7.40 (m, 1H), 7.28-7.24 (m, 2H), 7.18 (d, J = 8.0 Hz, 2H), 6.92 (d, J = 5.2 Hz, 1H), 6.66 (dd, J = 4.0, 5.2 Hz, 1H), 6.59 (dd, J = 0.8, 3.2 Hz, 1H), 5.66 (d, J = 11.2 Hz, 1H), 3.96 (dd, J = 3.6, 11.2 Hz, 1H), 2.45-2.37 (m, 1H), 2.33 (s, 3H), 2.07-2.04 (m, 1H), 1.81-1.77 (m, 1H), 1.70-1.61 (m, 2H), 1.51-1.42 (m, 1H), 1.39-1.13 (m, 3H), 1.03-0.94 (m, 1H), 0.89-0.80 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.3, 145.1, 139.1, 137.3, 135.0, 133.0, 129.8 (2x), 129.4 (2x), 128.3 (2x), 128.1 (2x), 127.7, 126.0, 124.2, 71.1, 46.6, 38.5, 32.2, 27.4, 26.6, 26.24, 26.17, 21.5. 3-Cyclopentyl-1-phenyl-3-thiophen-2-yl-2-(toluene-4sulfonyl)-propan-1-one (3af). 3af was synthesized according to general synthetic procedure from 4r (368 mg, 1.0 mmol) and cC5H9MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 78% (342 mg); Colorless solid; mp = 156-158 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C25H27O3S2 439.1402, found 439.1403; 1H NMR (400 MHz, CDCl3): δ 7.62-7.57 (m, 4H), 7.47-7.43 (m, 1H), 7.317.27 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.95 (dd, J = 1.2, 4.4 Hz, 1H), 6.71-6.67 (m, 2H), 5.52 (d, J = 10.0 Hz, 1H), 4.17-4.13 (m, 1H), 2.84-2.78 (m, 1H), 2.32 (s, 3H), 1.95-1.89 (m, 1H), 1.72-1.65 (m, 2H), 1.55-1.37 (m, 4H), 1.19-1.09 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.4, 145.0, 139.6, 137.3, 134.9, 133.2, 129.7 (2x), 129.4 (2x), 128.41, 128.39 (2x), 128.2

Page 16 of 30

(2x), 125.9, 124.7, 73.5, 44.5, 41.6, 30.7, 27.6, 25.14, 25.11, 21.5. 4-Methyl-1-phenyl-3-thiophen-2-yl-2-(toluene-4sulfonyl)pentan-1-one (3ag). 3ag was synthesized according to general synthetic procedure from 4r (368 mg, 1.0 mmol) and iPrMgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (330 mg); Colorless solid; mp = 162-164 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C23H24O3S2 413.1245, found 413.1246; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.4 Hz, 2H), 7.57-7.55 (m, 2H), 7.447.40 (m, 1H), 7.31-7.24 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 5.2 Hz, 1H), 6.67 (dd, J = 3.6, 5.2 Hz, 1H), 6.61 (dd, J = 1.2, 3.6 Hz, 1H), 5.58 (d, J = 11.2 Hz, 1H), 3.97 (dd, J = 3.6, 11.2 Hz, 1H), 2.90-2.82 (m, 1H), 2.33 (s, 3H), 1.13 (d, J = 6.4 Hz, 3H), 0.84 (d, J = 6.8 Jz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.3, 145.2, 138.1, 137.3, 134.8, 133.1, 129.8 (2x), 129.4 (2x), 128.3 (2x), 128.1 (2x), 128.0, 126.0, 124.3, 72.0, 46.8, 28.2, 21.6, 21.5, 16.7. 3-(1-Benzyl-1H-pyrrol-2-yl)-3-cyclohexyl-1-phenyl-2(toluene-4-sulfonyl)propan-1-one (3ah). 3ah was synthesized according to general synthetic procedure from 4aj (441 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (420 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H36NO3S 526.2416, found 526.2418; 1 H NMR (400 MHz, CDCl3): δ 8.01-7.99 (m, 2H), 7.63-7.59 (m, 1H), 7.53-7.49 (m, 2H), 7.38-7.28 (m, 5H), 7.21 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.42 (dd, J = 1.6, 2.8 Hz, 1H), 5.82 (t, J = 3.2 Hz, 1H), 5.59-5.55 (m, 2H), 5.22 (d, J = 15.2 Hz, 1H), 5.16 (d, J = 15.2 Hz, 1H), 4.08 (dd, J = 4.0, 11.2 Hz, 1H), 2.34 (s, 3H), 1.60-1.42 (m, 3H), 1.41-1.25 (m, 4H), 1.02-0.64 (m, 3H), 0.50-0.40 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.9, 144.0, 137.7, 137.6, 137.5, 133.7, 129.2 (2x), 128.9 (2x), 128.59 (4x), 128.55 (2x), 128.1 (2x), 128.0, 127.6, 120.4, 109.3, 107.2, 73.9, 50.4, 41.3, 41.2, 31.2, 28.0, 26.2, 26.1, 25.7, 21.5. 3-Cyclohexyl-1-phenyl-3-pyridin-2-yl-2-(toluene-4sulfonyl)propan-1-one (3ai). 3ai was synthesized according to general synthetic procedure from 4al (363 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 82% (367 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H30NO3S 448.1946, found 448.1953; 1H NMR (400 MHz, CDCl3): δ 8.10 (ddd, J = 0.8, 1.6, 8.4 Hz, 1H), 7.70-7.67 (m, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.45-7.38 (m, 2H), 7.30-7.24 (m, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 7.6 Hz, 1H), 6.90 (ddd, J = 1.2, 5.2, 7.6 Hz, 1H), 6.20 (d, J = 10.8 Hz, 1H), 3.82 (dd, J = 3.2, 10.8 Hz, 1H), 2.57-2.51 (m, 1H), 2.33 (s, 3H), 2.09-2.06 (m, 1H), 1.88-1.58 (m, 3H), 1.44-1.13 (m, 3H), 1.01-0.80 (m, 2H), 0.75-0.64 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 194.3, 158.1, 148.0, 144.9, 138.0, 135.5, 135.4, 132.6, 129.6 (2x), 129.3 (2x), 128.7 (2x), 127.9 (2x), 125.2, 121.6, 70.4, 52.1, 38.5, 32.6, 27.3, 26.8, 26.33, 26.26, 21.5. 3-Cyclohexyl-3-furan-2-yl-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3aj). 3aj was synthesized according to general synthetic procedure from 4am (352 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (349 mg); Colorless solid; mp = 108-109 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C26H29O4S 437.1787, found 437.1786; 1H NMR (400 MHz, CDCl3): δ 7.68-7.61 (m, 3H), 7.48-7.43 (m, 1H), 7.32-


Page 17 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


7.28 (m, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 1.2 Hz, 1H), 6.04 (dd, J = 2.0, 3.2 Hz, 1H), 5.86 (dd, J = 0.8, 3.2 Hz, 1H), 5.75 (d, J = 10.8 Hz, 1H), 3.67 (dd, J = 3.2, 10.8 Hz, 1H), 2.402.33 (m, 1H), 2.35 (s, 3H), 2.10-2.04 (m, 1H), 1.76-1.55 (m, 4H), 1.43-1.23 (m, 3H), 1.04-0.83 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.8, 151.4, 145.2, 141.2, 137.0, 134.9, 133.1, 129.8 (2x), 129.4 (2x), 128.3 (2x), 128.2 (2x), 110.1, 109.1, 69.1, 45.1, 38.4, 32.1, 27.9, 26.5, 26.2 (2x), 21.6. 2-Benzenesulfonyl-3-cyclohexyl-1-phenyl-3-thiophen-2ylpropan-1-one (3ak). 3ak was synthesized according to general synthetic procedure from 4ak (354 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 86% (377 mg); Colorless solid; mp = 230-231 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C25H27O3S2 439.1402, found 439.1405; 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 7.6 Hz, 2H), 7.51-7.47 (m, 1H), 7.43-7.37 (m, 3H), 7.27-7.24 (m, 2H), 6.92 (d, J = 8.8 Hz, 1H), 6.66 (dd, J = 3.2, 8.4 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H), 5.69 (d, J = 10.8 Hz, 1H), 4.00 (dd, J = 3.6, 10.8 Hz, 1H), 2.44-2.37 (m, 1H), 2.06-2.03 (m, 1H), 1.80-1.77 (m, 1H), 1.70-1.52 (m, 3H), 1.42-1.29 (m, 2H), 1.24-1.14 (m, 1H), 1.03-0.94 (m, 1H), 0.90-0.79 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.2, 139.0, 138.1, 137.2, 134.0, 133.2, 129.7 (2x), 128.8 (2x), 128.2 (4x), 127.8, 126.0, 124.3, 71.0, 46.7, 38.6, 32.2, 27.4, 26.6, 26.23, 26.17. 3-Benzo[b]furan-2-yl-3-cyclohexyl-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3al). 3al was synthesized according to general synthetic procedure from 4an (402 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 83% (404 mg); Colorless solid; mp = 203-204 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H31O4S 487.1943, found 487.1945; 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H), 7.43-7.19 (m, 6H), 7.07-7.04 (m, 3H), 6.30 (s, 1H), 5.89 (d, J = 10.8 Hz, 1H), 3.82 (dd, J = 3.2, 10.8 Hz, 1H), 2.52-2.42 (m, 1H), 2.35 (s, 3H), 2.17-2.13 (m, 1H), 1.76-1.61 (m, 4H), 1.45-1.28 (m, 3H), 1.08-0.92 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.7, 154.4, 154.0, 145.3, 137.0, 134.8, 133.1, 129.8 (2x), 129.4 (2x), 128.3 (2x), 128.1 (2x), 128.0, 123.5, 122.6, 120.6, 110.5, 106.0, 68.9, 45.6, 38.4, 32.2, 28.1, 26.5, 26.0, 26.1, 21.5. 3-Benzo[b]thiophen-2-yl-3-cyclohexyl-1-phenyl-2-(toluene4-sulfonyl)propan-1-one (3am). 3am was synthesized according to general synthetic procedure from 4ao (418 mg, 1.0 mmol) and cC6H11MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 80% (402 mg); Colorless solid; mp = 225-226 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H31O3S2 503.1715, found 503.1718; 1H NMR (400 MHz, CDCl3): δ 7.60-7.52 (m, 5H), 7.46 (d, J = 7.2 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.22-7.09 (m, 6H), 6.81 (s, 1H), 5.72 (d, J = 11.2 Hz, 1H), 3.98 (dd, J = 3.6, 10.8 Hz, 1H), 2.462.41 (m, 1H), 2.28 (s, 3H), 2.07-2.04 (m, 1H), 1.77-1.74 (m, 1H), 1.66-1.56 (m, 4H), 1.35-1.18 (m, 3H), 0.96-0.88 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 191.9, 145.2, 140.6, 139.3, 138.9, 137.2, 134.9, 133.1, 129.8 (2x), 129.4 (2x), 128.5 (2x), 128.2 (2x), 124.6, 124.0, 123.8, 123.0, 121.7, 70.8, 47.3, 38.6, 32.3, 27.7, 26.6, 26.23, 26.21, 21.5. 3-(2-Allyl-3,4-dimethoxyphenyl)-3-cyclopentyl-1-phenyl-2(toluene-4-sulfonyl)propan-1-one (3an). 3an was synthesized according to general synthetic procedure from 4p (362 mg, 1.0

mmol) and cC5H9MgBr (2 mL, 1.0 M in THF, 2.0 mmol). Yield = 72% (383 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37O5S 533.2362, found 533.2366; 1 H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.4 Hz, 2H), 7.557.53 (m, 2H), 7.45-7.40 (m, 1H), 7.30-7.26 (m, 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.54 (d, J = 8.8 Hz, 1H), 6.29 (d, J = 8.8 Hz, 1H), 5.83-5.73 (m, 1H), 5.61 (d, J = 10.4 Hz, 1H), 4.95-4.90 (m, 2H), 4.02 (dd, J = 5.2, 10.4 Hz, 1H), 3.70 (s, 3H), 3.64 (s, 3H), 3.41 (dd, J = 8.0, 15.2 Hz, 1H), 3.34-3.28 (m, 1H), 2.812.74 (m, 1H), 2.35 (s, 3H), 1.93-1.87 (m, 1H), 1.75-1.68 (m, 1H), 1.54-1.41 (m, 4H), 1.35-1.27 (m, 1H), 0.89-0.82 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 192.9, 151.2, 147.4, 145.0, 138.1, 136.8, 134.8, 134.2, 132.8, 129.9 (2x), 129.3 (2x), 129.0, 128.2 (2x), 128.1 (2x), 124.2, 115.0, 109.0, 73.8, 60.5, 55.3, 42.5, 41.5, 31.2, 30.3, 27.4, 24.2, 24.0, 21.5. General synthetic procedure of compounds 3ao-3as is as follows: NaBH4 (38 mg, 1.0 mmol) was added to a solution of 4a, 4b, 4e, 4w and 4x (0.3 mmol) in THF and MeOH (v/v =1/1, 10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 30 min. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product under reduced pressure. Without further purification, PCC (216 mg, 1.0 mmol) was added to a solution of the resulting crude products in a CH2Cl2 (10 mL) at 25 oC. Then, Celite (200 mg) was added to the reaction mixture at 25 oC. The reaction mixture was stirred at 25 oC for 3 h. The reaction mixture was filtrated, and the combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product mixture under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 3ao-3a. 3-(3,4-Dimethoxyphenyl)-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3ao). 3ao was synthesized according to general synthetic procedure from 4a (127 mg, 0.3 mmol). Yield = 90% (114 mg); Colorless solid; mp = 125-126 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H25O5S 425.1423; Found 425.1430; 1H NMR (400 MHz, CDCl3): δ 7.73-7.71 (m, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.47-7.43 (m, 1H), 7.32-7.26 (m, 4H), 6.60 (d, J = 1.2 Hz, 2H), 6.55 (br s, 1H), 5.32 (dd, J = 2.8, 11.2 Hz, 1H), 3.69 (s, 3H), 3.66 (s, 3H), 3.41 (dd, J = 2.8, 13.2 Hz, 1H), 3.27 (dd, J = 11.2, 13.2 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.4, 148.7, 147.7, 145.3, 137.1, 133.6, 133.2, 129.6 (2x), 129.4 (2x), 128.5 (2x), 128.4 (2x), 128.1, 120.8, 111.8, 111.2, 71.3, 55.5 (2x), 35.5, 21.5. 3-Benzo[1,3]dioxol-5-yl-1-phenyl-2-(toluene-4sulfonyl)propan-1-one (3ap). 3ap was synthesized according to general synthetic procedure from 4b (122 mg, 0.3 mmol). Yield = 86% (105 mg); Colorless solid; mp = 123-125 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O5S 409.1110; Found 409.1118; 1H NMR (400 MHz, CDCl3): δ 7.73-7.70 (m, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.48-7.44 (m, 1H), 7.33-7.25 (m, 4H), 6.54-6.48 (m, 3H), 5.77 (d, J = 1.2 Hz, 1H), 5.76 (d, J = 1.2 Hz, 1H), 5.22 (dd, J = 3.2, 11.6 Hz, 1H), 3.33 (dd, J = 3.2, 13.6 Hz, 1H), 3.22 (dd, J = 11.6, 13.6 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.1, 147.7, 146.5, 145.5, 137.2, 133.7,



133.3, 129.7 (2x), 129.5 (2x), 129.4, 128.7 (2x), 128.5 (2x), 122.0, 109.2, 108.4, 100.9, 71.5, 33.6, 21.6. 1-Phenyl-2-(toluene-4-sulfonyl)-3-(3,4,5trimethoxyphenyl)propan-1-one (3aq). 3aq was synthesized according to general synthetic procedure from 4e (136 mg, 0.3 mmol). Yield = 90% (123 mg); Colorless solid; mp = 153-155 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27O6S 455.1528; Found 455.1536; 1 H NMR (400 MHz, CDCl3): δ 7.76-7.73 (m, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.49-7.45 (m, 1H), 7.34-7.28 (m, 4H), 6.24 (s, 2H), 5.35 (dd, J = 3.2, 11.6 Hz, 1H), 3.67 (s, 3H), 3.63 (s, 6H), 3.42 (dd, J = 2.8, 13.2 Hz, 1H), 3.26 (dd, J = 11.6, 13.2 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 192.5, 153.0 (2x), 145.4, 137.1, 136.6, 133.7, 133.2, 131.3, 129.7 (2x), 129.5 (2x), 128.6 (2x), 128.4 (2x), 105.7 (2x), 71.1, 60.5, 55.8 (2x), 34.3, 21.5. 3-(3,4-Dimethoxyphenyl)-2-(toluene-4-sulfonyl)-1-(4trifluoromethylphenyl)propan-1-one (3ar). 3ar was synthesized according to general synthetic procedure from 4w (147 mg, 0.3 mmol). Yield = 84% (124 mg); Colorless solid; mp = 120-122 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H24F3O5S 493.1297; Found 493.1299; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.59-6.58 (m, 3H), 5.40 (dd, J = 3.2, 11.6 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 3.44 (dd, J = 3.2, 13.2 Hz, 1H), 3.27 (dd, J = 12.0, 13.2 Hz, 1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.8, 148.7, 147.8, 145.6, 139.6, 134.4 (q, J = 32.6 Hz), 133.0, 129.53 (2x), 129.49 (2x), 128.8 (2x), 127.7, 125.3 (q, J = 3.8 Hz, 2x), 123.1 (q, J = 271.4 Hz), 120.7, 111.8, 111.1, 71.6, 55.5, 55.4, 33.3, 21.3. 3-(3,4-Dimethoxyphenyl)-1-(4-nitrophenyl)-2-(toluene-4sulfonyl)propan-1-one (3as). 3as was synthesized according to general synthetic procedure from 4x (140 mg, 0.3 mmol). Yield = 90% (127 mg); Colorless solid; mp = 148-150 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H24NO7S 470.1274; Found 470.1274; 1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.61-6.55 (m, 3H), 5.36 (dd, J = 2.8, 11.6 Hz, 1H), 3.69 (s, 3H), 3.68 (s, 3H), 3.41 (dd, J = 2.8, 13.2 Hz, 1H), 3.22 (dd, J = 11.6, 13.2 Hz, 1H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 191.7, 150.2, 148.9, 147.9, 145.9, 141.4, 132.8, 129.7 (4x), 129.6 (2x), 127.5, 123.6 (2x), 120.8, 111.9, 111.2, 72.1, 55.6, 55.5, 33.7, 21.5. General synthetic procedure of skeleton 1 is as follows: A15 (100 mg) was added to a solution of 3 (0.2 mmol) in toluene (10 mL) at 25 oC. The reaction mixture was stirred at reflux for 10 h under Dean-Stark distillation apparatus. The reaction mixture was cooled to 25 oC. A-15 was filtered by filter paper and the A-15 was washed with toluene (3 x 5 mL). The combined toluene layers were concentrated. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product mixture under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 1.

Page 18 of 30

1-Cyclohexyl-5,6-dimethoxy-3-phenyl-2-(toluene-4sulfonyl)-1H-indene (1a). 1a was synthesized according to general synthetic procedure from 3g (101 mg, 0.2 mmol). Yield = 90% (88 mg); Colorless solid; mp = 178-181 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H33O4S 489.2100, found 489.2101; 1H NMR (400 MHz, CDCl3): δ 7.41-7.33 (m, 5H), 7.31 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.49 (s, 1H), 4.06 (d, J = 3.2 Hz, 1H), 3.95 (s, 3H), 3.71 (s, 3H), 2.76-2.69 (m, 1H), 2.31 (s, 3H), 2.04-2.03 (m, 1H), 1.86-1.83 (m, 1H), 1.74-1.64 (m, 3H), 1.54-1.39 (m, 2H), 1.23-0.97 (m, 2H), 0.49-0.38 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.4, 149.7, 148.8, 143.2, 141.4, 139.1, 139.0, 136.4, 132.5, 128.8 (2x), 128.4 (2x), 127.9 (3x), 127.5 (2x), 108.1, 105.4, 57.4, 56.3, 56.0, 39.7, 32.5, 27.2, 26.5, 26.1 (2x), 21.4. Single-crystal X-Ray diagram: crystal of 1a was grown by slow diffusion of EtOAc into a solution of 1a in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 12.0497(17) Å , b = 14.261(2) Å , c = 15.114(2) Å , V = 2549.5(7) Å 3, Z = 4, dcalcd = 1.273 g/cm3, F(000) = 1040, 2θ range 1.981~26.451o, R indices (all data) R1 = 0.0544, wR2 = 0.0985. 5-Cyclohexyl-7-phenyl-6-(toluene-4-sulfonyl)-5Hindeno[5,6-d][1,3]dioxole (1b). 1b was synthesized according to general synthetic procedure from 3h (98 mg, 0.2 mmol). Yield = 86% (81 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H29O4S 473.1787, found 473.1788; 1H NMR (400 MHz, CDCl3): δ 7.39-7.30 (m, 3H), 7.31 (d, J = 8.4 Hz, 2H), 7.04 (s, 1H), 7.01 (d, J = 8.4 Hz, 2H), 6.45 (s, 1H), 5.97 (d, J = 1.2 Hz, 1H), 5.96 (d, J = 1.2 Hz, 1H), 4.02 (d, J = 3.2 Hz, 1H), 2.74-2.67 (m, 1H), 2.31 (s, 3H), 2.04-2.03 (m, 1H), 1.86-1.83 (m, 1H), 1.74-1.64 (m, 3H), 1.54-1.39 (m, 3H), 1.200.99 (m, 3H), 0.51-0.40 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.2, 148.4, 147.2, 143.2, 141.6, 140.6, 139.1, 137.8, 132.4, 128.9 (2x), 128.5 (2x), 127.9 (2x), 127.5 (3x), 105.8, 103.2, 101.5, 57.2, 39.8, 32.6, 27.2, 26.4, 26.13, 26.06, 21.5. 1-Cyclohexyl-4,5,6-trimethoxy-3-phenyl-2-(toluene-4sulfonyl)-1H-indene (1c). 1c was synthesized according to general synthetic procedure from 3i (107 mg, 0.2 mmol). Yield = 90% (93 mg); Colorless solid; mp = 150-152 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H35O5S 519.2205, found 519.2204; 1H NMR (400 MHz, CDCl3): δ 7.34-7.26 (m, 3H), 7.23 (d, J = 8.0 Hz, 2H), 7.16-7.13 (m, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 4.08 (d, J = 2.8 Hz, 1H), 3.92 (s, 3H), 3.76 (s, 3H), 3.22 (s, 3H), 2.77-2.68 (m, 1H), 2.32 (s, 3H), 2.04-2.01 (m, 1H), 1.86-1.83 (m, 1H), 1.73-1.64 (m, 3H), 1.55-1.38 (m, 2H), 1.24-0.85 (m, 2H), 0.53-0.42 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 154.3, 151.7, 150.1, 143.1, 142.6, 141.7, 141.5, 139.1, 134.0, 129.2, 128.9, 128.8 (2x), 128.4, 127.6, 127.5 (2x), 127.0, 126.9, 104.4, 60.92, 60.88, 57.6, 56.3, 40.0, 32.2, 27.2, 26.4, 26.1, 26.0, 21.4. 5,6-Dimethoxy-1,3-diphenyl-2-(toluene-4-sulfonyl)-1Hindene (1d). 1d was synthesized according to general synthetic procedure from 3j (100 mg, 0.2 mmol). Yield = 89% (86 mg); Colorless solid; mp = 194-196 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H27O4S 483.1630, found 483.1631; 1H NMR (400 MHz, CDCl3): δ 7.50-7.47 (m, 3H), 7.39 (br s, 2H), 7.24-7.17 (m,


Page 19 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


3H), 7.05-7.03 (m, 2H), 6.88 (br s, 4H), 6.71 (s, 1H), 6.58 (s, 1H), 5.13 (s, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 2.28 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 153.6, 150.9, 149.2, 143.00, 142.96, 142.3, 139.1, 137.4, 135.4, 132.4, 129.0, 128.78 (2x), 128.75 (2x), 128.7 (2x), 128.6 (2x), 128.1 (2x), 127.4 (2x), 127.2, 107.1, 105.4, 57.3, 56.2, 56.1, 21.4. 1-(4-Fluorophenyl)-5,6-dimethoxy-3-phenyl-2-(toluene-4sulfonyl)-1H-indene (1e). 1e was synthesized according to general synthetic procedure from 3k (104 mg, 0.2 mmol). Yield = 85% (85 mg); Colorless solid; mp = 155-156 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H26FO4S 501.1536, found 501.1533; 1H NMR (400 MHz, CDCl3): δ 7.50-7.47 (m, 3H), 7.39 (br s, 2H), 7.026.97 (m, 2H), 6.95-6.86 (m, 6H), 6.69 (s, 1H), 6.57 (s, 1H), 5.11 (s, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 2.29 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.1 (d, J = 244.1 Hz), 153.6, 151.0, 149.3, 143.2, 142.8, 142.0, 139.1, 135.2, 133.1 (d, J = 3.0 Hz), 132.2, 130.3 (d, J = 8.3 Hz, 2x), 129.0, 128.82 (2x), 128.78 (2x), 128.1 (2x), 127.3 (2x), 115.4 (d, J = 21.2 Hz, 2x), 107.0, 105.5, 56.4, 56.2, 56.1, 21.4. Single-crystal X-Ray diagram: crystal of 1e was grown by slow diffusion of EtOAc into a solution of 1e in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 14.241(2) Å , b = 11.0536(15) Å , c = 15.619(2) Å , V = 2442.6(6) Å 3, Z = 4, dcalcd= 1.361 g/cm3, F(000) = 1048, 2θ range 1.834~26.922o, R indices (all data) R1 = 0.1087, wR2 = 0. 1785. 5,6-Dimethoxy-1-(4-methoxyphenyl)-3-phenyl-2-(toluene-4sulfonyl)-1H-indene (1f). 1f was synthesized according to general synthetic procedure from 3l (106 mg, 0.2 mmol). Yield = 92% (94 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H29O5S 513.1736, found 513.1736; 1H NMR (400 MHz, CDCl3): δ 7.49-7.46 (m, 3H), 7.38 (br s, 2H), 6.986.88 (m, 6H), 6.73 (d, J = 8.4 Hz, 2H), 6.71 (s, 1H), 6.56 (s, 1H), 5.09 (s, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.74 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.8, 153.2, 150.9, 149.1, 143.04, 142.95, 142.4, 139.2, 135.2, 132.4, 129.8 (2x), 129.0 (2x), 128.7 (3x), 128.1 (2x), 127.4 (2x), 124.4, 114.0 (2x), 107.1, 105.3, 56.6, 56.2, 56.1, 55.3, 21.4. 1-Isopropyl-5,6-dimethoxy-3-phenyl-2-(toluene-4-sulfonyl)1H-indene (1g). 1g was synthesized according to general synthetic procedure from 3p (93 mg, 0.2 mmol). Yield = 74% (66 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C27H29O4S 449.1787, found 449.1788; 1H NMR (400 MHz, CDCl3): δ 7.41-7.30 (m, 5H), 7.30 (d, J = 8.4 Hz, 2H), 7.09 (s, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.51 (s, 1H), 4.07 (d, J = 3.2 Hz, 1H), 3.94 (s, 3H), 3.72 (s, 3H), 3.20-3.13 (m, 1H), 2.30 (s, 3H), 1.39 (d, J = 6.8 Hz, 3H), 0.50 (d, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.3, 149.7, 148.8, 143.1, 141.9, 139.1, 138.4, 136.5, 132.4, 128.8 (3x), 128.5 (2x), 128.0 (2x), 127.4 (2x), 108.0, 105.4, 57.5, 56.2, 56.0, 29.2, 21.9, 21.4, 15.4. 1-Cyclopentyl-5,6-dimethoxy-3-phenyl-2-(toluene-4sulfonyl)-1H-indene (1h). 1h was synthesized according to general synthetic procedure from 3q (98 mg, 0.2 mmol). Yield = 86% (82 mg); Colorless solid; mp = 206-207 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H31O4S 475.1943, found 475.1944; 1H NMR (400 MHz, CDCl3): δ 7.40-7.33 (m, 5H), 7.29 (d, J = 8.4 Hz, 2H), 7.11 (s, 1H), 6.98 (d, J = 8.0 Hz, 2H), 6.50 (s, 1H), 4.30 (d, J = 3.6 Hz, 1H), 3.93 (s, 3H), 3.71 (s, 3H), 3.28-3.22 (m, 1H),

2.30 (s, 3H), 2.13-1.90 (m, 1H), 1.90-1.81 (m, 1H), 1.63-1.44 (m, 4H), 0.90-0.83 (m, 1H), 0.59-0.52 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 151.6, 149.6, 148.9, 143.1, 142.9, 139.1, 138.8, 136.8, 132.5, 128.8 (2x), 128.4 (2x), 127.9 (3x), 127.4 (2x), 108.2, 105.3, 56.3, 56.0, 54.1, 40.5, 30.8, 25.7, 25.6, 25.1, 21.4. Single-crystal X-Ray diagram: crystal of 1h was grown by slow diffusion of EtOAc into a solution of 1h in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 11.8975(5) Å , b = 14.8380(7) Å , c = 14.1035(7) Å , V = 2480.8(2) Å 3, Z = 4, dcalcd = 1.271 g/cm3, F(000) = 1008, 2θ range 1.996~26.405o, R indices (all data) R1 = 0.0525, wR2 = 0.1060. 1-Cyclohexyl-3-(4-fluorophenyl)-5,6-dimethoxy-2-(toluene4-sulfonyl)-1H-indene (1i). 1i was synthesized according to general synthetic procedure 3r (105 mg, 0.2 mmol). Yield = 89% (90 mg); Colorless solid; mp = 166-167 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H32FO4S 507.2005, found 507.2004; 1H NMR (400 MHz, CDCl3): δ 7.33 (d, J = 8.4 Hz, 2H), 7.15 (br s, 2H), 7.09-7.04 (m, 5H), 6.46 (s, 1H), 4.04 (d, J = 2.8 Hz, 1H), 3.95 (s, 3H), 3.72 (s, 3H), 2.75-2.68 (m, 1H), 2.33 (s, 3H), 2.04-2.01 (m, 1H), 1.86-1.83 (m, 1H), 1.73-1.64 (m, 3H), 1.55-1.38 (m, 2H), 1.24-0.96 (m, 2H), 0.48-0.38 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.9 (d, J = 246.4 Hz), 151.4, 149.8, 148.9, 143.4, 141.9, 139.1, 139.0, 136.2, 131.0 (2x), 128.9 (2x), 128.42 (d, J = 3.0 Hz), 127.4 (2x), 115.1 (d, J = 21.3 Hz, 2x), 108.2, 105.1, 57.4, 56.3, 56.0, 39.8, 32.5, 27.2, 26.4, 26.2, 26.1, 21.4. 1-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)-3-ptolyl-1H-indene (1j). 1j was synthesized according to general synthetic procedure from 3s (104 mg, 0.2 mmol). Yield = 90% (90 mg); Colorless solid; mp = 167-168 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H35O4S 503.2256, found 503.2254; 1H NMR (400 MHz, CDCl3): δ 7.34 (d, J = 8.4 Hz, 2H), 7.15 (br s, 2H), 7.07 (s, 3H), 7.02 (d, J = 7.6 Hz, 2H), 6.52 (s, 1H), 4.02 (d, J = 2.8 Hz, 1H), 3.94 (s, 3H), 3.72 (s, 3H), 2.74-2.67 (m, 1H), 2.42 (s, 3H), 2.32 (s, 3H), 2.04-2.01 (m, 1H), 1.86-1.83 (m, 1H), 1.73-1.64 (m, 3H), 1.55-1.38 (m, 2H), 1.24-0.96 (m, 2H), 0.47-0.37 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 152.7, 149.6, 148.8, 143.1, 141.1, 139.3, 139.1, 138.4, 136.6, 129.5, 129.2 (2x), 128.8 (2x), 128.6 (2x), 127.5 (2x), 108.1, 105.4, 57.3, 56.3, 56.0, 39.7, 32.5, 27.2, 26.5, 26.1 (2x), 21.44, 21.41. 1-Cyclohexyl-5,6-dimethoxy-3-(4-methoxyphenyl)-2(toluene-4-sulfonyl)-1H-indene (1k). 1k was synthesized according to general synthetic procedure from 3t (107 mg, 0.2 mmol). Yield = 93% (96 mg); Colorless solid; mp = 184-185 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H35O5S 519.2205, found 519.2207; 1 H NMR (400 MHz, CDCl3): δ 7.33 (d, J = 8.4 Hz, 2H), 7.15 (br s, 2H), 7.07 (s, 1H), 7.2 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 6.54 (s, 1H), 4.02 (d, J = 3.2 Hz, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.73 (s, 3H), 2.74-2.67 (m, 1H), 2.31 (s, 3H), 2.04-2.01 (m, 1H), 1.86-1.83 (m, 1H), 1.69-1.63 (m, 3H), 1.531.41 (m, 2H), 1.29-0.99 (m, 2H), 0.44-0.40 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.9, 152.4, 149.6, 148.8, 143.1, 141.0, 139.3, 139.1, 136.6, 130.7 (2x), 128.8 (2x), 127.4 (2x), 124.7, 113.4 (2x), 108.1, 105.4, 57.3, 56.3, 56.0, 55.3, 39.8, 32.5, 27.2, 26.5, 26.2, 26.1, 21.4.



1-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)-3-(4trifluoromethylphenyl)-1H-indene (1l). 1l was synthesized according to general synthetic procedure from 3u (115 mg, 0.2 mmol). Yield = 89% (99 mg); Colorless solid; mp = 223-225 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H32F3O4S 557.1973, found 557.1974; 1H NMR (400 MHz, CDCl3): δ 7.60 (br s, 4H), 7.32 (d, J = 8.0 Hz, 2H), 7.09 (s, 1H), 7.02 (d, J = 8.0 Hz, 2H), 6.40 (s, 1H), 4.07 (d, J = 2.8 Hz, 1H), 3.96 (s, 3H), 3.72 (s, 3H), 2.76-2.69 (m, 1H), 2.32 (s, 3H), 2.05-2.02 (m, 1H), 1.87-1.84 (m, 1H), 1.74-1.53 (m, 3H), 1.48-1.39 (m, 1H), 1.32-1.27 (m, 1H), 1.24-0.96 (m, 2H), 0.52-0.42 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 150.4, 150.0, 149.0, 143.7, 142.7, 139.1, 138.7, 136.5, 135.7, 130.7, 130.5 (q, J = 32.6 Hz, 2x), 129.0 (2x), 127.5 (2x), 125.7 (q, J = 224.3 Hz), 124.9 (d, J = 3.8 Hz, 2x), 108.2, 105.0, 57.5, 56.3, 56.1, 39.8, 32.5, 27.2, 26.4, 26.2, 26.1, 21.4. 4-[3-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)-3Hinden-1-yl]biphenyl (1m). 1m was synthesized according to general synthetic procedure from 3v (116 mg, 0.2 mmol). Yield = 85% (96 mg); Colorless solid; mp = 254-256 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C36H37O4S 565.2413, found 565.2412; 1H NMR (400 MHz, CDCl3): δ 7.67-7.65 (m, 2H), 7.56 (br s, 4H), 7.527.48 (m, 2H), 7.42-7.39 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.10 (s, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.56 (s, 1H), 4.10 (d, J = 3.2 Hz, 1H), 3.96 (s, 3H), 3.74 (s, 3H), 2.78-2.71 (m, 1H), 2.30 (s, 3H), 2.06-2.04 (m, 1H), 1.88-1.84 (m, 1H), 1.75-1.65 (m, 3H), 1.48-1.39 (m, 1H), 1.32-1.27 (m, 1H), 1.24-0.85 (m, 2H), 0.530.42 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.0, 149.7, 148.8, 143.2, 141.7, 141.3, 140.5, 139.12, 139.10, 136.3, 131.5, 129.7 (2x), 128.9 (2x), 128.8 (2x), 127.6, 127.6 (2x), 127.0 (2x), 126.6 (2x), 108.1, 105.4, 57.5, 56.3, 56.1, 39.9, 32.5, 27.2, 26.5, 26.2, 26.1, 21.5. 2-[3-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)-3Hinden-1-yl]naphthalene (1n). 1n was synthesized according to general synthetic procedure from 3w (111 mg, 0.2 mmol). Yield = 86% (93 mg); Colorless solid; mp = 173-174 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C34H35O4S 539.2256, found 539.2255; 1H NMR (400 MHz, CDCl3): δ 7.90-7.79 (m, 4H), 7.58-7.54 (m, 3H), 7.25 (d, J = 8.8 Hz, 2H), 7.12 (s, 1H), 6.79 (d, J = 8.0 Hz, 2H), 6.49 (s, 1H), 4.14 (d, J = 2.8 Hz, 1H), 3.97 (s, 3H), 3.66 (s, 3H), 2.80-2.74 (m, 1H), 2.17 (br s, 3H), 2.09-2.05 (m, 1H), 1.89-1.85 (m, 1H), 1.77-1.63 (m, 3H), 1.49-1.36 (m, 1H), 1.321.27 (m, 1H), 1.24-0.84 (m, 2H), 0.57-0.47 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.1, 149.7, 148.9, 143.2, 142.1, 139.0, 138.9, 136.6, 133.0, 132.8, 130.1, 128.7 (3x), 128.2 (2x), 127.7, 127.6 (3x), 126.6, 126.3, 108.1, 105.4, 57.5, 56.4, 56.0, 39.9, 32.5, 27.2, 26.5, 26.3, 26.2, 21.3. 2-Benzenesulfonyl-1-cyclohexyl-5,6-dimethoxy-3-phenyl-1Hindene (1o). 1o was synthesized according to general synthetic procedure from 3x (98 mg, 0.2 mmol). Yield = 88% (83 mg); Colorless solid; mp = 172-173 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H31O4S 475.1943, found 475.1942; 1H NMR (400 MHz, CDCl3): δ 7.43-7.35 (m, 6H), 7.33 (br s, 2H), 7.22-7.18 (m, 2H), 7.09 (s, 1H), 6.49 (s, 1H), 4.09 (d, J = 2.8 Hz, 1H), 3.95 (s, 3H), 3.71 (s, 3H), 2.76-2.69 (m, 1H), 2.06-2.04 (m, 1H), 1.861.83 (m, 1H), 1.74-1.63 (m, 3H), 1.59-1.35 (m, 2H), 1.24-0.96

Page 20 of 30

(m, 2H), 0.50-0.40 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.8, 149.8, 148.8, 142.0, 141.1, 139.1, 136.3, 132.4, 132.3, 129.3, 128.5 (2x), 128.2 (2x), 128.0 (2x), 127.4 (2x), 108.1, 105.4, 57.4, 56.3, 56.0, 39.8, 32.5, 27.2, 26.4, 26.14, 26.08. 1-Cyclohexyl-2-methanesulfonyl-5,6-dimethoxy-3-phenyl1H-indene (1p). 1p was synthesized according to general synthetic procedure from 3y (86 mg, 0.2 mmol). Yield = 90% (74 mg); Colorless solid; mp = 147-149 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H29O4S 413.1787, found 413.1788; 1H NMR (400 MHz, CDCl3): δ 7.54-7.48 (m, 5H), 7.11 (s, 1H), 6.66 (s, 1H), 4.05 (d, J = 2.8 Hz, 1H), 3.97 (s, 3H), 3.78 (s, 3H), 2.66-2.59 (m, 1H), 2.64 (s, 3H), 2.04-2.01 (m, 1H), 1.85-1.77 (m, 1H), 1.73-1.69 (m, 3H), 1.66-1.59 (m, 2H), 1.25-0.97 (m, 2H), 0.58-0.47 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 151.5, 149.9, 148.9, 140.8, 138.9, 135.8, 132.5, 129.2 (2x), 129.0, 128.7 (2x), 108.1, 105.5, 57.1, 56.3, 56.0, 44.3, 39.9, 32.4, 27.1, 26.5, 26.3, 26.2. 1-Cyclohexyl-5,6-dimethoxy-2-(4-methoxybenzenesulfonyl)3-phenyl-1H-indene (1q). 1q was synthesized according to general synthetic procedure from 3z (104 mg, 0.2 mmol). Yield = 91% (92 mg); Colorless solid; mp = 179-181 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C30H33O5S 505.2049, found 505.2051; 1H NMR (400 MHz, CDCl3): δ 7.38-7.32 (m, 5H), 7.34 (d, J = 8.8 Hz, 2H), 7.08 (s, 1H), 6.66 (d, J = 8.8 Hz, 2H), 6.48 (s, 1H), 4.06 (d, J = 3.2 Hz, 1H), 3.94 (s, 3H), 3.76 (s, 3H), 3.70 (s, 3H), 2.762.69 (m, 1H), 2.09-2.03 (m, 1H), 1.86-1.83 (m, 1H), 1.74-1.64 (m, 3H), 1.55-1.39 (m, 2H), 1.28-0.96 (m, 2H), 0.49-0.39 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 162.6, 151.9, 149.6, 148.7, 141.8, 138.9, 136.4, 133.7, 132.5, 129.5 (2x), 129.0 (2x), 128.4, 127.9 (2x), 113.4 (2x), 108.1, 105.3, 57.3, 56.3, 55.9, 55.5, 39.8, 32.5, 27.2, 26.4, 26.10, 26.06. Single-crystal X-Ray diagram: crystal of 1q was grown by slow diffusion of EtOAc into a solution of 1q in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal system, space group P - 1, a = 10.3709(18) Å , b = 111.1980(17) Å , c = 12.307(2) Å , V = 1245.4(4) Å 3, Z = 2, dcalcd = 1.346 g/cm3, F(000) = 536, 2θ range 1.822~26.455o, R indices (all data) R1 = 0.0464, wR2 = 0.1100. 1-Cyclohexyl-2-(4-fluorobenzenesulfonyl)-5,6-dimethoxy-3phenyl-1H-indene (1r). 1r was synthesized according to general synthetic procedure from 3aa (102 mg, 0.2 mmol). Yield = 92% (91 mg); Colorless solid; mp = 118-120 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C29H30FO4S 493.1849, found 493.1845; 1H NMR (400 MHz, CDCl3): δ 7.42-7.32 (m, 7H), 7.09 (s, 1H), 6.876.82 (m, 2H), 6.49 (s, 1H), 4.10 (d, J = 2.8 Hz, 1H), 3.95 (s, 3H), 3.71 (s, 3H), 2.75-2.68 (m, 1H), 2.05-2.03 (m, 1H), 1.871.84 (m, 1H), 1.74-1.54 (m, 3H), 1.49-1.32 (m, 2H), 1.28-0.97 (m, 2H), 0.54-0.43 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.8 (d, J = 253.2 Hz), 152.7, 149.9, 148.9, 141.1, 139.0, 138.0 (d, J = 3.0 Hz), 136.1, 132.3, 130.2 (d, J = 9.8 Hz, 2x), 128.6 (2x), 128.1 (3x), 115.3 (d, J = 22.7 Hz, 2x), 108.1, 105.3, 57.5, 56.3, 56.0, 40.0, 32.4, 27.2, 26.4, 26.2, 26.1. 1-Cyclohexyl-2-(4-isopropylbenzenesulfonyl)-5,6-dimethoxy3-phenyl-1H-indene (1s). 1s was synthesized according to general synthetic procedure from 3ab (107 mg, 0.2 mmol). Yield = 86% (89 mg); Colorless solid; mp = 133-135 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C32H37O4S 517.2413, found 517.2411; 1H NMR (400


Page 21 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


MHz, CDCl3): δ 7.35-7.26 (m, 7H), 7.09 (s, 1H), 7.03 (d, J = 8.4 Hz, 2H), 6.48 (s, 1H), 4.09 (d, J = 3.2 Hz, 1H), 3.95 (s, 3H), 3.70 (s, 3H), 2.88-2.81 (m, 1H), 2.75-2.68 (m, 1H), 2.07-2.02 (m, 1H), 1.86-1.83 (m, 1H), 1.74-1.63 (m, 3H), 1.54-1.25 (m, 2H), 1.17 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 7.2 Hz, 3H), 1.050.97 (m, 2H), 0.51-0.41 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 153.8, 152.1, 149.6, 148.7, 141.5, 139.2, 139.0, 136.4, 132.5, 128.3, 129.8 (2x), 127.9 (2x), 127.6 (2x), 126.2 (2x), 108.1, 105.3, 57.4, 56.3, 56.0, 39.8, 34.0, 32.4, 27.2, 26.4, 26.2, 26.1, 23.6, 23.5. 2-(4-n-Butylbenzenesulfonyl)-1-cyclohexyl-5,6-dimethoxy-3phenyl-1H-indene (1t). 1t was synthesized according to general synthetic procedure from 3ac (110 mg, 0.2 mmol). Yield = 86% (91 mg); Colorless solid; mp = 138-140 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H39O4S 531.2569, found 531.2567; 1H NMR (400 MHz, CDCl3): δ 7.39-7.31 (m, 7H), 7.09 (s, 1H), 6.99 (d, J = 8.4 Hz, 2H), 6.49 (s, 1H), 4.08 (d, J = 3.2 Hz, 1H), 3.95 (s, 3H), 3.71 (s, 3H), 2.75-2.69 (m, 1H), 2.55 (t, J = 7.6 Hz, 2H), 2.062.03 (m, 1H), 1.86-1.83 (m, 1H), 1.74-1.63 (m, 3H), 1.55-1.37 (m, 4H), 1.33-1.05 (m, 4H), 0.90 (t, J = 7.2 Hz, 3H), 0.50-0.39 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.3, 149.7, 148.8, 148.0, 141.5, 139.2, 139.0, 136.4, 132.5, 129.4 (2x), 128.4, 128.2 (2x), 127.9 (2x), 127.4 (2x), 108.1, 105.3, 57.4, 56.3, 56.0, 39.8, 35.4, 33.1, 32.5, 27.2, 26.4, 26.14, 26.09, 22.0, 13.8. 8-Cyclopentyl-4-methoxy-2-methyl-6-phenyl-7-(toluene-4sulfonyl)-1,8-dihydro-2H-3-oxaasindacene (1u). 1u was synthesized according to general synthetic procedure from 3an (106 mg, 0.2 mmol). Yield = 80% (80 mg); Colorless solid; mp = 167-169 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C31H33O4S 501.2100, found 501.2101; 1H NMR (400 MHz, CDCl3): δ 7.36-7.33 (m, 2H), 7.30 (br s, 3H), 7.22 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.38 (s, 1H), 5.13-5.08 (m, 1H), 4.38 (d, J = 3.2 Hz, 1H), 3.70 (s, 3H), 3.52 (dd, J = 9.2, 15.6 Hz, 1H), 3.08-3.02 (m, 1H), 2.93 (dd, J = 6.8, 15.6 Hz, 1H), 2.28 (s, 3H), 1.78-1.69 (m, 2H), 1.62-1.39 (m, 5H), 1.49 (d, J = 6.4 Hz, 3H), 1.23-1.15 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3): δ 152.2, 149.4, 144.2, 142.9, 142.2, 139.3, 137.4, 136.2, 132.7, 128.6 (2x), 128.4, 127.9 (4x), 127.5 (2x), 123.7, 105.8, 80.8, 56.0, 53.6, 41.8, 37.7, 30.2, 28.0, 25.0, 24.9, 21.8, 21.4. 5,6-Dimethoxy-3-phenyl-2-(toluene-4-sulfonyl)-1H-indene (1v). 1v was synthesized according to general synthetic procedure from 3ao (85 mg, 0.2 mmol). Yield = 78% (63 mg); Colorless solid; mp = 153-155 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H23O4S 407.1317; Found 407.1322; 1H NMR (400 MHz, CDCl3): δ 7.47-7.43 (m, 5H), 7.33-7.31 (m, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.07 (s, 1H), 6.60 (d, J = 0.4 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 2H), 3.73 (s, 3H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.3, 150.3, 149.0, 143.5, 138.9, 137.9, 136.7, 135.9, 132.1, 129.3 (2x), 129.0 (2x), 128.6, 128.0 (2x), 127.3 (2x), 107.2, 105.5, 56.2, 56.1, 39.8, 21.4. 7-Phenyl-6-(toluene-4-sulfonyl)-5H-indeno[5,6d][1,3]dioxole (1w). 1w was synthesized according to general synthetic procedure from 3ap (82 mg, 0.2 mmol). Yield = 74% (58 mg); Colorless solid; mp = 170-172 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H19O4S 391.1004; Found 391.1007; 1H NMR (400 MHz,

CDCl3): δ 7.47 (d, J = 8.0 Hz, 2H), 7.44-7.41 (m, 3H), 7.307.27 (m, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.98 (s, 1H), 6.56 (d, J = 0.4 Hz, 1H), 5.95 (s, 2H), 3.87 (s, 2H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.1, 148.8, 147.5, 143.6, 138.9, 138.2, 138.1, 137.5, 132.0, 129.3 (2x), 129.0 (2x), 128.7, 128.0 (2x), 127.4 (2x), 105.0, 103.3, 101.5, 39.7, 21.5. 4,5,6-Trimethoxy-3-phenyl-2-(toluene-4-sulfonyl)-1H-indene (1x). 1x was synthesized according to general synthetic procedure from 3aq (91 mg, 0.2 mmol). Yield = 83% (72 mg); Colorless solid; mp = 153-155 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H25O5S 437.1423; Found 437.1432; 1H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.0 Hz, 2H), 7.37-7.31 (m, 3H), 7.33-7.20 (m, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.88 (s, 1H), 3.92 (s, 2H), 3.89 (s, 3H), 3.75 (s, 3H), 3.26 (s, 3H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.0, 151.7, 150.1, 143.4, 141.9, 139.3, 138.8, 137.9, 133.6, 129.6, 129.2 (2x), 128.5 (2x), 127.8, 127.4 (2x), 127.0 (2x), 103.7, 60.9, 60.8, 56.2, 40.1, 21.4. 5,6-Dimethoxy-2-(toluene-4-sulfonyl)-3-(4trifluoromethylphenyl)-1H-indene (1y). 1y was synthesized according to general synthetic procedure from 3ar (98 mg, 0.2 mmol). Yield = 82% (78 mg); Colorless solid; mp = 149-151 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H22F3O4S 475.1191; Found 475.1196; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.08 (s, 1H), 6.51 (s, 1H), 3.93 (s, 3H), 3.91 (s, 2H), 3.74 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 150.6, 150.5, 149.2, 144.0, 139.1, 138.6, 136.9, 136.1, 136.0, 129.5 (4x), 129.1, 127.4 (2x), 126.0 (q, J = 270.3 Hz), 125.0 (q, J = 3.8 Hz, 2x), 107.3, 105.1, 56.23, 56.17, 39.8, 21.4. 5,6-Dimethoxy-3-(4-nitrophenyl)-2-(toluene-4-sulfonyl)-1Hindene (1z). 1z was synthesized according to general synthetic procedure from 3as (94 mg, 0.2 mmol). Yield = 75% (68 mg); Colorless solid; mp = 190-192 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H22NO6S 452.1168; Found 452.1162; 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.8 Hz, 2H), 7.55-7.51 (m, 4H), 7.21 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 6.48 (s, 1H), 3.92 (s, 3H), 3.88 (s, 2H), 3.73 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 150.8, 149.7, 149.2, 147.9, 144.2, 139.3, 139.2, 138.5, 136.0, 135.6, 130.1 (2x), 129.7 (2x), 127.3 (2x), 123.3 (2x), 107.4, 104.9, 56.2, 56.1, 39.8, 21.5. Single-crystal X-Ray diagram: crystal of 1z was grown by slow diffusion of EtOAc into a solution of 1z in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 14.6355(18) Å , b = 8.3230(10) Å , c = 17.421(2) Å , V = 2098.0(4) Å 3, Z = 4, dcalcd = 1.429 g/cm3, F(000) = 944, 2θ range 1.697~26.424o, R indices (all data) R1 = 0.0519, wR2 = 0.1143. General synthetic procedure of skeletons 2 and 7 is as follows: NaBH4 (38 mg, 1.0 mmol) was added to a solution of 4, 3v-3w and 3ad (0.3 mmol) in THF and MeOH (v/v =1/1, 10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 30 min. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product



under reduced pressure. Without further purification, A-15 (100 mg) was added to a solution of the resulting crude products in a toluene (10 mL) at 25 oC. The reaction mixture was stirred at reflux for 10 h under Dean-Stark distillation apparatus. A-15 was filtered by filter paper and the A-15 was washed with toluene (3 x 5 mL). The combined organic layers were concentrated. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product mixture under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 2 and 7. 5,6-Dimethoxy-1-phenyl-2-(toluene-4-sulfonyl)indan (2a). 2a was synthesized according to general synthetic procedure from 4a (127 mg, 0.3 mmol). Yield = 84% (103 mg); Colorless solid; mp = 152-154 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H25O4S 409.1474; Found 409.1476; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.18-7.12 (m, 3H), 6.89-6.87 (m, 2H), 6.72 (s, 1H), 6.32 (s, 1H), 4.79 (d, J = 5.6 Hz, 1H), 3.96 (dt, J = 6.0, 9.2 Hz, 1H), 3.82 (s, 3H), 3.65 (s, 3H), 3.48 (dd, J = 10.0, 16.4 Hz, 1H), 3.30 (dd, J = 9.2, 16.4 Hz, 1H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.0, 148.8, 144.4, 142.8, 135.0, 134.9, 131.1, 129.5 (2x), 128.4 (2x), 128.3 (2x), 127.7 (2x), 126.7, 107.5, 106.7, 71.8, 55.8, 55.7, 52.1, 32.7, 21.3. 5-Phenyl-6-(toluene-4-sulfonyl)-6,7-dihydro-5H-indeno[5,6d][1,3]dioxole (2b). 2b was synthesized according to general synthetic procedure from 4b (121 mg, 0.3 mmol). Yield = 86% (101 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H21O4S 393.1161; Found 393.1160; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.18-7.12 (m, 3H), 6.92-6.90 (m, 2H), 6.63 (s, 1H), 6.24 (s, 1H), 5.82 (d, J = 1.2 Hz, 1H), 5.80 (d, J = 1.2 Hz, 1H), 4.74 (d, J = 6.0 Hz, 1H), 4.03 (dt, J = 6.4, 8.8 Hz, 1H), 3.45 (dd, J = 6.4, 16.8 Hz, 1H), 3.25 (dd, J = 9.2, 16.8 Hz, 1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 147.4, 147.2, 144.3, 142.5, 136.1, 134.9, 131.9, 129.4 (2x), 128.3 (4x), 127.6 (2x), 126.6, 105.0, 104.0, 100.9, 71.6, 51.7, 32.4, 21.2. 5-Methoxy-1-phenyl-2-(toluene-4-sulfonyl)indan (2c). 2c was synthesized according to general synthetic procedure from 4c (118 mg, 0.3 mmol). Yield = 88% (100 mg); Colorless solid; mp = 107-109 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H23O3S 379.1368; Found 379.1365; 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.18-7.14 (m, 3H), 6.94-6.92 (m, 2H), 6.77 (d, J = 1.6 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H), 6.68 (dd, J = 2.4, 8.4 Hz, 1H), 4.81 (d, J = 6.4 Hz, 1H), 4.06 (dt, J = 6.8, 8.8 Hz, 1H), 3.74 (s, 3H), 3.56 (dd, J = 6.4, 16.8 Hz, 1H), 3.35 (dd, J = 8.8, 16.8 Hz, 1H), 2.37 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 159.3, 144.3, 142.7, 140.6, 135.5, 134.9, 129.4 (2x), 128.3 (2x), 128.2 (2x), 127.6 (2x), 126.5, 125.5, 113.6, 108.8, 71.6, 55.1, 51.3, 32.8, 21.2. 6-Methoxy-1-phenyl-2-(toluene-4-sulfonyl)indan (2d). 2d was synthesized according to general synthetic procedure from 4d (118 mg, 0.3 mmol). Yield = 86% (98 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H23O3S 379.1368; Found 379.1367; 1H NMR (400 MHz, CDCl3): δ

Page 22 of 30

7.70 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.18-7.12 (m, 3H), 7.11 (d, J = 8.4 Hz, 1H), 6.95-6.92 (m, 2H), 6.75 (dd, J = 2.0, 8.4 Hz, 1H), 6.36 (d, J = 1.6 Hz, 1H), 4.84 (d, J = 6.4 Hz, 1H), 4.06 (dt, J = 6.4, 9.2 Hz, 1H), 3.60 (s, 3H), 3.51 (dd, J = 6.8, 16.8 Hz, 1H), 3.30 (dd, J = 9.2, 16.8 Hz, 1H), 2.35 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 159.3, 145.0, 144.5, 142.4, 135.1, 131.2, 129.6 (2x), 128.4 (4x), 127.9 (2x), 126.7, 124.8, 114.0, 109.9, 71.8, 55.1, 52.3, 32.1, 21.4. 5,6,7-Trimethoxy-1-phenyl-2-(toluene-4-sulfonyl)indan (2e). 2e was synthesized according to general synthetic procedure from 4e (136 mg, 0.3 mmol). Yield = 91% (120 mg); Colorless solid; mp = 169-171 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27O5S 439.1579; Found 439.1581; 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.13-7.05 (m, 3H), 6.83 (d, J = 8.4 Hz, 2H), 6.49 (s, 1H), 4.87 (d, J = 3.6 Hz, 1H), 3.82 (dt, J = 3.6, 8.8 Hz, 1H), 3.75 (s, 3H), 3.69 (s, 3H), 3.44 (dd, J = 4.4, 17.6 Hz, 1H), 3.36 (dd, J = 9.2, 17.6 Hz, 1H), 3.28 (s, 3H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.0, 149.3, 144.3, 143.1, 141.9, 135.2, 134.4, 129.4 (2x), 128.4 (2x), 128.1 (2x), 127.9, 126.8 (2x), 126.4, 102.5, 71.6, 60.3, 59.5, 55.7, 50.0, 32.9, 21.2. Single-crystal X-Ray diagram: crystal of 2e was grown by slow diffusion of EtOAc into a solution of 2e in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P21/n, a = 11.9401(5) Å , b = 11.1292(5) Å , c = 17.5921(7) Å , V = 2281.61(17) Å 3, Z = 4, dcalcd = 1.277 g/cm3, F(000) = 928, 2θ range 1.886~26.389o, R indices (all data) R1 = 0.0642, wR2 = 0.1588. 1-Phenyl-2-(toluene-4-sulfonyl)indan (2f). 2f was synthesized according to general synthetic procedure from 4f (109 mg, 0.3 mmol). Yield = 84% (88 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21O2S 349.1262; Found 349.1265; 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.0 Hz, 2H), 7.25-7.17 (m, 7H), 7.12 (t, J = 7.6 Hz, 1H), 6.976.95 (m, 2H), 6.84 (d, J = 8.0 Hz, 1H), 4.90 (d, J = 6.8 Hz, 1H), 4.10 (dt, J = 6.8, 8.8 Hz, 1H), 3.62 (dd, J = 6.8, 16.8 Hz, 1H), 3.40 (dd, J = 9.2, 16.8 Hz, 1H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 144.3, 143.5, 142.3, 139.1, 134.9, 129.4 (2x), 128.24 (2x), 128.21 (2x), 127.7 (2x), 127.3, 127.1, 126.6, 124.8, 123.9, 71.2, 52.0, 32.7, 21.2. 1-Phenyl-2-(toluene-4-sulfonyl)-2,3-dihydro-1Hcyclopenta[a]naphthalene (2g). 2g was synthesized according to general synthetic procedure from 4g (124 mg, 0.3 mmol). Yield = 86% (103 mg); Colorless solid; mp = 169-171 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H23O2S 399.1419; Found 399.1418; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.29 (dd, J = 1.2, 6.4 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.20-7.16 (m, 3H), 6.90 (d, J = 8.8 Hz, 1H), 6.89 (d, J = 6.0 Hz, 1H), 5.410 (d, J = 2.8 Hz, 1H), 3.98 (dt, J = 3.6, 8.4 Hz, 1H), 3.66 (dd, J = 3.6, 17.6 Hz, 1H), 3.58 (dd, J = 8.4, 17.6 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 144.7, 143.0, 138.1, 137.3, 134.7, 133.3, 129.71, 129.68 (2x), 129.0, 128.81 (2x), 128.75 (2x), 128.4, 127.4 (2x), 126.9, 126.3, 125.2, 124.4, 122.3, 72.1, 51.6, 33.7, 21.5. Single-crystal X-Ray diagram: crystal of 2g was grown by slow diffusion of EtOAc into a solution of 2g in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclin-


Page 23 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ic crystal system, space group P - 1, a = 7.1922(6) Å , b = 8.1888(7) Å , c = 17.2964(15) Å , V = 1007.88(15) Å 3, Z = 2, dcalcd = 1.313 g/cm3, F(000) = 420, 2θ range 1.189~26.415o, R indices (all data) R1 = 0.0896, wR2 = 0.1604.

group P21/n, a = 10.4333(7) Å , b = 8.3721(5) Å , c = 20.9050(12) Å , V = 1813.91(19) Å 3, Z = 4, dcalcd = 1.565 g/cm3, F(000) = 872, 2θ range 2.093~26.382o, R indices (all data) R1 = 0.0277, wR2 = 0.0609.

6-Chloro-1-phenyl-2-(toluene-4-sulfonyl)indan (2h). 2h was synthesized according to general synthetic procedure from 4h (119 mg, 0.3 mmol). Yield = 83% (95 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H20ClO2S 383.0873; Found 383.0874; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.19-7.14 (m, 5H), 6.89-6.86 (m, 2H), 6.80 (s, 1H), 4.80 (d, J = 6.4 Hz, 1H), 4.04 (dt, J = 6.4, 9.2 Hz, 1H), 3.54 (dd, J = 6.4, 17.2 Hz, 1H), 3.34 (dd, J = 9.2, 17.2 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.7, 144.8, 141.8, 137.9, 135.0, 133.3, 129.7 (2x), 128.7, 128.6 (2x), 128.0, 127.93, 127.89 (2x), 127.1, 125.3 (2x), 71.6, 52.3, 32.5, 21.5.

3-(3-Nitrophenyl)-1-phenyl-2-(toluene-4-sulfonyl)propan-1ol (7l). 7l was synthesized according to general synthetic procedure from 4l (122 mg, 0.3 mmol). Yield = 96% (118 mg); Colorless solid; mp = 58-60 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H22NO5S 412.1219; Found 412.1221; 1H NMR (400 MHz, CDCl3 + DMSO-d6): δ 7.68 (dd, J = 2.0, 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.13-6.99 (m, 9H), 6.86 (d, J = 8.4 Hz, 1H), 5.02 (dd, J = 3.6, 7.6 Hz, 1H), 4.91 (d, J = 3.6 Hz, 1H), 3.66 (dt, J = 5.6, 7.6 Hz, 1H), 2.98 (dd, J = 5.6, 15.2 Hz, 1H), 2.60 (dd, J = 6.0, 15.2 Hz, 1H), 2.23 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3+ DMSO-d6): δ 147.3, 144.4, 139.5, 139.3, 135.6, 134.3, 129.3 (2x), 128.6, 128.1 (2x), 127.93, 127.88 (2x), 127.0 (2x), 122.9, 120.7, 72.1, 71.4, 31.2, 21.0. Single-crystal X-Ray diagram: crystal of 7l was grown by slow diffusion of EtOAc into a solution of 7l in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/c, a = 10.8179(10) Å , b = 10.4282(10) Å , c = 16.7152(16) Å , V = 1885.4(3) Å 3, Z = 4, dcalcd = 1.450 g/cm3, F(000) = 864, 2θ range 1.883~26.422o, R indices (all data) R1 = 0.0546, wR2 = 0.0943.

3-(3,4-Dichlorophenyl)-1-phenyl-2-(toluene-4sulfonyl)propan-1-ol (7i). 7i was synthesized according to general synthetic procedure from 4i (129 mg, 0.3 mmol). Yield = 96% (125 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21Cl2O3S 435.0589; Found 435.0591; 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 8.4 Hz, 2H), 7.29 (br s, 1H), 7.28-7.23 (m, 6H), 7.03 (d, J = 8.8 Hz, 1H), 6.36-6.34 (m, 2H), 5.13 (d, J = 8.0 Hz, 1H), 4.48 (br s, 1H), 3.64 (dt, J = 6.0, 8.4 Hz, 1H), 2.95 (dd, J = 6.0, 15.2 Hz, 1H), 2.45 (dd, J = 6.0, 15.2 Hz, 1H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.5, 139.0, 137.4, 135.2, 131.9, 130.4, 130.3, 129.9, 129.8 (2x), 128.8, 128.6 (2x), 128.5 (2x), 127.6, 127.4 (2x), 73.2, 72.0, 31.9, 21.6. 6-Fluoro-1-phenyl-2-(toluene-4-sulfonyl)indan (2j). 2j was synthesized according to general synthetic procedure from 4j (114 mg, 0.3 mmol). Yield = 88% (97 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H20FO2S 367.1168; Found 367.1169; 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.20-7.15 (m, 4H), 6.93-6.86 (m, 3H), 6.52 (dd, J = 2.0, 8.4 Hz, 1H), 4.83 (d, J = 6.4 Hz, 1H), 4.08 (dt, J = 6.4, 9.2 Hz, 1H), 3.54 (dd, J = 6.4, 16.8 Hz, 1H), 3.34 (dd, J = 9.2, 16.8 Hz, 1H), 2.38 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 162.4 (d, J = 243.3 Hz), 145.8 (d, J = 8.3 Hz), 144.6, 141.7, 134.9, 134.8 (d, J = 3.0 Hz), 129.6 (2x), 128.5 (2x), 128.4 (2x), 127.8 (2x), 127.0, 125.2 (d, J = 8.4 Hz), 114.7 (d, J = 22.7 Hz), 111.9 (d, J = 22.0 Hz), 71.7, 52.2 (d, J = 1.5 Hz), 32.1, 21.4. 4-Bromo-1-phenyl-2-(toluene-4-sulfonyl)indan (2k). 2k was synthesized according to general synthetic procedure from 4k (132 mg, 0.3 mmol). Yield = 87% (111 mg); Colorless solid; mp = 131-133 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H20BrO2S 427.0367; Found 427.0368; 1H NMR (400 MHz, CDCl3): δ 7.72 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.21-7.17 (m, 3H), 7.00 (t, J = 7.6 Hz, 1H), 6.936.91 (m, 2H), 6.78 (d, J = 7.6 Hz, 1H), 4.96 (d, J = 6.4 Hz, 1H), 4.03 (dt, J = 6.4, 9.2 Hz, 1H), 3.57 (dd, J = 6.4, 17.6 Hz, 1H), 3.39 (dd, J = 9.2, 17.6 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.4, 144.8, 142.1, 140.0, 134.8, 130.6, 129.7 (2x), 129.2, 128.6 (2x), 128.5 (2x), 127.8 (2x), 127.1, 124.0, 119.4, 70.4, 53.2, 34.5, 21.5. Single-crystal X-Ray diagram: crystal of 2k was grown by slow diffusion of EtOAc into a solution of 2k in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space

3-Phenyl-2-(toluene-4-sulfonyl)indan-5-ol (2m). 2m was synthesized according to general synthetic procedure from 4m (113 mg, 0.3 mmol). Yield = 86% (94 mg); Colorless solid; mp = 170-172 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21O3S 365.1212; Found 365.1213; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.18-7.14 (m, 3H), 7.05 (d, J = 8.0 Hz, 1H), 6.91-6.89 (m, 2H), 6.67 (dd, J = 2.4, 8.0 Hz, 1H), 6.26 (d, J = 2.0 Hz, 1H), 4.88 (br s, 1H), 4.76 (d, J = 6.4 Hz, 1H), 4.02 (dt, J = 6.4, 9.2 Hz, 1H), 3.47 (dd, J = 6.4, 16.4 Hz, 1H), 3.28 (dd, J = 9.2, 16.4 Hz, 1H), 2.39 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3): δ 155.4, 145.4, 144.6, 142.3, 135.2, 131.3, 129.7 (2x), 128.6 (2x), 128.5 (2x), 128.0 (2x), 126.9, 125.0, 115.2, 111.9, 71.9, 52.3, 32.2, 21.6. 1,6-Diphenyl-2-(toluene-4-sulfonyl)indan (2n). 2n was synthesized according to general synthetic procedure from 4n (131 mg, 0.3 mmol). Yield = 84% (107 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H25O2S 425.1575; Found 425.1578; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.4 Hz, 2H), 7.46-7.44 (m, 3H), 7.38-7.17 (m, 9H), 7.04 (s, 1H), 6.98-6.95 (m, 2H), 4.91 (d, J = 6.4 Hz, 1H), 4.09 (dt, J = 6.8, 8.8 Hz, 1H), 3.63 (dd, J = 6.8, 16.8 Hz, 1H), 3.43 (dd, J = 6.8, 16.8 Hz, 1H), 2.40 (s, 3H); 113C{1H} NMR (100 MHz, CDCl3): δ 144.6, 144.4, 142.5, 140.9, 140.8, 138.6, 135.2, 129.7 (2x), 128.64 (2x), 128.62 (2x), 128.58 (2x), 128.1 (2x), 127.2, 127.0 (2x), 126.9, 126.8, 124.5, 123.9, 71.8, 52.4, 32.8, 21.5. 6-Methyl-1-phenyl-2-(toluene-4-sulfonyl)indan (2o). 2o was synthesized according to general synthetic procedure from 4o (113 mg, 0.3 mmol). Yield = 82% (89 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H23O2S 363.1419; Found 363.1423; 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.22-7.18 (m, 3H), 7.14 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 7.6 Hz, 1H), 6.976.95 (m, 2H), 6.66 (s, 1H), 4.85 (d, J = 6.4 Hz, 1H), 4.08 (dt, J



= 6.8, 8.8 Hz, 1H), 3.58 (dd, J = 6.8, 16.8 Hz, 1H), 3.37 (dd, J = 9.2, 16.8 Hz, 1H), 2.40 (s, 3H), 2.23 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 144.4, 143.7, 142.6, 136.9, 136.2, 135.1, 129.54, 129.49 (2x), 128.4 (2x), 128.3 (2x), 127.9 (2x), 126.6, 125.4, 123.7, 71.5, 52.1, 32.5, 21.3, 21.0. 4-Allyl-5,6-dimethoxy-1-phenyl-2-(toluene-4-sulfonyl)indan (2p). 2p was synthesized according to general synthetic procedure from 4p (139 mg, 0.3 mmol). Yield = 80% (108 mg); Colorless solid; mp = 112-114 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H29O4S 449.1787; Found 449.1785; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.20-7.16 (m, 3H), 6.91-6.89 (m, 2H), 6.26 (s, 1H), 5.96-5.86 (m, 1H), 5.05 (dq, J = 1.6, 10.4 Hz, 1H), 4.97 (dq, J = 1.6, 17.2 Hz, 1H), 7.80 (d, J = 5.6 Hz, 1H), 3.95 (dt, J = 6.0, 8.8 Hz, 1H), 3.76 (s, 3H), 3.66 (s, 3H), 3.40 (dd, J = 6.0, 16.8 Hz, 1H), 3.37 (d, J = 6.0 Hz, 2H), 3.24 (dd, J = 9.2, 16.8 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 152.8, 146.9, 144.4, 142.8, 138.5, 135.7, 135.1, 131.4, 129.6 (2x), 128.7 (2x), 128.5 (3x), 127.9 (2x), 126.9, 115.3, 106.6, 71.7, 60.9, 55.7, 52.6, 31.7, 31.1, 21.5. 1-Phenyl-3-pyridin-3-yl-2-(toluene-4-sulfonyl)propan-1-ol (7q). 7q was synthesized according to general synthetic procedure from 4q (109 mg, 0.3 mmol). Yield = 96% (106 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H22NO3S 368.1320; Found 368.1322; 1H NMR (400 MHz, CDCl3): δ 8.16 (t, J = 3.2 Hz, 1H), 7.68-7.65 (m, 3H), 7.24 (d, J = 8.0 Hz, 2H), 7.20-7.16 (m, 5H), 6.88 (br s, 1H), 6.87 (d, J = 1.6 Hz, 1H), 5.09 (d, J = 8.0 Hz, 1H), 4.20 (br s, 1H), 3.72-3.67 (m, 1H), 3.04 (dd, J = 5.2, 15.2 Hz, 1H), 2.54 (dd, J = 6.8, 15.6 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.2, 147.1, 145.0, 139.1, 135.8, 135.4, 133.2, 129.8 (2x), 128.51, 128.46 (2x), 128.4 (2x), 127.2 (2x), 122.9, 72.9, 71.7, 29.6, 21.5.

Page 24 of 30

Calcd for C24H24FO4S 427.1379; Found 427.1384; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 6.89-6.82 (m, 4H), 6.71 (s, 1H), 6.28 (s, 1H), 4.78 (d, J = 6.0 Hz, 1H), 3.91 (dt, J = 6.4, 8.8 Hz, 1H), 3.83 (s, 3H), 3.67 (s, 3H), 3.46 (dd, J = 6.4, 16.4 Hz, 1H), 3.26 (dd, J = 9.2, 16.4 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.6 (d, J = 244.1 Hz), 149.2, 149.0, 144.6, 138.7 (d, J = 3.8 Hz), 135.1, 134.8, 131.0, 129.6 (2x), 129.4 (d, J = 8.4 Hz, 2x), 128.5 (2x), 115.2 (d, J = 21.2 Hz, 2x), 107.5, 106.8, 72.0, 55.9, 55.8, 51.5, 32.8, 21.4. 5,6-Dimethoxy-1-(4-methoxyphenyl)-2-(toluene-4sulfonyl)indan (2u). 2u was synthesized according to general synthetic procedure from 4u (136 mg, 0.3 mmol). Yield = 82% (108 mg); Colorless solid; mp = 100-102 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27O5S 439.1579; Found 439.1581; 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.70 (s, 1H), 6.68 (d, J = 8.8 Hz, 2H), 6.31 (s, 1H), 4.74 (d, J = 6.0 Hz, 1H), 3.91 (dt, J = 6.4, 8.8 Hz, 1H), 3.81 (s, 3H), 3.70 (s, 3H), 3.65 (s, 3H), 3.46 (dd, J = 6.4, 16.8 Hz, 1H), 3.26 (dd, J = 8.8, 16.8 Hz, 1H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.2, 148.9, 148.8, 144.3, 135.2, 135.1, 134.8, 130.9, 129.5 (2x), 128.7 (2x), 128.4 (2x), 113.7 (2x), 107.5, 106.6, 71.9, 55.74, 55.68, 54.9, 51.3, 32.6, 21.3. 5,6-Dimethoxy-2-(toluene-4-sulfonyl)-1-p-tolylindan (2v). 2v was synthesized according to general synthetic procedure from 4v (131 mg, 0.3 mmol). Yield = 82% (104 mg); Colorless solid; mp = 172-174 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27O4S 423.1630; Found 423.1630; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 7.6 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 6.71 (s, 1H), 6.34 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 3.93 (dt, J = 6.4, 8.8 Hz, 1H), 3.83 (s, 3H), 3.66 (s, 3H), 3.46 (dd, J = 6.4, 16.4 Hz, 1H), 3.28 (dd, J = 8.8, 16.4 Hz, 1H), 2.38 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.9, 148.8, 144.4, 139.8, 136.3, 135.1, 131.0, 129.5 (2x), 129.0 (2x), 128.4 (2x), 127.6 (3x), 107.5, 106.7, 71.9, 55.8, 55.7, 51.7, 32.7, 21.3, 20.9.

4-Phenyl-5-(toluene-4-sulfonyl)-5,6-dihydro-4Hcyclopenta[b]thiophene (2r). 2r was synthesized according to general synthetic procedure from 4r (110 mg, 0.3 mmol). Yield = 80% (85 mg); Colorless solid; mp = 109-111 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H19O2S2 355.0827; Found 355.0826; 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.22-7.17 (m, 3H), 7.15 (d, J = 5.2 Hz, 1H), 6.96-6.93 (m, 2H), 6.51 (d, J = 4.8 Hz, 1H), 4.78 (d, J = 4.8 Hz, 1H), 4.27 (dt, J = 5.2, 9.2 Hz, 1H), 3.51 (dd, J = 5.2, 16.4 Hz, 1H), 3.33 (dd, J = 9.2, 16.4 Hz, 1H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.1, 144.7, 142.3, 138.6, 134.8, 129.6 (2x), 129.4, 128.5 (2x), 128.4 (2x), 127.3 (2x), 126.9, 121.8, 76.2, 48.2, 29.6, 21.4. Single-crystal X-Ray diagram: crystal of 2r was grown by slow diffusion of EtOAc into a solution of 2r in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group C2/c, a = 17.258(3) Å , b = 11.1864(19) Å , c = 17.603(3) Å , V = 3377.5(10) Å 3, Z = 8, dcalcd = 1.394 g/cm3, F(000) = 1488, 2θ range 2.174~26.580o, R indices (all data) R1 = 0.0713, wR2 = 0.1309.

3-(3,4-Dimethoxyphenyl)-2-(toluene-4-sulfonyl)-1-(4trifluoromethylphenyl)propan-1-ol (7w). 7w was synthesized according to general synthetic procedure from 4w (147 mg, 0.3 mmol). Yield = 98% (145 mg); Colorless solid; mp = 121-123 o C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H26F3O5S 495.1453; Found 495.1456; 1H NMR (400 MHz, CDCl3): δ 7.54 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.53 (d, J = 8.0 Hz, 1H), 6.23 (br s, 1H), 6.22 (dd, J = 2.0, 8.0 Hz, 1H), 5.09 (t, J = 6.0 Hz, 1H), 4.54 (br d, J = 5.6 Hz, 1H), 3.75 (s, 3H), 3.74-3.70 (m, 1H), 3.67 (s, 3H), 3.21 (dd, J = 4.4, 14.8 Hz, 1H), 2.69 (dd, J = 8.8, 14.8 Hz, 1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.7, 147.7, 144.9, 143.6, 135.4, 129.7, 129.6 (2x), 129.0, 128.2 (2x), 127.05 (2x), 126.2 (q, J = 269.9 Hz), 124.9 (q, J = 3.8 Hz, 2x), 120.6, 111.4, 111.1, 71.4, 71.2, 55.7, 55.5, 31.3, 21.3.

1-(4-Fluorophenyl)-5,6-dimethoxy-2-(toluene-4sulfonyl)indan (2t). 2t was synthesized according to general synthetic procedure from 4t (132 mg, 0.3 mmol). Yield = 82% (105 mg); Colorless solid; mp = 164-166 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+

3-(3,4-Dimethoxyphenyl)-1-(4-nitrophenyl)-2-(toluene-4sulfonyl)propan-1-ol (7x). 2x was synthesized according to general synthetic procedure from 4x (140 mg, 0.3 mmol). Yield = 94% (133 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H26NO7S 472.1430; Found 472.1430; 1H


Page 25 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 8.8 Hz, 1H), 6.26-6.24 (m, 2H), 5.14 (t, J = 5.6 Hz, 1H), 4.50 (br d, J = 5.2 Hz, 1H), 3.76-3.74 (m, 1H), 3.74 (s, 3H), 3.65 (s, 3H), 3.13 (dd, J = 4.4, 14.8 Hz, 1H), 2.70 (dd, J = 8.8, 14.8 Hz, 1H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.7, 147.7, 147.1, 147.0, 145.0, 135.2, 129.5 (2x), 128.5, 128.2 (2x), 127.5 (2x), 122.9 (2x), 120.6, 111.5, 111.1, 71.0 (2x), 55.7, 55.5, 31.4, 21.3. 4-[5,6-Dimethoxy-2-(toluene-4-sulfonyl)indan-1-yl]biphenyl (2y). 2y was synthesized according to general synthetic procedure from 4y (149 mg, 0.3 mmol). Yield = 86% (125 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C30H29O4S 485.1787; Found 485.1788; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.0 Hz, 2H), 7.55-7.53 (m, 2H), 7.447.41 (m, 4H), 7.35-7.31 (m, 1H), 7.25 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.75 (s, 1H), 6.39 (s, 1H), 4.87 (d, J = 5.6 Hz, 1H), 4.02 (dt, J = 6.0, 9.2 Hz, 1H), 3.87 (s, 3H), 3.71 (s, 3H), 3.52 (dd, J = 6.4, 16.8 Hz, 1H), 3.34 (dd, J = 9.2, 16.8 Hz, 1H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.2, 149.1, 144.6, 141.9, 140.5, 139.8, 135.3, 135.0, 131.2, 129.6 (2x), 128.7 (2x), 128.6 (2x), 128.3 (2x), 127.23, 127.18 (2x), 126.9 (2x), 107.7, 106.8, 72.0, 55.9 (2x), 52.0, 32.9, 21.5. 2-[5,6-Dimethoxy-2-(toluene-4-sulfonyl)indan-1yl]naphthalene (2z). 2z was synthesized according to general synthetic procedure from 4z (142 mg, 0.3 mmol). Yield = 87% (120 mg); Colorless solid; mp = 99-102 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C28H27O4S 459.1630; Found 459.1629; 1H NMR (400 MHz, CDCl3): δ 7.77-7.75 (m, 1H), 7.70-7.61 (m, 4H), 7.47-7.42 (m, 2H), 7.23 (s, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.01 (dd, J = 1.6, 8.4 Hz, 1H), 6.79 (s, 1H), 6.32 (s, 1H), 4.91 (d, J = 6.4 Hz, 1H), 4.10 (dt, J = 6.8, 9.2 Hz, 1H), 3.88 (s, 3H), 3.64 (s, 3H), 3.60 (dd, J = 6.8, 16.8 Hz, 1H), 3.40 (dd, J = 9.2, 16.8 Hz, 1H), 2.24 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.2, 149.1, 144.6, 139.9, 135.3, 135.0, 133.1, 132.3, 131.2, 129.5 (2x), 128.5 (3x), 127.6, 127.5, 127.1, 126.1, 125.7, 125.4, 107.7, 106.9, 71.6, 56.0, 55.9, 52.7, 32.6, 21.3. 2-Benzenesulfonyl-5,6-dimethoxy-1-phenylindan (2aa). 2aa was synthesized according to general synthetic procedure from 4aa (122 mg, 0.3 mmol). Yield = 87% (103 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H23O4S 395.1317; Found 395.1318; 1H NMR (400 MHz, CDCl3): δ 7.85-7.82 (m, 2H), 7.58-7.54 (m, 1H), 7.46-7.42 (m, 2H), 7.197.13 (m, 3H), 6.88-6.86 (m, 2H), 6.73 (s, 1H), 6.33 (s, 1H), 4.81 (d, J = 5.2 Hz, 1H), 3.98 (dt, J = 6.0, 9.2 Hz, 1H), 3.84 (s, 3H), 3.67 (s, 3H), 3.51 (dd, J = 6.0, 16.8 Hz, 1H), 3.33 (dd, J = 9.2, 16.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.1, 149.0, 142.8, 138.1, 134.9, 133.5, 131.1, 129.0 (2x), 128.5 (4x), 127.7 (2x), 126.9, 107.6, 106.7, 71.8, 55.9, 55.8, 52.2, 32.7. 2-(4-Fluorobenzenesulfonyl)-5,6-dimethoxy-1-phenylindan (2ab). 2ab was synthesized according to general synthetic procedure from 4ab (128 mg, 0.3 mmol). Yield = 88% (109 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H22FO4S 413.1223; Found 413.1225; 1H NMR (400 MHz, CDCl3): δ 7.85-7.80 (m, 2H), 7.21-7.16 (m, 3H), 7.13-7.07 (m, 2H), 6.90-6.87 (m, 2H), 6.73 (s, 1H), 6.31 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 3.99 (dt, J = 6.0, 9.2 Hz, 1H), 3.85 (s, 3H), 3.67 (s, 3H), 3.51 (dd, J = 6.0, 16.4 Hz, 1H), 3.35 (dd, J = 9.2, 16.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 165.7 (d, J = 254.7

Hz), 149.2, 149.1, 142.5, 134.9, 134.3, 131.3 (d, J = 9.9 Hz, 2x), 130.9, 128.6 (2x), 127.8 (2x), 127.0, 116.3 (d, J = 22.0 Hz, 2x), 107.6, 106.8, 72.1, 55.94, 55.90, 52.4, 32.7. 5,6-Dimethoxy-2-(4-methoxybenzenesulfonyl)-1-phenylindan (2ac). 2ac was synthesized according to general synthetic procedure from 4ac (131 mg, 0.3 mmol). Yield = 86% (109 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C24H25O5S 425.1423; Found 425.1421; 1H NMR (400 MHz, CDCl3): δ 7.75 (d, J = 8.4 Hz, 2H), 7.20-7.15 (m, 3H), 6.916.87 (m, 4H), 6.72 (s, 1H), 6.32 (s, 1H), 4.78 (d, J = 5.6 Hz, 1H), 3.95 (dt, J = 5.6, 9.2 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.67 (s, 3H), 3.48 (dd, J = 6.0, 16.4 Hz, 1H), 3.32 (dd, J = 8.8, 16.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 163.6, 149.1, 149.0, 142.9, 135.1, 131.3, 130.7 (2x), 129.6, 128.5 (2x), 127.8 (2x), 126.8, 114.2 (2x), 107.7, 106.8, 72.2, 55.90, 55.87, 55.6, 52.4, 32.8. 2-(4-Ethylbenzenesulfonyl)-5,6-dimethoxy-1-phenylindan (2ad). 2ad was synthesized according to general synthetic procedure from 4ad (131 mg, 0.3 mmol). Yield = 84% (106 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C25H27O4S 423.1630; Found 423.1631; 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.17-7.12 (m, 3H), 6.87-6.85 (m, 2H), 6.73 (s, 1H), 6.32 (s, 1H), 4.79 (d, J = 6.0 Hz, 1H), 3.97 (dt, J = 6.0, 8.8 Hz, 1H), 3.84 (s, 3H), 3.66 (s, 3H), 3.51 (dd, J = 6.0, 16.8 Hz, 1H), 3.32 (dd, J = 8.8, 16.8 Hz, 1H), 2.67 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 150.6, 149.0, 148.9, 142.8, 135.2, 135.0, 131.2, 128.6 (2x), 128.4 (4x), 127.7 (2x), 126.7, 107.6, 106.7, 71.8, 55.82, 55.78, 52.3, 32.6, 28.7, 15.1. 2-(4-t-Butylbenzenesulfonyl)-5,6-dimethoxy-1-phenylindan (2ae). 2ae was synthesized according to general synthetic procedure from 4ae (139 mg, 0.3 mmol). Yield = 86% (116 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C27H31O4S 451.1943; Found 451.1940; 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.15-7.11 (m, 3H), 6.85-6.82 (m, 2H), 6.73 (s, 1H), 6.30 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 3.98 (dt, J = 6.0, 9.2 Hz, 1H), 3.85 (s, 3H), 3.67 (s, 3H), 3.54 (dd, J = 6.4, 16.8 Hz, 1H), 3.35 (dd, J = 9.2, 16.8 Hz, 1H), 1.31 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.5, 149.1, 149.0, 142.8, 135.1, 135.0, 131.2, 128.44 (2x), 128.41 (2x), 127.8 (2x), 126.8, 126.0 (2x), 107.7, 106.8, 71.9, 55.90, 55.87, 52.5, 35.1, 32.6, 30.9 (3x). 2-Methanesulfonyl-5,6-dimethoxy-1-phenylindan (2af). 2af was synthesized according to general synthetic procedure from 4af (104 mg, 0.3 mmol). Yield = 89% (89 mg); Colorless solid; mp = 135-137 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H21O4S 333.1161; Found 333.1162; 1H NMR (400 MHz, CDCl3): δ 7.28-7.13 (m, 5H), 6.76 (s, 1H), 6.33 (s, 1H), 4.78 (d, J = 6.0 Hz, 1H), 3.83-3.78 (m, 1H), 3.79 (s, 3H), 3.61 (s, 3H), 3.40 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.0, 148.9, 142.3, 134.7, 130.5, 128.7 (2x), 127.8 (2x), 127.1, 107.4, 106.8, 70.9, 55.7, 55.6, 52.1, 38.9, 32.1. 2-(Butane-1-sulfonyl)-5,6-dimethoxy-1-phenylindan (2ag). 2ag was synthesized according to general synthetic procedure from 4ag (116 mg, 0.3 mmol). Yield = 86% (96 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H27O4S 375.1630; Found 375.1629; 1H NMR (400 MHz, CDCl3): δ



7.34-7.19 (m, 5H), 6.78 (s, 1H), 6.31 (s, 1H), 4.79 (d, J = 7.2 Hz, 1H), 3.88 (dt, J = 7.2, 9.2 Hz, 1H), 3.85 (s, 3H), 3.66 (s, 3H), 3.50 (dd, J = 7.6, 16.4 Hz, 1H), 3.39 (dd, J = 9.2, 16.4 Hz, 1H), 2.75-2.62 (m, 2H), 1.71-1.61 (m, 1H), 1.50-1.39 (m, 1H), 1.28-1.12 (m, 2H), 0.75 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.1, 149.0, 142.5, 135.2, 130.6, 128.9 (2x), 128.1 (2x), 127.4, 107.6, 106.8, 69.2, 55.9, 55.8, 52.4, 51.6, 31.8, 23.3, 21.4, 13.2. 1-(3,4-Dichlorophenyl)-2-(toluene-4-sulfonyl)indan (2ah). 2ah was synthesized according to general synthetic procedure from 4ah (129 mg, 0.3 mmol). Yield = 82% (102 mg); Colorless solid; mp = 115-117 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19Cl2O2S 417.0483; Found 417.0485; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 2H), 7.27-7.21 (m, 5H), 7.15 (dt, J = 2.4, 8.0 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 6.80 (dd, J = 2.4, 8.4 Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 4.74 (d, J = 7.2 Hz, 1H), 3.98 (dt, J = 7.6, 9.2 Hz, 1H), 3.61 (dd, J = 7.6, 16.8 Hz, 1H), 3.37 (dd, J = 9.2, 16.8 Hz, 1H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 145.1, 142.7, 142.6, 139.3, 135.1, 132.4, 131.0, 130.5, 130.2, 129.8 (2x), 128.5 (2x), 128.0, 127.7, 127.5, 124.9, 124.4, 71.4, 51.6, 32.7, 21.6. 2-[3-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)indan1-yl]naphthalene (2ai). 2ai was synthesized according to general synthetic procedure from 3w (167 mg, 0.3 mmol). Yield = 75% (122 mg); Colorless solid; mp = 230-232 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++1) calcd for C34H37O4S 541.2413, found 541.2410; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.4 Hz, 2H), 7.78 (dd, J = 3.2, 9.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.57-7.55 (m, 1H), 7.46-7.41 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.06-7.02 (m, 2H), 6.79 (s, 1H), 6.47 (s, 1H), 4.99 (d, J = 4.0 Hz, 1H), 3.92 (s, 3H), 3.75-3.71 (m, 1H), 3.71 (s, 3H), 2.62 (t, J = 4.0 Hz, 1H), 2.46 (s, 3H), 1.67-1.43 (m, 6H), 1.19-1.82 (m, 5H); 13C NMR (100 MHz, CDCl3): δ 149.2, 149.1, 144.8, 140.7, 135.2, 135.1, 133.9, 133.0, 132.2, 129.8 (2x), 129.2 (2x), 128.2, 127.7, 127.5, 126.9, 126.1 (2x), 125.8, 107.8, 107.6, 74.7, 56.0, 55.9, 51.6 (2x), 43.2, 30.7, 30.4, 26.5, 26.4, 26.1, 21.6. Single-crystal X-Ray diagram: crystal of 2ai was grown by slow diffusion of EtOAc into a solution of 2ai in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/n, a = 10.2968(4) Å , b = 20.9708(10) Å , c = 14.9988(7) Å , V = 3199.4(2) Å 3, Z = 4, dcalcd = 1.243 g/cm3, F(000) = 1280, 2θ range 1.683~26.400o, R indices (all data) R1 = 0.0603, wR2 = 0. 1142. 4-[3-Cyclohexyl-5,6-dimethoxy-2-(toluene-4-sulfonyl)indan1-yl]biphenyl (2aj). 2aj was synthesized according to general synthetic procedure from 3v (175 mg, 0.3 mmol). Yield = 70% (119 mg); Colorless solid; mp = 238-240 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++1) calcd for C36H39O4S 567.2569, found 567.2575; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.4 Hz, 2H), 7.57-7.55 (m, 2H), 7.447.41 (m, 4H), 7.37-7.31 (m, 3H), 6.93 (d, J = 8.0 Hz, 2H), 6.74 (s, 1H), 6.51 (s, 1H), 4.94 (d, J = 4.0 Hz, 1H), 3.90 (s, 3H), 3.76 (s, 3H), 3.65 (t, J = 4.0 Hz, 1H), 3.57 (t, J = 3.6 Hz, 1H), 2.47 (s, 3H), 2.05-1.60 (m, 4H), 1.57-1.38 (m, 3H), 1.24-1.01 (m, 2H), 0.99-0.78 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 149.2, 149.0, 144.8, 142.6, 140.6, 139.6, 135.11, 135.05, 133.9, 129.8 (2x), 129.3 (2x), 128.8 (2x), 128.6 (2x), 127.3, 127.0

Page 26 of 30

(2x), 126.9 (2x), 107.8, 107.6, 75.1, 56.1, 55.9, 51.9, 50.9, 43.2, 30.7, 30.4, 26.5, 26.4, 26.1, 21.7. 1-(4-Fluorophenyl)-5,6-dimethoxy-3-phenyl-2-(toluene-4sulfonyl)indan (2ak). 2ak was synthesized according to general synthetic procedure from 3ad (137 mg, 0.3 mmol). Yield = 62% (93 mg); Colorless solid; mp = 200-202 oC (recrystallized from hexanes and EtOAc); HRMS (ESI, M++1) calcd for C30H28FO4S 503.1692, found 503.1698; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 8.0 Hz, 2H), 7.22-7.16 (m, 5H), 7.016.87 (m, 6H), 6.39 (s, 1H), 6.38 (s, 1H), 4.92 (d, J = 6.0 Hz, 1H), 4.88 (d, J = 6.0 Hz, 1H), 3.90 (t, J = 6.0 Hz, 1H), 3.74 (s, 3H), 3.73 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.7 (d, J = 244.1 Hz), 149.8, 144.8, 143.2 (2x), 139.2, 135.5, 135.0, 134.8, 129.8 (d, J = 7.6 Hz, 2x), 129.7 (2x), 128.7 (2x), 128.6 (2x), 128.2 (2x), 126.9, 115.4 (d, J = 21.2 Hz, 2x), 107.4, 107.2, 80.3, 56.0 (2x), 51.8, 51.0, 21.6. 3-(3,4-Dichlorophenyl)indan-1-one (8). Freshly prepared Na(Hg) (~6%, 1 g) was added to a solution of 2ah (83 mg, 0.2 mmol) in MeOH (10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 2 h. Mercury was filtered by filter paper and the fitrates were concentrated. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude products under reduced pressure. Without further purification, PDC (380 mg, 1.0 mmol) was added to a solution of the resulting crude products in DMF (5 mL) at 25 oC. The reaction mixture was stirred at reflux for 2 h. The reaction mixture was filtered, washed with CH2Cl2 (3 x 20 mL), and the fitrates were concentrated. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 8. Yield = 64% of two-step (35 mg); Colorless solid; mp = 113-115 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C15H11Cl2O 277.0187; Found 277.0188; 1H NMR (400 MHz, CDCl3): δ 7.82 (dd, J = 0.8, 7.6 Hz, 1H), 7.60 (dt, J = 1.6, 7.6 Hz, 1H), 7.45 (dt, J = 0.4, 7.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.27-7.25 (m, 1H), 7.00 (d, J = 2.0 Hz, 1H), 6.95 (dd, J = 2.0, 8.4 Hz, 1H), 4.54 (dd, J = 3.6, 8.0 Hz, 1H), 3.23 (dd, J = 8.0, 19.2 Hz, 1H), 2.62 (dd, J = 4.0, 19.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 204.9, 156.5, 143.9, 136.7, 135.3, 132.9, 131.1, 130.9, 129.6, 128.3, 126.9, 126.7, 123.7, 46.4, 43.5. 2-Phenyl-3-(toluene-4-sulfonyl)quinoline (9). SnCl2 was added to a solution of 4ai (81 mg, 0.2 mmol) in CH2Cl2 (10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 10 min. HCl(aq) (12N, 1mL) was added to the reaction mixture at 25 oC. The reaction mixture was stirred at 25 oC for 3 h. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 9. Yield = 75% (54 mg); Colorless solid; mp = 179180 oC (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z: [M + H]+ Calcd for C22H18NO2S 360.1058; Found 360.1058; 1H NMR (400 MHz, CDCl3): δ 9.29 (s, 1H), 8.16 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 0.8, 8.0 Hz, 1H), 7.89 (dt, J = 1.2, 8.4 Hz, 1H), 7.71 (dt, J = 1.2, 8.4 Hz, 1H), 7.42-7.37 (m, 1H),


Page 27 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


7.30-7.26 (m, 2H), 7.21-7.19 (m, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.1, 148.7, 143.9, 138.9, 138.2, 136.9, 134.9, 132.8, 129.7 (2x), 129.4, 129.1 (2x), 129.0, 128.6, 128.1, 128.0 (2x), 127.5 (2x), 125.8, 21.5. Single-crystal X-Ray diagram: crystal of 9 was grown by slow diffusion of EtOAc into a solution of 9 in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P 21/c, a = 12.5407(14) Å , b = 5.3966(6) Å , c = 25.050(3) Å , V = 1692.5(3) Å 3, Z = 4, dcalcd = 1.411 g/cm3, F(000) = 752, 2θ range 1.626~26.451o, R indices (all data) R1 = 0.0542, wR2 = 0.0970. 2-Phenyl-3-(toluene-4-sulfonyl)chroman (10). NaBH4 (38 mg, 1.0 mmol) was added to a solution of 4k (130 mg, 0.3 mmol) in THF and MeOH (v/v =1/1, 10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 30 min. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. Without further purification, K3PO4 (170 mg, 0.8 mmol), CuI (19 mg, 0.1 mmol), KI (50 mg, 0.3 mmol), 1,10phenanthroline (1,10-Phen, 36 mg, 0.2 mmol) were added to the resulting crude products in a toluene (10 mL) at 25 oC. The reaction mixture was stirred at reflux for 48 h. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 15/1~4/1 as eluent) affording 10. Yield = 48% (52 mg); Colorless solid; mp = 92-94 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21O3S 365.1211; Found 365.1219; 1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.0 Hz, 2H), 7.18 (br s, 5H), 7.13 (d, J = 8.0 Hz, 2H), 7.01 (dt, J = 1.6, 8.0 Hz, 1H), 6.69 (dd = 0.8, 8.0 Hz, 1H), 6.64 (dt, J = 1.2, 7.6 Hz, 1H), 6.55 (dd, J = 1.6, 7.6 Hz, 1H), 5.05 (d, J = 6.4 Hz, 1H), 4.00 (dt, J = 6.0, 7.6 Hz, 1H), 3.27 (dd, J = 5.2, 14.8 Hz, 1H), 2.85 (dd, J = 8.0, 14.8 Hz, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.4, 144.5, 139.1, 136.1, 130.9, 129.5 (2x), 128.41, 128.36 (2x), 128.2 (2x), 128.1, 126.6 (2x), 122.9, 120.6, 116.5, 72.7, 69.6, 27.7, 21.5. 2-Phenylchroman-4-one (11). Freshly prepared Na(Hg) (~6%, 1 g) was added to a solution of 10 (110 mg, 0.3 mmol) in MeOH (10 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 2 h. Mercury was filtered by filter paper and the fitrates were concentrated. The residue was diluted with saturated NaHCO3(aq) (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. Without further purification, PDC (380 mg, 1.0 mmol) was added to a solution of the resulting crude products in DMF (5 mL) at 25 oC. The reaction mixture was stirred at reflux for 2 h. The reaction mixture was filterated, washed with CH2Cl2 (3 x 20 mL), and the fitrates were concentrated. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 10/1~4/1 as eluent) affording 11. Yield = 52%

(35 mg); Colorless solid; mp = 76-78 oC (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H13O2 225.0916, found 225.0924; 1H NMR (400 MHz, CDCl3): δ 7.95 (dd, J = 2.0, 8.0 Hz, 1H), 7.54-7.38 (m, 6H), 7.08-7.04 (m, 2H), 5.49 (dd, J = 2.8, 13.2 Hz, 1H), 3.10 (dd, J = 13.2, 16.8 Hz, 1H), 2.90 (dd, J = 2.8, 16.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 191.9, 161.5, 138.7, 136.2, 128.8 (2x), 128.7, 127.0, 126.1 (2x), 121.6, 120.9, 118.1, 79.6, 44.6. 6,7-Dimethoxy-1-phenylisoquinoline (12). A solution of 1% OsO4 (3 mL, in THF) was added to a solution of 1v (120 mg, 0.3 mmol) in the co-solvent of THF (10 mL) and water (3 mL). NMO (50% in water, 210 mg, 0.9 mmol) was added to the reaction mixture at 25 oC. The reaction mixture was stirred at 60 oC for 20 h. The reaction mixture was cooled to 25 oC, and NaIO4 (214 mg, 1.0 mmol) in water (1 mL) was added to the reaction mixture. The reaction mixture was stirred at 60 oC for 10 h. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. Without further purification, NH4OAc (77 mg, 1.0 mmol) was added to the resulting crude products in MeOH (10 mL) at 25 oC. The reaction mixture was stirred at 60 o C for 10 h. The overall synthetic procedure had to be monitored by TLC until the reaction was completed. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 10/1~4/1 as eluent) affording 12. Yield = 27% (21 mg); Colorless liquid; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H16NO2 266.1181, found 266.1188; 1H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 5.6 Hz, 1H), 7.72-7.69 (m, 2H), 7.55-7.46 (m, 4H), 7.37 (s, 1H), 7.13 (s, 1H), 4.05 (s, 3H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.3, 152.7, 150.0, 141.3, 140.0, 133.8, 129.6 (2x), 128.4 (3x), 122.5, 118.7, 105.6, 105.0, 56.0, 55.9. Gram-Scale Synthesis of Compound 8. Amberlyst® 15 (A-15, 2.58 g) was added to a solution of 5p (3.42 g, 10 mmol) in toluene (200 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 10 min under Dean-Stark distillation apparatus. 6f (1.12 g, 11 mmol) was added to the reaction mixture at 25 oC. The reaction mixture was stirred at reflux for 10 h. The reaction was monitored by TLC. The reaction mixture was cooled to 25 oC. A-15 was filtered by filter paper and the A-15 was washed with toluene (3 x 20 mL). The combined toluene layers were concentrated. The residue was diluted with saturated NaHCO3(aq) (30 mL) and the mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 4ah (3.66 g, 85%). Next, NaBH4 (570 mg, 15 mmol) was added to a solution of 4ah (3.66 g, 8.5 mmol) in THF and MeOH (v/v =1/1, 100 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 2 h. The reaction mixture was cooled to 25 oC and the solvent was concentrated. The residue was diluted with water (30 mL)



and the mixture was extracted with CH2Cl2 (3 x 50 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. Without further purification, A-15 (3.0 g) was added to a solution of the resulting crude products in a toluene (150 mL) at 25 oC. The reaction mixture was stirred at reflux for 40 h under Dean-Stark distillation apparatus. The reaction was monitored by TLC. A-15 was filtered by filter paper and the A-15 was washed with toluene (3 x 20 mL). The combined organic layers were concentrated. The residue was diluted with saturated NaHCO3(aq) (30 mL) and the mixture was extracted with CH2Cl2 (3 x 50 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (MgSO4), filtered and evaporated to afford crude product under reduced pressure. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 2ah (2.55 g, 72%). Finally, freshly prepared Na(Hg) (~6%, 8 g) was added to a solution of 2ah (2.55 g, 6.1 mmol) in MeOH (100 mL) at 25 oC. The reaction mixture was stirred at 25 oC for 6 h. Mercury was filtered by filter paper and the fitrates were concentrated. The residue was diluted with saturated NaHCO3(aq) (30 mL) and the mixture was extracted with CH2Cl2 (3 x 50 mL). The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude products under reduced pressure. Without further purification, PDC (9.4 g, 25 mmol) was added to a solution of the resulting crude products in DMF (60 mL) at 25 oC. The reaction mixture was stirred at reflux for 8 h. The reaction mixture was filterated, washed with CH2Cl2 (3 x 100 mL), and the fitrates were concentrated. The remaining mixture was separated by column chromatography (silica gel, hexanes/EtOAc = 8/1~4/1 as eluent) affording 8 (995 mg, 59% of two steps). DFT calculations. All calculations were carried out with the Gaussian 09 program.49 The combination of pure functional M06L with Def2-SVP basis sets was adopted for gas-phase geometry optimizations and vibrational frequency calculations. Density fitting approximation50 using W06 fitting set was exploited to speed up the calculations. To properly model the dispersion force, the D3 version of Grimme’s empirical dispersion correction51 was added in the calculations. Single point energy calculations with hybrid functional M06-2X and Def2TZVP basis sets were performed to provide more accurate energies. The solvent effect (solvent = THF) was taken into account in the single point energy calculations by using the SMD continuum solvation model. Numerical integration was done with the setting of ultrafine grid. Thermal correction to Gibbs free energy was made at the standard conditions of 298.15 K and 1 atm. The natural steric analysis52 was carried out by using the NBO 6.0 program.53

ASSOCIATED CONTENT Supporting Information Scanned photocopies of NMR spectral data for all compounds, DFT theoretical calculations data and X-ray analysis data of 1a, 1e, 1h, 1q, 1z, 2e, 2g, 2k, 2r, 2ai, 4n, 7l and 9. This information is available free of charge via the Internet at http: //pubs.acs.org.

AUTHOR INFORMATION

Page 28 of 30

Corresponding Author *Email: [email protected] *Email: [email protected] ORCID Meng-Yang Chang: 0000-0002-1983-8570 Hsing-Yin Chen: 0000-0003-3948-8915

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT The authors would like to thank the Ministry of Science and Technology of the Republic of China for financial support (MOST 1062628-M-037-001-MY3).

REFERENCES (1) Recent reviews on synthesis of indane, indene and their related derivatives, see: (a) Gabriele, B.; Mancuso, R.; Veltri, L. Recent Advances in the Synthesis of Indanes and Indenes. Chem. Eur. J. 2016, 22, 5056-5094. (b) Kuck, D. Three-Dimensional Hydrocarbon Cores Based on Multiply Fused Cyclopentane and Indane Units: Centropolyindanes. Chem. Rev. 2006, 106, 4885-4925. (c) Hong, B.-C.; Sarshar, S. Recent Advances in the Synthesis of Indan Systems. A Review. Org. Prep. Proced. Int. 1999, 31, 1-86. (2) For selected examples on synthetic applications, see: (a) Kotha, S.; Goyal, D.; Chavan, A. S. Diversity-Oriented Approaches to Unusual α-Amino Acids and Peptides: Step Economy, Atom Economy, Redox Economy, and Beyond. J. Org. Chem. 2013, 78, 12288-12313. (b) Tran, D. N.; Cramer, N. Enantioselective Rhodium(I)-Catalyzed [3+2] Annulations of Aromatic Ketimines Induced by Directed C-H Activations. Angew. Chem. Int. Ed. 2011, 50, 11098-11102. (c) Zhou, F.; Han, X.; Lu, X. Palladium(II)Catalyzed Synthesis of Functionalized Indenes from oAlkynylbenzylidene Ketones. J. Org. Chem. 2011, 76, 1491-1494. (d) Sato, T.; Onuma, T.; Nakamura, I.; Terada, M. PlatinumCatalyzed Cycloisomerization of 1,4-Enynes via 1,2-Alkenyl Rearrangement. Org. Lett. 2011, 13, 4992-4995. (e) Tran, D. N.; Cramer, N. syn-Selective Rhodium(I)-Catalyzed Allylations of Ketimines Proceeding through a Directed C-H Activation/Allene Addition Sequence. Angew. Chem. Int. Ed. 2010, 49, 8181-8184. (f) Zhou, Q.; Li, S.; Zhang, Y.; Wang, J. Rhodium(II)- or Copper(I)-Catalyzed Formal Intramolecular Carbene Insertion into Vinylic C(sp2)-H Bonds: Access to Substituted 1H-Indenes. Angew. Chem. Int. Ed. 2017, 56, 16013-16017. (3) For bioactivity of indanes, indenes and their related derivatives, see: (a) Huffman, J. W.; Padgett, L. W. Recent Developments in the Medicinal Chemistry of Cannabimimetic Indoles, Pyrroles and Indenes. Curr. Med. Chem. 2005, 12, 1395-1411. (b) Di Stefano, A.; Sozio, P.; Cacciatore, I.; Cocco, A.; Giorgioni, G.; Costa, B.; Montali, M.; Lucacchini, A.; Martini, C.; Spoto, G.; Di Pietrantonio, F.; Di Matteo, E.; Pinnen, F. Preparation and Pharmacological Characterization of trans-2-Amino-5(6)-fluoro-6(5)hydroxy-1-phenyl-2,3-dihydro-1H-indenes as D2-Like Dopamine Receptor Agonists. J. Med. Chem. 2005, 48, 2646-2654. (c) Gross, M. F.; Beaudoin, S.; McNaughton-Smith, G.; Amato, G. S.; Castle, N. A.; Huang, C.; Zou, A.; Yu, W. Aryl Sulfonamido Indane Inhibitors of the Kv1.5 Ion Channel. Bioorg. Med. Chem. Lett. 2007, 17, 2849-2853. For functionalized materials, see: (d) Yang, J.; Lakshmikantham, M. V.; Cava, M. P.; Lorcy, D.; Bethelot, J. R. Synthesis and Characterization of 5,10-Bis(2thienyl)indeno[2,1-a]indene Derivatives: The First Examples of Conducting Polymers Containing a Rigid Bis(thienyl)butadiene Core. J. Org. Chem. 2000, 65, 6739-6742. (e) Nakano, M.; Osaka, I.; Takimiya, K.; Koganezawa, T. Novel Dibenzo[a,e]pentaleneBased Conjugated Polymers. J. Mater. Chem. C 2014, 2, 64-70.


Page 29 of 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(4) For TfOH, see: (a) Suresh, R.; Muthusubramanian, S.; Boominathan, M.; Manickam, G. Acid Controlled Generation of Indanes and Oxazolines from β-Hydroxyarylethanamide. Tetrahedron Lett. 2013, 54, 2315-2320. (b) Vasilyev, A. V.; Walspurger, S.; Pale, P.; Sommer, J. A New, Fast and Efficient Synthesis of 3-Aryl Indenones: Intramolecular Cyclization of 1,3Diarylpropynones in Superacids. Tetrahedron Lett. 2004, 45, 3379-3381. For Tf2NH, see: (c) Reddel, J. C. T.; Wang, W.; Koukounas, K.; Thomson, R. J. Triflimide-Catalyzed Allylsilane Annulations of Benzylic Alcohols for the Divergent Synthesis of Indanes and Tetralins. Chem. Sci. 2017, 8, 2156-2060. (5) For Ph3CB(C6F5)4, see: (a) Cai, X.; Keshavarz, A.; Omaque, J. D.; Stokes, B. J. Brønsted Acid-Catalyzed Intramolecular Hydroarylation of β-Benzylstyrenes. Org. Lett. 2017, 19, 26262629. For BF3·OEt2, see: (b) Sarnpitak, P.; Trongchit, K.; Kostenko, Y.; Sathalalai, S.; Gleeson, M. P.; Ruchirawat, S.; Ploypradith, P. Synthesis of Substituted 2-Arylindanes from E(2-Stilbenyl)methanols via Lewis Acid-Mediated Cyclization and Nucleophililc Transfer from Trialkylsilyl Reagents. J. Org. Chem. 2013, 78, 8281-8296. For Ca(NTf2)2, see: (c) Begouin, J.-M.; Capitta, F.; Wu, X.; Niggemann, M. Diastereoselective Synthesis of Indanes and Tetralins via Intramolecular Friedel-Crafts Reaction. Org. Lett. 2013, 15, 1370-1373. For In(OTf)3, see: (d) Zhu, L.; Xi, Z.-G.; Luo, S. In(III)/PhCO2H Binary Acid Catalyzed Tandem [2 + 2] Cycloaddition and Nazarov Reaction between Alkynes and Acetals. Org. Lett. 2013, 15, 4496-4499. (6) Zhu, M.; Liu, J.; Yu, J.; Chen, L.; Zhang, C.; Wang, L. AlCl3Promoted Formal [2 + 3]-Cycloaddition of 1,1-Cyclopropane Diesters with N-Benzylic Sulfonamides To Construct Highly Stereoselective Indane Derivatives. Org. Lett. 2014, 16, 18561859. (7) (a) Gutman, E. S.; Arredondo, V.; van Vranken, D. L. Cyclization of η3-Benzylpalladium Intermediates Derived from Carbene Insertion. Org. Lett. 2014, 16, 5498-5501. (b) Fan, Y. C.; Kwon, O. Synthesis of Functionalized Alkylidene Indanes and Indanones through Tandem Phosphine-Palladium Catalysis. Org. Lett. 2015, 17, 2058-2061. (8) Gourdet, B.; Rudkin, M. E.; Lam, H. W. Rhodium-Catalyzed Annulation of Ynamides with Bifunctional Arylboron Reagents. Org. Lett. 2010, 12, 2554-2557. (9) Kramer, N. J.; Hoang, T. T.; Dudley, G. B. Reaction Discovery Using Neopentylene-Tethered Coupling Partners: Cycloisomerization/Oxidation of Electron-Deficient Dienynes. Org. Lett. 2017, 19, 4636-4639. (10) Zhou, X.; Yu, S.; Qi, Z.; Li, X. Rhodium(III)-Catalyzed [3+2] Annulative Coupling between Oximes and Electron-Deficient Alkynes. Sci. China Chem. 2015, 58, 1297-1301. (11) Lv, N.; Chen, Z.; Liu, Y.; Liu, Z.; Zhang, Y. Synthesis of Functionalized Indenones via Rh-Catalyzed C-H Activation Cascade Reaction. Org. Lett. 2017, 19, 2588-2591. (12) Oswald, C.; Peterson, J. A.; Lam, H. W. Enantioselective Copper-Catalyzed Reductive Michael Cyclizations. Org. Lett. 2009, 11, 4504-4507. (13) Dethe, D. H.; Muhade, G. FeCl3 Catalyzed Prins-Type Cyclization for the Synthesis of Highly Substituted Indenes: Application to the Total Synthesis of (±)-Jungianol and epi-Jungianol. Org. Lett. 2013, 15, 429-431. (14) Deng, R.; Sun, L.; Li, Z. Nickel-Catalyzed Carboannulation Reaction of o-Bromobenzyl Zinc Bromide with Unsaturated Compounds. Org. Lett. 2007, 9, 5207-5210. (15) Kelly, P. A.; Berger, G. O.; Wyatt, J. K.; Nantz, M. H. Synthesis of [Ethylene-1-(η5-4,5,6,7-tetrahydro-1-indenyl)-2-(η54’,5’,6’,7’-tetrahydro-2’-indenyl)]titanium Dichloride, the Elusive Isomer of the Brintzinger-Type ansa-Titanocenes. J. Org. Chem. 2003, 68, 8447-8452. (16) Kezuka, S.; Tanaka, S.; Ohe, T.; Nakaya, Y.; Takeuchi, R. Iridium Complex-Catalyzed [2+2+2] Cycloaddition of α,ω-Diynes with Monoynes and Monoenes. J. Org. Chem. 2006, 71, 543-552.

(17) Coppola, A.; Sanchez-Alonso, P.; Sucunza, D.; Burgos, C.; Alajarin, R.; Alvarez-Bullia, J.; Mosquera, M. E. G.; Vaquero, J. J. Remote Aryl Cyanation via Isocyanide-Cyanide Rearrangement on Tosylmethyl Isocyanide Derivatives. Org. Lett. 2013, 15, 3388-3391. (18) Jiang, Y.; Loh, T.-P. Catalytic and Direct Methyl Sulfonylation of Alkenes and Alkynes Using a Methyl Sulfonyl Radical Generated from a DMSO, Dioxygen and Copper System. Chem. Sci. 2014, 5, 4939-4943. (19) Legarda, P. D.; Garcia-Rubia, A.; Arrayas, R. G.; Carretero, J. C. Palladium-Catalyzed Remote ortho-C-H Alkenylation of Alkyl Aryl Sulfones: Access to Densely Functionalized Indane Derivatives. Adv. Synth. Catal. 2016, 358, 1065-1072. (20) Wen, J.; Shi, W.; Zhang, F.; Liu, D.; Tang, S.; Wang, H.; Lin, X.M.; Lei, A. Electrooxidative Tandem Cyclization of Activated Alkynes with Sulfinic Acids To Access Sulfonated Indenones. Org. Lett. 2017, 19, 3131-3134. (21) Wolf, W. The Fungicidal Activity of β-Keto Sulfones. Molecular Conformation of α-Phenylhydrazono-β-ketosulfones as Determined by an X-ray Analysis. J. Mol. Struct. 1999, 474, 113-124. (22) Ettari, R.; Nizi, E.; Di Francesco, M. E.; Dude, M.-A.; Pradel, G.; Vicik, R.; Schirmeister, T.; Micale, N.; Grasso, S.; Zappala, M. Development of Peptidomimetics with a Vinyl Sulfone Warhead as Irreversible Falcipain-2 Inhibitors. J. Med. Chem. 2008, 51, 988-996. (23) Li, X.; Xu, X.; Zhou, C. Tetrabutylammonium Iodide Catalyzed Allylic Sulfonylation of α-Methyl Styrene Derivatives with Sulfonylhydrazides. Chem. Commun. 2012, 48, 12240-12242. (24) Li, X.; Xu, X.; Hu, P.; Xiao, X.; Zhou, C. Synthesis of Sulfonated Oxindoles by Potassium Iodide Catalyzed Arylsulfonylation of Activated Alkenes with Sulfonylhydrazides in Water. J. Org. Chem. 2013, 78, 7343-7348. (25) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang, H. Direct and Metal-Free Arylsulfonylation of Alkynes with Sulfonylhydrazides for the Construction of 3-Sulfonated Coumarins. Chem. Commun. 2015, 51, 768-771. (26) Prasad, C. D.; Sattar, M.; Kumar, S. Transition-Metal-Free Selective Oxidative C(sp3)-S/Se Coupling of Oxindoles, Tetralone, and Arylacetamides: Synthesis of Unsymmetrical Organochalcogenides. Org. Lett. 2017, 19, 774-777. (27) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H. CatalystFree Direct Arylsulfonylation of N-Arylacrylamides with Sulfinic acids: A Convenient and Efficient Route to Sulfonated Oxindoles. Green Chem. 2014, 16, 2988-2991. (28) Reviews on Amberlyst 15 mediated reactions, see: (a) Pal, R.; Sarkar, T.; Khasnobis, S. Amberlyst-15 in Organic Synthesis. ARKIVOC 2012, i, 570-609. (b) Clark, J. H., Ed.; Catalysis of Organic Reaction by Supported Reagents; VCH Publishers: New York, 1994. (29) Choudhary, D.; Paul, S.; Gupta, R.; Clark, J. H. Catalytic Properties of Several Palladium Complexes Covalently Anchored onto Silica for the Aerobic Oxidation of Alcohols. Green Chem. 2006, 8, 479482. (30) Lee, S. H.; Park, D. R.; Kim, H.; Lee, J.; Jung, J. C.; Woo, S. Y.; Song, W. S.; Kwon, M. S.; Song, I. K. Direct Preparation of Dichloropropanol (DCP) from Glycerol Using Heteropolyacid (HPA) Catalysts: A Catalyst Screen Study. Catal. Commun. 2008, 9, 1920-1923. (31) Corma, A. Inorganic Solid Acids and Their Use in AcidCatalyzed Hydrocarbon Reactions. Chem. Rev. 1995, 95, 559-614. (32) Kozhevnikov, I. V. Heteropoly Acids and Related Compounds as Catalysts for Fine Chemical Synthesis. Catal. Rev. Sci. Eng. 1995, 37, 311-352. (33) Chang, M.-Y.; Chen, Y.-C.; Lin, S.-Y.; Chan, C.-K. One-Pot Synthesis of Sulfonyl (E)-Stilbenes by Nitrobenzene-Mediated Dimerizative Desulfonation of Benzylic Sulfones. Tetrahedron 2014, 70, 1740-1747. (34) Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. One-pot Access to Sulfonylmethyl Arylpyrroles via the Domino Aerobic Wacker-



(35) (36)

(37)

(38)

(39) (40)

(41)

(42)

(43)

(44)

(45)

type Aminocyclization/1,4-Sulfonyl Migration. Org. Lett. 2014, 16, 6252-6255. Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Bi(OTf)3-Mediated Cycloisomerization of γ-Alkynyl Arylketones: Application to the Synthesis of Substituted Furans. Org. Lett. 2015, 17, 1264-1267. Chang, M.-Y.; Cheng, Y.-C.; Lu, Y.-J. Synthesis of Substituted Benzenes via Bi(OTf)3-Mediated Intramolecular Carbonyl Allylation of α-Prenyl or α-Gernyl β-Arylketosulfones. Org. Lett. 2015, 17, 3142-3145. Chang, M.-Y.; Cheng, Y.-C. Synthesis of Substituted Tetralins and Benzosuberans via BF3·OEt2 Mediated Formal (4+2) and (5+2) Stereocontrolled Cycloaddition of 4-Alkenols with Veratrol. Org. Lett. 2016, 18, 608-611. Chang, M.-Y.; Hsiao, Y.-T. H2SO4 Mediated Stereocontrolled Annulation of Sulfonyl 4-Alkenols and Oxygenated Naphthalenes: One-Pot Synthesis of Sulfonyl Tetanthrenes. J. Org. Chem. 2017, 82, 11594-11602. Commercially available Amberlyst-15 is brown-grey solid. The concentration of active sites is 4.7 equiv/kg. CCDC 1909541 (1a), 1909544 (1e), 1909543 (1h), 1909542 (1q), 1909540 (1z), 1909549 (2e), 1909548 (2g), 1909550 (2k), 1909552 (2r), 1909551 (2ai), 1909558 (4n), 1909559 (7l) and 1909557 (9) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-mail: [email protected]). (a) Gung, B. W. Diastereofacial Selection in Nucleophilic Additions to Unsymmetrically Substituted Trigonal Carbons. Tetrahedron 1996, 52, 5263-5301. (b) Chang, M.-Y.; Lu, Y.-J.; Cheng, Y.-C. mCPBA-Mediated Stereoselective Synthesis of Sulfonyl Tetrahydropyrans. Tetrahedron 2015, 71, 1192-1201. For recent synthesis of indatraline, see: (a) Lee, S. W.; Park, S. J.; Kim, I. S.; Jung, Y. H. Asymmetric Total Synthesis of (+)Indatraline via Diastereoselective Amination of Chiral Ethers Using Chlorosulfonyl Isocyanate. Tetrahedron 2013, 69, 1877-1880. (b) Silva, L. F.; Siqueira, F. A.; Pedozo, E. C.; Vieira, F. Y. M.; Doriguetto, A. C. Iodine(III)-Promoted Ring Contraction of 1,2Dihydronaphthalenes: A Diastereoselective Total Synthesis of (±)-Indatraline. Org. Lett. 2007, 9, 1433-1436. Wang, F.; Xu, P.; Wang, S. Y.; Ji, S.-J. Cu(II)/Ag(I)-Catalyzed Cascade Reaction of Sulfonylhydrazone with Anthranils: Synthesis of 2-Aryl-3-sulfonyl Substituted Quinoline Derivatives. Org. Lett. 2018, 20, 2204-2207. Imrich, H.-G.; Conrad, J.; Beifuss, U. Copper-Catalyzed Double Intramolecular Ullmann Coupling for the Synthesis of Diastereomerically and Enantiomerically Pure 4b,9bDihydrobenzofuro[3,2-b]benzofurans. Eur. J. Org. Chem. 2015, 7718-7734. A review on synthesis of chroman, see: Shen, H. C. Asymmetric

Page 30 of 30

Synthesis of Chiral Chromans. Tetrahedron 2009, 65, 3931-3952. (46) (a) Shaikh, M.; Atyam, K. K.; Sahu, M.; Ranganath, K. V. S. Enhanced Reactivity and Selectivity of Asymmetric Oxa-Michael Addition of 2'-Hydroxychalcones in Carbon Confined Spaces. Chem. Commun. 2017, 53, 6029-6032. (b) Ren, X.; Han, C.; Feng, X.; Du, H. A Borane-Catalyzed Metal-Free Hydrosilylation of Chromones and Flavones. Synlett 2017, 28, 2421-2424. (47) A review on synthesis of isoquinoline, see: Chrzanowska, M.; Rozwadowska, M. D. Asymmetric Synthesis of Isoquinoline Alkaloids. Chem. Rev. 2004, 104, 3341-3370. (48) Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Improved Procedure for the Oxidative Cleavage of Olefins by OsO4-NaIO4. Org. Lett. 2004, 6, 3217-3219. (49) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A. Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T. ; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian, Inc.: Wallingford, CT, 2009. Gaussian, Inc., Wallingford CT, 2009. (50) (a) Dunlap, B. I. Fitting the Coulomb Potential Variationally in X-Alpha Molecular Calculations. J. Chem. Phys. 1983, 78, 31403142. (b) Dunlap, B. I. Robust and Variational Fitting: Removing the Four-Center Integrals from Center Stage in Quantum Chemistry. J. Mol. Struct. (Theochem) 2000, 529, 37-40. (51) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and Accurate ab initio Parametrization of Density Functional Dispersion Correction (DFT-D) for the 94 Elements H-Pu. J. Chem. Phys. 2010, 132, 154104. (52) (a) Badenhoop, J. K.; Weinhold, F. Natural Bond Orbital Analysis of Steric Interactions. J. Chem. Phys. 1997, 107, 5406-5421. (b) Badenhoop, J. K.; Weinhold, F. Natural Steric Analysis of Internal Rotation Barriers. Int. J. Quantum Chem. 1999, 72, 269280. (53) Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.; Carpenter, J. E.; Bohmann, J. A.; Morales, C. M.; Landis, C. R.; Weinhold, F. NBO 6.0; Theoretical Chemistry Institute, University of Wisconsin: Madison, WI, 2013; http://nbo6.chem.wisc.edu/.


Synthesis of 2-Sulfonyl Indenes and Indanes

Recommend Documents