Stereocontrolled Construction of 1-Vinylindanes ... - ACS Publications

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Cite This: J. Org. Chem. 2018, 83, 11415−11424

Stereocontrolled Construction of 1‑Vinylindanes via Intramolecular Cyclization of o‑Cinnamyl Chalcones Nein-Chen Hsueh,† Kai-Shang Lai,† and Meng-Yang Chang*,†,‡ †

Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

‡

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ABSTRACT: In this paper, a concise route for the synthesis of 1-vinylindanes is described, including (i) NaBH4-mediated reduction of o-cinnamyl chalcones and (ii) sequential BF3·OEt2-mediated intramolecular annulation of the resulting alkenols. The plausible mechanism is proposed and discussed herein. This protocol provides highly effective stereocontrolled cinnamyl-enone cross-coupling to construct three contiguous trans-trans stereocenters and one (E)-configured alkenyl or styryl group.

T

mediated cationic cycloisomerization of o-yne-enone-conjugated arenes (eq 2).3b For o-benzyl-vinyl arene 3, the Polypradith group explored a BF3·OEt2-mediated cyclization of stilbenyl methanol followed by hydride transfer from Et3SiH.4a The work in our group has involved a Bi(OTf)3mediated intramolecular olefinic cyclization of styryl-tethered benzylic methanol (eq 3).4b With recombining o-bis-arms in the structure of arene to o-ene-enones 4, Luo et al. examined Cu(OTf)2-catalyzed direct intramolecular conjugate addition of o-allyl chalcones (eq 4).5 Despite these advances in domino intramolecular cyclization by the use of two side chains on the arene core, examples of intramolecular cyclization from alkene to enone, a versatile strategy to access carbocycles, are scarce. Therefore, further investigation on the novel annulation mode of o-disubstituted arenes is still highly desired. Continuing our research on the recent efforts on the synthetic applications of o-cinnamyl benzaldehydes 4,6 herein, we present a stereocontrolled construction of 1-vinylindanes via NaBH4-mediated reduction of o-cinnamyl chalcones (prepared from aldol condensation of o-cinnamyl benzaldehydes with methyl ketones in moderate to good yields in the presence of NaOH and MeOH) in a cosolvent of MeOH and THF, followed by BF3·OEt2-promoted intramolecular cyclization of the resulting alcohols in CH2Cl2 (Scheme 1, eq 4). In particular, the formed products possessed three contiguous trans-trans stereocenters and one (E)-configured styryl group. Alkenyl and styryl benzocycles are the key core structures that serve as the building blocks for natural products (e.g., mutisianthol,7a,b jungianol,7c 7,8-dimethoxycalamenene,8a and helioporin E8b) and other bioactive compounds.9 They are also used as versatile intermediates or precursors for the preparation of functionalized molecules, so the development of pioneering strategies for the synthesis of structurally diverse alkenyl or styryl benzocycles is of great importance in the involvement of various Lewis acids, transition metal complexes,

he establishment of efficient methods for the construction of structurally diverse benzocyclic frameworks derived from o-disubstituted arenes via intramolecular sequential multibond formation is an important ongoing research focus under a transition metal-catalyzed or Brønsted/Lewis acidmediated series of domino cyclization processes.1 Among these routes, tandem annulation that makes use of o-diyne- and oyne-enone-conjugated arenes 1 and 2 has emerged as a favorite, thanks to their specific reactivity and diversification (Scheme 1).2,3 For example, Jiang et al. reported a double SO2 Scheme 1. Benzannulated Routes of o-Disubstituted Arenes

insertion/multicomponent bicyclization of arene-linked 1,7diynes with aryldiazonium salts and DABSO.2a The Alabugin group developed a Bu3SnH/AIBN-mediated radical ring closure of benzo-fused o-diynes (eq 1).2b Li et al. demonstrated a CuCl2-catalyzed intramolecular cascade oxidative 6-exo-trig cyclization of aryl-substituted yne-enones with water and molecular oxygen.3a Balamurugan et al. described a TfOH© 2018 American Chemical Society

Received: July 9, 2018 Published: August 18, 2018 11415

DOI: 10.1021/acs.joc.8b01729 J. Org. Chem. 2018, 83, 11415−11424

Note

The Journal of Organic Chemistry or bases.10 By taking advantage of the intramolecular domino cyclization and in view of the success in using two ortho arms on an aromatic ring to achieve unique benzocarbocycles, 4a was chosen as the model substrate to examine the initial study via NaBH4 (1 equiv)-mediated 1,2-reduction and sequential BF3·OEt2 (1 equiv)-promoted intramolecular annulation of the resulting allylic alcohol 5a at 25 °C, as shown in Table 1.11

6a (3%, 5%), as shown in entries 8 and 9. Furthermore, an elongated time (60 min) did not change the yield ratio of 6a and 7a (entry 10). From the results, we found that the diluted reaction concentration (0.05−0.1 M) could generate 7a. Controlling BF3·OEt2 as the Lewis acid, other solvents (CHCl3, (CHCl)2) were tested, and no better yields of 6a (15%, 14%) and 7a (58%, 61%) were observed (entries 11 and 12). On the basis of the above phenomenon, five Lewis acids (AlCl3, FeCl3, BiCl3, InCl3, Cu(OTf)2) were studied next. However, only the complex mixture having chloro products was produced in a range of 69%−78% (entries 13−17). Obviously, this meant that a metal complex was an inappropriate Lewis acid for the annulation due to the stronger reactivity. On the other hand, a Brønsted acid (TfOH) was also studied. However, the product was still complex; no desired 6a or 7a was isolated, and complex results were detected (entry 18). From these observations, we concluded that the combination of BF3·OEt2 (1 equiv) and CH2Cl2 (10 mL) provided optimal conditions (25 °C, 15−30 min) under a 0.1 M reaction concentration condition for a cascade intramolecular ring-closure procedure. Therefore, we thought that BF3·OEt2 is the key driving force to trigger the reaction pathway. On the basis of the experimental results, a plausible mechanism for the formation of 6a and 7a is illustrated in Scheme 2. Initially, NaBH4-mediated reduction of 4a followed

Table 1. Reaction Conditionsa,b

yield (%)c entry

Lewis acid (equiv)

solvent, concentration (M)

temp (°C)

6a

7a

1 2d 3 4 5 6 7 8 9 10e 11 12 13 14 15 16 17 18

BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (0.5) BF3·OEt2 (1.5) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) BF3·OEt2 (1) AlCl3 (1) FeCl3 (1) BiCl3 (1) InCl3 (1) Cu(OTf)2 (1) TfOH (1)

CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.2) CH2Cl2 (0.1) CH2Cl2 (0.05) CH2Cl2 (0.1) CHCl3 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1) CH2Cl2 (0.1)

25 40 0 10 −10 25 25 25 25 25 25 25 25 25 25 25 25 25

20 trace 20 20 18 8 10 3 5 3 15 14 d d d d d d

65 30 63 62 60 32 38 76 72 75 58 61 d d d d d d

Scheme 2. Plausible Mechanism

a

The reduction reactions were run on a 1.0 mmol scale with 4a, NaBH4 (1 equiv), and MeOH/THF (10 mL, v/v = 1:1) for 15 min at 25 °C and were monitored by TLC. bReduction reaction conditions: resulting alcohol 5a, Lewis acid (0.5, 1.5 equiv), solvents, concentration (0.05, 0.1, 0.2 M), 15−30 min, −10 to +40 °C, monitored by TLC. cIsolated yields. dUnknown mixture (entry 2, 50%; entry 13, 69%; entry 14, 76%; entry 15, 78%; entry 16, 70%; entry 17, 71%; entry 18, 65%). e60 min.

However, two products, 6a (a benzodiquinane skeleton)12 and 7a (a 1-vinylindane skeleton), were isolated in 20% and 65% yields, respectively, along with trace amounts of a complex mixture (entry 1). In particular, when the reaction mixture was heated to 40 °C for 15 min in the annulation step, a complex mixture (∼50%) was observed as the major product, and it replaced the desired 6a (trace) and 7a (30%). From the results, we found that a refluxing temperature could cause the decrease of yields (entry 2). With this idea in mind, the temperature was decreased (25 → 10, 0, or −10 °C); the isolated yields of 6a (20%, 20%, 18%) and 7a (63%, 62%, 60%) were similar to 25 °C (entries 3−5). To increase the overall yields of 6a and 7a, the equiv of Lewis acid (BF3·OEt2) from 1 to 0.5 or 1.5 was examined. However, poorer yields of 6a (8%, 10%) and 7a (32%, 38%) were observed (entries 6 and 7). It showed that 1 equiv was suitable under room temperature conditions. Subsequently, when the solvent volume (CH2Cl2) was increased from 5 to 10 or 20 mL, higher yields of 7a (76%, 72%) were obtained than

by BF3-chelated the resulting alcohol 5a yields A1 and A2.13 For the relative configuration of two arms on the aryl ring, A1 is preferred to generate than A2 due to it possessing a transconfigured six-membered chairlike intermediate. According to the formed conformation, the hydroxyl group could be stereoselectively transferred into the benzylic site from the equatorial face via BF3-mediated intramolecular migration. By in situ formed intramolecular dehydroxylative olefin migration on A1, 7a was provided along with the recovery of BF3; two hydrogen groups on 7a could be orientated at that axial position via carbon−carbon and carbon−oxygen bond formations (green marks). Also, the propenyl group on C-1 of the indane skeleton is organized as a trans-conformation. In the pathway of A2, intramolecular olefin migration on two cisconfigured arms forces the removal of BF3−OH to give B2 a secondary benzylic carbocation.13b,c Following the single bond rotation between the propenyl group and indane ring, the double bond of B2′ traps the carbocation to lead to C. After 11416


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The Journal of Organic Chemistry

via one carbon−carbon and one carbon−oxygen bond formations under easy-operational and open-vessel conditions in moderate to good yields (60%−81%). Among entries 1−9, 11, and 12, the efficient formation of 7a−7i and 7k−7l showed that these substituents (Ar = dioxygenated aryl, R = Me, Et, iPr, n-Bu, i-amyl, R′ = Ph) of 4a−4i and 4k−4l did not affect the yield changes (70%−81%), and some trace amounts (3%− 8%) of 6a−6e could be isolated. However, when R was a tbutyl group (for 4j, entry 10), a complex mixture was observed and no desired 7j was isolated due to the t-Bu being unstable in the presence of BF3·OEt2. By changing the alkyl to an aryl group (for R substituent on 4m), entry 13 showed that 7m was provided in a 65% yield. Also, entry 14 showed that a simple Ar (for 4n, no oxygenated group) could afford 73% yield of 7n and 5% yield of 6n. Furthermore, when a methyl (for R′) group was applied to the reaction conditions, a complex mixture was isolated (entry 15). From the results, we understood that R′ = Ph could provide a rich π-electron density to initiate the intramolecular annulation easier than R′ = Me. For the electronic nature of aryl substituents (R) of 4p− 4r and 4t−4w, not only the electron-neutral group (4biphenyl, 2-naphthyl), electron-withdrawing group (4NO2C6H4, 3,4-Cl2C6H3), and electron-donating group (3,4CH2O2C6H3, 3,4,5-(MeO)3C6H2) but also a heterocyclic ring (2-thienyl) were suitable and the yields of 7p−7r and 7t−7w were distributed in a range from 66% to 73% (entries 16−18 and 20−23). However, the 2-pyridyl group (for 4s) produced a complex mixture due to the lone pair of nitrogen atoms caused (entry 19). For aryl substituents (Ar) of 4x and 4y, both the electron-donating 5-methoxy group and electron-withdrawing 4-fluoro group were well-tolerated; 7x and 7y were produced in 64% and 60% yields, respectively (entries 24 and 25). An 8% yield of 6y was obtained. To change the position of the dioxygenated group from 4,5- to 3,5-, 4z and 4aa were converted into 7z and 7aa in 72% and 70% yields, respectively (entries 26 and 27). A 6% yield of 6z was obtained. Strangely, many attempts to afford 7ab failed (entry 28). Furthermore, the relative stereochemical structures of 6n and 7p were determined by single-crystal X-ray crystallography.14 In summary, we developed a two-step approach to construct the skeleton of 1-vinylindanes 7 having three contiguous transtrans stereocenters and one (E)-configured alkenyl or styryl group via (1) NaBH4-mediated 1,2-reduction of o-cinnamyl chalcones 4 in a cosolvent of MeOH and THF at 25 °C within 30 min and (2) BF3·OEt2-mediated intramolecular annulation of the resulting alkenols in CH2Cl2 at 25 °C for 30 min. The stereocontrolled process provides a straightforward pathway for one carbon−oxygen bond formation and one carbon− carbon bond formation. The substrate scope and limitations were investigated for the facile and efficient transformation. Related plausible mechanisms have been proposed. The structures of the key products were confirmed by X-ray crystallography. Further investigations regarding the synthetic application of o-cinnamyl benzaldehydes will be conducted and published in due course.

the 1,2-hydride shift of C and deprotonation of D, 6a with a tricyclic benzodiquinane skeleton is obtained. For the formation of 6a and 7a, the reaction mechanism not only explains the stereospecific orientation of 7a (three contiguous trans-trans chiral centers and E-olefin) and 6a (cis-ring junction) but also demonstrates 7a as the domain isomer. We envisioned that the temperature efficiently controlled the formation of the BF3-chelated intermediate and increased the yield of generation of 7a. From the proposed mechanism (Scheme 2) and reaction conditions (Table 1, entry 6), we understood that intramolecular cyclization of o-cinnamyl benzaldehydes could be catalyzed by BF3·OEt2; however, 1 equiv of BF3·OEt2 owned enough amounts to promote the cyclization efficiently and obtain satisfied results (Table 1, entry 8). To study the scope and limitations of this two-step approach, 4 was reduced with NaBH4 followed by BF3·OEt2-mediated intramolecular annulation of the resulting alcohol 5a to afford diversified 7 along with trace amounts of 6, as shown in Table 2. With optimal conditions established (Table 1, entry 8), we found that this latter route allowed a novel intramolecular annulation fashion Table 2. Synthesis of 7a

entry

4, Ar =, R =, R′ =

7, (%)b

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

4a, 4-MeO-5-HOC6H2, Me, Ph 4b, 4,5-(MeO)2C6H2, Me, Ph 4c, 4-MeO-5-allylOC6H2, Me, Ph 4d, 4-MeO-5-n-BuOC6H2, Me, Ph 4e, 4-MeO-5-BnOC6H2, Me, Ph 4f, 4-MeO-5-cC5H9OC6H2, Me, Ph 4g, 4-MeO-5-i-PrOC6H2, Me, Ph 4h, 4,5-(MeO)2C6H2, Et, Ph 4i, 4,5-(MeO)2C6H2, i-Pr, Ph 4j, 4,5-(MeO)2C6H2, t-Bu, Ph 4k, 4,5-(MeO)2C6H2, n-Bu, Ph 4l, 4,5-(MeO)2C6H2, (CH2)2CHMe2, Ph 4m, 4,5-(MeO)2C6H2, Ph, Ph 4n, Ph, Me, Ph 4o, 4,5-(MeO)2C6H2, Me, Me 4p, 4,5-(MeO)2C6H2, 3,4-CH2O2C6H3, Ph 4q, 4,5-(MeO)2C6H2, 4-PhC6H4, Ph 4r, 4,5-(MeO)2C6H2, 2-naphthyl, Ph 4s, 4,5-(MeO)2C6H2, 2-pyridyl, Ph 4t, 4,5-(MeO)2C6H2, 3,4-Cl2C6H3, Ph 4u, 4,5-(MeO)2C6H2, 3,4,5-(MeO)3C6H2, Ph 4v, 4,5-(MeO)2C6H2, 2-thienyl, Ph 4w, 4,5-(MeO)2C6H2, 4-NO2C6H4, Ph 4x, 5-MeOC6H3, Me, Ph 4y, 4-FC6H3, Me, Ph 4z, 3,5-(MeO)2C6H2, Me, Ph 4aa, 3-MeO-5-nBuOC6H2, Me, Ph 4ab, 3-MeO-5-BnOC6H2, Me, Ph

7a, 76 7b, 80 7c, 81 7d, 73 7e, 70 7f, 76 7g, 78 7h, 74 7i, 70 7jc 7k, 70 7l, 73 7m, 65 7n, 73 7oc 7p, 68 7q, 70 7r, 66 7sc 7t, 67 7u, 70 7v, 73 7w, 73 7x, 64 7y, 60 7z, 72 7aa, 70 7abc

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EXPERIMENTAL SECTION

General. All other reagents and solvents were obtained from commercial sources and used without further purification. Reactions were routinely carried out under an atmosphere of dry nitrogen with magnetic stirring. Products in organic solvents were dried with anhydrous magnesium sulfate before concentration in vacuo. Melting points were determined with a SMP3 melting apparatus. 1H and 13C

a

The reactions were run on a 1.0 mmol scale with 4a−4ab, NaBH4 (1.0 equiv), and MeOH/THF (v/v = 1:1, 10 mL) at 25 °C for 15−30 min, then BF3·OEt2 (1.0 equiv) and CH2Cl2 (10 mL) at 25 °C for 15−30 min. bIsolated yields. cComplex mixture. d6 was isolated (for 6a, 3%; 6b, 6n, 5%; 6c, 6z, 6%; 6d, 6y, 8%; 6e, 7%). 11417


Note


16.0 Hz, 1H), 5.16 (s, 2H), 3.91 (s, 3H), 3.65 (d, J = 5.2 Hz, 2H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 151.9, 147.0, 140.4, 137.1, 136.7, 134.2, 131.4, 128.6 (3x), 128.5 (2x), 128.0, 127.4 (2x), 127.3, 126.3, 126.1 (2x), 125.3, 113.4, 111.8, 71.3, 56.0, 36.4, 27.4. 4-[5-Cyclopentyloxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3en-2-one (4f): 87% yield (327 mg); colorless solid; mp 88−90 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C25H28O3Na 399.1936, found 399.1929; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 16.0 Hz, 1H), 7.34−7.25 (m, 4H), 7.21−7.17 (m, 1H), 7.15 (s, 1H), 6.75 (s, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.38 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 4.82− 4.78 (m, 1H), 3.86 (s, 3H), 3.65 (d, J = 5.6 Hz, 2H), 2.35 (s, 3H), 2.01−1.80 (m, 6H), 1.67−1.60 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 198.2, 152.2, 146.4, 140.6, 137.0, 133.4, 131.1, 128.6, 128.4 (2x), 127.1, 126.0, 125.9 (2x), 125.1, 113.3, 112.4, 80.5, 55.8, 36.2, 32.6 (2x), 27.1, 23.9 (2x). 4-[5-Isopropoxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4g): 81% yield (284 mg); colorless gum; HRMS (ESI-TOF) m/ z [M + Na]+ calcd for C23H26O3Na 373.1780, found 373.1775; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 16.0 Hz, 1H), 7.34−7.26 (m, 4H), 7.22−7.19 (m, 1H), 7.18 (s, 1H), 6.76 (s, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.39 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 4.58−4.52 (m, 1H), 3.88 (s, 3H), 3.66 (d, J = 5.6 Hz, 2H), 2.35 (s, 3H), 1.39 (d, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 198.3, 152.6, 146.0, 140.5, 137.0, 133.9, 131.2, 128.6, 128.4 (2x), 127.2, 126.1, 126.0 (2x), 125.2, 113.5, 113.4, 71.6, 55.8, 36.3, 27.2, 22.0 (2x). 1-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]pent-1-en-3-one (4h): 78% yield (262 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C22H24O3Na 359.1623, found 359.1618; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 16.0 Hz, 1H), 7.33−7.26 (m, 4H), 7.22−7.18 (m, 1H), 7.12 (s, 1H), 6.75 (s, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 3.66 (d, J = 5.2 Hz, 2H), 2.68 (q, J = 7.6 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.9, 151.1, 147.9, 139.3, 137.1, 133.7, 131.3, 128.7, 128.5 (2x), 127.2, 126.1 (2x), 125.4, 125.2, 113.0, 108.7, 56.0, 55.9, 36.3, 33.7, 8.3. 1-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-4-methylpent-1-en3-one (4i): two isomers (ratio of EE/EZ = 1:1); 68% yield (238 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H26O3Na 373.1780, found 373.1775. One isomer: 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 16.0 Hz, 1H), 7.35−7.18 (m, 5H), 7.13 (s, 1H), 6.75 (s, 1H), 6.59 (d, J = 16.4 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.66 (d, J = 5.6 Hz, 2H), 2.99−2.88 (m, 1H), 1.16 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 190.6, 151.1, 148.5, 139.8, 132.5, 131.3, 128.7 (2x), 127.6, 126.3, 126.1 (2x), 125.6, 124.2, 112.9, 109.3, 108.8, 56.0, 55.9, 39.6, 38.8, 18.6 (2x). 1-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-4,4-dimethylpent-1en-3-one (4j): 45% yield (164 mg); colorless gum; HRMS (ESITOF) m/z [M + Na]+ calcd for C24H28O3Na 387.1936, found 387.1930; 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 15.6 Hz, 1H), 7.33−7.25 (m, 4H), 7.20−7.16 (m, 1H), 7.11 (s, 1H), 6.93 (d, J = 15.6 Hz, 1H), 6.75 (s, 1H), 6.36 (d, J = 16.0 Hz, 1H), 6.30 (dt, J = 5.2, 16.0 Hz, 1H), 3.94 (s, 3H), 3.90 (s, 3H), 3.65 (d, J = 5.2 Hz, 2H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 204.1, 151.0, 147.7, 140.1, 137.3, 134.1, 131.3, 128.7, 128.4 (2x), 127.1, 126.1 (2x), 125.9, 120.0, 113.0, 109.2, 56.1, 55.9, 43.1, 36.2, 26.4 (3x). 1-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]hept-1-en-3-one (4k): 67% yield (244 mg); colorless solid; mp 182−184 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H28O3Na 387.1936, found 387.1929; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 16.0 Hz, 1H), 7.32−7.24 (m, 4H), 7.20−7.16 (m, 1H), 7.12 (s, 1H), 6.75 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H), 3.65 (d, J = 5.2 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H), 1.67− 1.60 (m, 2H), 1.37−1.28 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.6, 151.0, 147.8, 139.3, 137.0, 133.6, 131.2,

NMR spectra were recorded on a Varian INOVA-400 spectrometer operating at 400 and at 100 MHz, respectively. Chemical shifts (δ) are reported in parts per million (ppm), and the coupling constants (J) are given in hertz. High-resolution mass spectra (HRMS) were measured with a mass spectrometer, Finnigan/Thermo Quest MAT 95XL. X-ray crystal structures were obtained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa CCD). Representative Synthetic Procedure of Skeleton 4. Sodium hydroxide (NaOH, 100 mg, 2.5 mmol) was added to a solution of methyl ketones (1.2 mmol) in MeOH (10 mL) at 25 °C. A solution of o-cimmanyl benzaldehydes (1.0 mmol) in THF (10 mL) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at 25 °C for 20−28 h (monitored by TLC). The solvent was concentrated under reduced pressure. The residue was diluted with water (10 mL), and the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product. Purification on silica gel (hexanes/EtOAc = 10:1 to 6:1) afforded skeleton 4. 4-[5-Hydroxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4a): 73% yield (225 mg); colorless gum; HRMS (ESI-TOF) m/ z [M + Na]+ calcd for C20H20O3Na 331.1310, found 331.1306; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 15.6 Hz, 1H), 7.33−7.26 (m, 4H), 7.24 (s, 1H), 7.22−7.17 (m, 1H), 6.73 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.30 (dt, J = 5.2, 16.0 Hz, 1H), 6.11 (br s, 1H), 3.88 (s, 3H), 3.64 (d, J = 5.2 Hz, 2H), 2.33 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 198.5, 148.8, 144.5, 140.3, 137.6, 132.8, 131.1, 128.7, 128.4 (2x), 127.1, 126.1, 126.0 (2x), 125.8, 112.3, 112.1, 55.8, 36.2, 27.5. 4-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]but-3-en-2-one (4b): 82% yield (264 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H22O3Na 345.1467, found 345.1459; 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 16.0 Hz, 1H), 7.33−7.26 (m, 4H), 7.22−7.17 (m, 1H), 7.13 (s, 1H), 6.75 (s, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.37 (d, J = 16.4 Hz, 1H), 6.31 (dt, J = 5.2, 16.4 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H), 3.66 (d, J = 5.2 Hz, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 151.2, 147.9, 140.4, 137.0, 133.6, 131.3, 128.6, 128.5 (2x), 127.3, 126.2, 126.0 (2x), 125.3, 113.0, 108.7, 55.92, 55.90, 26.3, 27.3. 4-[5-Allyloxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2-one (4c): 84% yield (292 mg); colorless solid; mp 114−116 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H24O3Na 371.1623, found 371.1620; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 16.0 Hz, 1H), 7.33−7.26 (m, 4H), 7.22−7.18 (m, 1H), 7.14 (s, 1H), 6.76 (s, 1H), 6.51 (d, J = 16.0 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.30 (dt, J = 5.2, 16.0 Hz, 1H), 6.14−6.05 (m, 1H), 5.43 (dq, J = 1.6, 17.2 Hz, 1H), 5.32 (dq, J = 1.6, 10.4 Hz, 1H), 4.64 (dt, J = 1.2, 5.2 Hz, 2H), 3.90 (s, 3H), 3.66 (d, J = 5.2 Hz, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 151.7, 146.8, 140.5, 137.1, 134.0, 133.0, 131.3, 128.6, 128.5 (2x), 127.3, 126.3, 126.1 (2x), 125.2, 118.3, 113.3, 111.1, 70.0, 55.9, 36.4, 27.3. 4-[5-n-Butoxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4d): 86% yield (313 mg); colorless solid; mp 103−104 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H28O3Na 387.1936, found 387.1928; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 16.0 Hz, 1H), 7.33−7.26 (m, 4H), 7.22−7.18 (m, 1H), 7.13 (s, 1H), 6.75 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 4.04 (t, J = 6.8 Hz, 2H), 3.89 (s, 3H), 3.65 (d, J = 5.2 Hz, 2H), 2.35 (s, 3H), 1.88−1.81 (m, 2H), 1.56−1.47 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 198.4, 151.7, 147.5, 140.6, 137.1, 133.6, 131.3, 128.7, 128.5 (2x), 127.3, 126.2, 126.1 (2x), 125.2, 113.3, 110.4, 68.9, 56.0, 36.4, 31.2, 27.2, 19.2, 13.8. 4-[5-Benzyloxy-4-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4e): 85% yield (338 mg); colorless solid; mp 123−125 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H26O3Na 421.1780, found 421.1775; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 16.0 Hz, 1H), 7.48−7.47 (m, 2H), 7.41−7.26 (m, 7H), 7.23−7.18 (m, 1H), 7.17 (s, 1H), 6.77 (s, 1H), 6.44 (d, J = 16.0 Hz, 1H), 6.37 (d, J = 16.0 Hz, 1H), 6.30 (dt, J = 5.2, 11418


Note


°C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C30H26O3Na 457.1780, found 457.1773; 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 8.16 (d, J = 16.0 Hz, 1H), 8.07 (dd, J = 1.6, 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.89 (d, J = 8.0 Hz, 1H), 7.60 (dt, J = 1.2, 8.4 Hz, 1H), 7.54 (dt, J = 1.2, 8.4 Hz, 1H), 7.47 (d, J = 15.6 Hz, 1H), 7.31−7.24 (m, 5H), 7.21−7.17 (m, 1H), 6.79 (s, 1H), 6.34−6.32 (m, 2H), 4.00 (s, 3H), 3.94 (s, 3H), 3.69 (d, J = 3.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 190.8, 151.4, 147.9, 142.2, 137.2, 135.8, 135.3, 134.4, 132.5, 131.3, 129.8, 129.4, 128.7, 128.5 (2x), 128.4, 128.2, 127.8, 127.2, 126.7, 126.1 (2x), 125.9, 124.6, 121.7, 113.1, 109.2, 56.2, 56.0, 36.3. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-1-pyridin-2-ylpropenone (4s): 87% yield (335 mg); colorless solid; mp 159−161 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C25H23NO3Na 408.1576, found 408.1566; 1H NMR (400 MHz, CDCl3) δ 8.74−8.73 (m, 1H), 8.30 (d, J = 15.6 Hz, 1H), 8.18 (dt, J = 1.6, 8.0 Hz, 1H), 8.11 (d, J = 15.6 Hz, 1H), 7.87 (dt, J = 1.6, 8.0 Hz, 1H), 7.48 (ddd, J = 1.2, 4.8, 8.0 Hz, 1H), 7.38 (s, 1H), 7.34−7.31 (m, 2H), 7.28−7.23 (m, 2H), 7.20−7.15 (m, 1H), 6.77 (s, 1H), 6.39 (d, J = 16.0 Hz, 1H), 6.33 (dt, J = 5.6, 16.0 Hz, 1H), 3.98 (s, 3H), 3.92 (s, 3H), 3.74 (d, J = 4.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 189.3, 154.5, 151.4, 148.7, 147.8, 141.9, 137.3, 137.0, 134.8, 131.3, 128.9, 128.4 (2x), 127.1, 126.7, 126.2 (2x), 126.1, 122.9, 119.6, 112.8, 109.2, 56.2, 55.9, 36.2. 1-(3,4-Dichlorophenyl)-3-[4,5-dimethoxy-2-(3-phenylallyl)phenyl]propenone (4t): 73% yield (330 mg); colorless solid; mp 134−136 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + Na]+ calcd for C26H22Cl2O3Na 475.0844, found 475.0836; 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 15.2 Hz, 1H), 8.05 (d, J 2.0 Hz, 1H), 7.78 (dd, J = 2.0, 8.0 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.32−7.17 (m, 7H), 6.78 (s, 1H), 6.32−6.30 (m, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3.67 (dd, J = 2.0, 4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 188.3, 151.7, 147.9, 143.2, 138.0, 137.0, 136.9, 134.8, 133.1, 131.4, 130.5, 130.3, 128.5, 128.4 (2x), 127.5, 127.2, 126.1 (2x), 125.4, 120.2, 113.0, 109.0, 56.1, 55.9, 36.2. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-1-(3,4,5trimethoxyphenyl)propenone (4u): 86% yield (408 mg); colorless solid; mp 70−72 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C29H30O6Na 497.1940, found 497.1935; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 15.2 Hz, 1H), 7.31−7.17 (m, 9H), 6.78 (s, 1H), 6.32−6.31 (m, 2H), 3.95 (s, 3H), 3.92 (s, 3H), 3.91 (s, 3H), 3.88 (s, 6H), 3.67 (d, J = 5.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 189.6, 153.0 (2x), 151.3, 147.8, 142.2, 142.1, 137.1, 134.2, 133.7, 131.3, 128.6, 128.4 (2x), 127.2, 126.0 (2x), 125.9, 121.5, 113.0, 109.4, 106.0 (2x), 60.9, 50.3 (2x), 56.1, 55.9, 36.2. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-1-thiophen-2-ylpropenone (4v): 84% yield (328 mg); colorless solid; mp 145−148 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H22O3SNa 413.1187, found 413.1179; 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 15.2 Hz, 1H), 7.84 (dd, J = 1.2, 4.0 Hz, 1H), 7.63 (dd, J = 1.2, 4.8 Hz, 1H), 7.33−7.11 (m, 8H), 6.78 (s, 1H), 6.39−6.32 (m, 2H), 3.96 (s, 3H), 3.91 (s, 3H), 3.68 (d, J = 5.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 182.0, 151.3, 147.7, 145.5, 144.1, 141.1, 137.1, 134.4, 133.5, 131.5, 131.2, 128.6, 128.3 (2x), 128.0, 127.1, 126.0 (2x), 120.7, 112.9, 108.9, 56.0, 55.8, 36.1. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-1-(4-nitrophenyl)propenone (4w): 72% yield (309 mg); colorless solid; mp 164−166 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H23NO5Na 452.1474, found 452.1467; 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 15.2 Hz, 1H), 8.05 (d, J = 9.2 Hz, 2H), 7.31−7.18 (m, 7H), 6.79 (s, 1H), 6.31−6.29 (m, 2H), 3.97 (s, 3H), 3.94 (s, 3H), 3.67 (d, J = 4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 189.6, 152.0, 149.8, 148.0, 144.1, 143.4, 137.0, 135.0, 131.4, 129.4 (2x), 128.54, 128.52 (2x), 127.4, 126.1 (2x), 125.2, 123.7 (2x), 120.7, 113.2, 108.9, 56.1, 56.0, 36.3. 4-[5-Methoxy-2-(3-phenylallyl)phenyl]but-3-en-2-one (4x): two isomers (ratio of EE/EZ = 8:1); 70% yield (204 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C20H20O2Na 315.1361,

128.6, 128.4, 127.2 (2x), 126.0 (2x), 125.44, 125.40, 112.9, 108.7, 55.9, 55.8, 40.3, 36.3, 26.6, 22.4, 13.8. 1-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-6-methylhept-1-en3-one (4l): 72% yield (272 mg); colorless solid; mp 99−101 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C25H30O3Na 401.2093, found 401.2086; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 16.0 Hz, 1H), 7.33−7.25 (m, 4H), 7.21−7.17 (m, 1H), 7.13 (s, 1H), 6.75 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 6.31 (dt, J = 5.2, 16.0 Hz, 1H), 3.92 (s, 3H), 3.91 (s, 3H), 3.66 (d, J = 5.2 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 1.60−1.52 (m, 3H), 0.90 (d, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 200.8, 151.1, 147.8, 139.4, 137.1, 133.7, 131.2, 128.6, 128.4 (2x), 127.2, 126.1 (2x), 126.0, 125.4, 113.0, 108.7, 56.0, 55.9, 38.7, 36.3, 33.4, 27.8, 22.3 (2x). 3-[4,5-Dimethoxy-2-(3-phenylallyl)-phenyl]-1-phenylpropenone (4m): 90% yield (346 mg); colorless solid; mp 128−130 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H24O3Na 407.1623, found 407.1618; 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 15.6 Hz, 1H), 8.01−7.97 (m, 2H), 7.58−7.54 (m, 1H), 7.51−7.44 (m, 2H), 7.35−7.25 (m, 6H), 7.21−7.17 (m, 1H), 6.78 (s, 1H), 6.37−6.28 (m, 2H), 3.97 (s, 3H), 3.92 (s, 3H), 3.68 (d, J = 4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 190.9, 151.3, 147.8, 142.1, 138.4, 137.1, 134.3, 132.5, 131.2, 128.6, 128.5 (2x), 128.43 (2x), 128.41 (2x), 127.2, 126.1 (2x), 125.8, 121.5, 112.9, 108.9, 56.0, 55.9, 36.2. 4-[2-(3-Phenylallyl)phenyl]but-3-en-2-one (4n): 74% yield (194 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H18ONa 285.1255, found 285.1259. Major product: 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 16.0 Hz, 1H), 7.65−7.63 (m, 1H), 7.41−7.28 (m, 7H), 7.24−7.20 (m, 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.42 (d, J = 16.0 Hz, 1H), 6.35 (dt, J = 6.0, 16.0 Hz, 1H), 3.71 (d, J = 6.0 Hz, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.0, 140.5, 139.4, 136.9, 133.2, 131.4, 130.3, 130.2, 128.33 (2x), 128.28, 128.2, 127.1, 126.9, 126.5, 125.9 (2x), 36.6, 27.4. 4-(2-But-2-enyl-4,5-dimethoxyphenyl)but-3-en-2-one (4o): 78% yield (203 mg); colorless solid; mp 65−66 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C16H20O3Na 283.1310, found 283.1306; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 16.0 Hz, 1H), 7.05 (s, 1H), 6.65 (s, 1H), 6.51 (d, J = 16.0 Hz, 1H), 5.55−5.48 (m, 1H), 5.44−5.36 (m, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.39 (d, J = 6.0 Hz, 2H), 2.33 (s, 3H), 4.63 (dd, J = 1.6, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 151.0, 147.5, 140.6, 134.5, 129.4, 126.6, 125.9, 124.9, 112.7, 108.5, 55.79, 55.74, 36.0, 27.1, 17.7. 1-Benzo[1,3]dioxol-5-yl-3-[4,5-dimethoxy-2-(3-phenylallyl)phenyl]propenone (4p): 84% yield (360 mg); colorless solid; mp 139−141 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + Na]+ calcd for C27H24O5Na 451.1522, found 451.1514; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 15.6 Hz, 1H), 7.61 (dd, J = 1.6, 8.0 Hz, 1H), 7.51 (d, J = 1.6 Hz, 1H), 7.33−7.17 (m, 7H), 6.88 (d, J = 8.0 Hz, 1H), 6.77 (s, 1H), 6.38−6.32 (m, 2H), 6.05 (s, 2H), 3.96 (s, 3H), 3.92 (s, 3H), 3.70 (d, J = 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 188.5, 151.5, 151.2, 148.2, 147.8, 141.5, 137.2, 134.2, 133.1, 131.3, 128.7, 128.4 (2x), 127.2, 126.1 (2x), 125.9, 124.6, 121.1, 113.0, 109.0, 108.4, 107.8, 101.8, 56.1, 55.9, 36.2. 1-Biphenyl-4-yl-3-[4,5-dimethoxy-2-(3-phenylallyl)phenyl]propenone (4q): two isomers (ratio of EE/EZ = 10:1); 89% yield (409 mg); colorless solid; mp 145−147 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C32H28O3Na 483.1936, found 483.1930. Major products: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 15.2 Hz, 1H), 8.09 (d, J = 8.8 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.64−7.61 (m, 2H), 7.49−7.38 (m, 4H), 7.35−7.25 (m, 5H), 7.21−7.18 (m, 1H), 6.80 (s, 1H), 6.41− 6.35 (m, 2H), 3.99 (s, 3H), 3.92 (s, 3H), 3.69 (d, J = 4.4 Hz, 2H); 13 C NMR (100 MHz, CDCl3) δ 190.1, 151.2, 147.7, 144.9, 141.8, 139.7, 137.0, 136.9, 134.2, 131.1, 129.0 (2x), 128.7 (2x), 128.5, 128.3 (2x), 128.0, 127.0 (3x), 126.9 (2x), 126.0 (2x), 125.7, 121.2, 112.8, 108.8, 55.9, 55.7, 36.1. 3-[4,5-Dimethoxy-2-(3-phenylallyl)phenyl]-1-naphthalen-2-ylpropenone (4r): 88% yield (382 mg); colorless solid; mp 168−170 11419


Note

The Journal of Organic Chemistry found 315.1357. Major product: 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 16.0 Hz, 1H), 7.33−7.26 (m, 4H), 7.22−7.18 (m, 2H), 7.13 (d, J = 2.4 Hz, 1H), 6.93 (dd, J = 2.4, 8.4 Hz, 1H), 6.63 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.4 Hz, 1H), 6.31 (dt, J = 10.4, 16.4 Hz, 1H), 3.83 (s, 3H), 3.64 (d, J = 5.2 Hz, 2H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.3, 158.4, 140.8, 134.3, 131.9, 131.5, 131.2, 129.9, 128.8, 128.6, 128.5 (2x), 127.2, 126.0 (2x), 116.5, 111.2, 55.3, 36.0, 27.5. 4-[4-Fluoro-2-(3-phenylallyl)phenyl]but-3-en-2-one (4y): 67% yield (188 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H17FONa 303.1161, found 303.1158. Major product: 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 16.0 Hz, 1H), 7.60 (dd, J = 5.6, 8.4 Hz, 1H), 7.35−7.28 (m, 3H), 7.24−7.20 (m, 2H), 7.03−6.96 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.29 (dt, J = 10.4, 15.6 Hz, 1H), 3.68 (d, J = 6.4 Hz, 2H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 197.9, 163.8 (d, J = 249.4 Hz), 142.3 (d, J = 7.5 Hz), 139.4, 136.8, 132.1, 129.5 (d, J = 3.0 Hz), 128.6 (d, J = 8.3 Hz), 128.5 (2x), 128.1 (d, J = 1.5 Hz), 127.4, 127.2, 126.1 (2x), 117.0 (d, J = 21.3 Hz), 114.2 (d, J = 21.2 Hz), 36.5, 27.7. 4-[3,5-Dimethoxy-2-(3-phenylallyl)phenyl]but-3-en-2-one (4z): 70% yield (225 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H22O3Na 345.1467, found 345.1460; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 16.4 Hz, 1H), 7.31−7.24 (m, 4H), 7.19−7.15 (m, 1H), 6.72 (d, J = 2.4 Hz, 1H), 6.62 (d, J = 16.0 Hz, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.32−6.27 (m, 2H), 3.843 (s, 3H), 3.836 (s, 3H), 3.67 (d, J = 4.4 Hz, 2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.4, 159.1, 158.6, 141.3, 137.4, 135.0, 130.1, 129.1, 128.7, 128.4 (2x), 126.9, 126.0 (2x), 121.1, 101.7, 100.6, 55.8, 55.4, 28.5, 27.3. 4-[5-n-Butoxy-3-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4aa): 67% yield (244 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H28O3Na 387.1936, found 387.1931; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 16.4 Hz, 1H), 7.33−7.22 (m, 4H), 7.20−7.15 (m, 1H), 6.73 (d, J = 2.4 Hz, 1H), 6.62 (d, J = 16.0 Hz, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.34−6.25 (m, 2H), 4.00 (t, J = 7.2 Hz, 2H), 3.84 (s, 3H), 3.67 (d, J = 4.4 Hz, 2H), 2.37 (s, 3H), 1.84− 1.77 (m, 2H), 1.58−1.49 (m, 2H), 1.01 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 198.4, 158.59, 158.57, 141.4, 137.4, 134.9, 130.0, 129.0, 128.7, 128.3 (2x), 126.9, 125.9 (2x), 120.8, 102.4, 101.1, 67.8, 55.7, 31.3, 28.5, 27.3, 19.2, 13.8. 4-[5-Benzyloxy-3-methoxy-2-(3-phenylallyl)phenyl]but-3-en-2one (4ab): 70% yield (279 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H26O3Na 421.1780, found 421.1776; 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 16.0 Hz, 1H), 7.49−7.17 (m, 10H), 6.82 (d, J = 2.4 Hz, 1H), 6.64 (d, J = 2.4 Hz, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.35−6.28 (m, 2H), 5.10 (s, 2H), 3.83 (s, 3H), 3.68 (d, J = 4.8 Hz, 2H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.4, 158.6, 158.2, 141.3, 137.4, 136.6, 135.1, 130.1, 129.1, 128.6 (2x), 128.4 (2x), 128.3, 128.1, 127.6 (2x), 126.9, 126.0 (2x), 121.3, 102.8, 101.4, 70.2, 55.8, 28.6, 27.4. Representative Synthetic Procedure of Skeletons 6 and 7. Sodium borohydride (NaBH4, 38 mg, 1.0 mmol) was added to a solution of skeleton 4 (1.0 mmol) in a cosolvent of MeOH and THF (10 mL, v/v = 1:1) at 25 °C. The reaction mixture was stirred at 25 °C for 15−30 min (monitored by TLC). The solvent was concentrated under reduced pressure. The residue was diluted with water (10 mL), and the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product. Without further purification, boron trifluoride etherate (BF3·OEt2, 142 mg, 1.0 mmol) was added to a solution of the resulting products in CH2Cl2 (10 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 15−30 min (monitored by TLC). The solvent was concentrated under reduced pressure. The residue was diluted with water (10 mL), and the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product. Purification on silica gel (hexanes/EtOAc = 25:1 to 10:1) afforded skeletons 6 and 7. 6-Methoxy-2-methyl-1-phenyl-3,3a,8,8a-tetrahydrocyclopenta[a]inden-5-ol (6a): Table 1, entry 8, 3% yield (9 mg); colorless solid;

mp 114−116 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C20H20O2Na 315.1361, found 315.1358; 1H NMR (400 MHz, CDCl3) δ 7.32−7.28 (m, 2H), 7.22− 7.17 (m, 3H), 6.80 (s, 1H), 6.54 (s, 1H), 5.47 (s, 1H), 4.08−4.03 (m, 1H), 3.81−3.74 (m, 1H), 3.77 (s, 3H), 2.97 (dd, J = 8.8, 16.0 Hz, 1H), 2.93 (dd, J = 8.8, 16.0 Hz, 1H), 2.60 (d, J = 16.0 Hz, 1H), 2.56 (d, J = 16.0 Hz, 1H), 1.69 (br t, J = 0.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.8, 144.6, 140.3, 137.9, 137.8, 133.8, 133.4, 128.5 (2x), 128.0 (2x), 126.1, 110.0, 107.0, 56.0, 52.9, 46.3, 45.7, 36.8, 15.4. 5,6-Dimethoxy-2-methyl-1-phenyl-3,3a,8,8atetrahydrocyclopenta[a]indene (6b): 5% yield (15 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H22O2Na 329.1518, found 329.1510; 1H NMR (400 MHz, CDCl3) δ 7.38−7.34 (m, 2H), 7.26−7.22 (m, 3H), 6.82 (s, 1H), 6.61 (s, 1H), 4.16−4.10 (m, 1H), 3.90 (s, 3H), 3.89−3.84 (m, 1H), 3.81 (s, 3H), 3.04 (dd, J = 8.8, 16.0 Hz, 1H), 3.01 (dd, J = 8.4, 16.4 Hz, 1H), 2.67 (d, J = 16.0 Hz, 1H), 2.64 (d, J = 16.4 Hz, 1H), 1.76 (br t, J = 1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.3, 148.2, 139.3, 137.9, 137.8, 133.9, 133.6, 128.4 (2x), 128.0 (2x), 126.1, 107.7, 107.3, 56.0, 55.9, 52.9, 46.3, 45.9, 36.8, 15.4. 5-Allyloxy-6-methoxy-2-methyl-1-phenyl-3,3a,8,8atetrahydrocyclopenta[a]indene (6c): 6% yield (20 mg); colorless solid; mp 60−63 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H24O2Na 355.1674, found 355.1671; 1H NMR (400 MHz, CDCl3) δ 7.39−7.35 (m, 2H), 7.32− 7.23 (m, 3H), 6.53 (s, 1H), 6.12−6.02 (m, 1H), 5.60 (s, 1H), 5.10 (dq, J = 1.6, 17.2 Hz, 1H), 5.07 (dq, J = 1.6, 10.0 Hz, 1H), 4.18−4.12 (m, 1H), 4.02 (dt, J = 4.0, 9.6 Hz, 1H), 3.82 (s, 3H), 3.54 (ddt, J = 1.6, 6.0, 15.2 Hz, 1H), 3.44 (ddt, J = 1.6, 6.0, 15.2 Hz, 1H), 3.06 (dd, J = 9.6, 16.0 Hz, 1H), 3.02 (dd, J = 9.6, 16.0 Hz, 1H), 2.62 (dd, J = 4.0, 16.0 Hz, 1H), 2.62 (dt, J = 2.4, 16.4 Hz, 1H), 1.76 (br t, J = 1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.8, 142.6, 139.0, 138.0, 136.2, 133.5, 132.8, 128.5 (3x), 128.1 (2x), 126.2, 121.2, 114.8, 105.2, 56.0, 52.8, 47.1, 45.2, 38.0, 31.8, 15.3. 5-Butoxy-6-methoxy-2-methyl-1-phenyl-3,3a,8,8atetrahydrocyclopenta[a]indene (6d): 8% yield (28 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H28O2Na 371.1987, found 371.1981; 1H NMR (400 MHz, CDCl3) δ 7.40−7.36 (m, 2H), 7.29−7.24 (m, 3H), 6.85 (s, 1H), 6.63 (s, 1H), 4.18−4.12 (m, 1H), 4.06 (t, J = 6.8 Hz, 2H), 3.87 (t, J = 7.2 Hz, 1H), 3.81 (s, 3H), 3.06 (dd, J = 8.8, 16.0 Hz, 1H), 3.03 (dd, J = 8.8, 16.0 Hz, 1H), 2.69 (d, J = 15.6 Hz, 1H), 2.65 (dd, J = 14.8 Hz, 1H), 1.91−1.84 (m, 2H), 1.78 (br t, J = 1.2 Hz, 3H), 1.60−1.51 (m, 2H), 1.03 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.8, 147.8, 139.4, 137.9, 137.8, 134.0, 133.5, 128.4 (2x), 128.0 (2x), 126.1, 109.2, 108.2, 69.0, 56.0, 52.9, 46.4, 45.8, 36.8, 31.3, 19.2, 15.4, 13.9. 5-Benzyloxy-6-methoxy-2-methyl-1-phenyl-3,3a,8,8atetrahydrocyclopenta[a]indene (6e): 7% yield (27 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H26O2Na 405.1831, found 405.1823; 1H NMR (400 MHz, CDCl3) δ 7.49−7.44 (m, 2H), 7.40−7.30 (m, 5H), 7.25−7.22 (m, 3H), 6.82 (s, 1H), 6.63 (s, 1H), 5.15 (s, 2H), 4.17−4.07 (m, 1H), 3.85−3.79 (m, 1H), 3.81 (s, 3H), 3.03 (dd, J = 8.8, 16.0 Hz, 1H), 2.95 (dd, J = 8.8, 16.0 Hz, 1H), 2.65 (d, J = 16.4 Hz, 1H), 2.53 (dd, J = 16.8 Hz, 1H), 1.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.1, 147.5, 139.5, 137.80, 137.77, 134.9, 133.6, 128.5 (2x), 128.4 (2x), 128.3, 128.0 (2x), 127.7, 127.4 (2x), 126.1, 110.5, 108.3, 71.5, 56.1, 52.9, 46.4, 45.8, 36.9, 15.4. 2-Methyl-1-phenyl-3,3a,8,8a-tetrahydrocyclopenta[a]indene (6n): 5% yield (12 mg); colorless solid; mp 100−102 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H18Na 269.1306, found 269.1301; 1H NMR (400 MHz, CDCl3) δ 7.49−7.22 (m, 9H), 4.27−4.21 (m, 1H), 4.02 (t, J = 8.8 Hz, 1H), 3.22 (dd, J = 8.8, 16.8 Hz, 1H), 3.17 (dd, J = 8.8, 16.4 Hz, 1H), 2.88 (d, J = 16.4 Hz, 1H), 2.79 (d, J = 16.4 Hz, 1H), 1.87 (d, J = 1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 147.9, 142.6, 137.8, 137.7, 133.8, 128.4 (2x), 128.0 (2x), 126.6, 126.3, 126.1, 124.8, 124.3, 52.3, 46.4, 45.9, 36.8, 15.4. For the single-crystal X-ray diagram, the crystal of compound 6n was grown by slow diffusion of EtOAc into a solution of compound 6n in CH2Cl2 to yield colorless prisms. The compound crystallizes in the orthorhombic crystal 11420


Note

The Journal of Organic Chemistry system, space group Pbca: a = 11.1361(7) Å, b = 7.7797(4) Å, c = 30.9551(19) Å, V = 2681.8(3) Å3, Z = 8, dcalcd = 1.220 g/cm3, F(000) = 1056, 2θ range = 1.316−26.379°, R indices (all data) R1 = 0.0522, wR2 = 0.1114. 6-Fluoro-2-methyl-1-phenyl-3,3a,8,8a-tetrahydrocyclopenta[a]indene (6y): 8% yield (21 mg); colorless gum; HRMS (ESI-TOF) m/ z [M + Na]+ calcd for C19H17FNa 287.1212, found 287.1218; 1H NMR (400 MHz, CDCl3) δ 7.40−7.33 (m, 2H), 7.27−7.19 (m, 4H), 6.89 (dt, J = 2.8, 9.2 Hz, 1H), 6.76 (dd, J = 2.4, 9.2 Hz, 1H), 4.17− 4.11 (m, 1H), 3.83 (t, J = 8.0 Hz, 1H), 3.10−3.01 (m, 2H), 2.71 (d, J = 16.4 Hz, 1H), 2.61 (d, J = 16.8 Hz, 1H), 1.75 (t, J = 1.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 162.2 (d, J = 241.1 Hz), 144.7 (d, J = 8.4 Hz), 143.4, 137.6, 133.8, 128.4 (2x), 128.1 (2x), 127.6, 126.3, 125.1 (d, J = 9.1 Hz), 113.3 (d, J = 22.8 Hz), 111.5 (d, J = 22.0 Hz), 52.9, 46.5, 45.1, 36.9 (d, J = 1.5 Hz), 15.4. 5,7-Dimethoxy-2-methyl-1-phenyl-3,3a,8,8atetrahydrocyclopenta[a]indene (6z): 6% yield (18 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H22O2Na 329.1518, found 329.1514; 1H NMR (400 MHz, CDCl3) δ 7.35−7.31 (m, 2H), 7.26−7.19 (m, 3H), 6.44 (d, J = 2.4 Hz, 1H), 6.27 (d, J = 2.4 Hz, 1H), 4.16−4.11 (m, 1H), 3.89−3.78 (m, 2H), 3.82 (s, 3H), 3.71 (s, 3H), 3.04−2.97 (m, 1H), 2.90 (dd, J = 8.8, 16.0 Hz, 1H), 2.68−2.62 (m, 1H), 1.75 (dt, J = 1.2, 2.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.5, 156.7, 150.3, 138.0, 137.7, 133.4, 128.5 (2x), 128.0 (2x), 126.1, 122.4, 100.2, 96.7, 55.5, 55.1, 52.5, 46.5, 46.2, 33.2, 15.5. 2-(Hydroxyphenylmethyl)-6-methoxy-3-propenylindan-5-ol (7a): Table 1, entry 8, 76% yield (236 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C20H22O3Na 333.1467, found 333.1464; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.30− 7.25 (m, 1H), 6.69 (s, 1H), 6.65 (d, J = 0.8 Hz, 1H), 5.59 (br s, 1H), 5.40−5.31 (m, 1H), 5.25−5.19 (m, 1H), 4.79 (d, J = 5.6 Hz, 1H), 3.84 (s, 3H), 3.53 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 8.8, 15.6 Hz, 1H), 2.77 (dd, J = 8.8, 15.6 Hz, 1H), 2.54−2.46 (m, 1H), 2.05 (br s, 1H), 1.61 (dd, J = 1.6, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.7, 144.3, 143.8, 138.0, 132.93, 132.88, 128.2 (2x), 127.3, 126.7, 126.3 (2x), 110.5, 107.0, 75.0, 56.1, 54.6, 50.8, 32.6, 17.8. (5,6-Dimethoxy-1-propenylindan-2-yl)phenylmethanol (7b): 80% yield (259 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H24O3Na 347.1623, found 347.1618; 1H NMR (400 MHz, CDCl3) δ 7.37−7.34 (m, 4H), 7.28−7.24 (m, 1H), 6.70 (s, 1H), 6.59 (s, 1H), 5.40−5.32 (m, 1H), 5.27−5.21 (m, 1H), 4.76 (d, J = 5.6 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.56 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 9.2, 15.6 Hz, 1H), 2.76 (dd, J = 8.0, 15.6 Hz, 1H), 2.53−2.45 (m, 1H), 2.38 (br s, 1H), 1.64 (dd, J = 1.2, 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 148.1, 147.8, 143.8, 137.0, 133.5, 133.0, 128.0 (2x), 127.2, 126.7, 126.1 (2x), 107.51, 107.49, 74.7, 55.9, 55.8, 54.5, 51.0, 32.5, 17.8. (6-Allyloxy-5-methoxy-1-propenylindan-2-yl)phenylmethanol (7c): 81% yield (283 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H26O3Na 373.1780, found 373.1774; 1H NMR (400 MHz, CDCl3) δ 7.42−7.30 (m, 4H), 7.29−7.20 (m, 1H), 6.72 (s, 1H), 6.60 (s, 1H), 6.12−6.03 (m, 1H), 5.40−5.32 (m, 2H), 5.27− 5.20 (m, 2H), 4.81 (d, J = 5.6 Hz, 1H), 4.55 (dt, J = 1.2, 5.2 Hz, 2H), 3.83 (s, 3H), 3.55 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 8.8, 15.6 Hz, 1H), 2.77 (dd, J = 8.0, 15.6 Hz, 1H), 2.55−2.47 (m, 1H), 1.93 (br s, 1H), 1.62 (dd, J = 1.2, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.9, 147.0, 143.8, 137.1, 134.2, 133.6, 133.1, 128.3 (2x), 127.4, 126.8, 126.3 (2x), 117.8, 110.2, 108.1, 75.0, 70.2, 56.1, 54.7, 51.1, 32.6, 17.9. (6-n-Butoxy-5-methoxy-1-propenylindan-2-yl)phenylmethanol (7d): 73% yield (267 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H30O3Na 389.2093, found 389.2086; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.29−7.25 (m, 1H), 6.71 (s, 1H), 6.59 (s, 1H), 5.40−5.33 (m, 1H), 5.28−5.21 (m, 1H), 4.80 (d, J = 5.2 Hz, 1H), 3.98 (dt, J = 1.2, 7.2 Hz, 2H), 3.82 (s, 3H), 3.58 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 8.8, 15.6 Hz, 1H), 2.77 (dd, J = 8.0, 15.6 Hz, 1H), 2.55−2.47 (m, 1H), 2.00 (br s, 1H), 1.84−1.76 (m, 2H), 1.63 (dd, J = 1.2, 6.4 Hz, 3H), 1.53−1.44 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.8, 147.7, 143.8,

137.2, 133.7, 133.1, 128.2 (2x), 127.4, 126.8, 126.3 (2x), 109.7, 108.3, 75.0, 69.0, 56.2, 54.7, 51.1, 32.6, 31.3, 19.2, 17.9, 13.9. (6-Benzyloxy-5-methoxy-1-propenylindan-2-yl)phenylmethanol (7e): 70% yield (280 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H28O3Na 423.1936, found 423.1931; 1H NMR (400 MHz, CDCl3) δ 7.45−7.43 (m, 2H), 7.37−7.25 (m, 8H), 6.74 (s, 1H), 6.63 (s, 1H), 5.36−5.27 (m, 1H), 5.22−5.15 (m, 1H), 5.08 (s, 2H), 4.79 (d, J = 5.2 Hz, 1H), 3.84 (s, 3H), 3.53 (t, J = 8.8 Hz, 1H), 2.99 (dd, J = 8.8, 15.6 Hz, 1H), 2.78 (dd, J = 8.0, 15.6 Hz, 1H), 2.54−2.46 (m, 1H), 2.05 (br s, 1H), 1.60 (dd, J = 1.2, 6.4 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 149.1, 147.2, 143.8, 137.4, 137.2, 134.5, 133.0, 128.4 (2x), 128.2 (2x), 127.7, 127.5 (2x), 127.4, 126.7, 126.3 (2x), 111.0, 108.4, 75.0, 71.4, 56.2, 54.7, 50.9, 32.7, 17.9. (6-Cyclopentyloxy-5-methoxy-1-propenylindan-2-yl)phenylmethanol (7f): 76% yield (287 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C25H30O3Na 401.2093, found 401.2090; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.30− 7.24 (m, 1H), 6.70 (s, 1H), 6.59 (s, 1H), 5.41−5.32 (m, 1H), 5.27− 5.21 (m, 1H), 4.80 (d, J = 5.6 Hz, 1H), 4.74−4.69 (m, 1H), 3.79 (s, 3H), 3.56 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 9.2, 15.6 Hz, 1H), 2.77 (dd, J = 8.0, 15.6 Hz, 1H), 2.55−2.47 (m, 1H), 2.01 (br s, 1H), 1.92− 1.77 (m, 6H), 1.62 (dd, J = 1.2, 6.4 Hz, 3H), 1.61−1.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 149.5, 146.6, 143.8, 137.2, 133.9, 133.1, 128.2 (2x), 127.4, 126.7, 126.3 (2x), 111.9, 108.5, 80.7, 75.0, 56.2, 54.7, 51.0, 32.7 (2x), 32.6 (2x), 24.0, 17.9. (6-Isopropoxy-5-methoxy-1-propenylindan-2-yl)phenylmethanol (7g): 78% yield (275 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H28O3Na 375.1936, found 375.1933; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.31− 7.24 (m, 1H), 6.71 (s, 1H), 6.61 (s, 1H), 5.40−5.32 (m, 1H), 5.27− 5.20 (m, 1H), 4.80 (d, J = 5.2 Hz, 1H), 4.47−4.41 (m, 1H), 3.80 (s, 3H), 3.56 (t, J = 8.4 Hz, 1H), 2.99 (dd, J = 9.2, 15.6 Hz, 1H), 2.77 (dd, J = 8.0, 15.6 Hz, 1H), 2.55−2.47 (m, 1H), 1.90 (br s, 1H), 1.62 (dd, J = 1.6, 6.4 Hz, 3H), 1.33 (d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 150.0, 146.2, 143.8, 137.2, 134.5, 133.1, 128.2 (2x), 127.4, 126.8, 126.3 (2x), 113.0, 108.4, 75.0, 71.8, 56.1, 54.7, 51.0, 32.6, 22.2, 22.1, 17.9. (1-But-1-enyl-5,6-dimethoxyindan-2-yl)phenylmethanol (7h): 74% yield (250 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C22H26O3Na 361.1780, found 361.1772; 1H NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 4H), 7.31−7.24 (m, 1H), 6.71 (s, 1H), 6.58 (s, 1H), 5.44−5.37 (m, 1H), 5.24−5.18 (m, 1H), 4.79 (d, J = 5.6 Hz, 1H), 3.833 (s, 3H), 3.830 (s, 3H), 3.56 (t, J = 8.8 Hz, 1H), 3.00 (dd, J = 8.8, 15.6 Hz, 1H), 2.80 (dd, J = 8.0, 15.6 Hz, 1H), 2.56−2.48 (m, 1H), 2.11 (br s, 1H), 1.99−1.94 (m, 2H), 0.94 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.2, 147.9, 143.8, 137.1, 134.1, 133.6, 130.9, 128.2 (2x), 127.4, 126.3 (2x), 107.62, 107.59, 75.1, 56.0, 55.9, 54.8, 51.0, 32.7, 25.4, 13.9. [5,6-Dimethoxy-1-(3-methylbut-1-enyl)indan-2-yl]phenylmethanol (7i): 70% yield (246 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H28O3Na 375.1936, found 375.1929; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.31− 7.25 (m, 1H), 6.72 (s, 1H), 6.57 (s, 1H), 5.34 (dd, J = 6.4, 15.2 Hz, 1H), 5.15 (ddd, J = 0.8, 8.8, 15.2 Hz, 1H), 4.79 (d, J = 5.6 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H), 3.54 (t, J = 8.8 Hz, 1H), 3.01 (dd, J = 8.8, 15.6 Hz, 1H), 2.83 (dd, J = 8.0, 15.6 Hz, 1H), 2.58−2.50 (m, 1H), 2.24−2.16 (m, 1H), 1.96 (br s, 1H), 0.95 (d, J = 6.8 Hz, 3H), 0.91 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.4, 148.1, 143.8, 139.7, 137.2, 133.7, 129.0, 128.3 (2x), 127.5, 126.3 (2x), 107.74, 107.69, 75.5, 56.03, 56.00, 54.9, 51.0, 33.0, 30.9, 22.8, 22.6. (1-Hex-1-enyl-5,6-dimethoxyindan-2-yl)phenylmethanol (7k): 70% yield (256 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H30O3Na 389.2093, found 389.2089; 1H NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 4H), 7.30−7.25 (m, 1H), 6.71 (s, 1H), 6.59 (s, 1H), 5.38 (dt, J = 6.8, 15.2 Hz, 1H), 5.23 (dd, J = 8.8, 15.2 Hz, 1H), 4.81 (d, J = 5.6 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.58 (t, J = 8.8 Hz, 1H), 3.01 (dd, J = 8.8, 15.6 Hz, 1H), 2.78 (dd, J = 8.8, 15.6 Hz, 1H), 2.56−2.48 (m, 1H), 2.06 (br s, 1H), 2.00−1.95 (m, 2H), 1.34−1.24 (m, 4H), 0.91 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.3, 148.0, 143.8, 137.1, 133.6, 132.5, 132.0, 128.3 11421


Note


[5,6-Dimethoxy-1-(2-naphthalen-2-ylvinyl)indan-2-yl]phenylmethanol (7r): 66% yield (288 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C30H28O3Na 459.1936, found 459.1931; 1H NMR (400 MHz, CDCl3) δ 7.81−7.76 (m, 3H), 7.65 (s, 1H), 7.54−7.39 (m, 5H), 7.36−7.33 (m, 2H), 7.25−7.21 (m, 1H), 6.78 (s, 1H), 6.66 (s, 1H), 6.44 (d, J = 15.6 Hz, 1H), 6.16 (dd, J = 9.2, 15.6 Hz, 1H), 4.88 (d, J = 5.6 Hz, 1H), 3.89−3.86 (m, 1H), 3.87 (s, 3H), 3.81 (s, 3H), 3.12 (dd, J = 8.8, 15.6 Hz, 1H), 2.92 (dd, J = 8.4, 15.6 Hz, 1H), 2.75−2.70 (m, 1H), 2.00 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.5, 148.2, 143.6, 136.4, 134.7, 133.9, 133.5, 132.7, 132.7, 131.2, 128.5, 128.4 (2x), 128.0, 127.8, 127.61, 127.58, 126.3 (2x), 126.2, 125.8, 125.6, 123.6, 107.7, 75.2, 56.03, 56.00, 55.0, 51.7, 33.0. {1-[2-(3,4-Dichlorophenyl)vinyl]-5,6-dimethoxyindan-2-yl}phenylmethanol (7t): 67% yield (304 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H24Cl2O3Na 477.1000, found 477.0996; 1H NMR (400 MHz, CDCl3) δ 7.38−7.30 (m, 6H), 7.24−7.21 (m, 1H), 7.05 (dd, J = 2.0, 8.4 Hz, 1H), 6.76 (s, 1H), 6.55 (s, 1H), 6.07 (d, J = 15.6 Hz, 1H), 5.94 (dd, J = 8.4, 15.6 Hz, 1H), 4.78 (d, J = 6.4 Hz, 1H), 3.86 (s, 3H), 3.80 (s, 3H), 3.73 (t, J = 8.4 Hz, 1H), 3.08 (dd, J = 8.8, 16.0 Hz, 1H), 2.95 (dd, J = 8.4, 16.0 Hz, 1H), 2.69−2.61 (m, 1H), 2.02 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.7, 148.2, 143.4, 137.4, 135.7, 134.4, 133.9, 132.4, 130.6, 130.2, 128.6, 128.4 (2x), 127.84, 127.80, 126.4 (2x), 125.4, 107.8, 107.6, 75.9, 56.1, 56.0, 54.7, 51.5, 33.6. {5,6-Dimethoxy-1-[2-(3,4,5-trimethoxyphenyl)vinyl]indan-2-yl}phenylmethanol (7u): 70% yield (333 mg); colorless solid; mp 160− 161 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C29H32O6Na 499.2097, found 499.2088; 1H NMR (400 MHz, CDCl3) δ 7.40−7.32 (m, 4H), 7.27−7.22 (m, 1H), 6.75 (s, 1H), 6.63 (s, 1H), 6.53 (s, 2H), 6.21 (d, J = 15.6 Hz, 1H), 5.95 (dd, J = 8.8, 15.6 Hz, 1H), 4.84 (d, J = 5.2 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.84 (s, 3H), 3.83 (s, 3H), 3.81 (s, 3H), 3.86−3.84 (m, 1H), 3.09 (dd, J = 8.8, 16.0 Hz, 1H), 2.87 (dd, J = 8.0, 15.6 Hz, 1H), 2.69−2.63 (m, 1H), 2.05 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.1 (2x), 148.5, 148.1, 143.7, 137.4, 136.2, 133.9, 132.9, 131.7, 130.9, 128.3 (2x), 127.4, 126.2 (2x), 107.8, 107.7, 103.1 (2x), 74.9, 60.8, 56.02, 55.96 (2x), 55.9, 54.9, 51.3, 32.8. [ 5 , 6 - D i m e th o x y- 1 - ( 2 -t hi op he n - 2 - y l v i n y l ) i n d a n - 2 - y l ] phenylmethanol (7v): 73% yield (286 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H24O3SNa 415.1344, found 415.1337; 1H NMR (400 MHz, CDCl3) δ 7.40−7.32 (m, 4H), 7.27− 7.23 (m, 1H), 7.11 (d, J = 5.2 Hz, 1H), 6.94 (dd, J = 3.2, 5.2 Hz, 1H), 6.86 (d, J = 5.6 Hz, 1H), 6.74 (s, 1H), 6.61 (s, 1H), 6.39 (d, J = 15.6 Hz, 1H), 5.87 (dd, J = 9.2, 15.6 Hz, 1H), 4.83 (d, J = 6.0 Hz, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.79−3.73 (m, 1H), 3.07 (dd, J = 8.8, 16.0 Hz, 1H), 2.86 (dd, J = 8.0, 15.6 Hz, 1H), 2.66−2.62 (m, 1H), 1.98 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.2, 143.6, 142.5, 136.1, 133.9, 132.1, 128.4 (2x), 127.7, 127.2, 126.8, 126.3 (2x), 124.9, 124.3, 123.6, 107.8, 107.7, 75.2, 56.1, 56.0, 54.9, 51.4, 32.6. {5,6-Dimethoxy-1-[2-(4-nitrophenyl)vinyl]indan-2-yl}phenylmethanol (7w): 73% yield (315 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H25NO5Na 454.1630, found 454.1627; 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.8 Hz, 2H), 7.39−7.29 (m, 6H), 7.21−7.17 (m, 1H), 6.77 (s, 1H), 6.55 (s, 1H), 6.18 (d, J = 15.6 Hz, 1H), 6.11 (dd, J = 8.0, 15.6 Hz, 1H), 4.78 (d, J = 5.2 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 3.77 (t, J = 8.4 Hz, 1H), 3.09 (dd, J = 8.8, 16.0 Hz, 1H), 3.00 (dd, J = 8.0, 15.6 Hz, 1H), 2.73−2.65 (m, 1H), 2.08 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.7, 148.2, 146.5, 143.7, 143.3, 137.4, 135.3, 134.0, 128.8, 128.4 (2x), 127.9, 126.51 (2x), 126.45 (2x), 123.8 (2x), 107.7, 107.6, 76.2, 56.1, 56.0, 54.6, 51.7, 34.0. (6-Methoxy-1-propenylindan-2-yl)phenylmethanol (7x): 64% yield (188 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C20H22O2Na 317.1518, found 317.1511; 1H NMR (400 MHz, CDCl3) δ 7.40−7.30 (m, 4H), 7.28−7.19 (m, 1H), 7.07 (d, J = 8.0 Hz, 1H), 6.77−6.68 (m, 1H), 6.63 (d, J = 2.0 Hz, 1H), 5.47−5.39 (m, 1H), 5.30−5.24 (m, 1H), 4.82 (d, J = 5.2 Hz, 1H), 3.77 (s, 3H), 3.61 (t, J = 8.4 Hz, 1H), 2.98 (dd, J = 9.2, 15.2 Hz, 1H), 2.75 (dd, J = 8.0, 15.2 Hz, 1H), 2.56−2.48 (m, 1H), 1.99 (br s, 1H), 1.65 (dd, J =

(2x), 127.4, 126.2 (2x), 107.6 (2x), 74.9, 56.0, 55.9, 54.8, 51.2, 32.6, 21.0, 31.5, 22.1, 13.9. [5,6-Dimethoxy-1-(5-methylhex-1-enyl)indan-2-yl]phenylmethanol (7l): 73% yield (277 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C25H32O3Na 403.2249, found 403.2246; 1H NMR (400 MHz, CDCl3) δ 7.39−7.33 (m, 4H), 7.30− 7.25 (m, 1H), 6.71 (s, 1H), 6.58 (s, 1H), 5.37 (dt, J = 6.8, 15.2 Hz, 1H), 5.23 (dd, J = 8.8, 15.2 Hz, 1H), 4.80 (d, J = 5.6 Hz, 1H), 3.834 (s, 3H), 3.828 (s, 3H), 3.57 (t, J = 8.8 Hz, 1H), 3.01 (dd, J = 8.8, 15.6 Hz, 1H), 2.78 (dd, J = 8.8, 15.6 Hz, 1H), 2.56−2.48 (m, 1H), 2.06 (br s, 1H), 2.04−1.95 (m, 2H), 1.61−1.53 (m, 1H), 1.26−1.18 (m, 2H), 0.90 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.3, 148.0, 143.8, 137.2, 133.6, 132.7, 131.8, 128.3 (2x), 127.4, 126.2 (2x), 107.6 (2x), 75.0, 56.0, 55.9, 54.8, 51.2, 38.6, 32.6, 30.2, 27.3, 22.5, 22.4. (5,6-Dimethoxy-1-styrylindan-2-yl)phenylmethanol (7m): 65% yield (251 mg); colorless solid; mp 206−208 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C26H26O3Na 409.1780, found 409.1774; 1H NMR (400 MHz, CDCl3) δ 7.31−7.19 (m, 5H), 7.10−7.04 (m, 5H), 6.75 (s, 1H), 6.58 (s, 1H), 6.24 (d, J = 15.6 Hz, 1H), 6.03 (dd, J = 8.8, 15.6 Hz, 1H), 4.66 (d, J = 4.4 Hz, 1H), 3.97 (t, J = 9.2 Hz, 1H), 3.85 (s, 3H), 3.80 (s, 3H), 3.27 (dd, J = 9.6, 15.6 Hz, 1H), 2.80 (dd, J = 8.0, 15.2 Hz, 1H), 2.61−2.58 (m, 1H), 2.00 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.4, 148.1, 142.1, 137.3, 136.6, 134.1, 132.1, 131.9, 128.4 (2x), 127.6 (2x), 127.2 (3x), 126.9, 126.2 (2x), 107.9, 107.7, 81.7, 56.2, 56.1 (2x), 51.3, 33.1. Phenyl-(1-propenylindan-2-yl)methanol (7n): 73% yield (193 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H20ONa 287.1412, found 287.1409; 1H NMR (400 MHz, CDCl3) δ 7.40−7.32 (m, 5H), 7.31−7.26 (m, 1H), 7.19−7.14 (m, 3H), 5.48− 5.39 (m, 1H), 5.31−5.25 (m, 1H), 4.84 (d, J = 4.8 Hz, 1H), 3.65 (t, J = 8.4 Hz, 1H), 3.06 (dd, J = 9.6, 15.6 Hz, 1H), 2.82 (dd, J = 8.0, 15.2 Hz, 1H), 2.56−2.48 (m, 1H), 1.95 (br s, 1H), 1.64 (dd, J = 1.6, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 145.6, 143.8, 142.1, 132.6, 128.3 (2x), 127.4, 127.3, 126.6, 126.23 (2x), 126.17, 124.4 (2x), 74.7, 54.4, 51.0, 32.5, 17.9. [1-(2-Benzo[1,3]dioxol-5-ylvinyl)-5,6-dimethoxyindan-2-yl]phenylmethanol (7p): 68% yield (292 mg); colorless solid; mp 95− 97 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C27H26O5Na 453.1678, found 453.1674; 1H NMR (400 MHz, CDCl3) δ 7.39−7.31 (m, 4H), 7.26−7.21 (m, 1H), 6.84 (d, J = 1.2 Hz, 1H), 6.76−6.70 (m, 3H), 6.61 (s, 1H), 6.19 (d, J = 16.0 Hz, 1H), 5.93 (d, J = 2.0 Hz, 1H), 5.92 (d, J = 1.2 Hz, 1H), 5.85 (dd, J = 9.2, 16.0 Hz, 1H), 4.82 (d, J = 5.6 Hz, 1H), 3.85 (s, 3H), 3.82−3.74 (m, 1H), 3.80 (s, 3H), 3.07 (dd, J = 9.2, 16.0 Hz, 1H), 2.85 (dd, J = 8.0, 15.2 Hz, 1H), 2.66−2.58 (m, 1H), 2.24 (br s, 1H); 13 C NMR (100 MHz, CDCl3) δ 148.4, 148.1, 147.8, 146.7, 143.6, 136.5, 133.8, 131.8, 130.7, 130.5, 128.3 (2x), 127.5, 126.2 (2x), 120.6, 108.1, 107.72, 107.69, 105.5, 100.9, 75.0, 56.0, 55.9, 54.9, 51.4, 32.8. For the single-crystal X-ray diagram, the crystal of compound 7p was grown by slow diffusion of EtOAc into a solution of compound 7p in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P21/c: a = 11.796(3) Å, b = 17.150(5) Å, c = 13.523(4) Å, V = 2554.9(12) Å3, Z = 4, dcalcd = 1.307 g/cm3, F(000) = 1072, 2θ range = 1.849−26.565°, R indices (all data) R1 = 0.0956, wR2 = 0.1677. [1-(2-Biphenyl-4-ylvinyl)-5,6-dimethoxyindan-2-yl]phenylmethanol (7q): 70% yield (323 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C32H30O3Na 485.2093, found 485.2088; 1H NMR (400 MHz, CDCl3) δ 7.62−7.60 (m, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.47−7.33 (m, 9H), 7.27−7.25 (m, 1H), 6.77 (s, 1H), 6.64 (s, 1H), 6.33 (d, J = 15.6 Hz, 1H), 6.09 (dd, J = 8.8, 15.6 Hz, 1H), 4.87 (d, J = 6.0 Hz, 1H), 3.87 (s, 3H), 3.88−3.78 (m, 1H), 3.81 (s, 3H), 3.11 (dd, J = 8.8, 15.6 Hz, 1H), 2.89 (dd, J = 8.4, 15.6 Hz, 1H), 2.71−2.64 (m, 1H), 2.04 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 148.6, 148.2, 143.7, 140.7, 139.9, 136.4, 136.3, 133.8, 132.4, 130.7, 128.8 (2x), 128.4 (2x), 127.6, 127.2, 127.1 (2x), 126.9 (2x), 126.6 (2x), 126.3 (2x), 107.8, 107.7, 75.1, 56.1, 56.0, 55.0, 51.6, 32.9. 11422


Note

The Journal of Organic Chemistry 1.6, 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 158.7, 147.1, 143.8, 132.5, 128.3 (2x), 127.4 (2x), 126.3, 126.2 (2x), 124.9, 112.5, 109.9, 74.7, 55.4, 54.8, 51.2, 31.7, 17.9. (5-Fluoro-1-propenylindan-2-yl)phenylmethanol (7y): 60% yield (169 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C19H19FONa 305.1318, found 305.1315; 1H NMR (400 MHz, CDCl3) δ 7.40−7.34 (m, 4H), 7.32−7.26 (m, 1H), 7.01−6.98 (m, 1H), 6.86−6.83 (m, 2H), 5.48−5.40 (m, 1H), 5.29−5.22 (m, 1H), 4.82 (d, J = 5.2 Hz, 1H), 3.60 (t, J = 8.8 Hz, 1H), 3.05 (dd, J = 9.6, 16.0 Hz, 1H), 2.77 (dd, J = 8.4, 16.0 Hz, 1H), 2.55−2.47 (m, 1H), 2.04 (br s, 1H), 1.66 (dd, J = 1.6, 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 162.2 (d, J = 241.1 Hz), 144.2 (d, J = 7.6 Hz), 143.7, 132.5, 128.3 (2x), 127.5, 127.4, 126.8, 126.1 (2x), 125.3 (d, J = 9.1 Hz), 113.0 (d, J = 22.0 Hz), 111.3 (d, J = 22.0 Hz), 74.4, 54.9, 50.2, 32.4 (d, J = 1.5 Hz), 17.9. (4,6-Dimethoxy-1-propenylindan-2-yl)phenylmethanol (7z): 72% yield (233 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C21H24O3Na 347.1623, found 347.1620; 1H NMR (400 MHz, CDCl3) δ 7.40−7.29 (m, 4H), 7.28−7.24 (m, 1H), 6.29 (d, J = 2.0 Hz, 1H), 6.25 (s, 1H), 5.47−5.39 (m, 1H), 5.32−5.25 (m, 1H), 4.81 (d, J = 5.2 Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H), 3.61 (t, J = 8.4 Hz, 1H), 2.85 (dd, J = 9.2, 15.6 Hz, 1H), 2.76 (dd, J = 8.4, 15.6 Hz, 1H), 2.54−2.46 (m, 1H), 2.00 (br s, 1H), 1.65 (dd, J = 1.2, 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.3, 156.4, 148.0, 143.8, 132.6, 128.2 (2x), 127.3, 127.2, 126.2 (2x), 121.8, 100.7, 96.9, 74.6, 55.5, 55.2, 54.2, 51.7, 28.4, 17.9. (6-n-Butoxy-4-methoxy-1-propenylindan-2-yl)phenylmethanol (7aa): 70% yield (256 mg); colorless gum; HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H30O3Na 389.2093, found 389.2085; 1H NMR (400 MHz, CDCl3) δ 7.39−7.30 (m, 4H), 7.29−7.24 (m, 1H), 6.29 (d, J = 2.0 Hz, 1H), 6.24 (s, 1H), 5.46−5.38 (m, 1H), 5.31−5.25 (m, 1H), 4.81 (d, J = 5.2 Hz, 1H), 3.96−3.90 (m, 2H), 3.77 (s, 3H), 3.60 (t, J = 8.4 Hz, 1H), 2.85 (dd, J = 8.8, 15.6 Hz, 1H), 2.76 (dd, J = 8.0, 15.6 Hz, 1H), 2.54−2.46 (m, 1H), 1.99 (br s, 1H), 1.80−1.73 (m, 2H), 1.65 (dd, J = 1.2, 6.4 Hz, 3H), 1.54−1.45 (m, 2H), 0.98 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 156.3, 147.9, 143.8, 132.7, 128.2 (2x), 127.3, 127.2, 126.2 (2x), 121.6, 101.4, 97.3, 74.6, 67.9, 55.2, 54.2, 51.7, 31.4, 28.4, 19.3, 17.9, 13.9.

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108, 3239−3265. (c) Grondal, C.; Jeanty, M.; Enders, D. Organocatalytic Cascade Reactions as a New Tool in Total Synthesis. Nat. Chem. 2010, 2, 167−178. (d) Moyano, A.; Rios, R. Asymmetric Organocatalytic Cyclization and Cycloaddition Reactions. Chem. Rev. 2011, 111, 4703−4832. (e) Pellissier, H. Recent Developments in Asymmetric Organocatalytic Domino Reactions. Adv. Synth. Catal. 2012, 354, 237−294. (f) Lu, L.-Q.; Chen, J.-R.; Xiao, W.-J. Development of Cascade Reactions for the Concise Construction of Diverse Heterocyclic Architectures. Acc. Chem. Res. 2012, 45, 1278− 1293. (2) For selected examples on intramolecular annulation of diyneconjugated arenes, see: (a) Wang, A.-F.; Hao, W.-J.; Zhu, Y.-L.; Li, G.; Zhou, P.; Tu, S.-J.; Jiang, B. Double SO2 Insertion into 1,7-Diynes Leading to Functionalized Naphtho[1,2-c]thiophene 2,2-dioxides. ACS Omega 2018, 3, 1482−1491. (b) Pati, K.; dos Passos Gomes, G.; Harris, T.; Hughes, A.; Phan, H.; Banerjee, T.; Hanson, K.; Alabugin, I. V. Traceless Directing Groups in Radical Cascades: From Oligoalkynes to Fused Helicenes without Tethered Initiators. J. Am. Chem. Soc. 2015, 137, 1165−1180. (c) Sun, N.; Xie, X.; Wang, G.; Chen, H.; Liu, Y. Base-Catalyzed Cyclization of 1,6-Diynyl Carboxylates Involving Propargyl-Allenyl Isomerization: Efficient Synthesis of Benzo[b]fluorene and Its Analogues. Adv. Synth. Catal. 2017, 359, 1394−1401. (d) Wang, Q.; Aparaj, S.; Akhmedov, N. G.; Petersen, J. L.; Shi, X. Ambient Schmittel Cyclization Promoted by Chemoselective Triazole-Gold Catalyst. Org. Lett. 2012, 14, 1334− 1337. (e) Chen, Y.; Chen, M.; Liu, Y. Gold-Catalyzed Cascade Cyclizations of 1,6-Diynyl Carbonates to Benzo[b]fluorenes Involving Arylation of Oxocarbenium Ion Intermediates and Decarboxylative Etherification. Angew. Chem., Int. Ed. 2012, 51, 6493−6497. (3) For selected examples on intramolecular annulation of yneenone-conjugated arenes, see: (a) Wang, Z.-Q.; Zhang, W.-W.; Gong, L.-B.; Tang, R.-Y.; Yang, X.-H.; Liu, Y.; Li, J.-H. Copper-Catalyzed Intramolecular Oxidative 6-Exo-Trig Cyclization of 1,6-Enynes with H2O and O2. Angew. Chem., Int. Ed. 2011, 50, 8968−8973. (b) Mandal, M.; Balamurugan, R. Triflic acid-Mediated Expedient Synthesis of Benzo[a]fluorenes and Fluorescent Benzo[a]fluorenones. Adv. Synth. Catal. 2018, 360, 1453−1465. (c) Zhao, Q.; Hu, Q.; Wen, L.; Wu, M.; Hu, Y. Fused Benzo[b]fluorenols: Palladium-Catalyzed Intramolecular Dehydroaromatization and Carbonyl Reduction. Adv. Synth. Catal. 2012, 354, 2113−2116. (d) Zhou, F.; Han, X.; Lu, X. Palladium(II)-Catalyzed Synthesis of Functionalized Indenes from o-Alkynylbenzylidene Ketones. J. Org. Chem. 2011, 76, 1491−1494. (4) (a) 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. (b) Chan, C.K.; Hsueh, N.-C.; Tsai, Y.-L.; Chang, M.-Y. Bi(OTf)3-Mediated Intramolecular Olefinic Cyclization: Synthesis of Substituted ArylDihydronaphthalenes and Indenes. J. Org. Chem. 2017, 82, 7077− 7084. (5) Qin, Y.; Lv, J.; Luo, S.; Cheng, J.-P. Direct Intramolecular Conjugate Addition of Simple Alkenes to α,β-Unsaturated Carbonyls Catalyzed by Cu(OTf)2. Org. Lett. 2014, 16, 5032−5035. (6) (a) Chang, M.-Y.; Wu, M.-H. Synthesis of Tetrahydroanthracen9-ones by the Domino Aldol Condensation/Diels-Alder Cycloaddition. Tetrahedron Lett. 2012, 53, 3173−3177. (b) Chang, M.-Y.; Wu, M.-H. Synthesis of Benzo[g]chysenes. Tetrahedron 2013, 69, 129−136. (c) Hsueh, N.-C.; Chen, H.-Y.; Chang, M.-Y. Construction of Sulfonyl Oxabenzo[3.3.1]bicyclic Core via Cyclocondensation of βKetosulfones and o-Formyl Allylbenzenes. J. Org. Chem. 2017, 82, 13324−13332. (7) For selected examples on the synthesis of natural products with the 1-vinylindane skeleton, for mutisianthol, see: (a) Bianco, G. G.; Ferraz, H. M. C.; Costa, A. M.; Costa-Lotufo, L. V.; Pessoa, C.; de Moraes, M. O.; Schrems, M. G.; Pfaltz, A.; Silva, L. F. (+)- and (−)-Mutisianthol: First Total Synthesis, Absolute Configuration, and Antitumor Activity. J. Org. Chem. 2009, 74, 2561−2566. (b) Bhorkade,

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b01729. Crystal data of compounds 6n and 7p (CIF) Scanned photocopies of NMR spectral data for all new compounds and X-ray analysis data of 6n and 7p (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Meng-Yang Chang: 0000-0002-1983-8570 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors would like to thank the Ministry of Science and Technology of the Republic of China for financial support (MOST 106-2628-M-037-001-MY3).

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REFERENCES

(1) For reviews on domino reactions, see: (a) Hussain, M. M.; Walsh, P. J. Tandem Reactions for Streamlining Synthesis: Enantioand Diastereoselective One-Pot Generation of Functionalized Epoxy Alcohols. Acc. Chem. Res. 2008, 41, 883−893. (b) Li, Z.; Brouwer, C.; He, C. Gold-Catalyzed Organic Transformations. Chem. Rev. 2008, 11423


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Diastereoselective Synthesis of Functionalized 1,2,3-Trisubstituted Benzocyclopentenes through the Cycloaddition of Bis(phenylsulfonyl)iodonium Ylides to Cyclic Alkenes. J. Org. Chem. 2003, 68, 9155−9158. (d) Cheng, Y.; Peng, J.-H.; Li, Y.-J.; Shi, X.-Y.; Tang, M.-S.; Tan, T.-Y. N-Heterocyclic Carbene Catalyzed Reaction of Phthalaldehydes: Controllable Stereoselective Synthesis of Polyhydroxylated Spiro- and Fused Indenones Dictated by the Structure of NHC Catalysts. J. Org. Chem. 2011, 76, 1844−1851. (13) (a) Chang, M.-Y.; Lin, C.-H.; Chen, Y.-L.; Chang, C.-Y.; Hsu, R.-T. BF 3 -Promoted Synthesis of Diarylhexahydrobenzo[f ]isoquinoline. Org. Lett. 2010, 12, 1176−1179. (b) Chang, M.-Y.; Cheng, Y.-C. Synthesis of Substituted 1-Aryltetralins and 1Arylnaphthalenes via (4 + 2) Annulation of β-Ketosulfones with Styryl Bromides. Org. Lett. 2016, 18, 1682−1685. (c) 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. (14) CCDC 1842809 (6n) and 1842810 (7p) 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]).

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