Selective divergent synthesis of indanols, indanones, and indenes via

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Selective divergent synthesis of indanols, indanones, and indenes via acid-mediated cyclization of (Z)- and (E)-(2-stilbenyl)methanols and its application for the synthesis of paucifloral F derivatives Jira Jongcharoenkamol, Patsapon Chuathong, Yuka Amako, Masato Kono, Kasam Poonswat, Somsak Ruchirawat, and Poonsakdi Ploypradith J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01921 • Publication Date (Web): 11 Oct 2018 Downloaded from http://pubs.acs.org on October 12, 2018

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The Journal of Organic Chemistry

Selective divergent synthesis of indanols, indanones, and indenes via acid-mediated cyclization of (Z)- and (E)-(2-stilbenyl)methanols and its application for the synthesis of paucifloral F derivatives Jira Jongcharoenkamol,† Patsapon Chuathong,† Yuka Amako,‡ Masato Kono,‡ Kasam Poonswat, ‡

Somsak Ruchirawat,†,‡,§ and Poonsakdi Ploypradith†,‡,§,*

†

Program in Chemical Biology, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, and

‡

Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6

Road, Laksi, Bangkok, Thailand 10210 §

Centre of Excellence on Environmental Health and Toxicology, Commission on Higher

Education (CHE), Ministry of Education, Thailand E-mail: [email protected]

Abstract

Starting from bromo/iodobenzaldehyde derivatives, the corresponding (Z)- and (E)-(2stilbenyl)methanols could be prepared in 2-5 steps via Pd-catalyzed cross-coupling reactions (Sonogashira and Heck reactions) followed by aryllithium/aryl Grignard addition. For the (E)stilbenes, subsequent acid-mediated cyclization using p-TsOH immobilized on silica (PTS-Si) at

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low temperatures furnished the 2,3-trans-1-indanols with complete stereocontrol at the C2-C3. Further oxidization of the alcohol provided the indanones which are structurally related to the natural product paucifloral F. At higher temperatures, 1,2- and 2,3-disubstituted indenes could be selectively prepared in good to excellent yields. On the other hand, the (Z)-stilbenes, under similar conditions (PTS-Si), did not give the indanols; only the 1,2-disubstituted indenes could be obtained. To gain further insights into the stereochemistry at C2-C3 for the (Z)-stilbenes, hydride or azide were employed as nucleophiles; the corresponding indane products were obtained with the cis stereochemistry at the C2-C3. Thus, the (Z)- or (E)-olefin geometry of the substrate directed the stereoselective indanyl cyclization to furnish the cis or trans at the C2-C3 ring junction, respectively, while reaction conditions controlled the selectivity of the product types.

Introduction Indane skeleton, a cyclopentane ring fused with a benzene ring, together with indenes, 1indanols, and 1-indanones, is an important core of various natural as well as synthetic compounds many of which exhibit a wide range of interesting biological activities. As shown in Figure 1, caraphenol B (1) is a natural indane used for the treatment of asthenia syndrome and vascular hypertension1-3 while indinavir (2) is a synthetic indanol which has been clinically used as an inhibitor against HIV protease.4,5 In addition, trikentramine (3) is a natural 1,2-disubstituted indene6 while sulindac (4), a synthetic 2,3-disubstituted indene, is a non-steroidal antiinflammatory agent.7 Paucifloral F (5), a trans-2,3-diaryl-1-indanone secondary metabolite, was reportedly isolated from the stem bark of Vatica pauciflora.8 In addition, daphenylline as well as rubriflordilactones A and B are complex natural products containing indane as their core.9,10


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Figure 1. Representative examples of natural and synthetic indane-containing compounds

As a member of the resveratrol oligomer family and its biosynthetically derivable congeners, the potential medicinal use of paucifloral F as an elixir or an agent to prevent cancers, osteoporosis, or inflammation11 have been reported; however, its low natural abundance (0.0004%)8 has limited further studies on its direct biological/pharmacological profiling. While synthesis of paucifloral F has been accomplished by different research groups,12-14 synthesis of other structurally related derivatives with different patterns of the methoxy/hydroxy substituents on the three aromatic rings has not been systematically studied. Recently, our research group has investigated the preparation of various indanes from the Brønsted/Lewis acid-mediated cyclization of carbocations generated from (E)-(2-stilbenyl)methanols followed by nucleophilic addition of trialkylsilyl-based reagents.15 Herein, we wish to report our systematic study on the selective synthesis of indanols (6), indanones (7), and 1,2- as well as 2,3-disubstituted indenes (8 and 9), with the focus on those which are structurally related to paucifloral F, from the corresponding (E)-(2-stilbenyl)methanols via the intermediacy of common secondary bisbenzylic



and indanyl-type carbocations 10 and 11, respectively (Scheme 1). In addition, some (Z)-(2stilbenyl)methanols would be prepared and the results from their acid-mediated cyclization to the corresponding indanyl systems 12 and 13 would be compared to those obtained from the (E)isomers for the selectivity profiles.

Scheme 1. Strategy towards selective formation of 6-9 via 10 and 11.

Results and discussion Based on the previously reported chemistry, starting from 2-bromobenzaldehyde derivatives, the corresponding (E)-(2-stilbenyl)methanols could be straightforwardly prepared via the Pdcatalyzed Heck reaction (to introduce Ar2) followed by nucleophilic addition of aryllithium and arylmagnesium reagents (to introduce Ar1). In addition, we anticipated that generating the first secondary bisbenzylic carbocation (e.g. 10) from the Lewis/Brønsted acid-mediated ionization of the corresponding alcohol would be facile. However, the subsequent addition of the cation center to the stilbene alkene could be challenging, especially those substrates with Ar1/Ar2 containing one or more electron-donating group. Previously, we demonstrated that the BF3.Et2O-mediated cyclization followed by hydride transfer from triethylsilane of the alcohol with Ar2 = 4-


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MeOC6H4 furnished the corresponding indane only in 51-58% yield, depending on the reaction conditions.15 Moreover, similar reactions of different substrates furnished the corresponding 1,2and 2,3-disubstituted indenes (e.g. 8 and 9) as by-products. Thus, synthesis of our desired 2,3trans-1-indanols (e.g. 6) with the Ar2 = 4-MeOC6H4 which is structurally related to paucifloral F would require optimization of reaction conditions. Ideally, from the same (E)-(2stilbenyl)methanols as starting materials, using the same acid as a mediator, it would be desirable to selectively affect the formation of the corresponding indanols under one condition and that of the 1,2- or 2,3-disubstituted indenes under other sets of condition.

Optimization of selective formation of indanols and indenes First, using the alcohol 14 as a model, the effects of employing different Lewis or Brønsted acids under different reaction conditions on the selective formation of the corresponding indanol 15, 1,2- and 2,3-disubstituted indenes 16 and 17 were investigated (Table 1).

Table 1. Screening reaction conditions for the selective formation of 15-17 from 14a

yield (%)b entry

mediator

temperature (° C)

time (h) 15

16

17

1

PTS-Si

rt

0.25

80

0

0

2

PTS-Si

rt

18

0

85

0

3c

PTS-Si

80

6

0

78

17



a

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4c

PTS-Si

80

18

0

0

88d

5

p-TsOH

80

18

0

76

7

6e,f

La(OTf)3

0 or rt

18

0

0

0

7e

Bi(OTf)3

rt

18

50

35

0

8e

InCl3

rt

18

35

65

0

9g

PtCl4

rt

6

87

0

0

10e

PtCl4

rt

48

53

--h

0

11e,f

PtCl4

0

18

0

0

0

12e

PtCl4

40

18

0

85

0

Unless otherwise noted, the reactions were performed in CH2Cl2 as solvent at the final

concentration of 0.1 M in the presence of 1.1 equivalent of the mediator. bIsolated yields. cThe reaction was run in toluene. dSimilar yield was also obtained when the reaction was performed in the presence of 20 equivalents of methanol. eCatalytic amount (10 mol%) of the mediator was employed. fThe alcohol 14 was fully recovered. gSubstoichiometric (0.4 equivalent) of PtCl4 was used. h16 was contaminated with other impurities; thus, its exact yield could not be determined.

From Table 1, PTS-Si was the best mediator to affect the selective formation of indanol 15, 1,2disubstituted indene 16, and 2,3-disubstituted indene 17 using CH2Cl2 or toluene as solvent at different temperatures in 80, 85, and 88% yields, respectively (entries 1, 2, and 4). Indanol 15 was exclusively produced at room temperature with short reaction time while both indenes 16 and 17 required either longer reaction time and/or elevated temperature. It was anticipated that, under acidic conditions, 15 was one of the intermediates which could subsequently lead to the indene product(s). In addition, between the two possible indene products, the 1,2-disubstituted indene 16 was the kinetic product while the 2,3-disubstituted indene 17 would arise from the thermodynamic process. Indeed, heating 16 with PTS-Si in toluene at 80 °C for 18 h produced


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17 quantitatively. When compared with the use of p-TsOH under similar conditions, the use of PTS-Si accelerated reaction rates dramatically.16 In fact, heating 14 in the presence of stoichiometric amount of p-TsOH at 80 °C in toluene for 18 h gave 16 as the major product (76% yield) together with 17 as the minor product (7% yield) without any indanol 15 (entry 5). Use of Lewis acids such as La(OTf)3, Bi(OTf)3, and InCl3 gave 15, 16, or 17 in poorer yields or selectivities (entries 6-8). Using substoichiometric amount (40 mol%) of PtCl4 gave 15 in 87% yield (entry 9), which was slightly better than using stoichiometric amount of PTS-Si (entry 1), but the reaction using PtCl4 required longer reaction time. Catalytic amount (5-10 mol%) of PtCl4 under different conditions (entries 10-12) gave poorer results.17

Scope of substrates Preparation of (E)-(2-stilbenyl)methanols With the optimized conditions in hand, we next investigated the scope of substrates (18a-g; Figure 2) bearing different numbers and patterns of the methoxy groups on all three aromatic rings. All (E)-(2-stilbenyl)methanols were prepared accordingly from the corresponding 2bromobenzaldehydes via the two-step reactions of Heck and ArLi/ArMgBr addition in yields up to 98%. Interestingly, 2-bromo-5-methoxybenzaldehyde A underwent the Heck reaction under various conditions to not only provide the expected (E)-5-methoxy-2-styrylbenzaldehydes B and C (41 and 32% yields) but also, surprisingly, the (E)-4-methoxy-2-styrylbenzaldehydes B’ and C’ (34 and 31% yields) as shown in Scheme 2.18

Scheme 2. Heck reactions of A yielding products B, B’, C, and C’.



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Figure 2. Scope of substrates bearing different numbers and patterns of methoxy groups; R = OMe. aNumbers in parenthesis refer to yields from Heck and ArLi/ArMgBr reactions, respectively.


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Selective synthesis of indanols, indenes, and indanones The (E)-(2-stilbenyl)methanols 14 and 18a-g were subjected to cyclization using PTS-Si at low temperatures (0 °C or rt) for the selective synthesis of the corresponding 2,3-trans-diaryl-1indanols 15 and 19a-g, each of which was obtained as a ca.1:1 mixture of diastereomers at C1. Subsequent Dess-Martin periodinane (DMP) oxidation furnished some of the corresponding indanones 20 and 21a-g (Figure 3). The presence of two methoxy groups at the 3- and 5-position on the Ar1 significantly lowered the yields of the corresponding indanols (80% for 15 vs 47% for 19b; 72% for 19f vs 43% for 19h). The substrates 18f-k, with a methoxy group on the 4-position of the fused aromatic ring, gave higher yields of the indanol products (19f-k) than those with a methoxy group on the 5-position (18l-q). In addition, two series of the substrates 18l-q and 18x-g which possess at least one methoxy group on the 5-position of the fused aromatic ring did not give the corresponding indanols (19l-q and 19x-g). The corresponding 1,2-disubstituted indenes (22l-q and 22x-g) were obtained instead. This could be due to the electron-donating property via resonance of the 5-methoxy group which facilitated the regeneration of the indanyl cations from the elusive indanols; such indanyl cations then eventually underwent the subsequent loss of proton to furnish the 1,2-disubstituted indenes. Thus, without the indanols, the corresponding indanones (21l-q and 21x-g) could not be obtained. The substrates 18r-w, with two methoxy groups on the 4- and 6-position of the fused aromatic ring, gave the corresponding indanols 19rw but these products displayed instability upon purification on silica; yields of the corresponding oxidized products, namely the indanones 21r-w, were evaluated instead. Similar results were obtained for the substrates 18e and 18k. Over two steps, the substrates not bearing a methoxy group at the 5-position of the fused aromatic ring could furnish the corresponding indanones in moderate to good yields (27- 80%).



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Figure 3. 2,3-trans-Diaryl-1-indanols 15 and 19a-g, each obtained as ca. 1:1 mixture of diastereomers at C1, from the reactions of 14 and 18a-g and the subsequent oxidation by Dess-Martin periodinane (DMP) to furnish 20 and 21a-g; R = OMe. Dichloromethane was used as solvent for all reactions. aThese indanols appeared to be rather unstable under reaction conditions or towards purification and their isolated yields could not be obtained. The yields over two steps of cyclization followed by DMP oxidation were reported for the indanones. bThese indanols could not be obtained under all conditions successfully employed for other substrates; the reactions of the corresponding starting materials proceeded to furnish the corresponding 1,2-disubstituted indenes as the major products. Thus, no corresponding indanones could be prepared. ACS Paragon Plus Environment

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It should be noted that the indanone 21w was the known and reported precursor of the natural product paucifloral F. Thus, using our developed strategy, this intermediate indanone 21w could be prepared in 4 steps from the corresponding benzaldehyde and styrene derivatives via Heck reaction, ArLi addition, PTS-Si mediated cyclization, and DMP oxidation in 21% overall yield.19

We next turned our attention to the selective synthesis of the 1,2-disubstituted indenes. On the basis of the reaction condition developed for converting 14 to 16, substrates 18a-g were treated with PTS-Si at temperature (up to 40 °C) as well as reaction time (up to 18 h) as indicated for each substrate in Figure 4. Moderate to good yields of the desired products 22a-g could be obtained. Some trends similar to the results obtained for indanols could be observed. The presence of two methoxy groups at the 3- and 5-position on the Ar1 lowered the yields of the products significantly (85% for 16 vs 54% for 22b and 44% for 22e; 61% for 22f vs 41% for 22h and 47% for 22k; 78% for 22l vs 0% for 22n and 0% (instability) for 22q; 76% for 22r vs 17% for 22t and 29% for 22w; 68% for 22x vs 25% for 22z and 0% (instability) for 22g).

As shown in Figure 5, the corresponding 2,3-disubstituted indenes 23a-g could also be obtained selectively in moderate to excellent yields (up to 93%) over the 1,2-disubstituted indenes at higher temperatures (up to 110 °C). The substrates 18r-w, with the presence of two methoxy groups on the 4- and 6-position of the fused aromatic ring, did not furnish the corresponding products 23r-w; only the decomposition of the starting materials was observed. Similar to the results obtained for the indanols and the 1,2-disubstituted indenes, the presence of two methoxy groups at the 3- and 5-position on the Ar1 also lowered the yields of the corresponding products.



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Figure 4. 1,2-Disubstituted indenes 16 and 22a-g from the reactions of 14, 18a-g; R = OMe. Dichloromethane was used as solvent for those reactions performed at temperatures lower than 40 °C while dichloroethane for those at 40 °C. aThese 1,2-disubstituted indenes decomposed either under all reaction conditions successfully employed for other substrates or upon purification.


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Figure 5. 2,3-Disubstituted indenes 17 and 23a-g from the reactions of 14, 18a-g; R = OMe. Dichloromethane was used as solvent for reactions performed at temperatures lower than 40 °C while toluene for those at 80-110 °C. aThese 2,3-disubstituted indenes decomposed either under all reaction conditions successfully employed for other substrates or upon purification.



Preparation of (Z)-2-(stilbenyl)methanols In order to compare reactivity and reaction profiles between the substrates bearing an (E)- or (Z)olefin geometry, some (Z)-2-(stilbenyl)methanols 24a-d were synthesized as shown in Scheme 3. For simplicity, both Ar1 and Ar2 were arbitrarily chosen to be phenyl groups. First, the Sonogashira cross-coupling reactions20 between 2-bromo- or 2-iodobenzaldehydes 25a-d and phenylacetylene provided the diarylacetylene aldehydes 26a-d in good to excellent yields (up to 97%). Unfortunately, subsequent hydrogenation using Lindlar’s catalyst did not proceed to give 27a-d. Moreover, PhMgBr addition to the diarylacetylene aldehyde 26a gave the corresponding alkyne-containing diarylmethanol product; however, Lindlar’s hydrogenation under various conditions was not successful. Thus, the aldehyde of 26a-d was first reduced to the corresponding benzyl alcohols 28a-d which then underwent the hydrogenation smoothly to furnish the (Z)-stilbenylmethanols 29a-d in good to excellent yields (up to 97%). The ensuing PCC/DMP oxidation then re-installed the requisite aldehyde functional group and furnished 27ad for the final PhMgBr addition to give the (Z)-2-(stilbenyl)methanols 24a-d.

Acid-mediated cyclization of the (Z)-(2-stilbenyl)methanols First, it was anticipated that the PTS-Si-mediated cyclization of the (Z)-24a would lead to an indanol product 25 whose C2-C3 relative stereochemistry would be compared directly with the C2-C3 trans relative stereochemistry of the indanol 15 from the similar reaction of (E)-14. Unfortunately, upon treating (Z)-24a with PTS-Si at rt, only the 1,2-disubstituted indene 16 was obtained in 90% yield. Lowering the temperature to 0, -20 or even -40 °C did not affect the outcome of this reaction. Similar results were also obtained from treating (Z)-24c with PTS-Si at low temperatures; only the 1,2-disubstituted indene 22l was obtained in 95% yield (Scheme 4).


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Scheme 3. Preparation of (Z)-(2-stilbenyl)methanols 24a-d.

Since it is not possible to infer the mode of cyclization involving in the PTS-Si-mediated cyclization of both (Z)-24a and (Z)-24c due to the loss of stereochemical outcome on C2, we considered the use of hydride (Et3SiH) or azide (TMSN3) as the nucleophile while employing BF3·Et2O as Lewis acid instead of PTS-Si. As shown in Scheme 4, the presence of a methoxy group at the 5-position of the fused aromatic ring (24c and 24d) directed the reactions towards the formation of the corresponding indane derivatives (30a-d) as the products in moderate to excellent yields (41-94%). More importantly, all the products were obtained as single diastereomers with the cis C2-C3 relationship. This is in sharp contrast to similar reactions using the substrates with (E)-olefin (14, 18f, 18l, and 18x) all of which furnished the indane products (32a-32h) with the trans C2-C3 relationship exclusively in moderate to good yields (58-90%). It



should be noted that the indane azide derivatives 32d, 32f, and 32h were obtained as 2.5:1, 4.6:1, and 5.9:1 mixtures of diastereomers at C1, respectively, with the denoted diastereomers in Scheme 4 as the major isomers. Compound 32e was also obtained as a 7.7:1 mixture of diastereomers of C2-C3 trans and C2-C3 cis.

Scheme 4. Modes of acid-mediated cyclization of (Z)- and (E)-(2-stilbenyl)methanols. Compounds 32a, 32b, and 32g were previously reported.15 aThese indane azide derivatives were obtained as mixtures of diastereomers at C1 with the major isomers as denoted (32d as a 2.5:1 mixture; 32f as a 4.6:1 mixture; 32h as a 5.9:1 mixture). bA mixture of C2-C3 trans:C2-C3 cis (7.7:1) was obtained.


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As shown in Figure 6, NOE could be utilized to distinguish between 2,3-cis and 2,3-trans indane products (ca. 3% NOE was observed on H3 upon irradiating H2 for the 2,3-cis isomer; only 1% NOE was observed on H3 for the 2,3-trans isomer).

Figure 6. Selected NOE data for indane derivatives 30a, 30b, and 30d with 2,3-cis relationship and 32h with 2,3-trans relationship. In contrast to the results obtained from (Z)-24c and (Z)-24d, (Z)-24a and (Z)-24b, upon reacting with Et3SiH and TMSN3, gave the corresponding diarylmethane 31a-31d instead of the indane derivatives (Scheme 4).

Mechanistic implications The formation of 31a-d, with the intact (Z)-olefin, from the substrates (Z)-24a and (Z)-24b indicated that no isomerization of the (Z)- to (E)-olefin occurred during the acid-mediated cyclization (Scheme 5). The fact that the products (30a-d) with the exclusive C2-C3 cis relationship were obtained from the substrates (Z)-24c, d while the products (32a-h) with the exclusive C2-C3 trans relationship from the substrates (E)-14, and (E)-18f, l, x implied no common intermediates (i.e. 33 and 34) for the acid-mediated cyclization/nucleophilic transfer between these two geometrical isomers of the substrates. Instead, distinct species (i.e. 35 and 36) were plausible intermediates for the cyclization reactions of (Z)-24c, d to account for the C2-C3 cis relationship in the products.21



Scheme 5. Mechanistic understanding of the BF3·Et2O-mediated cyclization/nucleophilic transfer of (Z)- and (E)-(2-stilbenyl)methanols.

For the (Z)-olefin containing substrates, isolation of the diarylmethanes 31a-d, also containing the (Z)-olefin, clearly supported the intermediacy of the carbocation 35 formed as a result of BF3·Et2O-mediated ionization of the hydroxy group. Generation of different types of products (indanes vs diarylmethanes) obtained from the reactions of the substrates bearing the (Z)- or (E)olefin also suggested that the p electrons of the (E)-geometry could achieve better alignment with the empty p-orbital of the carbocation 33 via sigma bond rotation ((E)-s-trans and the (E)-scis),22 leading to cyclization which then afforded the indane derivatives upon nucleophilic addition to the 2,3-trans-indanyl cation 34. On the other hand, in case of 24a, b, due to the steric


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factor which restricted the sigma bond rotation from (Z)-s-trans to (Z)-s-cis to achieve appropriate alignment for cyclization,22 the intermolecular nucleophilic addition by hydride/azide to the carbocation 35 prevailed over the intramolecular addition by the p electrons of the (Z) olefin. As a result, the diarylmethanes were obtained instead of the indanes. This type of preferential modes of reactions for the (Z)-olefin could be overcome by the presence of a methoxy group on the 5-position of the fused aromatic ring. Resonance of the lone pair electrons on the 5-methoxy substituent (Scheme 6; A, B, and D) through the aromatic ring increased the nucleophilicity of the p electrons of the (Z)-olefin, thus facilitating the intramolecular cyclization over the intermolecular nucleophilic addition and providing the indane products over the diarylmethanes.



Scheme 6. Contribution of the 5-methoxy substituent on the increased nucleophilicity to facilitate cyclization and formation of the 1,2-disubstituted indenes and 18O incorporation of the indanol 15 when H218O was employed.

When PTS-Si was employed as the mediator and water as the nucleophile, the substrates bearing a methoxy group at the 5-position, regardless of the olefin geometry (18l-q and 18x-g for the (E)substrates and 24c for the (Z)-substrate), did not furnish the expected indanols (Scheme 6; E) as the products. Instead, the 1,2-disubstituted indenes (F) were produced in good yields. This observation could also be accounted for by the contribution of the lone pair electrons of the 5methoxy substituent via resonance (A and B). It is likely that the indanols were formed but underwent further reactions to furnish the 1,2-disubstituted indenes under the acidic reaction condition. In case of 24a, even without the 5-methoxy substituent, the corresponding indanol was not obtained. Assumingly, cyclization of 24a was likely to provide the corresponding indanyl cation bearing the 2,3-cis relationship while that of 14 would provide the indanyl cation bearing the 2,3-trans relationship (similar to C and D, Scheme 6). This difference may contribute greatly to the stability of the final indanol—15 from the 2,3-trans indanyl cation was sufficiently stable while the other from the 2,3-cis indanyl cation was not. The 2,3-cis indanyl cation then underwent the subsequent loss of proton more readily to generate the corresponding 1,2disubstituted indene 16. In addition, the use of H218O during the formation of the indanol 15 from 14 also ascertained that the hydroxy group in the indanol was likely to arise from the intermolecular quenching of water to the corresponding indanyl cation.23

Conclusion


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A selective divergent process which converted the common intermediate 2-stilbenylmethanols into the corresponding distinct products—diarylmethanes, indanols, 1,2-, and 2,3-disubstituted indenes—could be successfully developed by using PTS-Si or BF3·Et2O as the mediator under different sets of reaction conditions. The olefin geometry in the substrates determined the extent of delocalization of the p electrons of the olefin with the empty p-orbital of the initial carbocation. The (E)-olefin provided better alignment for this overlapping and the reactions favored the cyclization to form the indanyl cation which subsequently underwent nucleophilic addition to furnish the corresponding indane derivatives. The (Z)-olefin, on the other hand, disallowed the required optimal alignment for cyclization; the diarylmethanes were virtually obtained as the exclusive products. However, the cyclized products could be obtained from the substrates containing the (Z)-olefin and a 5-methoxy substituent on the fused aromatic ring; the 5-methoxy substituent could increase the nucleophilicity of the olefin towards the intramolecular cyclization via resonance. In addition, the difference in the olefin geometry also determined the stereochemical outcome at C2 and C3 of the cyclized indane products: 2,3-cis from the (Z)-olefin and 2,3-trans from the (E)-olefin. Upon ionization of 2-stilbenylmethanols using PTS-Si, water was the by-product which, in the absence of other nucleophiles, could act as a nucleophile to quench the indanyl cation to furnish the corresponding indanols. With the use of H218O labelling, we demonstrated clearly that the quenching was intermolecular in nature. The presence of a 5-methoxy substituent on the fused aromatic ring also favored the cyclization; however, the corresponding indanols could not be obtained from both (Z)- and (E)-substrates. Presumably, the elusive indanols were formed but not stable under reaction conditions and underwent further reactions to give the more stable 1,2disubstituted indenes as the products. Heating the reactions to approximately 40 °C also helped



direct them towards the formation of the kinetically favored 1,2-disubstituted indenes while heating to 80-100 °C would favor the formation of the thermodynamic 2,3-disubstituted indenes. Further DMP oxidation of the indanols also furnished the corresponding indanones, which are structurally related to the natural product, paucifloral F. Thus, over 3-6 steps, the desired stereochemically defined products could be obtained exclusively under different reaction conditions in moderate to excellent yields with complete stereocontrol. Applications of this developed chemistry towards the synthesis of other biologically active compounds and their biological evaluations will be reported in due course.

Experimental

General Experimental Methods. Unless otherwise noted, reactions were run in oven-dried round-bottomed flasks. Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl or purified by the solvent purification system while dichloromethane (CH2Cl2) was also purified by the solvent purification system prior to use. All other compounds were used as received from the suppliers; PTS-Si (p-TsOH immobilized on silica) employed in these experiments possessed the surface area of 500 m2/g as indicated by the supplier. The crude reaction mixtures were concentrated under reduced pressure by removing organic solvents on rotary evaporator. Column chromatography was performed using silica gel 60 (particle size 0.06-0.2 mm; 70-230 mesh ASTM). Analytical thin-layer chromatography (TLC) was performed with silica gel 60 F254 aluminum sheets. Chemical shifts for 1H nuclear magnetic resonance (NMR) spectra were reported in parts per million (ppm, d) downfield from tetramethylsilane. Splitting patterns are described as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), broad (br), doublet of


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doublet (dd), doublet of triplet (dt), and doublet of doublet of doublet (ddd). Resonances for infrared (IR) spectra were reported in wavenumbers (cm-1). Low resolution (LRMS) mass spectra were obtained either using electron ionization (EI) or time-of-flight (TOF) while high resolution (HRMS) mass spectra were obtained using time-of-flight (TOF) via the atmosphericpressure chemical ionization (APCI) or electrospray ionization (ESI). Melting points were uncorrected.

General Procedure for the Heck Reaction. To a stirred solution bromobenzaldehyde (1 equiv) in N, N-dimethylformamide (DMF) was added

styrene

(2

equiv),

sodium

carbonate

(Na2CO3,

2

equiv),

and

bis-

(triphenylphosphine)palladium(II) for i1-6, 9, 10 or Tris(dibenzylideneacetone)dipalladium(0) with Tri(o-tolyl)phosphine for i7-8 (0.1 equiv). The reaction mixture was heated to 120 °C for 18 h. Then, the reaction was allowed to cool to room temperature. The palladium was removed through cilite followed by added water and ethyl acetate (EtOAc); the two phases were separated. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was further purified by column chromatography on silica (EtOAc/hexanes) to furnish the desired products (i1-10).

(E)-2-Styrylbenzaldehyde (i1)



Page 24 of 110

Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow oil (854 mg, 4.105 mmol, 68%). Rf (20% EtOAc/hexane) 0.50. IR (UATR): nmax 3061, 2739, 1690, 1595, 1186 cm-1. 1H NMR (300 MHz, CDCl3): δ 10.19 (s, 1H), 7.98 (d, J = 16.2 Hz, 1H), 7.71 (dd, J = 7.7, 1.5 Hz, 1H), 7.64 – 7.54 (m, 1H), 7.53 – 7.38 (m, 3H), 7.38 – 7.16 (m, 4H), 6.95 (d, J = 16.2 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 192.2, 139.4, 136.6, 133.5, 133.3, 132.6, 132.1, 128.5, 128.0, 127.3, 126.7, 126.7, 124.4. LRMS (EI) m/z (rel intensity) 208 (M+, 100), 179 (48), 165 (32). TOF-HRMS calcd for C15H13O (M+H+) 209.0961, found 209.0954. These spectroscopic data were identical to those reported previously.15

(E)-2-(4-Methoxystyryl)benzaldehyde (i2) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow solid (2.03 g, 8.54 mmol, 99%) mp 83-84 °C. Rf (10% EtOAc/hexane) 0.25. IR (UATR): nmax 2836, 1690, 1605, 1510, 1247, 1173 cm-1. 1H NMR (400 MHz, CDCl3): δ 10.31 (s, 1H), 7.92 (d, J = 16.2 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.40 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 16.2 Hz, 1H), 6.92 (d, J = 8.4 Hz, 2H), 3.83 (s, 3H).

13

C NMR (101 MHz,

CDCl3): 192.66, 159.74, 140.23, 133.60, 133.51, 132.61, 132.15, 129.63, 128.22, 127.12, 126.84, 122.31, 114.12, 55.25. LRMS (EI) m/z (rel intensity) 238 (M+, 100), 209 (24), 179 (40), 108 (47). TOF-HRMS calcd for C16H15O2 (M+H+) 239.1067, found 239.1070. These spectroscopic data were identical to those reported previously.14b


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(E)-4-Methoxy-2-styrylbenzaldehyde (i3) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (436 mg, 1.83 mmol, 78%). Rf (20% EtOAc/hexane) 0.37. IR (UATR): nmax 1682, 1592, 1290, 1234 cm-1. 1H NMR (300 MHz, CDCl3): d 10.16 (s, 1H), 8.06 (d, J = 16.2 Hz, 1H), 7.78 (d, J = 8.6 Hz, 1H), 7.55 (d, J = 7.4 Hz, 2H), 7.40 – 7.23 (m, 3H), 7.15 (d, J = 2.5 Hz, 1H), 7.03 (d, J = 16.2 Hz, 1H), 6.92 (dd, J = 8.6, 2.5 Hz, 1H), 3.91 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 191.1, 163.7, 142.2, 136.7, 135.0,

133.7, 128.7, 128.3, 126.9, 126.8, 124.8, 113.1, 111.9, 55.5. LRMS (EI) m/z (rel intensity) 238 (M+, 100), 194 (21), 165 (26). TOF-HRMS calcd for C16H14NaO2 (M+Na+) 261.0886, found 261.0890. These spectroscopic data were identical to those reported previously.24

(E)-4-Methoxy-2-(4-methoxystyryl)benzaldehyde (i4) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow solid (1.19 g, 4.43 mmol, 63%) mp 79-80 °C. Rf (20% EtOAc/hexane) 0.26. IR (UATR): nmax 1677, 1593, 1509, 1248, 1173 cm-1. 1H NMR (300 MHz, CDCl3): d 10.14 (s, 1H), 7.91 (d, J = 16.2 Hz, 1H), 7.74 (d, J = 8.6 Hz, 1H), 7.51 – 7.44 (m, 2H), 7.12 (d, J = 2.5 Hz, 1H), 6.98 (d, J = 16.2 Hz, 1H), 6.95 – 6.81 (m, 3H), 3.88 (s, 3H), 3.80 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 191.0, 163.6, 142.1, 136.71, 135.0, 133.7,



128.7, 128.2, 126.9, 126.7, 124.8, 113.1, 111.8, 55.5. LRMS (EI) m/z (rel intensity) 268 (M+, 100), 253 (30). TOF-HRMS calcd for C17H16NaO3 (M+Na+) 291.0992, found 291.0993. These spectroscopic data were identical to those reported previously.25

(E)-5-Methoxy-2-styrylbenzaldehyde (i5) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow sticky (380 mg, 1.60 mmol, 34%). Rf (20% EtOAc/hexane) 0.37. IR (UATR): nmax 3422, 1768, 1687, 1602, 1495, 1264, 1028 cm-1. 1H NMR (300 MHz, CDCl3): d 10.32 (s, 1H), 7.89 (d, J = 16.1 Hz, 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.57 – 7.49 (m, 2H), 7.42 – 7.25 (m, 4H), 7.11 (dd, J = 8.7, 2.8 Hz, 1H), 6.93 (d, J = 16.2 Hz, 1H), 3.83 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 191.5, 158.9, 136.8, 133.5, 132.7 132.2, 128.5, 128.3,

127.7, 126.5, 123.5, 120.7, 113.8, 55.2. LRMS (EI) m/z (rel intensity) 238 (M+, 100), 178 (44). TOF-HRMS calcd for C16H14NaO2 (M+Na+) 261.0886, found 261.0889. These spectroscopic data were identical to those reported previously.14b

(E)-5-Methoxy-2-(4-methoxystyryl)benzaldehyde (i6) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow solid (399 mg, 1.49 mmol, 32%) mp 93-95 °C. Rf (30% EtOAc/hexane) 053. IR (UATR): nmax 3453, 1685, 1606, 1510, 1249 cm-1. 1H NMR (300 MHz, CDCl3): d 10.31 (s, 1H), 7.71 (d, J = 16.1 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.48 –


Page 26 of 110

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7.40 (m, 2H), 7.30 (d, J = 2.8 Hz, 1H), 7.09 (dd, J = 8.7, 2.9 Hz, 1H), 6.91 – 6.81 (m, 3H), 3.83 (s, 3H), 3.79 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 191.7, 159.5, 158.8, 133.5, 133.5, 132.2,

129.8, 128.4, 127.9, 121.3, 121.1, 114.1, 113.5, 55.4, 55.2. LRMS (EI) m/z (rel intensity) 268 (M+, 100), 160 (24). TOF-HRMS calcd for C17H16NaO3 (M+Na+) 291.0992, found 291.0988.

(E)-2,4-Dimethoxy-6-styrylbenzaldehyde (i7) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow solid (267 mg, 0.998 mmol, 82%) mp 75-76 °C. Rf (20% EtOAc/hexane) 0.33. IR (UATR): nmax 1669, 1589, 1340, 1203, 1149 cm-1. 1H NMR (300 MHz, CDCl3): d 10.47 (s, 1H), 8.14 (d, J = 16.2 Hz, 1H), 7.56 – 7.50 (m, 2H), 7.35 – 7.20 (m, 3H), 6.95 (d, J = 16.2 Hz, 1H), 6.69 (d, J = 2.3 Hz, 1H), 6.31 (d, J = 2.3 Hz, 1H), 3.81 (s, 3H), 3.78 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 190.5, 164.9, 164.6, 142.8, 137.1, 132.4,


(E)-2,4-Dimethoxy-6-(4-methoxystyryl)benzaldehyde (i8) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as brown solid (542 mg, 1.82 mmol, 74%) mp 115118 °C. Rf (20% EtOAc/hexane) 0.25. IR (UATR): nmax 1667, 1591, 1510, 1246, 1151 cm-1. 1H



Page 28 of 110

NMR (300 MHz, CDCl3): d 1H NMR (300 MHz, Chloroform-d) δ 10.51 (s, 1H), 8.06 (d, J = 16.2 Hz, 1H), 7.52 – 7.46 (m, 2H), 6.96 (d, J = 16.2 Hz, 1H), 6.91 – 6.85 (m, 2H), 6.73 (d, J = 2.3 Hz, 1H), 6.36 (d, J = 2.3 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 3.81 (s, 3H).

13

C NMR (75

MHz, CDCl3): d 190.6, 164.9, 164.5, 159.6, 143.1, 132.1, 130.0, 128.3, 125.4, 116.0, 114.0, 103.3, 96.8, 55.8, 55.5, 55.2. LRMS (EI) m/z (rel intensity) 298 (M+, 46), 190 (100). TOFHRMS calcd for C18H18NaO4 (M+Na+) 321.1097, found 321.1104. These spectroscopic data were identical to those reported previously.26

(E)-4,5-Dimethoxy-2-styrylbenzaldehyde (i9) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow solid (226 mg, 0.84 mmol, 69%) mp 133134 °C. Rf (30% EtOAc/hexane) 0.39. IR (UATR): nmax 1663, 1589, 1508, 1272, 1097 cm-1. 1H NMR (400 MHz, CDCl3): d 10.32 (s, 1H), 7.89 (d, J = 16.1 Hz, 1H), 7.55 (d, J = 7.6 Hz, 2H), 7.44 – 7.25 (m, 4H), 7.10 (s, 1H), 6.97 (d, J = 16.1 Hz, 1H), 4.03 (s, 3H), 3.96 (s, 3H). 13C NMR (101 MHz, CDCl3): d 190.0, 153.7, 148.9, 136.8, 135.6, 133.3, 128.8, 128.3, 126.8, 126.5, 123.6, 111.1, 108.8, 56.2, 56.1. TOF-HRMS calcd for C17H17O3 (M+H+) 269.1172, found 269.1179. These spectroscopic data were identical to those reported previously.15

(E)-4,5-Dimethoxy-2-(4-methoxystyryl)benzaldehyde (i10)


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Following the general procedure and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as yellow solid (235 mg, 0.79 mmol, 65%) mp 122124 °C. Rf (30% EtOAc/hexane) 0.33. IR (UATR): nmax 2933, 1669, 1593, 1509, 1268, 1099 cm. H NMR (300 MHz, CDCl3): d 10.29 (s, 1H), 7.72 (d, J = 16.1 Hz, 1H), 7.50 – 7.43 (m, 2H),

1 1

7.34 (s, 1H), 7.06 (s, 1H), 6.94 – 6.86 (m, 3H), 4.00 (s, 3H), 3.93 (s, 3H), 3.82 (s, 3H). 13C NMR (75 MHz, CDCl3): d 189.9, 159.6, 153.6, 148.5, 135.9, 132.7, 129.5, 127.9, 126.2, 121.1, 114.1, 110.9, 108.5, 56.0, 55.9, 55.2. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 267 (22). TOFHRMS calcd for C18H18NaO4 (M+Na+) 321.1097, found 321.1095.

General Procedure for the Synthesis of (E)-(2-stilbenyl)methanol A: To a stirred solution 0.1 M (1 equiv) of (E)-2-styrylbenzaldehyde in dry ether for phenylmagnesium bromide or dry THF for 4-methoxyphenyl magnesium bromide at 0°C under argon atmosphere was added phenylmagnesium bromide or 4-methoxyphenyl magnesium bromide (1.2 equiv). The reaction mixture was stirred at 0 °C for 30 min, then warmed to room temperature and stirred until all of the starting material was consumed as monitored by TLC. B: To a stirred solution 0.1 M (2 equiv) of 1-Bromo-3,5-dimethylbenzene in dry THF at -78 °C under argon atmosphere was added tert-Butyllithium (3 equiv). The reaction mixture was stirred at -78 °C for 30 min then added of (E)-2-styrylbenzaldehyde (1 equiv) and stirred at -78 °C for 30 min before warmed to room temperature and stirred until all of the starting material was consumed as monitored by TLC. Water and EtOAc were added, and the two phases were separated. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was



Page 30 of 110

further purified by column chromatography on silica (EtOAc/hexanes) to furnish the desired products.

(E)-Phenyl(2-styrylphenyl)methanol (14) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (580 mg, 2.03 mmol, 91%) mp 110-111 °C. Rf (20% EtOAc/hexane) 0.33. 1H NMR (400 MHz, CDCl3): d 7.65 – 7.57 (m, 1H), 7.54 – 7.45 (m, 1H), 7.43 – 7.19 (m, 13H), 6.93 (d, J = 16.1 Hz, 1H), 6.21 (s, 1H), 2.17 (brs, 1H). 13C NMR (101 MHz, CDCl3): d 143.0, 140.7, 137.3, 135.8, 131.1, 128.6, 128.5, 127.9, 127.7, 127.7, 127.5, 127.1, 126.6, 126.3, 125.8, 73.3. These spectroscopic data were identical to those reported previously.15

(E)-(4-Methoxyphenyl)(2-styrylphenyl)methanol (18a) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (622 mg, 1.97 mmol, 84%). Rf (20% EtOAc/hexane) 0.22. 1H NMR (300 MHz, CDCl3): d 7.58 – 7.43 (m, 2H), 7.41 – 7.12 (m, 10H), 6.92 – 6.68 (m, 3H), 6.02 (s, 1H), 3.68 (s, 3H), 2.60 (brs, 1H).

13

C NMR (75 MHz,

CDCl3): d 159.0, 141.0, 137.4, 135.7, 135.4, 131.1, 128.7, 128.2, 127.8, 127.8, 127.7, 126.8, 126.6, 126.3, 126.0, 114.0, 73.0, 55.3.LRMS (EI) m/z (rel intensity) 316 (M+, 12), 298 (23), 225 (100). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1360. These spectroscopic data were identical to those reported previously.12h

(E)-(3,5-Dimethoxyphenyl)(2-styrylphenyl)methanol (18b)


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Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (631 mg, 1.82 mmol, 81%). Rf (20% EtOAc/hexane) 0.22. IR (UATR): nmax 3416, 1596, 1460, 1203, 1154 cm-1. 1H NMR (300 MHz, CDCl3): d 7.55 – 7.44 (m, 1H), 7.43 – 7.32 (m, 4H), 7.31 – 7.11 (m, 5H), 6.85 (d, J = 16.1 Hz, 1H), 6.48 (d, J = 2.3 Hz, 2H), 6.28 (t, J = 2.3 Hz, 1H), 5.94 (s, 1H), 3.59 (s, 6H), 2.97 (s, 1H). 13

C NMR (75 MHz, CDCl3): d 160.6, 145.6, 140.5, 137.2, 135.6, 130.7, 128.5, 127.7, 127.6,

127.5, 126.9, 126.4, 126.0, 125.9, 104.6, 99.3, 73.0, 55.0. LRMS (EI) m/z (rel intensity) 346 (M+, 46), 254 (89), 178 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1467.

(E)-(2-(4-Methoxystyryl)phenyl)(phenyl)methanol (18c) Following the general procedure A and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as pale yellow solid (386 mg, 1.22 mmol, 88%) mp 79-80 °C. Rf (20% EtOAc/hexane) 0.45. IR (UATR): nmax 3421, 3029, 1605, 1510, 1248, 1175, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.61 – 7.54 (m, 1H), 7.51 – 7.42 (m, 1H), 7.42 – 7.19 (m, 10H), 6.93 – 6.81 (m, 3H), 6.18 (s, 1H), 3.81 (s, 3H), 2.24 (s, 1H).

13

C NMR (75 MHz,

CDCl3): d 159.4, 143.1, 140.5, 136.1, 130.7, 130.2, 128.5, 127.9, 127.8, 127.5, 127.4, 127.1, 126.8, 126.2, 123.7, 114.1, 73.4, 55.3. LRMS (EI) m/z (rel intensity) 316 (M+, 6), 121 (100). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1369. These spectroscopic data were identical to those reported previously.15,12h

(E)-(4-Methoxyphenyl)(2-(4-methoxystyryl)phenyl)methanol (18d)



Page 32 of 110

Following the general procedure A and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as yellow sticky (182 mg, 0.53 mmol, 83%). Rf (30% EtOAc/hexane) 0.24. IR (UATR): nmax 3482, 1606, 1509, 1246, 1173 cm-1. 1H NMR (300 MHz, CDCl3): d 7.48 – 7.33 (m, 2H), 7.26 – 7.04 (m, 7H), 6.79 – 6.67 (m, 5H), 5.96 (s, 1H), 3.67 (s, 3H), 3.62 (s, 3H), 2.43 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.2, 158.8, 140.7, 135.8, 135.4, 130.4, 130.2, 128.1, 127.7, 127.6, 127.3, 126.6, 125.9, 123.7, 114.0, 113.8, 72.7, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 346 (M+, 6), 225 (35), 121 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1444.

(E)-(3,5-Dimethoxyphenyl)(2-(4-methoxystyryl)phenyl)methanol (18e) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (167 mg, 0.44 mmol, 99%). Rf (30% EtOAc/hexane) 0.37. IR (UATR): nmax 3451, 1595, 1510, 1248, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 – 7.44 (m, 1H), 7.36 – 7.14 (m, 6H), 6.86 – 6.74 (m, 3H), 6.49 – 6.45 (m, 2H), 6.27 (t, J = 2.3 Hz, 1H), 6.01 (s, 1H), 3.73 (s, 3H), 3.64 (s, 6H), 2.29 (brs, 1H).

13

C NMR (75

MHz, CDCl3): d 160.8, 159.3, 145.7, 140.3, 136.2, 130.7, 130.2, 127.9, 127.8, 127.4, 127.1, 126.1, 123.9, 114.1, 104.8, 99.5, 73.3, 55.3, 55.3. LRMS (EI) m/z (rel intensity) 376 (M+, 6), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1572.

(E)-(4-Methoxy-2-styrylphenyl)(phenyl)methanol (18f) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (187 mg, 0.59 mmol, 94%) mp 101-102 °C. Rf (20% EtOAc/hexane) 0.20. IR (UATR): nmax 3421, 1602, 1493, 1279 cm-1. 1H NMR (300


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MHz, CDCl3): d 7.36 – 7.13 (m, 12H), 7.04 (d, J = 2.7 Hz, 1H), 6.84 (d, J = 16.1 Hz, 1H), 6.74 (dd, J = 8.6, 2.7 Hz, 1H), 6.05 (s, 1H), 3.75 (s, 3H), 2.20 (brs, 1H). 13C NMR (75 MHz, CDCl3):

d 159.2, 143.4, 137.2, 133.5, 131.3, 128.8, 128.7, 128.4, 127.8, 127.4, 126.6, 126.6, 125.8, 113.2, 111.5, 73.0, 55.3. LRMS (EI) m/z (rel intensity) 316 (M+, 15), 225 (100). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1354.

(E)-(4-Methoxy-2-styrylphenyl)(4-methoxyphenyl)methanol (18g) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (573 mg, 1.66 mmol, 95%). Rf (20% EtOAc/hexane) 0.17. IR (UATR): nmax 3461, 2835, 1602, 1509, 1281, 1246, 1170, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.43 – 7.13 (m, 9H), 7.08 (d, J = 2.7 Hz, 1H), 6.92 – 6.71 (m, 4H), 5.99 (s, 1H), 3.76 (s, 3H), 3.69 (s, 3H), 2.79 – 2.63 (m, 1H).

13

C NMR (75 MHz,

CDCl3): d 158.8, 158.7, 137.2, 136.8, 135.6, 133.7, 130.9, 128.5, 128.3, 127.9, 127.6, 126.5, 125.8, 113.7, 113.0, 111.3, 72.3, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 346 (M+, 14), 255 (100), 165 (41). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1456.

(E)-(3,5-Dimethoxyphenyl)(4-methoxy-2-styrylphenyl)methanol (18h) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (535 mg, 1.42 mmol, 84%). Rf (20% EtOAc/hexane) 0.12. IR (UATR): nmax 3462, 1595, 1457, 1288, 1203, 1152, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.45 – 7.35 (m, 3H), 7.32 – 7.15 (m, 4H), 7.06 (d, J = 2.7 Hz, 1H), 6.87 (d, J = 16.1 Hz, 1H), 6.73 (dd, J = 8.6, 2.7 Hz, 1H), 6.50 (d, J = 2.3 Hz, 2H), 6.29 (s, 1H), 5.94 (s,



1H), 3.73 (s, 3H), 3.62 (s, 6H), 3.14 (brs, 1H).

13

C NMR (75 MHz, CDCl3): d 160.6, 158.9,

146.0, 137.2, 137.0, 133.3, 130.9, 128.6, 128.5, 127.6, 126.5, 125.9, 113.0, 111.2, 104.5, 99.2, 72.6, 55.0, 55.0. LRMS (EI) m/z (rel intensity) 376 (M+, 36), 284 (100), 254 (42). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1563.

(E)-(4-Methoxy-2-(4-methoxystyryl)phenyl)(phenyl)methanol (18i) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (469 mg, 1.35 mmol, 91%) mp 116-117 °C. Rf (40% EtOAc/hexane) 0.50. IR (UATR): nmax 3422, 1602, 1510, 1283, 1249, 1174, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.40 – 7.20 (m, 9H), 7.10 (d, J = 2.7 Hz, 1H), 6.91 – 6.84 (m, 3H), 6.80 (dd, J = 8.6, 2.7 Hz, 1H), 6.13 (s, 1H), 3.83 (s, 3H), 3.81 (s, 3H), 2.24 (d, J = 3.2 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 159.4, 159.1, 143.5, 137.5, 133.3, 130.8, 130.1, 128.7, 128.4, 127.9, 127.3, 126.6, 123.6, 114.1, 112.9, 111.3, 72.9, 55.3. LRMS (EI) m/z (rel intensity) 346 (M+, 3), 121 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1461.

(E)-(4-methoxy-2-(4-methoxystyryl)phenyl)(4-methoxyphenyl)methanol (18j) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as light yellow sticky (448 mg, 1.19 mmol, 99%). Rf (20% EtOAc/hexane) 0.19. IR (UATR): nmax 3482, 1601, 1509, 1246, 1172, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.36 – 7.31 (m, 3H), 7.28 – 7.23 (m, 2H), 7.18 (s, 1H), 7.08 (d, J = 2.7 Hz, 1H), 6.89 – 6.77 (m, 6H), 6.06 (s, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 3.75 (s, 3H), 2.33 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.4, 159.0, 158.8, 137.3, 135.7, 133.5, 130.6, 130.1, 128.3, 127.9, 127.8, 123.7, 114.1, 113.8, 112.8, 111.2, 72.5, 55.3, 55.2. LRMS (EI) m/z (rel intensity) 376 (M+,


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8), 358 (25), 255 (63), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1577.

(E)-(3,5-Dimethoxyphenyl)(4-methoxy-2-(4-methoxystyryl)phenyl)methanol (18k) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (454 mg, 1.12 mmol, 60%). Rf (40% EtOAc/hexane) 0.41. IR (UATR): nmax 3482, 1598, 1510, 1462, 1284, 1249, 1153, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.42 – 7.34 (m, 3H), 7.31 (d, J = 2.8 Hz, 1H), 7.11 (d, J = 2.6 Hz, 1H), 6.94 – 6.85 (m, 3H), 6.78 (dd, J = 8.6, 2.7 Hz, 1H), 6.56 (d, J = 1.8 Hz, 2H), 6.35 (t, J = 2.3 Hz, 1H), 6.02 (s, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.71 (s, 6H), 2.94 (s, 1H). 13C NMR (75 MHz, CDCl3): d 160.6, 159.2, 158.9, 146.1, 137.4, 133.2, 130.5, 130.0, 128.6, 127.7, 123.7, 113.9, 112.7, 111.0, 104.5, 99.1, 72.6, 55.1, 55.1, 55.1. LRMS (EI) m/z (rel intensity) 406 (M+, 10), 121 (100). TOF-HRMS calcd for C25H26NaO5 (M+Na+) 429.1672, found 429.1672.

(E)-(5-Methoxy-2-styrylphenyl)(phenyl)methanol (18l) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (391 mg, 1.24 mmol, 98%) mp 84-85 °C. Rf (20% EtOAc/hexane) 0.26. IR (UATR): nmax 3428, 2925, 1605, 1496, 1450 cm-1. 1H NMR (400 MHz, CDCl3): d 7.49 (d, J = 8.6 Hz, 1H), 7.38 – 7.24 (m, 8H), 7.24 – 7.17 (m, 3H), 7.07 (s, 1H), 6.84 – 6.74 (m, 2H), 6.07 (s, 1H), 3.74 (s, 3H), 2.55 (s, 1H). 13C NMR (100 MHz, CDCl3):

d 159.3, 142.8, 142.2, 137.6, 129.1, 128.6, 128.5, 128.1, 127.5, 127.4, 127.3, 126.8, 126.9, 125.3, 113.4, 112.2, 73.0, 55.2. LRMS (EI) m/z (rel intensity) 316 (M+, 23), 225 (100). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1342.



(E)-(5-Methoxy-2-styrylphenyl)(4-methoxyphenyl)methanol (18m) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (528 mg, 1.53 mmol, 91%). Rf (20% EtOAc/hexane) 0.19. 1H NMR (400 MHz, CDCl3): d 7.53 (d, J = 8.6 Hz, 1H), 7.40 – 7.18 (m, 8H), 7.15 (s, 1H), 6.90 – 6.78 (m, 4H), 6.12 (s, 1H), 3.83 (s, 3H), 3.77 (s, 3H), 2.20 (s, 1H). 13

C NMR (75 MHz, CDCl3): d 159.1, 158.6, 142.5, 137.5, 135.1, 128.6, 128.4, 128.1, 127.7,

127.1, 126.1, 125.2, 113.6, 113.0, 111.7, 72.3, 55.0, 54.9. TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1459.

(E)-(3,5-Dimethoxyphenyl)(5-methoxy-2-styrylphenyl)methanol (18n) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (182 mg, 0.48 mmol, 41%). Rf (20% EtOAc/hexane) 0.15. IR (UATR): nmax 3445, 1595, 1462, 1203, 1153 cm-1. 1H NMR (400 MHz, CDCl3): d 7.49 (d, J = 8.6 Hz, 1H), 7.40 – 7.25 (m, 5H), 7.24 – 7.16 (m, 1H), 7.04 (s, 1H), 6.83 – 6.76 (m, 2H), 6.51 (s, 2H), 6.31 (s, 1H), 6.00 (s, 1H), 3.75 (s, 3H), 3.67 (s, 6H), 2.68 (s, 1H). 13C NMR (101 MHz, CDCl3): d 160.7, 159.3, 145.4, 142.1, 137.6, 129.1, 128.5, 128.2, 127.4, 127.3, 126.3, 125.5, 113.4, 112.3, 104.7, 99.5, 73.0, 55.2, 55.2. TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1558.

(E)-(5-Methoxy-2-(4-methoxystyryl)phenyl)(phenyl)methanol (18o) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow solid (487 mg, 1.41 mmol, 94%) mp


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81-88 °C. Rf (20% EtOAc/hexane) 0.15. IR (UATR): nmax 3462, 1606, 1509, 1248, 1174, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.51 (d, J = 8.6 Hz, 1H), 7.40 – 7.20 (m, 7H), 7.14 (d, J = 16.0 Hz, 1H), 7.08 (d, J = 2.8 Hz, 1H), 6.89 – 6.73 (m, 4H), 6.14 (s, 1H), 3.80 (s, 6H), 2.32 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.1, 159.1, 142.9, 142.0, 130.5, 128.9, 128.6, 128.5, 127.6, 127.5, 127.4, 126.8, 123.3, 114.1, 113.5, 112.3, 73.1, 55.3. LRMS (EI) m/z (rel intensity) 346 (M+, 13), 225 (36), 121 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1470.

(E)-(5-Methoxy-2-(4-methoxystyryl)phenyl)(4-methoxyphenyl)methanol (18p) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (325 mg, 0.87 mmol, 93%). Rf (20% EtOAc/hexane) 0.10. IR (UATR): nmax 3461, 3001, 1607, 1509, 1246, 1174, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.42 (d, J = 8.6 Hz, 1H), 7.27 – 7.15 (m, 4H), 7.10 (d, J = 2.7 Hz, 1H), 7.05 (d, J = 16.1 Hz, 1H), 6.82 – 6.64 (m, 6H), 5.96 (s, 1H), 3.68 (s, 3H), 3.68 (s, 3H), 3.63 (s, 3H), 3.04 (s, 1H).

13

C NMR (75 MHz, CDCl3): d 158.9, 158.8, 158.7, 142.2, 135.2, 130.3,

128.2, 128.1, 127.3, 126.9, 123.1, 113.9, 113.6, 113.0, 111.7, 72.3, 55.0, 54.9. LRMS (EI) m/z (rel intensity) 376 (M+, 30), 255 (99), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1566.

(E)-(3,5-Dimethoxyphenyl)(5-methoxy-2-(4-methoxystyryl)phenyl)methanol (18q) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (559 mg, 1.38 mmol, 74%). Rf (20% EtOAc/hexane) 0.10. IR (UATR): nmax 3480, 1606, 1511, 1462, 1248, 1154, 1030 cm-1. 1H NMR



(300 MHz, CDCl3): d 7.43 (d, J = 8.6 Hz, 1H), 7.31 – 7.25 (m, 2H), 7.15 (d, J = 16.1 Hz, 1H), 7.02 (d, J = 2.7 Hz, 1H), 6.84 – 6.67 (m, 4H), 6.50 (d, J = 2.3 Hz, 2H), 6.28 (t, J = 2.3 Hz, 1H), 5.96 (s, 1H), 3.71 (s, 3H), 3.69 (s, 3H), 3.62 (s, 6H), 3.08 (s, 1H). 13C NMR (75 MHz, CDCl3): d 160.6, 158.9, 158.8, 145.5, 141.8, 130.4, 128.5, 128.4, 127.4, 127.1, 123.3, 113.9, 113.2, 112.1, 104.7, 99.3, 72.8, 55.0. LRMS (EI) m/z (rel intensity) 406 (M+, 41), 285 (47), 253 (38). TOFHRMS calcd for C25H26NaO5 (M+Na+) 429.1673, found 429.1671.

(E)-(2,4-Dimethoxy-6-styrylphenyl)(phenyl)methanol (18r) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (210 mg, 0.61 mmol, 97%) mp 113-115 °C. Rf (20% EtOAc/hexane) 0.23. IR (UATR): nmax 3526, 1598, 1449, 1200, 1144 cm-1. 1H NMR (300 MHz, CDCl3): d 7.43 – 7.15 (m, 11H), 6.92 (d, J = 16.0 Hz, 1H), 6.75 (d, J = 2.4 Hz, 1H), 6.46 (d, J = 2.4 Hz, 1H), 6.27 (d, J = 9.6 Hz, 1H), 3.87 (s, 3H), 3.70 (s, 3H), 1.59 (s, 1H). 13

C NMR (75 MHz, CDCl3): d 159.9, 158.8, 144.6, 138.8, 137.1, 132.1, 128.6, 128.0, 127.8,

126.6, 126.6, 126.5, 125.6, 122.2, 103.2, 99.1, 70.2, 55.7, 55.4. LRMS (EI) m/z (rel intensity) 346 (M+, 17), 255 (100), 239 (36). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1460.

(E)-(2,4-Dimethoxy-6-styrylphenyl)(4-methoxyphenyl)methanol (18s) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (530 mg, 1.41 mmol, 92%. Rf (20% EtOAc/hexane) 0.17. IR (UATR): nmax 3526, 1598, 1508, 1244, 1143 cm-1. 1H NMR (400 MHz, CDCl3): d 7.42 – 7.35 (m, 3H), 7.33 – 7.26 (m, 2H), 7.26 – 7.18 (m, 3H), 6.90 (d, J = 16.0 Hz,


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1H), 6.81 (d, J = 6.9 Hz, 2H), 6.74 (s, 1H), 6.45 (s, 1H), 6.22 (d, J = 9.7 Hz, 1H), 3.87 (d, J = 10.1 Hz, 1H), 3.84 (s, 3H), 3.73 (s, 3H), 3.68 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 159.6,

158.6, 158.1, 138.2, 137.0, 136.6, 131.7, 128.4, 127.6, 126.7, 126.6, 126.5, 122.1, 113.2, 103.1, 98.8, 69.6, 55.5, 55.2, 55.0. LRMS (EI) m/z (rel intensity) 376 (M+, 24), 358 (90), 285 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1562.

(E)-(2,4-Dimethoxy-6-styrylphenyl)(3,5-dimethoxyphenyl)methanol (18t) Following the general procedure B and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as yellow sticky (419 mg, 1.03 mmol, 66%). Rf (30% EtOAc/hexane) 0.32. IR (UATR): nmax 3502, 1595, 1456, 1425, 1312, 1201, 1147 cm-1. 1H NMR (400 MHz, CDCl3): d 7.46 – 7.35 (m, 3H), 7.27 (t, J = 7.5 Hz, 2H), 7.22 – 7.15 (m, 1H), 6.89 (d, J = 16.1 Hz, 1H), 6.72 (s, 1H), 6.52 (s, 2H), 6.41 (s, 1H), 6.29 (s, 1H), 6.24 (s, 1H), 3.80 (s, 3H), 3.68 (s, 6H), 3.66 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 160.4, 159.7, 158.5, 147.3, 138.3,

137.0, 131.6, 128.4, 127.6, 126.6, 126.4, 121.8, 103.7, 103.0, 98.7, 98.2, 69.6, 55.5, 55.1, 55.0. LRMS (EI) m/z (rel intensity) 406 (M+, 64), 314 (100), 269 (56). TOF-HRMS calcd for C25H26NaO5 (M+Na+) 429.1672, found 429.1666.

(E)-(2,4-Dimethoxy-6-(4-methoxystyryl)phenyl)(phenyl)methanol (18u) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow solid (370 mg, 0.98 mmol,72%) mp 115-117 °C. Rf (20% EtOAc/hexane) 0.20. IR (UATR): nmax 3526, 1598, 1510, 1452, 1247, 1143 cm-1. 1H NMR (300 MHz, CDCl3): d 7.36 – 7.13 (m, 8H), 6.90 – 6.81 (m, 3H), 6.73 (d, J = 2.4 Hz, 1H), 6.42 (d, J = 2.4 Hz, 1H), 6.28 (d, J = 9.1 Hz, 1H), 3.83 (s, 3H), 3.76 (s, 3H), 3.65 (s, 3H), 1.76 (s,



1H).

13

C NMR (75 MHz, CDCl3): d 159.8, 159.4, 158.7, 144.7, 138.7, 131.5, 129.9, 127.9,

127.8, 126.4, 125.5, 124.3, 122.0, 114.0, 103.0, 98.7, 70.0, 55.6, 55.3, 55.2. LRMS (EI) m/z (rel intensity) 376 (M+, 3), 255 (41), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1561.

(E)-(2,4-Dimethoxy-6-(4-methoxystyryl)phenyl)(4-methoxyphenyl)methanol (18v) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow solid (622 mg, 1.53 mmol, 75%) mp 98-100 °C. Rf (20% EtOAc/hexane) 0.17. IR (UATR): nmax 3545, 1599, 1509, 1244, 1172, 1144, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.36 – 7.18 (m, 5H), 6.88 – 6.76 (m, 5H), 6.72 (d, J = 2.4 Hz, 1H), 6.43 (d, J = 2.4 Hz, 1H), 6.23 (d, J = 7.1 Hz, 1H), 3.93 – 3.86 (m, 1H), 3.82 (s, 3H), 3.75 (s, 3H), 3.72 (s, 3H), 3.66 (s, 3H).13C NMR (75 MHz, CDCl3): d 159.6, 159.3, 158.6, 158.2, 138.5, 136.7, 131.3, 129.8, 127.7, 126.8, 124.3, 121.9, 113.9, 113.2, 103.0, 98.6, 69.8, 55.6, 55.2, 55.1, 55.0. LRMS (EI) m/z (rel intensity) 406 (M+, 8), 285 (73), 121 (100). TOF-HRMS calcd for C25H25O4 (M-OH+) 389.1747, found 389.1756.

(E)-(2,4-dimethoxy-6-(4-methoxystyryl)phenyl)(3,5-dimethoxyphenyl)methanol (18w) Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow solid (326 mg, 0.75 mmol, 62%) mp 151152 °C. Rf (20% EtOAc/hexane) 0.11. IR (UATR): nmax 3510, 1595, 1456, 1309, 1201 cm-1. 1H NMR (300 MHz, CDCl3): d 7.36 – 7.24 (m, 3H), 6.89 – 6.79 (m, 3H), 6.71 (d, J = 2.4 Hz, 1H), 6.52 (dd, J = 2.3, 0.9 Hz, 2H), 6.41 (d, J = 2.4 Hz, 1H), 6.30 (t, J = 2.3 Hz, 1H), 6.21 (s, 1H), 3.82 (s, 3H), 3.76 (s, 3H), 3.70 (s, 6H), 3.68 (s, 3H). 13C NMR (75 MHz, CDCl3): d 160.4, 159.7,


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159.3, 158.6, 147.5, 138.7, 131.4, 129.9, 127.7, 124.4, 121.7, 113.9, 103.8, 103.0, 98.5, 98.3, 69.8, 55.6, 55.2, 55.1, 55.1. LRMS (EI) m/z (rel intensity) 436 (M+, 27), 314 (30), 257 (27). TOF-HRMS calcd for C26H28NaO6 (M+Na+) 459.1778, found 459.1771. These spectroscopic data were identical to those reported previously.12c

(E)-(4,5-Dimethoxy-2-styrylphenyl)(phenyl)methanol (18x) Following the general procedure A and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as yellow solid (447 mg, 1.29 mmol, 90%) mp 119121 °C. Rf (40% EtOAc/hexane) 0.44. IR (UATR): nmax 3502, 1597, 1508, 1273, 1096 cm-1. 1H NMR (300 MHz, CDCl3): d 7.49 – 7.32 (m, 9H), 7.32 – 7.24 (m, 2H), 7.10 (d, J = 16.4 Hz, 2H), 6.89 (d, J = 16.0 Hz, 1H), 6.17 (s, 1H), 3.94 (s, 3H), 3.84 (s, 3H), 3.15 (s, 1H).

13

C NMR (75

MHz, CDCl3): d 148.6, 148.1, 143.3, 137.3, 133.8, 128.9, 128.4, 128.2, 127.8, 127.2, 127.2, 126.4, 126.2, 125.3, 109.9, 108.5, 72.2, 55.7, 55.6. LRMS (EI) m/z (rel intensity) 346 (M+, 43), 255 (100), 224 (40). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1456. These spectroscopic data were identical to those reported previously.15

(E)-(4,5-Dimethoxy-2-styrylphenyl)(4-methoxyphenyl)methanol (18y) Following the general procedure A and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as yellow sticky (325 mg, 0.87 mmol, 95%). Rf (30% EtOAc/hexane) 0.24. IR (UATR): nmax 3510, 1606, 1508, 1247 cm-1. 1H NMR (400 MHz, CDCl3): d 7.38 – 7.35 (m, 2H), 7.32 – 7.15 (m, 6H), 7.04 (s, 2H), 6.84 – 6.75 (m, 3H), 6.03 (s, 1H), 3.85 (s, 3H), 3.77 (s, 3H), 3.66 (s, 3H), 3.03 (s, 1H). 13C NMR (101 MHz, CDCl3): d 158.5, 148.5, 147.9, 137.3, 135.5, 134.0, 128.7, 128.4, 127.8, 127.5, 127.2, 126.1, 125.2, 113.5, 109.5,



108.4, 71.7, 55.6, 55.6, 54.9. TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1561.

(E)-(4,5-Dimethoxy-2-styrylphenyl)(3,5-dimethoxyphenyl)methanol (18z) Following the general procedure B and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as light yellow sticky (413 mg, 1.02 mmol, 91%). Rf (30% EtOAc/hexane) 0.24. IR (UATR): nmax 3490, 1595, 1509, 1462, 1273 cm-1. 1H NMR (400 MHz, CDCl3): d 7.48 – 7.31 (m, 5H), 7.30 – 7.22 (m, 1H), 7.10 (s, 1H), 7.04 (s, 1H), 6.87 (d, J = 16.0 Hz, 1H), 6.57 (d, J = 2.3 Hz, 2H), 6.36 (t, J = 2.3 Hz, 1H), 6.07 (s, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 3.71 (s, 6H), 3.09 (s, 1H). 13C NMR (101 MHz, CDCl3): d 160.5, 148.6, 148.1, 145.9, 137.3, 133.7, 128.9, 128.4, 127.9, 127.2, 126.1, 125.4, 109.9, 108.5, 104.5, 99.1, 72.2, 55.7, 55.6, 55.0. TOF-HRMS calcd for C25H26NaO5 (M+Na+) 429.1672, found 429.1665.

(E)-(4,5-Dimethoxy-2-(4-methoxystyryl)phenyl)(phenyl)methanol (18a) Following the general procedure A and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as yellow solid (191 mg, 0.51 mmol, 99%) mp 124126 °C. Rf (40% EtOAc/hexane) 0.23. IR (UATR): nmax 3503, 1606, 1510, 1247, 1174, 1096 cm. H NMR (400 MHz, CDCl3): d 7.43 – 7.33 (m, 6H), 7.31 – 7.20 (m, 2H), 7.10 (s, 1H), 7.04 (s,

1 1

1H), 6.93 – 6.88 (m, 2H), 6.83 (d, J = 16.1 Hz, 1H), 6.21 (s, 1H), 3.96 (s, 3H), 3.87 (s, 3H), 3.84 (s, 3H), 2.38 (s, 1H). 13C NMR (101 MHz, CDCl3): d 159.2, 148.6, 148.4, 143.4, 133.5, 130.3, 129.0, 128.4, 127.5, 127.4, 126.6, 123.3, 114.1, 110.1, 108.6, 72.5, 55.9, 55.9, 55.3. LRMS (EI) m/z (rel intensity) 376 (M+, 31), 255 (65), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1561.


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(E)-(4,5-Dimethoxy-2-(4-methoxystyryl)phenyl)(4-methoxyphenyl)methanol (18β) Following the general procedure A and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (489 mg, 1.20 mmol, 97%) mp 84-85 °C. Rf (20% EtOAc/hexane) 0.10. IR (UATR): nmax 3503, 1607, 1510, 1247, 1174 cm-1. 1H NMR (300 MHz, CDCl3): d 7.33 – 7.27 (m, 2H), 7.26 – 7.19 (m, 2H), 7.13 (d, J = 16.0 Hz, 1H), 7.03 (d, J = 1.7 Hz, 2H), 6.84 – 6.71 (m, 5H), 6.05 (s, 1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.73 (s, 3H), 3.69 (s, 3H), 3.01 (s, 1H).

13

C NMR (75 MHz, CDCl3): d 158.9, 158.5, 148.3, 148.0, 135.6,

133.7, 130.1, 128.3, 127.9, 127.8, 127.3, 123.1, 113.9, 113.5, 109.7, 108.4, 71.8, 55.7, 55.6, 54.97, 55.0. LRMS (EI) m/z (rel intensity) 406 (M+, 42), 388 (85), 285 (100). TOF-HRMS calcd for C25H26NaO5 (M+Na+) 429.1672, found 429.1662.

(E)-(4,5-Dimethoxy-2-(4-methoxystyryl)phenyl)(3,5-dimethoxyphenyl)methanol (18γ) Following the general procedure B and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as pale yellow sticky (326 mg, 0.75 mmol, 74%). Rf (30% EtOAc/hexane) 0.33. IR (UATR): nmax 3482, 1703, 1592, 1461, 1296 cm-1. 1H NMR (300 MHz, CDCl3): d 1H NMR (300 MHz, Chloroform-d) δ 7.41 – 7.35 (m, 2H), 7.26 (d, J = 16.0 Hz, 1H), 7.08 (s, 1H), 7.01 (s, 1H), 6.92 – 6.87 (m, 2H), 6.82 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 2.3, 0.6 Hz, 2H), 6.37 (t, J = 2.3 Hz, 1H), 6.11 (s, 1H), 3.95 (s, 3H), 3.86 (s, 3H), 3.83 (s, 3H), 3.74 (s, 6H), 2.48 (s, 1H).

13

C NMR (75 MHz, CDCl3): d 160.8, 159.2, 148.6, 148.4, 146.0, 133.3,

130.3, 129.0, 128.6, 127.5, 123.5, 114.1, 110.1, 108.7, 104.6, 99.3, 72.5, 55.9, 55.9, 55.2. TOFHRMS calcd for C26H28NaO6 (M+Na+) 459.1778, found 459.1761.



General procedure for the synthesis of indanols or endocyclic indenes To a stirred solution 0.1 M (1 equiv) of (E)-(2-stilbenyl)methanol in dichloromethane (DCM), dichloroethane (DCE) or totuene was added PTS-Si (1.1 equiv). The reaction mixture was stirred until all of the starting material was consumed as monitored by TLC. The reaction mixture was filtrated through cotton or filter paper then concentrated organic solvent under reduced pressure to give the crude product which was further purified by column chromatography on silica to furnish the desired products.

General procedure for the synthesis of indanones To a stirred solution 0.025 M (1 equiv) of indanols in DCM was added Dess-Martin periodinane (DMP) (1.2 equiv) at room temperature. The reaction mixture was stirred until all of the starting material was consumed as monitored by TLC. Water and DCM were added, and the two phases were separated. The aqueous layer was extracted twice with DCM. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was further purified by column chromatography on silica to furnish the desired products.

2,3-Diphenyl-2,3-dihydro-1H-inden-1-ol (15) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as pale yellow sticky (20.1 mg, 0.07 mmol, 81%). Rf (20% EtOAc/hexane) 0.31. 1H NMR (300 MHz, CDCl3): d 7.54 – 7.44 (m, 2H), 7.38 – 7.05 (m, 24H), 7.03 – 6.98 (m, 1H), 6.93 (d, J = 7.4 Hz, 1H), 5.35 (d, J = 8.4 Hz, 1H), 5.25 (d, J = 5.4 Hz, 1H), 4.86 (d, J = 9.2 Hz, 1H), 4.32 (d, J = 10.1 Hz, 1H), 3.69 (dd, J = 9.2, 5.5 Hz, 1H), 3.33 (dd,


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J = 10.1, 8.4 Hz, 1H), 2.30 (s, 1H), 1.62 (s, 1H). 13C NMR (75 MHz, CDCl3) d 147.1, 143.9, 143.5, 143.1, 142.4, 142.2, 140.1, 137.7, 129.3, 129.1, 128.6, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.0, 127.5, 127.5, 127.2, 127.0, 126.7, 126.7, 125.3, 125.1, 124.9, 123.5, 81.1, 76.8, 67.3, 61.5, 55.8, 53.4. TOF-HRMS calcd for C21H18Na16O (M+Na+) 309.1250, found 309.1250, C21H18Na18O (M+Na+) 311.1292, found 311.1270. These spectroscopic data were identical to those reported previously.15

2,3-Diphenyl-2,3-dihydro-1H-inden-1-one (20) Following the general procedure and purification by preparative TLC (10% EtOAc/hexane), the product was obtained as yellow sticky (75.4 mg, 0.27 mmol, 99%). Rf (20% EtOAc/hexane) 0.43. 1H NMR (300 MHz, CDCl3): d 7.81 (d, J = 7.7 Hz, 1H), 7.55 (td, J = 7.5, 1.3 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.33 – 7.13 (m, 7H), 7.10 – 6.94 (m, 4H), 4.50 (d, J = 4.8 Hz, 1H), 3.73 (d, J = 4.8 Hz, 1H).

13

C NMR (75 MHz, CDCl3): d 205.2, 156.1, 142.5, 138.5, 136.1, 135.4, 128.9,

128.8, 128.3, 128.3, 127.9, 127.2, 126.7, 124.0 64.6, 54.8. These spectroscopic data were identical to those reported previously.27

3-(4-Methoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-ol (19a) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (33.2 mg, 0.11 mmol, 60%). Rf (20% EtOAc/hexane) 0.26. 1H NMR (300 MHz, CDCl3): d 7.54 – 7.44 (m, 2H), 7.45 – 7.18 (m, 14H), 7.15 – 6.88 (m, 6H), 6.83 – 6.70 (m, 4H), 5.34 (d, J = 6.5 Hz, 1H), 5.28 – 5.18 (m, 1H), 4.82 (d, J = 9.3 Hz, 1H), 4.27 (d, J = 10.2 Hz, 1H), 3.75 (d, J = 1.7 Hz, 3H), 3.74 (d, J = 1.8 Hz, 3H), 3.65 (dd, J = 9.4, 5.4 Hz, 1H), 3.29 (dd, J = 10.2, 8.4 Hz, 1H), 2.27 (d, J = 6.1 Hz, 1H), 1.60



(d, J = 3.5 Hz, 1H).

13

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C NMR (75 MHz, CDCl3): d 158.3, 158.3, 147.4, 144.2, 143.4, 143.0,

140.1, 137.7, 134.3, 134.2, 129.5, 129.3, 129.1, 128.6, 128.5, 128.4, 128.3, 128.1, 127.5, 127.4, 127.1, 126.9, 125.3, 125.1, 124.9, 123.5, 113.9, 113.8, 80.9, 76.8, 67.5, 61.6, 55.2, 55.0, 52.5. TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1351.

3-(4-Methoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-one (21a) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as pale yellow sticky (23.5 mg, 0.075 mmol, 87%). Rf (10% EtOAc/hexane) 0.21. IR (UATR): nmax 3030, 1713, 1603, 1511, 1248, 1177 cm-1. 1H NMR (300 MHz, CDCl3): d 7.88 (dd, J = 7.9, 1.3 Hz, 1H), 7.63 (td, J = 7.5, 1.3 Hz, 1H), 7.51 – 7.42 (m, 1H), 7.36 – 7.21 (m, 4H), 7.14 – 7.06 (m, 2H), 7.04 – 6.97 (m, 2H), 6.87 – 6.80 (m, 2H), 4.52 (d, J = 4.9 Hz, 1H), 3.79 (s, 3H), 3.77 (d (overlapping), J = 5.9 Hz, 1H).

13

C NMR (75

MHz, CDCl3): d 205.3, 158.7, 156.3, 138.5, 136.1, 135.3, 134.5, 128.9, 128.9, 128.3, 128.2, 127.1, 126.6, 123.9, 114.2, 64.8, 55.2, 54.2. LRMS (EI) m/z (rel intensity) 314 (M+, 100), 237 (13), 206 (17). TOF-HRMS calcd for C22H18NaO2 (M+Na+) 337.1199, found 337.1193. These spectroscopic data were identical to those reported previously.28

3-(3,5-Dimethoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-ol (19b) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as clear sticky (8.00 mg, 0.023 mmol, 47%). Rf (20% EtOAc/hexane) 0.26. IR (UATR): nmax 3422, 1595, 1457, 1204, 1154 cm-1. 1H NMR (300 MHz, CDCl3): d 7.54 – 7.46 (m, 2H), 7.40 – 7.21 (m, 15H), 7.10 – 7.04 (m, 1H), 7.00 (dq, J = 7.4, 1.1 Hz, 1H), 6.31 (d, J = 6.9 Hz, 3H), 6.25 (d, J = 2.3 Hz, 2H), 5.41 – 5.34 (m, 1H), 5.28 (d, J = 5.5


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Hz, 1H), 4.81 (d, J = 9.0 Hz, 1H), 4.28 (d, J = 10.1 Hz, 1H), 3.71 (d, J = 5.5 Hz, 1H), 3.69 (s, 6H), 3.68 (s, 6H), 3.36 (dd, J = 10.1, 8.3 Hz, 1H), 2.22 (brs, 2H). 13C NMR (75 MHz, CDCl3): d 160.8, 160.7, 146.6, 144.8, 144.5, 143.5, 143.3, 143.0, 140.1, 137.7, 129.2, 129.1, 128.6, 128.6, 128.5, 128.1, 127.6, 127.5, 127.2, 127.0, 125.4, 125.1, 125.0, 123.5, 106.6, 106.5, 98.6, 98.3, 81.1, 66.9, 61.1, 56.0, 55.2, 55.2, 53.6. LRMS (EI) m/z (rel intensity) 346 (M+, 45), 255 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1458.

3-(3,5-Dimethoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-one (21b) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as clear sticky (9.90 mg, 0.029 mmol, 91%). Rf (20% EtOAc/hexane) 0.32. IR (UATR): nmax 2936, 1714, 1594, 1457, 1153, 1065 cm-1. 1H NMR (300 MHz, CDCl3): d 7.88 (d, J = 7.7 Hz, 1H), 7.64 (td, J = 7.5, 1.3 Hz, 1H), 7.52 – 7.44 (m, 1H), 7.38 – 7.23 (m, 4H), 7.14 – 7.08 (m, 2H), 6.37 (t, J = 2.3 Hz, 1H), 6.22 (d, J = 2.3 Hz, 2H), 4.50 (d, J = 4.7 Hz, 1H), 3.82 (d, J = 4.7 Hz, 1H), 3.72 (s, 6H). 13C NMR (75 MHz, CDCl3): d 205.2, 161.1, 155.8, 144.9, 138.7, 136.1, 135.4, 128.8, 128.3, 127.2, 126.7, 124.0, 106.1, 98.7, 64.2, 55.3, 55.0. LRMS (EI) m/z (rel intensity) 344 (M+, 100), 178 (88). TOF-HRMS calcd for C23H20NaO3 (M+Na+) 367.1305, found 367.1298.

2-(4-Methoxyphenyl)-3-phenyl-2,3-dihydro-1H-inden-1-ol (19c) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as clear sticky (27.9 mg, 0.089 mmol, 70%). Rf (20% EtOAc/hexane) 0.18. IR (UATR): nmax 3394, 3028, 1611, 1512, 1247, 1178, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.49 (t, J = 6.8 Hz, 2H), 7.39 – 7.04 (m, 18H), 7.03 – 6.77 (m, 6H), 5.32



(d, J = 8.5 Hz, 1H), 5.22 (d, J = 5.5 Hz, 1H), 4.80 (d, J = 9.3 Hz, 1H), 4.27 (d, J = 10.2 Hz, 1H), 3.77 (s, 3H), 3.77 (s, 3H), 3.64 (dd, J = 9.3, 5.5 Hz, 1H), 3.28 (dd, J = 10.2, 8.5 Hz, 1H), 2.27 (brs, 1H), 1.62 (brs, 1H). 13C NMR (75 MHz, CDCl3): d 158.7, 158.5, 147.1, 143.9, 143.5, 143.1, 142.4, 142.2, 131.9, 130.2, 129.5, 129.0, 129.0, 128.6, 128.4, 128.4, 128.3, 127.5, 127.4, 126.7, 126.6, 125.3, 125.2, 124.9, 123.5, 114.0, 114.0, 81.0, 76.8, 66.7, 55.8, 55.2, 53.7. LRMS (EI) m/z (rel intensity) 316 (M+, 18), 195 (51), 121 (100). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1356, found 339.1353.

2-(4-Methoxyphenyl)-3-phenyl-2,3-dihydro-1H-inden-1-one (21c) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (16.0 mg, 0.051 mmol, 99%). Rf (20% EtOAc/hexane) 0.38. IR (UATR): nmax 1714, 1513, 1250, 1179,1031 cm-1. 1H NMR (400 MHz, CDCl3): d 7.88 (d, J = 7.7 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.35 – 7.23 (m, 4H), 7.09 (d, J = 7.2 Hz, 2H), 7.02 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.2 Hz, 2H), 4.52 (d, J = 4.9 Hz, 1H), 3.79 (s, 3H), 3.76 (d, J = 5.1 Hz, 1H). 13C NMR (101 MHz, CDCl3): d 205.5, 158.7, 156.0 142.5, 136.2, 135.3, 130.5, 129.4, 128.9, 128.2, 127.9, 127.1, 126.6, 124.0, 114.3. LRMS (EI) m/z (rel intensity) 314 (M+, 100), 178 (38), 149 (85). TOF-HRMS calcd for C22H18NaO2 (M+Na+) 337.1199, found 337.1193. These spectroscopic data were identical to those reported previously.12d

2,3-bis(4-Methoxyphenyl)-2,3-dihydro-1H-inden-1-ol (19d) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white sticky (35.3 mg, 0.102 mmol, 61%). Rf (20%


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EtOAc/hexane) 0.16. IR (UATR): nmax 3447, 1611, 1511, 1245, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 – 7.44 (m, 2H), 7.36 – 7.21 (m, 6H), 7.20 – 7.12 (m, 2H), 7.09 – 6.96 (m, 5H), 6.92 (d, J = 7.4 Hz, 1H), 6.90 – 6.74 (m, 8H), 5.30 (d, J = 8.5 Hz, 1H), 5.19 (d, J = 5.4 Hz, 1H), 4.75 (d, J = 9.4 Hz, 1H), 4.21 (d, J = 10.2 Hz, 1H), 3.77 (d, J = 1.0 Hz, 6H), 3.76 (s, 3H), 3.74 (s, 3H), 3.59 (dd, J = 9.4, 5.4 Hz, 1H), 3.23 (dd, J = 10.2, 8.5 Hz, 1H), 2.27 (s, 1H), 1.60 (s, 1H). 13

C NMR (75 MHz, CDCl3): d 158.7, 158.5, 158.3, 158.3, 147.4, 144.2, 143.5, 143.0, 134.4,

132.0, 130.2, 129.6, 129.5, 129.2, 129.0, 129.0, 128.3, 127.4, 127.4, 125.3, 125.1, 124.9, 123.4, 114.0, 114.0, 113.9, 113.8, 80.9, 76.7, 66.81, 60.9, 55.2, 55.1, 55.0, 52.8. LRMS (EI) m/z (rel intensity) 346 (M+, 20), 225 (70), 121 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1446.

2,3-bis(4-Methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21d) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange sticky (26.5 mg, 0.077 mmol, 82%). Rf (20% EtOAc/hexane) 0.29. IR (UATR): nmax 1714, 1609, 1509, 1246, 1177, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.87 (dt, J = 7.7, 1.0 Hz, 1H), 7.62 (td, J = 7.5, 1.3 Hz, 1H), 7.47 (tt, J = 7.4, 0.9 Hz, 1H), 7.29 (dq, J = 7.7, 1.0 Hz, 1H), 7.05 – 6.97 (m, 4H), 6.89 – 6.81 (m, 4H), 4.47 (d, J = 5.0 Hz, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 3.71 (d, J = 5.0 Hz, 1H).

13

C NMR (75 MHz,

CDCl3): d 205.6, 158.7, 156.2, 136.1, 135.3, 134.5, 130.5, 129.4, 128.9, 128.1, 126.6, 123.9, 114.3, 114.2, 64.2, 55.2, 54.2. LRMS (EI) m/z (rel intensity) 344 (M+, 100), 236 (29), 121 (20). TOF-HRMS calcd for C23H20NaO3 (M+Na+) 367.1305, found 367.1320. These spectroscopic data were identical to those reported previously.12b



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3-(3,5-Dimethoxyphenyl)-2-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21e) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as orange sticky (22.5 mg, 0.06 mmol, 41%). Rf (20% EtOAc/hexane) 0.42. IR (UATR): nmax 1715, 1595, 1460, 1248 cm-1. 1H NMR (300 MHz, CDCl3): d 7.87 (d, J = 7.6 Hz, 1H), 7.67 – 7.59 (m, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.34 (d, J = 7.5 Hz, 1H), 7.03 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 6.37 (t, J = 2.3 Hz, 1H), 6.25 – 6.20 (m, 2H), 4.45 (d, J = 4.8 Hz, 1H), 3.78 (s, 3H), 3.76 (d (overlapping), 1H), 3.72 (s, 6H).

13

C

NMR (75 MHz, CDCl3): d 205.5 161.1, 158.7, 155.6, 144.9, 136.1, 135.3, 130.6, 129.4, 128.3, 126.7, 124.0, 114.3, 106.1, 98.7, 63.5, 55.3, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 374 (M+, 100), 266 (65), 178 (25). TOF-HRMS calcd for C24H22NaO4 (M+Na+) 397.1410, found 397.1395.

6-Methoxy-2,3-diphenyl-2,3-dihydro-1H-inden-1-ol (19f) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (21.6 mg, 0.068 mmol, 72% (major:minor, 1.67:1)) mp 96-97 °C. Rf (20% EtOAc/hexane) 0.22. IR (UATR): nmax 3420, 1610, 1489, 1265 cm-1. 1H NMR (300 MHz, CDCl3): d 7.39 – 7.01 (m, 22H), 6.95 – 6.82 (m, 4H), 5.35 (d, J = 8.4 Hz, 1H, major), 5.25 (d, J = 5.6 Hz, 1H, minor), 4.79 (d, J = 8.7 Hz, 1H, minor), 4.28 (d, J = 9.8 Hz, 1H, major), 3.85 (s, 3H, major), 3.84 (s, 3H, minor), 3.70 (dd, J = 8.7, 5.6 Hz, 1H, minor), 3.32 (dd, J = 9.9, 8.4 Hz, 1H, major), 2.18 (brd, J = 7.8 Hz, 2H).

13

C NMR (75 MHz,

CDCl3): d 159.7 (major), 159.5 (minor), 144.8 (major), 144.4 (minor), 142.9 (minor), 142.5 (major), 140.1 (major), 138.8 (minor), 137.8 (minor), 135.8 (major), 129.3, 128.6, 128.6, 128.5, 128.4, 128.2, 128.1, 127.2, 127.0, 126.7, 126.7, 126.1, 125.8, 115.7 (minor), 115.3 (major),


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109.7 (minor), 108.0 (major), 81.1, 67.9, 62.0 (minor), 55.5 (major), 55.2 (major), 53.0 (minor). LRMS (EI) m/z (rel intensity) 316 (M+, 35), 225 (100), 209 (23). TOF-HRMS calcd for C22H24NO2 (M+NH4+) 334.1802, found 334.1792.

6-Methoxy-2,3-diphenyl-2,3-dihydro-1H-inden-1-one (21f) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange sticky (17.0 mg, 0.054 mmol, 95%). Rf (20% EtOAc/hexane) 0.48. IR (UATR): nmax 3028, 1709, 1488, 1279, 1026 cm-1. 1H NMR (300 MHz, CDCl3): d 7.37 – 7.16 (m, 9H), 7.14 – 7.04 (m, 4H), 4.50 (d, J = 4.4 Hz, 1H), 3.88 (s, 3H), 3.80 (d, J = 4.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 205.2, 160.0, 149.0, 142.7, 138.6, 137.4, 128.8, 128.8, 128.3, 127.7, 127.5, 127.2, 127.1, 124.8, 104.9, 65.3, 55.7, 54.3. LRMS (EI) m/z (rel intensity) 314 (M+, 100), 223 (32). TOF-HRMS calcd for C22H18NaO2 (M+Na+) 337.1199, found 337.1197. These spectroscopic data were identical to those reported previously.29

6-Methoxy-3-(4-methoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-ol (19g) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (18.6 mg, 0.054 mmol, 67%). Rf (20% EtOAc/hexane) 0.16. IR (UATR): nmax 3421, 2835, 1610, 1509, 1246, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.37 – 7.18 (m, 10H), 7.07 – 6.72 (m, 14H), 5.30 (d, J = 8.4 Hz, 1H), 5.19 (d, J = 5.5 Hz, 1H), 4.73 (d, J = 8.8 Hz, 1H), 4.20 (d, J = 9.9 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), 3.62 (dd, J = 8.9, 5.6 Hz, 1H), 3.25 (dd, J = 10.0, 8.4 Hz, 1H), 2.36 (s, 1H), 1.63 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.6, 159.4, 158.3, 158.2, 144.8, 144.3, 140.2, 139.1, 137.8, 136.1, 134.8, 134.6, 129.3, 129.3, 129.1, 128.5, 128.5, 128.1, 127.1, 126.9, 126.0,



125.7, 115.7, 115.2, 113.8, 113.8, 109.7, 107.9, 80.8, 76.8, 67.9, 62.1, 55.5, 55.5, 55.1, 54.4, 52.0. LRMS (EI) m/z (rel intensity) 346 (M+, 39), 255 (100), 121 (85). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1455.

6-Methoxy-3-(4-methoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-one (21g) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (14.3 mg, 0.042 mmol, 92%). Rf (20% EtOAc/hexane) 0.26. IR (UATR): nmax 1709, 1610, 1511, 1489, 1279 1246, 1027 cm-1. 1H NMR (300 MHz, CDCl3): d 7.36 – 7.16 (m, 6H), 7.13 – 7.05 (m, 2H), 7.02 – 6.95 (m, 2H), 6.87 – 6.80 (m, 2H), 4.45 (d, J = 4.5 Hz, 1H), 3.89 (s, 3H), 3.79 (s, 3H), 3.76 (d, J = 4.4 Hz, 1H). .

13

C NMR (75 MHz, CDCl3): d 205.3, 160.0, 158.7, 149.3, 138.7, 137.4, 134.7, 128.8, 128.7,

128.3, 127.4, 127.1, 124.8, 114.2, 104.9, 65.5, 55.7, 55.2, 53.6. LRMS (EI) m/z (rel intensity) 344 (M+, 100), 236 (34). TOF-HRMS calcd for C23H21O3 (M+H+) 345.1485, found 345.1489.

3-(3,5-Dimethoxyphenyl)-6-methoxy-2-phenyl-2,3-dihydro-1H-inden-1-ol (19h) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as clear sticky (6.40 mg, 0.017 mmol, 43% (major:minor, 1.28:1)). Rf (20% EtOAc/hexane) 0.08. IR (UATR): nmax 3462, 1594, 1489, 1457, 1203, 1148 cm-1. 1H NMR (300 MHz, CDCl3): d 7.37 – 7.23 (m, 10H), 7.06 – 6.80 (m, 6H), 6.33 – 6.21 (m, 6H), 5.32 (d, J = 8.3 Hz, 1H, major), 5.25 (d, J = 5.6 Hz, 1H, minor), 4.71 (d, J = 8.5 Hz, 1H, minor), 4.21 (d, J = 9.8 Hz, 1H, major), 3.84 (s, 3H, major), 3.83 (s, 3H, minor), 3.69 (s, 6H, minor), 3.67 (s, 6H, major), 3.67 (overlapping dd, 1H, minor), 3.32 (dd, J = 9.9, 8.3 Hz, 1H, major).

13

C NMR (75 MHz, CDCl3): d 160.8 (minor), 160.7 (major), 159.7 (major), 159.5


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(minor), 145.4, 144.9, 144.8, 144.4, 140.2, 138.3, 137.9, 135.4, 129.3 (minor), 128.6 (minor), 128.6 (major), 128.1 (major), 127.2 (minor), 127.0 (major), 126.2 (minor), 125.9 (major), 115.8 (minor), 115.3 (major), 109.6 (minor), 108.0 (major), 106.4 (major), 106.4 (minor), 98.7 (major), 98.3 (minor), 81.0, 76.9, 67.3 (major), 61.6 (minor), 55.5 (major), 55.5 (minor), 55.4, 55.2 (major), 55.2 (minor), 53.3. LRMS (EI) m/z (rel intensity) 376 (M+, 29), 285 (100), 253 (27). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1559.

3-(3,5-Dimethoxyphenyl)-6-methoxy-2-phenyl-2,3-dihydro-1H-inden-1-one (21h) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (15.8 mg, 0.042 mmol, 38% (2 steps)). Rf (20% EtOAc/hexane) 0.28. IR (UATR): nmax 1709, 1594, 1489, 1278, 1026 cm-1. 1H NMR (400 MHz, CDCl3): d 7.35 – 7.23 (m, 6H), 7.13 – 7.08 (m, 2H), 6.36 (t, J = 2.3 Hz, 1H), 6.21 (d, J = 2.2 Hz, 2H), 4.43 (d, J = 4.4 Hz, 1H), 3.89 (s, 3H), 3.81 (d, J = 4.4 Hz, 1H), 3.72 (s, 6H).

13

C NMR (101 MHz, CDCl3): d 205.3, 161.0, 160.0, 148.7, 145.1, 138.7, 137.4, 128.8,

128.3, 127.5, 127.2, 124.9, 105.9, 104.9, 98.6, 64.9, 55.7, 55.3, 54.4. LRMS (EI) m/z (rel intensity) 374 (M+, 100), 236 (21). TOF-HRMS calcd for C24H22NaO4 (M+Na+) 397.1410, found 397.1402.

6-Methoxy-2-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-inden-1-ol (19i) Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as white solid (18.1 mg, 0.052 mmol, 65% (major:minor, 1.41:1)) mp 121-124 °C. Rf (40% EtOAc/hexane) 0.32. IR (UATR): nmax 3421, 1611, 1513, 1489, 1248, 1178, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.30 – 6.98 (m, 17H),



6.94 – 6.76 (m, 7H), 5.26 (d, J = 6.8 Hz, 1H, major), 5.17 (d, J = 8.2 Hz, 1H, minor), 4.71 (d, J = 8.8 Hz, 1H, minor), 4.20 (d, J = 10.0 Hz, 1H, major), 3.83 (s, 6H), 3.76 (s, 6H), 3.62 (dd, J = 8.7, 6.0 Hz, 1H, minor), 3.25 (t, J = 9.3 Hz, 1H, major), 2.31 (d, J = 6.0 Hz, 1H, major), 1.64 (s, 1H, minor).

13

C NMR (75 MHz, CDCl3): d 159.6 (major), 159.4 (minor), 158.7 (minor), 158.5

(major), 144.9 (major), 144.5 (minor), 142.9 (minor), 142.5 (major), 138.8 (minor), 135.8 (major), 132.0 (major), 130.2, 129.6 (minor), 129.0, 128.4, 128.3, 128.1, 126.6 (major), 126.5 (minor), 126.1 (minor), 125.7 (major), 115.6 (minor), 115.1 (major), 114.0 (minor), 113.9 (major), 109.7 (minor), 107.9 (major), 81.0 (major), 76.8 (minor), 67.1 (major), 61.2 (minor), 55.5, 55.5, 55.2 (major), 53.2 (minor). LRMS (EI) m/z (rel intensity) 346 (M+, 28), 225 (87), 121 (100). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1460.

6-Methoxy-2-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-inden-1-one (21i) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (21.7 mg, 0.063 mmol, 88%) mp 137138 °C. Rf (40% EtOAc/hexane) 0.54. IR (UATR): nmax 2932, 1712, 1609, 1512, 1281, 1248 cm. H NMR (300 MHz, CDCl3): d 7.35 – 7.15 (m, 6H), 7.12 – 6.97 (m, 4H), 6.89 – 6.82 (m, 2H),

1 1

4.45 (d, J = 4.5 Hz, 1H), 3.88 (s, 3H), 3.78 (s, 3H), 3.75 (d, J = 4.5 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 205.5, 160.0, 158.7, 148.9, 142.7, 137.4, 130.6, 129.3, 128.8, 127.7, 127.4, 127.0, 124.8, 114.3, 104.9, 64.7, 55.7, 55.2, 54.4. LRMS (EI) m/z (rel intensity) 344 (M+, 26), 149 (100). TOF-HRMS calcd for C23H21O3 (M+H+) 345.1485, found 345.1484.

6-Methoxy-2,3-bis(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-ol (19j)


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Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as clear sticky (20.9 mg, 0.056 mmol, 73% (major:minor, 2.0:1)). Rf (40% EtOAc/hexane) 0.28. IR (UATR): nmax 3462, 1610, 1510, 1244, 1176 cm-1. 1H NMR (300 MHz, CDCl3): d 7.30 – 7.23 (m, 3H), 7.19 – 7.14 (m, 1H), 7.09 – 6.96 (m, 4H), 6.95 – 6.75 (m, 14H), 5.28 (d, J = 8.5 Hz, 1H, minor), 5.17 (d, J = 5.5 Hz, 1H, major), 4.68 (d, J = 8.8 Hz, 1H, major), 4.16 (d, J = 10.0 Hz, 1H, minor), 3.84 (s, 3H, minor), 3.83 (s, 3H, major), 3.78 (s, 6H), 3.77 (s, 3H, minor), 3.75 (s, 3H, major), 3.58 (dd, J = 8.9, 5.5 Hz, 1H, major), 3.21 (dd, J = 10.0, 8.6 Hz, 1H, minor).

13

C NMR (75 MHz, CDCl3): d 159.4 (major),

158.7 (major), 158.3 (major), 144.8 (minor), 144.4 (major), 139.2 (major), 136.1 (minor), 134.9 (major), 134.6 (minor), 130.3, 129.7, 129.4, 129.1, 129.0, 126.0 (major), 125.7 (minor), 115.7 (major), 115.2 (minor), 114.0 (major), 114.0 (minor), 113.9 (major), 113.8 (minor), 109.7 (major), 108.0 (minor), 80.9 (minor), 76.8 (major), 67.3 (minor), 61.4 (major), 55.5 (minor),55.5 (major), 55.2 (minor), 55.2 (major), 54.4 (minor), 52.4 (major). LRMS (EI) m/z (rel intensity) 376 (M+, 11), 255 (65), 121 (100). TOF-HRMS calcd for C24H24NaO4 (M+Na+) 399.1567, found 399.1564.

6-Methoxy-2,3-bis(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21j) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange sticky (17.7 mg, 0.047 mmol, 75%). Rf (20% EtOAc/hexane) 0.30. IR (UATR): nmax 1709, 1610, 1511, 1488, 1280, 1243, 1027 cm-1. 1H NMR (300 MHz, CDCl3): d 7.30 – 7.15 (m, 3H), 7.04 – 6.95 (m, 4H), 6.88 – 6.79 (m, 4H), 4.40 (d, J = 4.6 Hz, 1H), 3.88 (s, 3H), 3.79 (s, 3H), 3.79 (s, 3H), 3.70 (d, J = 4.6 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 205.7, 159.9, 158.7, 158.6, 149.1, 137.3, 134.7, 130.6, 129.3, 128.8, 127.4,



124.7, 114.2, 114.2, 104.8, 64.9, 55.7, 55.2, 53.7. LRMS (EI) m/z (rel intensity) 374 (M+, 100), 178 (26). TOF-HRMS calcd for C24H23O4 (M+H+) 375.1591, found 375.1583.

3-(3,5-Dimethoxyphenyl)-6-methoxy-2-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21k) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale orange sticky (10.8 mg, 0.027 mmol, 48% (2 steps)). Rf (30% EtOAc/hexane) 0.41. IR (UATR): nmax 1709, 1595, 1245, 1154, 1027, 829 cm-1. 1

H NMR (300 MHz, CDCl3): d 7.31 – 7.21 (m, 3H), 7.07 – 7.00 (m, 2H), 6.90 – 6.81 (m, 2H),

6.36 (t, J = 2.3 Hz, 1H), 6.21 (d, J = 2.3 Hz, 2H), 4.38 (d, J = 4.4 Hz, 1H), 3.88 (s, 3H), 3.79 (s, 3H), 3.75 (d, J = 4.4 Hz, 1H), 3.72 (s, 6H). 13C NMR (75 MHz, CDCl3): d 205.5, 161.1, 160.1, 158.8, 148.6, 145.2, 137.4, 130.8, 129.3, 127.5, 124.8, 114.3, 105.9, 105.0, 98.7, 64.3, 55.7, 55.3, 55.3, 54.6. LRMS (EI) m/z (rel intensity) 404 (M+, 100), 296 (71). TOF-HRMS calcd for C25H24NaO5 (M+Na+) 427.1516, found 427.1517.

4,6-Dimethoxy-2,3-diphenyl-2,3-dihydro-1H-inden-1-one (21r) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (21.6 mg, 0.063 mmol, 54% (2 steps)) mp 147-149 °C. Rf (20% EtOAc/hexane) 0.37. IR (UATR): nmax 1713, 1614, 1493, 1359, 1306, 1149 cm-1. 1H NMR (300 MHz, CDCl3): d 7.33 – 7.16 (m, 6H), 7.13 – 7.06 (m, 2H), 7.05 – 6.99 (m, 2H), 6.91 (d, J = 2.1 Hz, 1H), 6.70 (d, J = 2.1 Hz, 1H), 4.56 (d, J = 2.9 Hz, 1H), 3.87 (s, 3H), 3.72 (d, J = 2.9 Hz, 1H), 3.64 (s, 3H). 13C NMR (75 MHz, CDCl3): d 205.6, 162.0, 157.8, 143.3, 139.3, 138.7, 138.1, 128.8, 128.5, 127.8, 127.1, 127.0, 126.5, 106.5, 96.5, 65.1, 55.8, 55.6, 51.7.


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LRMS (EI) m/z (rel intensity) 344 (M+, 100), 253 (13). TOF-HRMS calcd for C23H20NaO3 (M+Na+) 367.1305, found 367.1311. These spectroscopic data were identical to those reported previously.12b

4,6-Dimethoxy-3-(4-methoxyphenyl)-2-phenyl-2,3-dihydro-1H-inden-1-one (21s) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (24.5 mg, 0.066 mmol, 57% (2 steps)) mp 137-139 °C. Rf (20% EtOAc/hexane) 0.30. 1H NMR (300 MHz, CDCl3): d 7.32 – 7.19 (m, 3H), 7.13 – 7.05 (m, 2H), 6.97 – 6.89 (m, 3H), 6.82 – 6.75 (m, 2H), 6.69 (d, J = 2.1 Hz, 1H), 4.52 (d, J = 2.8 Hz, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.69 (d, J = 2.8 Hz, 1H), 3.65 (s, 3H). 13C NMR (75 MHz, CDCl3): d δ 205.7, 161.9, 158.2, 157.8, 139.4, 138.5, 138.4, 135.4, 128.8, 127.9, 127.8, 127.0, 113.8, 106.5, 96.4, 65.3, 55.8, 55.6, 55.2, 50.9. TOF-HRMS calcd for C24H22NaO4 (M+Na+) 397.1410, found 397.1401.

3-(3,5-Dimethoxyphenyl)-4,6-dimethoxy-2-phenyl-2,3-dihydro-1H-inden-1-one (21t) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (6.30 mg, 0.016 mmol, 27% (2steps)). Rf (20% EtOAc/hexane) 0.29. IR (UATR): nmax 1712, 1593, 1455, 1302, 1202, 1150 cm-1. 1H NMR (400 MHz, CDCl3): d 7.33 – 7.22 (m, 3H), 7.10 (d, J = 7.3 Hz, 2H), 6.90 (s, 1H), 6.71 (s, 1H), 6.32 (s, 1H), 6.16 (s, 2H), 4.49 (s, 1H), 3.88 (s, 3H), 3.71 (s, 6H), 3.71 (s, 1H), 3.69 (s, 3H). 13C NMR (101 MHz, CDCl3): d 205.5, 162.0, 160.8, 157.8, 145.9, 139.4, 138.7, 137.7, 128.8, 127.8, 127.1, 106.5, 105.2, 98.2, 96.5, 64.8, 55.8, 55.7, 55.2, 51.8. LRMS (EI) m/z (rel



Page 58 of 110

intensity) 404 (M+, 100), 152 (22). TOF-HRMS calcd for C25H25O5 (M+H+) 405.1697, found 405.1690. These spectroscopic data were identical to those reported previously.12d

4,6-Dimethoxy-2-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1H-inden-1-one (21u) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (23.2 mg, 0.062 mmol, 67% (2 steps)). Rf (20% EtOAc/hexane) 0.30. IR (UATR): nmax 1711, 1610, 1509, 1492, 1304, 1248, 1148, 1030 cm-1. 1H NMR (400 MHz, CDCl3): d 7.28 – 7.17 (m, 3H), 7.04 – 6.99 (m, 4H), 6.91 (d, J = 2.1 Hz, 1H), 6.86 – 6.82 (m, 2H), 6.70 (d, J = 2.1 Hz, 1H), 4.51 (d, J = 3.0 Hz, 1H), 3.88 (s, 3H), 3.78 (s, 3H), 3.66 (d, J = 3.0 Hz, 1H), 3.64 (s, 3H).

13

C NMR (101 MHz, CDCl3): d

206.0, 161.9, 158.6, 157.7, 143.3, 138.6, 138.0, 131.3, 128.9, 128.4, 126.9, 126.4, 114.3, 106.5, 96.4, 64.4, 55.8, 55.6, 55.2, 51.8. LRMS (EI) m/z (rel intensity) 374 (M+, 84), 149 (88), 71 (100). TOF-HRMS calcd for C24H22NaO4 (M+Na+) 397.1410, found 397.1404.

4,6-Dimethoxy-2,3-bis(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21v) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (15.6 mg, 0.039 mmol, 42% (2 steps)) mp 172-174 °C. Rf (20% EtOAc/hexane) 0.26. IR (UATR): nmax 1712, 1610, 1509, 1303, 1245, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.04 – 6.98 (m, 2H), 6.96 – 6.89 (m, 3H), 6.86 – 6.76 (m, 4H), 6.69 (d, J = 2.1 Hz, 1H), 4.47 (d, J = 2.9 Hz, 1H), 3.87 (s, 3H), 3.78 (s, 6H), 3.66 (s, 3H), 3.63 (d, J = 2.9 Hz, 1H).13C NMR (75 MHz, CDCl3): d 206.1, 161.9, 158.7, 158.1, 157.8, 138.5. 138.2, 135.5, 131.4, 128.8, 127.9, 114.3, 113.8, 106.5, 96.5, 64.6, 55.8, 55.6, 55.3, 55.2, 51.1. LRMS (EI) m/z (rel intensity) 404 (M+, 100). TOF-HRMS calcd for C25H24NaO5 (M+Na+)


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427.1516, found 427.1521. These spectroscopic data were identical to those reported previously.12b

3-(3,5-Dimethoxyphenyl)-4,6-dimethoxy-2-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (21w) Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as clear sticky (31.1 mg, 0.072 mmol, 46% (2 steps). Rf (40% EtOAc/hexane) 0.33. 1H NMR (400 MHz, CDCl3): d 7.05 – 6.98 (m, 2H), 6.89 (s, 1H), 6.86 – 6.81 (m, 2H), 6.70 (s, 1H), 6.32 (s, 1H), 6.15 (s, 2H), 4.44 (s, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.71 (s, 6H), 3.68 (s, 3H), 3.65 (s, 1H).

13

C NMR (101 MHz, CDCl3): d 205.8, 162.00,

160.8, 158.7, 157.8, 145.9, 138.7, 137.6, 131.5, 128.8, 114.3, 106.5, 105.2, 98.2, 96.5, 64.1, 55.8, 55.6, 55.2, 51.9. TOF-HRMS calcd for C26H26NaO6 (M+Na+) 457.1622, found 457.1614. These spectroscopic data were identical to those reported previously.12c

1,2-Diphenyl-1H-indene (16) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (30.0 mg, 0.112 mmol, 85%) mp 176177 °C. Rf (20% EtOAc/hexane) 0.62. 1H NMR (300 MHz, CDCl3): d 7.53 – 7.45 (m, 2H), 7.40 (dt, J = 7.5, 1.0 Hz, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.29 – 7.05 (m, 11H), 4.95 (s, 1H). 13C NMR (75 MHz, CDCl3) d 149.8, 149.1, 143.2, 140.0, 135.0, 128.8, 128.4, 128.0, 127.8, 127.3, 127.0, 126.7, 126.6, 125.4, 123.8, 121.0, 56.2. These spectroscopic data were identical to those reported previously.15



1-(4-Methoxyphenyl)-2-phenyl-1H-indene (22a) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as orange solid (19.0 mg, 0.064 mmol, 65%) mp 171173 °C. Rf (20% EtOAc/hexane) 0.56. IR (UATR): nmax 2930, 1509, 1248, 1176, 1033 cm-1. 1H NMR (300 MHz, CDCl3): d 7.53 – 7.47 (m, 2H), 7.40 (dt, J = 7.4, 0.9 Hz, 1H), 7.33 (d, J = 1.5 Hz, 1H), 7.29 – 7.01 (m, 8H), 6.80 – 6.71 (m, 2H), 4.92 (d, J = 1.5 Hz, 1H), 3.72 (s, 3H). 13C NMR (101 MHz, CDCl3): d 158.3, 150.0, 149.4, 143.1, 135.1, 131.8, 128.8, 128.4, 127.7, 127.3, 126.9, 126.6, 125.4, 123.7, 121.0, 114.2, 55.4, 55.1. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 267 (10). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1433. These spectroscopic data were identical to those reported previously.12h

1-(3,5-Dimethoxyphenyl)-2-phenyl-1H-indene (22b) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (10.4 mg, 0.032 mmol, 54%) mp 99-101 °C. Rf (20% EtOAc/hexane) 0.49. IR (UATR): nmax 2937, 1592, 1457, 1202, 1153, 1063 cm-1. 1H NMR (300 MHz, CDCl3): d 7.54 – 7.48 (m, 2H), 7.42 – 7.37 (m, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.29 – 7.07 (m, 6H), 6.32 (d, J = 2.2 Hz, 2H), 6.26 (t, J = 2.3 Hz, 1H), 4.88 (s, 1H), 3.67 (s, 6H). 13

C NMR (75 MHz, CDCl3): d 160.9, 149.5, 148.6, 143.2, 142.3, 135.0, 128.4, 128.1, 127.3,


2-(4-Methoxyphenyl)-1-phenyl-1H-indene (22c)


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Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as pale red solid (18.7 mg, 0.063 mmol, 82%) mp 175177 °C. Rf (20% EtOAc/hexane) 0.54. IR (UATR): nmax 2932, 1716, 1603, 1511, 1249, 1178, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.47 – 7.33 (m, 3H), 7.28 – 7.10 (m, 8H), 7.11 – 7.02 (m, 1H), 6.83 – 6.74 (m, 2H), 4.91 (s, 1H), 3.75 (s, 3H). 13C NMR (75 MHz, CDCl3): d 159.0, 149.5, 149.0, 143.5, 140.3, 129.4, 129.1, 128.8, 127.8, 126.9, 126.6, 126.1, 125.0, 123.7, 120.7, 113.9, 56.3, 55.2. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 239 (24). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1430.

1,2-bis(4-Methoxyphenyl)-1H-indene (22d) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (24.7 mg, 0.075 mmol, 65%) mp 125126 °C. Rf (20% EtOAc/hexane) 0.43 IR (UATR): nmax 1607, 1508, 1246, 1176, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.47 – 7.39 (m, 2H), 7.36 (dt, J = 7.5, 0.9 Hz, 1H), 7.26 – 7.12 (m, 3H), 7.10 – 7.01 (m, 3H), 6.82 – 6.72 (m, 4H), 4.87 (s, 1H), 3.75 (s, 3H), 3.72 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.9, 158.3, 149.7, 149.2, 143.4, 132.1, 128.8, 127.9, 126.8, 125.9, 125.0, 123.6, 120.6, 114.3, 113.9, 55.5, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (15), 297 (13). TOF-HRMS calcd for C23H21O2 (M+H+) 329.1536, found 329.1549.

1-(3,5-Dimethoxyphenyl)-2-(4-methoxyphenyl)-1H-indene (22e) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as orange solid (8.90 mg, 0.025 mmol, 44%) mp 144147 °C. Rf (20% EtOAc/hexane) 0.41. 1H NMR (300 MHz, CDCl3): d 7.41 – 7.34 (m, 2H), 7.30



– 7.26 (m, 1H), 7.19 – 7.10 (m, 3H), 7.00 (td, J = 7.3, 1.2 Hz, 1H), 6.76 – 6.70 (m, 2H), 6.24 (d, J = 2.3 Hz, 2H), 6.19 (t, J = 2.3 Hz, 1H), 4.76 (s, 1H), 3.69 (s, 3H), 3.61 (s, 6H). 13C NMR (75 MHz, CDCl3): d 161.0, 159.0, 149.2, 148.4, 143.5, 142.6, 127.9, 127.8, 127.0, 126.2, 125.0, 123.5, 120.7, 113.9, 105.9, 98.3, 56.4, 55.2, 55.2. TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1646.

5-Methoxy-1,2-diphenyl-1H-indene (22f) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (14.4 mg, 0.048 mmol, 61%) mp 162164 °C. Rf (20% EtOAc/hexane) 0.39. IR (UATR): nmax 1613, 1466, 1235, 1033 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 – 7.45 (m, 2H), 7.31 – 7.03 (m, 10H), 6.97 (d, J = 2.4 Hz, 1H), 6.65 (dd, J = 8.2, 2.4 Hz, 1H), 4.92 (s, 1H), 3.81 (s, 3H). 13C NMR (75 MHz, CDCl3): d 159.2, 151.2, 144.5, 141.6, 140.3, 135.0, 128.8, 128.4, 127.8, 127.7, 127.4, 126.6, 126.6, 124.3, 111.2, 106.7, 55.5. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 178 (19). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1425.

5-Methoxy-1-(4-methoxyphenyl)-2-phenyl-1H-indene (22g) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (19.6 mg, 0.060 mmol, 74%) mp 134137 °C. Rf (20% EtOAc/hexane) 0.54. IR (UATR): nmax 1607, 1509, 1247, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.57 – 7.44 (m, 2H), 7.34 – 7.11 (m, 4H), 7.09 – 6.99 (m, 3H), 6.96 (d, J = 2.3 Hz, 1H), 6.81 – 6.70 (m, 2H), 6.69 – 6.61 (m, 1H), 4.88 (d, J = 1.6 Hz, 1H), 3.82 (s, 3H), 3.72 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.2, 158.2, 151.4, 144.4, 141.9, 135.1, 132.2,


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128.7, 128.4, 127.6, 127.3, 126.7, 124.2, 114.2, 111.2, 106.6, 55.5, 55.1, 54.7. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (25). TOF-HRMS calcd for C23H21O2 (M+H+) 329.1536, found 329.1533.

1-(3,5-Dimethoxyphenyl)-5-methoxy-2-phenyl-1H-indene (22h). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white solid (11.5 mg, 0.032 mmol, 41%) mp 122123 °C. Rf (20% EtOAc/hexane) 0.38. IR (UATR): nmax 1594, 1457, 1203, 1152, 1064 cm-1. 1H NMR (300 MHz, CDCl3): d 7.46 – 7.39 (m, 2H), 7.23 – 7.00 (m, 5H), 6.88 (d, J = 2.4 Hz, 1H), 6.59 (dd, J = 8.2, 2.4 Hz, 1H), 6.23 (d, J = 2.3 Hz, 2H), 6.19 – 6.15 (m, 1H), 4.77 (s, 1H), 3.74 (s, 3H), 3.60 (s, 6H).

13

C NMR (75 MHz, CDCl3): d 160.9, 159.3, 150.9, 144.5, 142.7, 141.1,

135.0, 128.4 128.0, 127.4, 126.5, 124.1, 111.2, 106.7, 105.9, 98.3, 55.6, 55.5, 55.2. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 178 (22). TOF-HRMS calcd for C24H22NaO3 (M+Na+) 381.1461, found 381.1460.

5-Methoxy-2-(4-methoxyphenyl)-1-phenyl-1H-indene (22i) Following the general procedure and purification by column chromatography on silica (30% DCM/hexane), the product was obtained as pale red solid (14.8 mg, 0.045 mmol, 44%) mp 148150 °C. Rf (60% DCM/hexane) 0.62. IR (UATR): nmax 1603, 1509, 1473, 1250, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.45 – 7.37 (m, 2H), 7.25 – 7.08 (m, 6H), 7.03 (d, J = 8.2 Hz, 1H), 6.93 (d, J = 2.3 Hz, 1H), 6.81 – 6.74 (m, 2H), 6.62 (dd, J = 8.2, 2.3 Hz, 1H), 4.87 (s, 1H), 3.80 (s, 3H), 3.74 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.2, 159.0, 150.9, 144.9, 141.3, 140.6,

128.8, 127.8, 127.7, 126.5, 125.9, 124.1, 113.9, 110.6, 106.4, 55.5, 55.4, 55.2. LRMS (EI) m/z



(rel intensity) 328 (M+, 100), 313 (25). TOF-HRMS calcd for C23H20NaO2 (M+Na+) 351.1356, found 351.1353.

5-Methoxy-1,2-bis(4-methoxyphenyl)-1H-indene (22j) Following the general procedure and purification by column chromatography on silica (30% DCM/hexane), the product was obtained as pale red solid (8.80 mg, 0.025 mmol, 46%) mp 131133 °C. Rf (60% DCM/hexane) 0.38. IR (UATR): nmax 1602, 1508, 1464, 1247, 1176, 1031 cm-1. 1

H NMR (300 MHz, CDCl3): d 7.45 – 7.39 (m, 2H), 7.14 (s, 1H), 7.07 – 7.00 (m, 3H), 6.92 (d, J

= 2.4 Hz, 1H), 6.81 – 6.72 (m, 4H), 6.62 (dd, J = 8.2, 2.4 Hz, 1H), 4.83 (s, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.72 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.2, 159.0, 158.2, 151.0, 144.8,

141.6, 132.5, 128.7, 127.9, 125.7, 124.0, 114.2, 113.9, 110.6, 106.3, 55.4, 55.2, 55.1, 54.8. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 178 (26). TOF-HRMS calcd for C24H22NaO3 (M+Na+) 381.1461, found 381.1451.

1-(3,5-Dimethoxyphenyl)-5-methoxy-2-(4-methoxyphenyl)-1H-indene (22k) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as red solid (11.2 mg, 0.029 mmol, 47%) mp 135-137 °C. Rf (20% EtOAc/hexane) 0.39. IR (UATR): nmax 1592, 1509, 1462, 1249, 1151 cm-1. 1H NMR (300 MHz, CDCl3): d 7.47 – 7.40 (m, 2H), 7.15 (s, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.92 (d, J = 2.4 Hz, 1H), 6.85 – 6.73 (m, 2H), 6.62 (dd, J = 8.2, 2.4 Hz, 1H), 6.33 – 6.21 (m, 3H), 4.79 (s, 1H), 3.81 (s, 3H), 3.77 (s, 3H), 3.68 (s, 6H).

13

C NMR (75 MHz, CDCl3): d 161.0, 159.3, 159.0,

150.5, 144.8, 143.0, 140.9, 127.9, 127.8, 126.1, 124.0, 113.9, 110.6, 106.5, 105.9, 98.3, 55.7,


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55.5, 55.2, 55.2. LRMS (EI) m/z (rel intensity) 388 (M+, 100), 178 (20). TOF-HRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1736.

6-Methoxy-1,2-diphenyl-1H-indene (22l) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (16.7 mg, 0.065 mmol, 78%) mp 160161 °C. Rf (20% EtOAc/hexane) 0.64. IR (UATR): nmax 1596, 1490, 1283, 1220 cm-1. 1H NMR (400 MHz, CDCl3): d 7.45 (d, J = 7.7 Hz, 2H), 7.33 – 7.25 (m, 2H), 7.26 – 7.18 (m, 4H), 7.17 – 7.10 (m, 4H), 6.82 – 6.73 (m, 2H), 4.92 (s, 1H), 3.73 (s, 3H).

13


158.4, 151.1, 147.8, 140.2, 136.2, 135.2, 128.9, 128.4, 127.8, 127.6, 126.9, 126.7, 126.3, 121.5, 112.3, 110.6, 56.3, 55.4. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 283 (20). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1433.

6-Methoxy-1-(4-methoxyphenyl)-2-phenyl-1H-indene (22m) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (17.0 mg, 0.052 mmol, 62%) mp 136137 °C. Rf (20% EtOAc/hexane) 0.47. IR (UATR): nmax 1596, 1509, 1283, 1247, 1220, 1030 cm. H NMR (300 MHz, CDCl3): d 7.49 – 7.42 (m, 2H), 7.32 – 7.19 (m, 4H), 7.16 – 7.09 (m, 1H),

1 1

7.08 – 7.02 (m, 2H), 6.81 – 6.72 (m, 4H), 4.87 (s, 1H), 3.73 (s, 3H), 3.71 (s, 3H).

13

C NMR (75

MHz, CDCl3): d 158.4, 158.3, 151.4, 148.0, 136.2, 135.3, 132.0, 128.8, 128.4, 127.3, 126.8, 126.3, 121.4, 114.3, 112.3, 110.4, 55.5, 55.4, 55.1. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (39). TOF-HRMS calcd for C23H20NaO2 (M+Na+) 351.1356, found 351.1354.



Page 66 of 110

6-Methoxy-2-(4-methoxyphenyl)-1-phenyl-1H-indene (22o) Following the general procedure and purification by column chromatography on silica (80% DCM/hexane), the product was obtained as pale orange solid (19.8 mg, 0.060 mmol, 64%) mp 130-132 °C. Rf (80% DCM/hexane) 0.67. IR (UATR): nmax 1608, 1508, 1477, 1279, 1249, 1221, 1179 cm-1. 1H NMR (300 MHz, CDCl3): d 1H NMR (300 MHz, Chloroform-d) δ 7.41 – 7.35 (m, 2H), 7.28 – 7.09 (m, 7H), 6.80 – 6.72 (m, 4H), 4.87 (s, 1H), 3.73 (s, 3H), 3.72 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.7, 158.1, 150.8, 147.5, 140.5, 136.6, 128.9, 128.1, 127.9, 127.5, 126.7, 125.7, 121.1, 113.9, 112.2, 110.6, 56.4, 55.5, 55.2. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (25). TOF-HRMS calcd for C23H20NaO2 (M+Na+) 351.1356, found 351.1367.

6-Methoxy-1,2-bis(4-methoxyphenyl)-1H-indene (22p) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as red sticky (19.8 mg, 0.055 mmol, 82%). Rf (20% EtOAc/hexane) 0.51. IR (UATR): nmax 1610, 1509, 1247, 1171, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.42 – 7.33 (m, 2H), 7.25 – 7.21 (m, 1H), 7.13 (d, J = 1.5 Hz, 1H), 7.08 – 7.01 (m, 2H), 6.80 – 6.73 (m, 6H), 4.83 s, 1H), 3.74 (s, 3H), 3.73 (s, 3H), 3.72 (s, 3H).

13

C NMR (75

MHz, CDCl3): d 158.6, 158.3, 158.1, 151.1, 147.7 136.5, 132.3, 128.8, 128.2, 127.5, 125.4, 121.0, 114.3, 113.8, 112.1, 110.5, 55.6, 55.4, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 358 (M+, 10), 178 (34), 135 (50). TOF-HRMS calcd for C24H22O3 (M+) 358.1563, found 358.1524.

5,7-Dimethoxy-1,2-diphenyl-1H-indene (22r) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (11.7 mg, 0.036 mmol, 76%) mp 154-


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157 °C. Rf (20% EtOAc/hexane) 0.55. IR (UATR): nmax 1597, 1339, 1209, 1140, 1101 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 – 7.43 (m, 2H), 7.29 – 7.04 (m, 9H), 6.63 (d, J = 2.0 Hz, 1H), 6.25 (d, J = 2.0 Hz, 1H), 5.02 (d, J = 1.3 Hz, 1H), 3.84 (s, 3H), 3.62 (s, 3H). 13C NMR (75 MHz, CDCl3): d 161.1, 155.8, 152.2, 145.6, 139.2, 134.9, 128.6, 128.4, 128.3, 128.1, 127.4, 127.3, 126.6, 126.1, 98.6, 96.7, 55.6, 55.6, 54.0. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (24). TOF-HRMS calcd for C23H21O2 (M+H+) 329.1536, found 329.1538.

5,7-Dimethoxy-1-(4-methoxyphenyl)-2-phenyl-1H-indene (22s) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (13.1 mg, 0.037 mmol, 39%) mp 154156 °C. Rf (20% EtOAc/hexane) 0.40. IR (UATR): nmax 1598, 1508, 1246, 1139, 1104, 1035 cm. H NMR (300 MHz, CDCl3): d 7.51 – 7.43 (m, 2H), 7.28 – 7.10 (m, 4H), 7.10 – 7.02 (m, 2H),

1 1

6.72 – 6.65 (m, 2H), 6.62 (d, J = 2.0 Hz, 1H), 6.25 (d, J = 2.0 Hz, 1H), 4.97 (d, J = 1.3 Hz, 1H), 3.83 (s, 3H), 3.70 (s, 3H), 3.63 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 161.0, 157.8, 155.8,

152.3, 145.5, 135.0, 131.0, 129.2, 128.8, 128.3, 127.3, 127.2, 126.7, 113.6, 98.6, 96.7, 55.6, 55.5, 55.0, 53.2. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 343 (24). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1639.

1-(3,5-Dimethoxyphenyl)-5,7-dimethoxy-2-phenyl-1H-indene (22t) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white foam (5.10 mg, 0.013 mmol, 17%). Rf (20% EtOAc/hexane) 0.33. 1H NMR (300 MHz, CDCl3): d 7.51 – 7.45 (m, 2H), 7.28 – 7.12 (m, 4H), 6.61 (d, J = 2.1 Hz, 1H), 6.36 (d, J = 2.3 Hz, 2H), 6.26 (d, J = 2.1 Hz, 1H), 6.21 (t, J = 2.3 Hz,



1H), 4.95 (d, J = 1.3 Hz, 1H), 3.83 (s, 3H), 3.67 (s, 6H), 3.66 (s, 3H).

Page 68 of 110

13

C NMR (75 MHz,

CDCl3): d 161.1, 160.3, 155.9, 151.9, 145.7, 141.6, 135.1, 128.4, 128.1, 127.5, 127.3, 126.6, 106.6, 98.8, 98.2, 96.8, 55.6, 55.5, 55.2, 54.1. TOF-HRMS calcd for C25H24NaO4 (M+Na+) 411.1567, found 411.1558.

5,7-Dimethoxy-2-(4-methoxyphenyl)-1-phenyl-1H-indene (22u) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow solid (14.1 mg, 0.039 mmol, 43%) mp 173175 °C. Rf (20% EtOAc/hexane) 0.44. IR (UATR): nmax 1599, 1510, 1255, 1140 cm-1. 1H NMR (300 MHz, CDCl3): d 7.43 – 7.36 (m, 2H), 7.18 – 7.04 (m, 6H), 6.80 – 6.72 (m, 2H), 6.60 (d, J = 2.1 Hz, 1H), 6.22 (d, J = 2.0 Hz, 1H), 4.96 (d, J = 1.3 Hz, 1H), 3.82 (s, 3H), 3.74 (s, 3H), 3.60 (s, 3H).13C NMR (75 MHz, CDCl3): d 161.1, 159.0, 155.7, 151.9, 145.9, 139.5, 128.3, 128.3, 128.1, 127.9, 127.8 126.1, 125.5, 113.8, 98.5, 96.3, 55.5, 55.4, 55.2, 54.1. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 343 (24). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1630.

5,7-Dimethoxy-1,2-bis(4-methoxyphenyl)-1H-indene (22v) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale red solid (13.2 mg, 0.034 mmol, 47%) mp 135137 °C. Rf (20% EtOAc/hexane) 0.36. IR (UATR): nmax 1598, 1509, 1464, 1250 cm-1. 1H NMR (300 MHz, CDCl3): d 7.41 (d, J = 8.4 Hz, 2H), 7.11 – 7.03 (m, 3H), 6.81 – 6.74 (m, 2H), 6.73 – 6.66 (m, 2H), 6.60 (d, J = 1.1 Hz, 1H), 6.22 (d, J = 1.7 Hz, 1H), 4.93 (s, 1H), 3.83 (s, 3H), 3.75 (s, 3H), 3.71 (s, 3H), 3.63 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 161.0, 158.9, 157.8, 155.7,

151.9, 145.8, 129.2, 128.5, 127.9, 127.8, 125.3, 113.8, 113.5, 98.4, 96.3. 55.5, 55.5, 55.2, 55.0,


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53.2. LRMS (EI) m/z (rel intensity) 388 (M+, 100), 373 (21), 178 (18). TOF-HRMS calcd for C25H24NaO4 (M+Na+) 411.1567, found 411.1558.

1-(3,5-Dimethoxyphenyl)-5,7-dimethoxy-2-(4-methoxyphenyl)-1H-indene (22w) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale yellow sticky (6.20 mg, 0.015 mmol, 29%). Rf (20% EtOAc/hexane) 0.24. IR (UATR): nmax 1594, 1461, 1340, 1253, 1203 cm-1. 1H NMR (300 MHz, CDCl3): d 7.44 – 7.38 (m, 2H), 7.05 (d, J = 1.2 Hz, 1H), 6.81 – 6.75 (m, 2H), 6.58 (d, J = 2.0 Hz, 1H), 6.36 (d, J = 2.3 Hz, 2H), 6.24 – 6.20 (m, 2H), 4.90 (d, J = 1.2 Hz, 1H), 3.83 (s, 3H), 3.76 (s, 3H), 3.68 (s, 6H), 3.66 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 161.1, 160.3, 159.0,

155.8, 151.6, 146.0, 141.9, 127.9, 127.8, 127.7, 125.6, 113.8, 106.6, 98.5, 98.1, 96.3, 55.6, 55.5, 55.2, 55.2, 54.1. LRMS (EI) m/z (rel intensity) 418 (M+, 100), 403 (15). TOF-HRMS calcd for C26H26NaO5 (M+Na+) 441.1672, found 441.1660. These spectroscopic data were identical to those reported previously.12f

5,6-Dimethoxy-1,2-diphenyl-1H-indene (22x) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (6.90 mg, 0.021 mmol, 68%) mp 139141 °C. Rf (20% EtOAc/hexane) 0.34. IR (UATR): nmax 1702, 1597, 1488, 1312, 1214cm-1. 1H NMR (300 MHz, CDCl3): d 7.47 – 7.41 (m, 2H), 7.26 – 7.08 (m, 9H), 6.97 (s, 1H), 6.74 (s, 1H), 4.89 (s, 1H), 3.91 (s, 3H), 3.78 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 149.0, 148.7, 147.8,

142.1, 140.3, 135.8, 135.2, 128.9, 128.4, 127.8, 127.7, 126.9, 126.6, 126.2, 107.9, 104.6, 56.3,



56.2, 56.1. TOF-HRMS calcd for C23H20NaO2 (M+Na+) 351.1356, found 351.1349. These spectroscopic data were identical to those reported previously.15

5,6-Dimethoxy-1-(4-methoxyphenyl)-2-phenyl-1H-indene (22y) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as white foam (33.6 mg, 0.094 mmol, 62%). Rf (20% EtOAc/hexane) 0.27. 1H NMR (400 MHz, CDCl3): d 7.47 (d, J = 7.2 Hz, 2H), 7.28 – 7.22 (m, 3H), 7.18 – 7.12 (m, 1H), 7.06 (d, J = 7.0 Hz, 2H), 6.98 (s, 1H), 6.81 – 6.74 (m, 3H), 4.86 (s, 1H), 3.93 (s, 3H), 3.81 (s, 3H), 3.74 (s, 3H). 13C NMR (101 MHz, CDCl3): d 158.2, 149.1, 148.5, 147.7, 142.3, 135.7, 135.2, 132.1, 128.7, 128.3, 127.4, 126.8, 126.2, 114.2, 107.8, 104.5, 55.4, 55.1. TOF-HRMS calcd for C24H22NaO3 (M+Na+) 381.1461, found 381.1455.

1-(3,5-Dimethoxyphenyl)-5,6-dimethoxy-2-phenyl-1H-indene (22z) Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as brown sticky (9.00 mg, 0.023 mmol, 25%). Rf (40% EtOAc/hexane) 0.39. IR (UATR): nmax 1704, 1592, 1455, 1298, 1204, 1154 cm-1. 1H NMR (400 MHz, CDCl3): d 7.51 – 7.47 (m, 2H), 7.30 – 7.24 (m, 3H), 7.20 – 7.14 (m, 1H), 6.99 (s, 1H), 6.82 (s, 1H), 6.33 (d, J = 2.3 Hz, 2H), 6.29 (t, J = 2.3 Hz, 1H), 4.83 (s, 1H), 3.95 (s, 3H), 3.84 (s, 3H), 3.71 (s, 6H).

13

C NMR (101 MHz, CDCl3): d 161.0, 148.6, 148.6, 147.7, 142.6, 141.6,

135.8, 135.3, 128.4, 127.8, 126.9, 126.2, 107.8, 106.0, 104.6, 98.2, 56.4, 56.2, 56.1, 55.2. TOFHRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1746.

5,6-Dimethoxy-2-(4-methoxyphenyl)-1-phenyl-1H-indene (22α)


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Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as red solid (22.4 mg, 0.063 mmol, 75%) mp 146-148 °C. Rf (20% EtOAc/hexane) 0.39. IR (UATR): nmax 1703, 1604, 1489, 1214 cm-1. 1H NMR (300 MHz, CDCl3): d 7.41 – 7.34 (m, 2H), 7.26 – 7.09 (m, 6H), 6.94 (s, 1H), 6.80 – 6.71 (m, 3H), 4.84 (s, 1H), 3.91 (s, 3H), 3.78 (s, 3H), 3.74 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.6, 148.6, 148.7, 147.4, 141.7 140.5, 136.1, 128.8, 128.1, 127.8, 127.4, 126.6, 125.7, 113.8, 107.9, 104.3, 56.3, 56.2, 56.1, 55.1. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 343 (19). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1636.

5,6-Dimethoxy-1,2-bis(4-methoxyphenyl)-1H-indene (22β) Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as deep red sticky (18.8 mg, 0.049 mmol, 66%). Rf (40% EtOAc/hexane) 0.31. IR (UATR): nmax 1604, 1509, 1490, 1248 cm-1. 1H NMR (400 MHz, CDCl3): d 7.44 – 7.38 (m, 2H), 7.13 (d, J = 1.4 Hz, 1H), 7.09 – 7.04 (m, 2H), 6.97 (s, 1H), 6.82 – 6.77 (m, 4H), 6.75 (s, 1H), 4.83 (d, J = 1.3 Hz, 1H), 3.94 (s, 3H), 3.82 (s, 3H), 3.78 (s, 3H), 3.76 (s, 3H). 13C NMR (101 MHz, CDCl3): d 158.6, 158.2, 148.8, 148.5, 142.0, 136.0, 132.4, 128.8, 128.2, 127.5, 125.5, 114.3, 113.8, 107.9, 104.3, 56.2, 56.1, 55.6, 55.2, 55.1. LRMS (EI) m/z (rel intensity) 388 (M+, 100), 149(20). TOF-HRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1744.

2,3-Diphenyl-1H-indene (17) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow solid (32.1 mg, 0.120 mmol, 88%) mp 100-



102 °C. Rf (20% EtOAc/hexane) 0.63. 1H NMR (300 MHz, CDCl3): δ 7.55 – 7.49 (m, 1H), 7.46 – 7.30 (m, 5H), 7.30 – 7.08 (m, 8H), 3.90 (s, 2H). 13C NMR (75 MHz, CDCl3): d 146.9, 142.4, 141.1, 139.9, 136.5, 136.0, 129.3, 128.8, 128.3, 128.1, 127.3, 126.9, 126.5, 125.0, 123.5, 120.4, 41.2. These spectroscopic data were identical to those reported previously.15

3-(4-Methoxyphenyl)-2-phenyl-1H-indene (23a) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow sticky (20.5 mg, 0.069 mmol, 67%). Rf (20% EtOAc/hexane) 0.57. IR (UATR): nmax 3059, 1705, 1509, 1460, 1247, 1176, 1029 cm-1. 1H NMR (300 MHz, CDCl3): d 7.55 – 7.46 (m, 1H), 7.36 – 7.11 (m, 10H), 7.00 – 6.88 (m, 2H), 3.89 (s, 2H), 3.85 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 158.9, 147.0, 142.4, 140.6, 139.5, 136.7,

130.5, 129.0, 128.2, 128.1, 126.8, 126.4, 124.9, 123.5, 120.3, 114.2, 55.2, 41.1. LRMS (EI) m/z (rel intensity) 298 (M+, 39), 178 (62), 149 (91), 83 (100). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1433. These spectroscopic data were identical to those reported previously.30

3-(3,5-Dimethoxyphenyl)-2-phenyl-1H-indene (23b) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow sticky (9.70 mg, 0.030 mmol, 49%). Rf (20% EtOAc/hexane) 0.53. IR (UATR): nmax 2936, 1708, 1588, 1458, 1204, 1154, 1062 cm-1. 1H NMR (300 MHz, CDCl3): d 7.55 – 7.49 (m, 1H), 7.35 – 7.31 (m, 2H), 7.31 – 7.14 (m, 6H), 6.54 – 6.46 (m, 3H), 3.91 (s, 2H), 3.73 (s, 6H).

13

C NMR (75 MHz, CDCl3): d 161.1, 146.8, 142.2,

141.0, 139.8, 138.1, 136.4, 128.2, 128.1, 127.0, 126.5, 125.0, 123.5, 120.4, 107.1, 99.9, 55.3,


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41.1. LRMS (EI) m/z (rel intensity) 328 (M+, 1.33), 178 (100), 161 (41). TOF-HRMS calcd for C23H20NaO2 (M+Na+) 351.1356, found 351.1353.

2-(4-Methoxyphenyl)-3-phenyl-1H-indene (23c) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as orange sticky (17.6 mg, 0.059 mmol, 78%). Rf (20% EtOAc/hexane) 0.59. IR (UATR): nmax 3008, 1598, 1510, 1250, 1177, 1026 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 – 7.47 (m, 1H), 7.45 – 7.30 (m, 4H), 7.30 – 7.12 (m, 6H), 6.78 – 6.70 (m, 2H), 3.87 (s, 2H), 3.75 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 158.5, 147.2, 142.1, 140.7,

138.4, 136.3, 129.4, 129.1, 128.8, 127.2, 126.4, 124.7, 123.4, 120.0, 113.6, 55.2, 41.1. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 283 (14). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1422. These spectroscopic data were identical to those reported previously.30

2,3-bis(4-Methoxyphenyl)-1H-indene (23d) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as red sticky (32.5 mg, 0.099 mmol, 93%). Rf (20% EtOAc/hexane) 0.41. IR (UATR): nmax 1705, 1504, 1245, 1028 cm-1. 1H NMR (300 MHz, CDCl3): d 7.43 – 7.38 (m, 1H), 7.24 – 7.08 (m, 7H), 6.91 – 6.84 (m, 2H), 6.71 – 6.64 (m, 2H), 3.77 (s, 3H), 3.77 (s, 2H), 3.68 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 158.8, 158.5, 147.3,

142.1, 140.3, 138.0, 130.5, 129.4, 129.3, 128.5, 126.4, 124.6, 123.4, 120.0, 114.3, 113.6, 55.2, 55.2, 41.1. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (14), 236 (23). TOF-HRMS calcd



for C23H20O2 (M+) 328.1458, found 328.1438. These spectroscopic data were identical to those reported previously.31

3-(3,5-Dimethoxyphenyl)-2-(4-methoxyphenyl)-1H-indene (23e) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange sticky (16.1 mg, 0.045 mmol, 42%). Rf (20% EtOAc/hexane) 0.46. IR (UATR): nmax 1587, 1459, 1248, 1154 cm-1. 1H NMR (300 MHz, CDCl3): d 7.42 (dt, J = 6.8, 1.3 Hz, 1H), 7.24 – 7.09 (m, 5H), 6.73 – 6.66 (m, 2H), 6.44 (d, J = 2.3 Hz, 2H), 6.41 (t, J = 2.3 Hz, 1H), 3.80 (s, 2H), 3.70 (s, 3H), 3.67 (s, 6H). 13C NMR (75 MHz, CDCl3): d 161.2, 158.6, 147.1, 142.0, 140.6, 138.4, 138.3, 129.3, 129.0, 126.5, 124.7, 123.4, 120.1, 113.6, 107.1, 99.8, 55.3, 55.2, 41.0. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 149 (13). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1645.

6-Methoxy-2,3-diphenyl-1H-indene (23f) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as red sticky (9.70 mg, 0.033 mmol, 73%). Rf (20% EtOAc/hexane) 0.63. IR (UATR): nmax 1596, 1226, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.34 – 7.24 (m, 5H), 7.19 – 7.00 (m, 7H), 6.74 (dd, J = 8.3, 2.5 Hz, 1H), 3.79 (s, 2H), 3.76 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 158.2, 144.2, 140.2, 139.5, 138.8, 136.7, 136.3, 129.3,

128.8, 128.1, 128.0, 127.3, 126.5, 120.8, 112.1, 110.1, 55.6, 41.1. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 283 (16). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1432. These spectroscopic data were identical to those reported previously.32


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6-Methoxy-3-(4-methoxyphenyl)-2-phenyl-1H-indene (23g) Following the general procedure and purification column chromatography on silica (10% EtOAc/hexane), the product was obtained as deep red sticky (22.0 mg, 0.067 mmol, 58%. Rf (20% EtOAc/hexane) 0.57. IR (UATR): nmax 1607, 1509, 1246, 1031 cm-1. 1H NMR (300 MHz, CDCl3): d 7.31 – 7.09 (m, 9H), 6.98 – 6.92 (m, 2H), 6.83 (d, J = 8.4 Hz, 1H), 3.85 (s, 8H). 13C NMR (75 MHz, CDCl3): d 158.8, 158.2, 144.2, 140.3, 139.1, 138.4, 136.9, 130.4, 128.8, 128.0, 128.1, 126.4, 120.8, 114.2, 112.1, 110.1, 55.6, 55.2, 41.0. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313(26). TOF-HRMS calcd for C23H21O2 (M+H+) 329.1536, found 329.1534. These spectroscopic data were identical to those reported previously.33

6-Methoxy-2-(4-methoxyphenyl)-3-phenyl-1H-indene (23i) Following the general procedure and purification by column chromatography on silica (30% DCM/hexane), the product was obtained as red sticky (8.90 mg, 0.027 mmol, 72%) Rf (60% DCM/hexane) 0.67. IR (UATR): nmax 1702, 1601, 1510, 1282, 1248 cm-1. 1H NMR (300 MHz, CDCl3): d 7.45 – 7.30 (m, 5H), 7.21 – 7.14 (m, 2H), 7.10 (d, J = 2.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.80 (dd, J = 8.4, 2.4 Hz, 1H), 6.76 – 6.70 (m, 2H), 3.84 (s, 5H), 3.75 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.3, 158.0, 143.9, 140.4, 138.5, 138.0, 136.5, 129.3, 129.1, 128.8, 127.2, 120.4, 113.6, 111.9, 110.1, 55.6, 55.2, 41.1. LRMS (EI) m/z (rel intensity) 328 (M+, 11), 135 (100). TOF-HRMS calcd for C23H20O2 (M+) 328.1458, found 328.1453. These spectroscopic data were identical to those reported previously.34

6-Methoxy-2,3-bis(4-methoxyphenyl)-1H-indene (23j)



Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as red sticky (10.3 mg, 0.029 mmol, 52%). Rf (20% EtOAc/hexane) 0.49. IR (UATR): nmax 1607, 1513, 1465, 1283, 1246, 1176 cm-1. 1H NMR (300 MHz, CDCl3): d 7.20 (dd, J = 10.1, 3.5 Hz, 2H), 7.16 – 7.08 (m, 2H), 7.04 – 6.99 (m, 2H), 6.91 – 6.83 (m, 2H), 6.73 (dd, J = 8.4, 2.5 Hz, 1H), 6.70 – 6.64 (m, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.74 (s, 2H), 3.69 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 158.7, 158.2, 157.9, 143.9, 140.6, 138.1,

137.5, 130.5, 129.5, 129.1, 128.6, 120.4, 114.2, 113.6, 111.9, 110.1, 55.6, 55.2, 55.2, 41.0. . LRMS (EI) m/z (rel intensity) 358 (M+, 100), 149 (12). TOF-HRMS calcd for C24H21O3 (M+H+) 357.1485, found 357.1496. These spectroscopic data were identical to those reported previously.32

3-(3,5-Dimethoxyphenyl)-6-methoxy-2-(4-methoxyphenyl)-1H-indene (23k) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as red sticky (11.2 mg, 0.029 mmol, 59%). Rf (20% EtOAc/hexane) 0.44. IR (UATR): nmax 1705, 1591, 1456, 1247 cm-1. 1H NMR (300 MHz, CDCl3): d 7.27 – 7.21 (m, 2H), 7.13 – 7.08 (m, 2H), 6.84 – 6.73 (m, 3H), 6.53 – 6.49 (m, 2H), 6.49 – 6.46 (m, 1H), 3.85 (s, 3H), 3.84 (s, 2H), 3.77 (s, 3H), 3.75 (s, 6H). 13C NMR (75 MHz, CDCl3): d 161.2, 158.4, 158.0, 143.8, 140.3, 138.6, 138.4, 137.9, 129.1, 120.5, 113.6, 112.0, 110.1, 107.1, 99.8, 55.6, 55.4, 55.2, 41.0. LRMS (EI) m/z (rel intensity) 388 (M+, 30), 135 (68). TOF-HRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1740.

5-Methoxy-2,3-diphenyl-1H-indene (23l)


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Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as white solid (9.10 mg, 0.0.31 mmol, 39%) mp 139142 °C. Rf (20% EtOAc/hexane) 0.57. IR (UATR): nmax 1702, 1600, 1475, 1285, 1221 cm-1. 1H NMR (300 MHz, CDCl3): d 7.45 – 7.32 (m, 6H), 7.28 – 7.13 (m, 5H), 6.82 – 6.75 (m, 2H), 3.86 (s, 2H), 3.78 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.2, 148.3, 142.6, 139.8, 136.6, 136.0,

134.6, 129.3, 128.8, 128.3, 128.1, 127.4, 126.9, 124.0, 111.1, 106.1, 55.6, 40.5. LRMS (EI) m/z (rel intensity) 298 (M+, 100), 178 (29). TOF-HRMS calcd for C22H19O (M+H+) 299.1430, found 299.1422.

5-Methoxy-3-(4-methoxyphenyl)-2-phenyl-1H-indene (23m) Following the general procedure and purification by column chromatography on silica (60% DCM/hexane), the product was obtained as white foam (22.2 mg, 0.068 mmol, 73%). Rf (60% DCM/hexane) 0.65. IR (UATR): nmax 1604, 1508, 1474, 1283, 1245, 1032 cm-1. 1H NMR (300 MHz, CDCl3): d 7.44 – 7.36 (m, 1H), 7.31 – 7.14 (m, 7H), 6.99 – 6.92 (m, 2H), 6.82 – 6.76 (m, 2H), 3.86 (s, 3H), 3.84 (d, J = 0.8 Hz, 2H), 3.78 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.1,

158.9, 148.5, 142.1, 139.4, 136.7, 134.5, 130.5, 129.4, 128.2, 128.1, 126.8, 124.0, 114.3, 111.0, 106.0, 55.5, 55.2, 40.4. LRMS (EI) m/z (rel intensity) 328 (M+, 100), 313 (24). TOF-HRMS calcd for C23H20O2 (M+) 328.1458, found 328.1447.

3-(3,5-Dimethoxyphenyl)-5-methoxy-2-phenyl-1H-indene (23n) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as clear sticky (26.9 mg, 0.075 mmol, 51%). Rf (20% EtOAc/hexane) 0.50. IR (UATR): nmax 1592, 1463, 1285, 1204, 1154 cm-1. 1H NMR (300 MHz,



CDCl3): d 1H NMR (300 MHz, Chloroform-d) δ 7.42 – 7.38 (m, 1H), 7.34 – 7.29 (m, 2H), 7.27 – 7.14 (m, 4H), 6.81 (s, 2H), 6.49 (s, 2H), 3.85 (d, J = 0.8 Hz, 2H), 3.78 (s, 3H), 3.73 (s, 6H). 13C NMR (75 MHz, CDCl3): d 161.2, 159.1, 148.2, 139.7, 138.0, 136.4, 134.4, 128.1, 128.1, 128.1, 127.0, 126.9, 124.0, 111.2, 107.0, 106.0, 100.0, 55.3, 40.3. LRMS (EI) m/z (rel intensity) 214 (M+, 100), 199 (54). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1648.

5-Methoxy-2-(4-methoxyphenyl)-3-phenyl-1H-indene (23o) Following the general procedure and purification by column chromatography on silica (40% DCM/hexane), the product was obtained as orange solid (15.1 mg, 0.046 mmol, 55%) mp 135137 °C. Rf (40% DCM/hexane) 0.43. IR (UATR): nmax 1601, 1511, 1474, 1285, 1248, 1027 cm-1. 1

H NMR (300 MHz, CDCl3): d 7.46 – 7.30 (m, 6H), 7.22 – 7.16 (m, 2H), 6.79 – 6.71 (m, 4H),

3.82 (s, 2H), 3.76 (s, 3H), 3.76 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 159.1, 158.6, 148.6,

142.2, 138.3, 136.2, 134.3, 129.4, 129.1, 128.8, 127.3, 123.9, 113.6, 110.6, 105.8, 55.5, 55.1, 40.4. TOF-HRMS calcd for C23H21O2 (M+H+) 329.1536, found 329.1534.

5-Methoxy-2,3-bis(4-methoxyphenyl)-1H-indene (23p) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange solid (13.0 mg, 0.036 mmol, 68%) mp 139140 °C. Rf (20% EtOAc/hexane) 0.49. IR (UATR): nmax 1602, 1504, 1474, 1289, 1244, 1175, 1028 cm-1. 1H NMR (300 MHz, CDCl3): d 7.38 (dd, J = 7.5, 0.9 Hz, 1H), 7.31 – 7.19 (m, 4H), 6.99 – 6.93 (m, 2H), 6.79 – 6.72 (m, 4H), 3.87 (s, 3H), 3.80 (s, 2H), 3.78 (s, 6H). 13C NMR (75 MHz, CDCl3): d 159.1, 158.8, 158.5, 148.8, 141.8, 137.9, 134.3, 130.5, 129.3, 128.4, 123.8,


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114.3, 113.6, 110.6, 105.8, 55.5, 55.2, 55.2, 40.3. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 343 (20). TOF-HRMS calcd for C24H23O3 (M+H+) 359.1642, found 359.1656.

3-(3,5-Dimethoxyphenyl)-5-methoxy-2-(4-methoxyphenyl)-1H-indene (23q) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as orange sticky (14.4 mg, 0.037 mmol, 59%). Rf (20% EtOAc/hexane) 0.5. IR (UATR): nmax 1599, 1463, 1286, 1248, 1204, 1153 cm-1. 1H NMR (300 MHz, CDCl3): d 7.40 – 7.35 (m, 1H), 7.28 – 7.22 (m, 2H), 6.80 – 6.72 (m, 4H), 6.51 – 6.47 (m, 3H), 3.81 (s, 2H), 3.77 (s, 3H), 3.77 (s, 3H), 3.75 (s, 6H).

13


161.2, 159.1, 158.7, 148.5, 142.0, 138.3, 138.2, 134.1, 129.3, 129.0, 123.8, 113.6, 110.7, 107.1, 105.8, 99.9, 55.5, 55.4, 55.2, 40.3. LRMS (EI) m/z (rel intensity) 388 (M+, 100), 357 (10). TOFHRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1739.

5,6-Dimethoxy-3-(4-methoxyphenyl)-2-phenyl-1H-indene (23y) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as pale red sticky (19.1 mg, 0.053 mmol, 46%). Rf (20% EtOAc/hexane) 0.28. 1H NMR (400 MHz, CDCl3): d 7.32 – 7.11 (m,8H), 7.00 – 6.96 (m, 2H), 6.77 (s, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 3.84 (s, 2H).

13

C NMR (101 MHz,

CDCl3): d 158.9, 148.5, 147.6, 139.9, 139.4, 139.3, 136.9, 134.9, 130.4, 128.4, 128.1, 128.0, 126.4, 114.3, 107.8, 104.0, 56.4, 56.2, 55.2, 40.9. TOF-HRMS calcd for C24H22NaO3 (M+Na+) 381.1461, found 381.1452.

3-(3,5-Dimethoxyphenyl)-5,6-dimethoxy-2-phenyl-1H-indene (23z)



Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as brown sticky (6.00 mg, 0.016 mmol, 21%). Rf (40% EtOAc/hexane) 0.38. IR (UATR): nmax 1702, 1590, 1454, 1303, 1204 cm-1. 1H NMR (400 MHz, CDCl3): d 7.34 – 7.15 (m, 6H), 6.83 (s, 1H), 6.55 – 6.50 (m, 3H), 3.97 (s, 3H), 3.87 (s, 2H), 3.86 (s, 3H), 3.77 (s, 6H). 13C NMR (101 MHz, CDCl3): d 161.2, 148.5, 147.7, 139.8, 139.6, 138.3, 136.5, 134.8, 128.1, 127.9, 126.6, 107.8, 107.0, 104.0, 99.9, 56.3, 56.2, 55.3, 40.9. TOF-HRMS calcd for C25H25O4 (M+H+) 389.1747, found 389.1746.

5,6-Dimethoxy-2-(4-methoxyphenyl)-3-phenyl-1H-indene (23α) Following the general procedure and purification by column chromatography on silica (60% DCM/hexane), the product was obtained as red sticky (20.9 mg, 0.058 mmol, 67%). Rf (60% DCM/hexane) 0.24. IR (UATR): nmax 1702, 1598, 1493, 1293, 1248 cm-1. 1H NMR (300 MHz, CDCl3): d 7.46 – 7.35 (m, 5H), 7.17 – 7.11 (m, 3H), 6.74 – 6.71 (m, 3H), 3.93 (s, 3H), 3.81 (s, 3H), 3.81 (s, 2H), 3.76 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.3, 148.4, 147.4, 140.0, 139.5, 138.2, 136.5, 134.5, 129.3, 129.1, 128.9, 127.2, 113.6, 107.9, 103.8, 56.3, 56.2, 55., 41.0. LRMS (EI) m/z (rel intensity) 358 (M+, 100), 343 (29). TOF-HRMS calcd for C24H22NaO3 (M+Na+) 381.1461, found 381.1450.

5,6-Dimethoxy-2,3-bis(4-methoxyphenyl)-1H-indene (23β) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as deep red sticky (13.9 mg, 0.036 mmol, 59%). Rf (20% EtOAc/hexane) 0.23. IR (UATR): nmax 1604, 1487, 1290, 1245, 1176, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.33 – 7.23 (m, 2H), 7.22 – 7.15 (m, 2H), 7.11 (s, 1H), 7.01 – 6.93 (m,


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2H), 6.78 – 6.71 (m, 3H), 3.93 (s, 3H), 3.87 (s, 3H), 3.82 (s, 3H), 3.79 (s, 2H), 3.77 (s, 3H). 13C NMR (75 MHz, CDCl3): d 158.8, 158.2, 148.4, 147.3, 140.2, 139.1, 137.8, 134.5, 130.4, 129.5, 129.1, 128.6, 114.3, 113.6, 107.9, 103.8, 56.4, 56.2, 55.2, 55.2, 40.9. LRMS (EI) m/z (rel intensity) 388 (M+, 100), 373 (20). TOF-HRMS calcd for C25H24NaO4 (M+Na+) 411.1567, found 411.1565.

General procedure for Sonogashira reaction To a solution of aldehyde bromo or iodobenzaldehyde (1.0 equiv), bis(triphenylphosphine) palladium(II) dichloride (10 mol %), triphenyl phosphine (20 mol %), copper(I) iodide (10 mol %), and triethylamine (1.5 mL/stating material 0.1 g) in tetrahydrofuran (THF) was strirred under argon gas at room temperature. The solution was flushed to remove other gases and substituted by degassing argon gas for 30 min. Phenylacetylene (2.0 equiv) was added to the solution and the reaction was allowed to stir for overnight until complete consumption of the starting materials aldehyde as indicated by TLC. The reaction mixture was filtered under vacuum the removed solvent. Water and EtOAc were added, and the two phases were separated. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography on silica gel.

2-(Phenylethynyl)benzaldehyde (26a) Following the general procedure and purification by column chromatography on silica (20% DCM/hexane), the product was obtained as pale yellow oil (262 mg, 1.27 mmol, 97%). Rf (20% EtOAc/hexane) 0.41. IR (UATR): nmax 2839, 2215, 1695, 1265, 755 cm-1. 1H NMR (300 MHz,



CDCl3): d 10.68 (s, 1H), 7.98 (dd, J = 7.8, 1.4 Hz, 1H), 7.70 – 7.53 (m, 4H), 7.52 – 7.36 (m, 4H). 13

C NMR (75 MHz, CDCl3): d 191.7, 135.9, 133.8, 133.2, 131.7, 129.1, 128.6, 128.5, 127.3,

126.9, 122.3, 96.3, 84.9. LRMS (EI) m/z (rel intensity) 206 (M+, 100), 176 (48), 152 (35), 71 (7). TOF-HRMS calcd for C15H10NaO (M+Na+) 229.0623, found 229.0621. These spectroscopic data were identical to those reported previously.35

4-Methoxy-2-(phenylethynyl)benzaldehyde (26b) Following the general procedure and purification by column chromatography on silica (20% DCM/hexane), the product was obtained as black sticky gum (846.00 mg, 3.5847 mmol, 96%). Rf (20% EtOAc/hexane) 0.55. IR (UATR): nmax 2840, 1771, 1677, 1596, 1239, 1027, 692 cm-1. 1

H NMR (300 MHz, CDCl3): d 10.51 (d, J = 0.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.62 – 7.52

(m, 2H), 7.45 – 7.34 (m, 3H), 7.10 (d, J = 2.5 Hz, 1H), 6.98 (ddd, J = 8.8, 2.6, 0.8 Hz, 1H), 3.91 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 190.2, 163.7, 131.6, 129.5, 129.3, 129.0, 128.8, 128.4,

122.2, 116.9, 115.5, 96.0, 84.8, 55.6. LRMS (EI) m/z (rel intensity) 236 (M+, 0.35), 178 (100), 161 (38), 123 (58), 112 (33), 83 (12), 71 (43). TOF-HRMS calcd for C16H13O2 (M+H+) 237.0910, found 237.0917. These spectroscopic data were identical to those reported previously.36

5-Methoxy-2-(phenylethynyl)benzaldehyde (26c) Following the general procedure and purification by column chromatography on silica (20% DCM/hexane), the product was obtained as yellow solid (884 mg, 3.73 mmol, 80%) mp 77-79 °C. Rf (20% EtOAc/hexane) 0.54. IR (UATR): nmax 2840, 1771, 1677, 1596, 1239, 1027, 692 cm-1. 1H NMR (300 MHz, CDCl3): d 10.59 (s, 1H), 7.56 – 7.47 (m, 3H), 7.40 (d, J = 2.8 Hz,


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1H), 7.38 – 7.32 (m, 3H), 7.11 (dd, J = 8.6, 2.8 Hz, 1H), 3.84 (s, 3H).

13

C NMR (75 MHz,

CDCl3): d 13C NMR (75 MHz, Chloroform-d) δ 191.4, 159.6, 137.1, 134.4, 131.4, 128.6, 128.4, 122.5, 121.5, 119.4, 109.7, 94.7, 84.8, 55.5. LRMS (EI) m/z (rel intensity) 236 (M+, 100), 221 (69), 193 (41), 165 (86), 97 (6). TOF-HRMS calcd for C16H13O2 (M+H+) 237.0910, found 237.0907. These spectroscopic data were identical to those reported previously.37

4,5-Dimethoxy-2-(phenylethynyl)benzaldehyde (26d) Following the general procedure and purification by column chromatography on silica (20% DCM/hexane), the product was obtained as orange solid (664 mg, 2.50 mmol, 96%) mp 120-123 °C. Rf (20% EtOAc/hexane) 0.23. IR (UATR): nmax 2937, 2835, 2377, 1734, 1734, 1680, 1589, 1506, 1218, 1089, 756 cm-1. 1H NMR (300 MHz, CDCl3): d 10.49 (s, 1H), 7.58 – 7.50 (m, 2H), 7.42 – 7.32 (m, 4H), 7.05 (s, 1H), 3.98 (s, 3H), 3.94 (s, 3H).

13


190.3, 153.5, 149.6, 131.4, 130.0, 128.8, 128.4, 122.3, 121.4, 114.2, 108.0, 94.9, 84.7, 56.2, 56.0. LRMS (EI) m/z (rel intensity) 266 (M+, 0.87), 193 (48), 178 (28), 105 (100), 97 (16), 71 (27). TOF-HRMS calcd for C17H14NaO3 (M+Na+) 289.0835, found 289.0837. These spectroscopic data were identical to those reported previously.38

General procedure for reduction reaction To a solution of aldehyde (26a-d) (1.0 equiv) in ethanol (1 mmol:10 mL) was added sodium borohydride (2.5 equiv) at room temperature and the reaction was allowed to stir until all of the starting material was consumed as monitored by TLC. The resulting mixture of product was concentrated. Water and EtOAc were added, and the two phases were separated. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine, dried



over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was further purified by column chromatography on silica to furnish the desired products.

(2-(Phenylethynyl)phenyl)methanol (28a) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as pale yellow solid (664 mg, 0.73 mmol, 82%) mp 60-64 °C. Rf (20% EtOAc/hexane) 0.65. IR (UATR): nmax 3325, 2917, 2867, 2323, 1490, 1027, 755 cm-1. 1H NMR (300 MHz, CDCl3): d 7.58 – 7.45 (m, 4H), 7.41 – 7.29 (m, 5H), 4.92 (s, 2H), 2.08 (s, 1H).

13

C NMR (75 MHz, CDCl3): d 142.5, 132.1, 131.5, 128.7, 128.5, 128.4, 127.5,

127.2, 122.9, 121.3, 94.2, 86.7, 64.0. LRMS (EI) m/z (rel intensity) 209 (M+, 15), 208 (100), 178 (96), 130 (77), 102 (42), 77 (9). TOF-HRMS calcd for C15H12NaO (M+Na+) 231.0780, found 231.0781. These spectroscopic data were identical to those reported previously.39

(5-Methoxy-2-(phenylethynyl)phenyl)methanol (28c) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as white solid (196 mg, 0.82 mmol, 85%) mp 95-97 °C. Rf (20% EtOAc/hexane) 0.21. IR (UATR): nmax 3340, 2914, 2212, 1745, 1494, 1222, 1040, 757 cm-1. 1H NMR (300 MHz, CDCl3): d 7.54 – 7.44 (m, 3H), 7.39 – 7.31 (m, 3H), 7.05 (d, J = 2.7 Hz, 1H), 6.82 (dd, J = 8.5, 2.7 Hz, 1H), 4.90 (s, 2H), 3.85 (s, 3H), 1.88 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.9, 144.4, 133.4, 131.3, 128.3, 128.1, 123.2, 113.1, 112.4, 92.8, 86.7, 63.8, 55.3. LRMS (EI) m/z (rel intensity) 238 (M+, 100), 223 (30), 178 (55), 149 (45), 71 (49), 57 (51). TOF-HRMS calcd for C16H15O2 (M+H+) 239.1066, found 239.1064. These spectroscopic data were identical to those reported previously.40


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General procedure for hydrogenation To a suspension of alcohol 28a-d (1.0 equiv), pyridine (3.0 equiv) and Pd on CaCO3 (10 mol %) in DCM was stirred at room temperature under H2 atmosphere (300 psi). The mixture was stirred for 4 h, the palladium catalyst was removed by filtration through Celite, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel.

(Z)-(2-Styrylphenyl)methanol (29a) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (175 mg, 0.83 mmol, 88%). Rf (20% EtOAc/hexane) 0.65. IR (UATR): nmax 3334, 2877, 1445, 1028, 778 cm-1. 1H NMR (300 MHz, CDCl3): d 7.37 (d, 1H), 7.20-7.17 (m, 1H), 7.11-7.06 (m, 5H), 7.01-6.98 (m, 2H), 6.67 (d, J = 12.0, 1H), 6.59 (d, J = 12.3, 1H), 4.56 (s, 2H). 13C NMR (75 MHz, CDCl3): d 138.4, 136.5, 136.3, 131.7, 129.3, 128.9, 128.2, 128.1, 127.9, 127.8, 127.6, 127.3, 63.5. LRMS (EI) m/z (rel intensity)

210 (M+, 9), 132 (7), 91 (100), 77 (6). TOF-HRMS calcd for C15H14NaO (M+Na+) 233.0937, found 233.0928.

(Z)-(4-Methoxy-2-styrylphenyl)methanol (29b) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as clear sticky gum (31.0 mg, 0.13 mmol, 76% (2steps)). Rf (20% EtOAc/hexane) 0.20. IR (UATR): nmax 3358, 2936, 1602, 1233, 1033, 695cm. H NMR (300 MHz, CDCl3): d 7.27 (s, 1H), 7.12 – 6.98 (m, 5H), 6.72 (dd, J = 8.4, 2.7 Hz,

1 1

1H), 6.68 – 6.54 (m, 3H), 4.46 (s, 2H), 3.55 (s, 3H), 1.78 (s, 1H). 13C NMR (75 MHz, CDCl3): d



159.0, 137.7, 136.5, 131.6, 130.7, 129.9, 128.9, 128.2, 128.0, 127.3, 114.1, 113.5, 63.0, 55.1. LRMS (EI) m/z (rel intensity) 240 (M+, 47), 178 (100), 149 (92), 91 (86), 69 (91), 57 (58). TOFHRMS calcd for C16H16O2 (M +) 240.1145, found 240.1112.

(Z)-(5-Methoxy-2-styrylphenyl)methanol (29c) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (32.0 mg, 0.13 mmol, 84%). Rf (20% EtOAc/hexane) 0.20. IR (UATR): nmax 3363, 2935, 2835, 1606, 1030, 694 cm-1. 1H NMR (300 MHz, CDCl3): d 7.19 – 7.08 (m, 6H), 7.02 (d, J = 2.7 Hz, 1H), 6.71 (dd, J = 8.4, 2.7 Hz, 1H), 6.67 – 6.56 (m, 2H), 4.61 (s, 2H), 3.81 (s, 3H), 1.72 (s, 1H). 13C NMR (101 MHz, CDCl3):

d 159.1, 139.9, 136.8, 131.2, 130.5, 128.9, 128.2, 127.6, 127.2, 113.3, 112.9, 63.4, 55.3. LRMS (EI) m/z (rel intensity) 240 (M+, 75), 149 (100), 121 (43), 91 (25). TOF-HRMS calcd for C16H16NaO2 (M+Na+) 263.1043, found 263.1043.

(Z)-(4,5-Dimethoxy-2-styrylphenyl)methanol (29d) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as orange sticky gum (64.0 mg, 0.24 mmol, 59% (2steps)). Rf (20% EtOAc/hexane) 0.06. IR (UATR): nmax 3485, 2935, 1603, 1509, 1208, 1093, 695cm-1. 1H NMR (300 MHz, CDCl3): d 7.22 – 7.10 (m, 5H), 6.96 (s, 1H), 6.73 – 6.61 (m, 3H), 4.59 (s, 2H), 3.91 (d, J = 1.7 Hz, 3H), 3.62 (d, J = 1.7 Hz, 3H), 1.56 (s, 1H). 13C NMR (75 MHz, CDCl3): d 148.0, 147.7, 136.6, 130.9, 130.7, 128.7, 128.0, 127.8, 127.4, 127.0, 112.0, 110.9, 62.5, 55.6, 55.4. LRMS (EI) m/z (rel intensity) 270 (M+, 1), 178 (74), 123 (56), 97 (50), 71 (87), 51 (100). TOF-HRMS calcd for C17H18NaO3 (M+Na+) 293.1148, found 293.1157.


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General procedure for oxidation by PCC To a solution of alcohol 29a and 29b (1.0 equiv) in DCM was strirred at room temperature. Pyridinium chlorochromate (PCC) (1.5 equiv) and Celite (2x of the alcohol) were added to the solution. The reaction was stirred until complete consumption of the starting materials (2 h) as indicated by TLC. The resulting mixture of product was filtered over Celite and concentrated. The crude product was purified by column chromatography on silica gel.

General procedure for oxidation by DMP To a stirred solution 0.025 M (1 equiv) of 29c or 29d in DCM was added Dess-Martin periodinane (DMP) (1.2 equiv) at room temperature. The reaction mixture was stirred until all of the starting material was consumed as monitored by TLC. Water and DCM were added, and the two phases were separated. The aqueous layer was extracted twice with DCM. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was further purified by column chromatography on silica to furnish the desired products.

(Z)-2-Styrylbenzaldehyde (27a) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (263 mg, 1.26 mmol, 96%). Rf (20% EtOAc/hexane) 0.58. IR (UATR): nmax 2925, 1771, 1692, 1192, 779, 659 cm-1. 1H NMR (300 MHz, CDCl3): d 10.17 (s, 1H), 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.40 (td, J = 7.5, 1.6 Hz, 1H), 7.32 (td, J = 7.5, 1.3 Hz, 1H), 7.23 – 7.17 (m, 1H), 7.09 – 7.05 (m, 3H), 6.96 (dd, J = 6.7, 3.0 Hz, 2H), 6.90 (d, J = 12.2 Hz, 1H), 6.76 (d, J = 12.2 Hz, 1H). 13C NMR (75 MHz, CDCl3): d



192.0, 141.0, 135.8, 133.9, 133.4, 133.3, 130.5, 129.2, 129.2, 128.3, 127.7, 127.5, 126.5 LRMS (EI) m/z (rel intensity) 208 (M+, 39), 178 (100), 149 (24), 97 (23), 71 (11). TOF-HRMS calcd for C15H13O (M+H+) 209.0960, found 209.0956.

(Z)-4-Methoxy-2-styrylbenzaldehyde (27b) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (26.0 mg, 0.11 mmol, 88%). Rf (20% EtOAc/hexane) 0.38. IR (UATR): nmax 2940, 2839, 1682, 1242, 1029, 695 cm-1. 1H NMR (400 MHz, CDCl3): d 10.11 (s, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.19 – 7.11 (m, 3H), 7.11 – 7.04 (m, 2H), 6.96 (d, J = 12.2 Hz, 1H), 6.90 (dd, J = 8.7, 2.6 Hz, 1H), 6.82 (d, J = 12.2 Hz, 1H), 6.73 (d, J = 2.5 Hz, 1H), 3.71 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 190.6, 163.8, 143.3, 135.8,

133.4, 131.7, 129.1, 128.3, 127.6, 127.0, 126.4, 114.6, 114.0, 55.4. LRMS (EI) m/z (rel intensity) 239 (M+, 16), 238 (100), 178 (71), 165 (53), 97 (40), 57 (58). TOF-HRMS calcd for C16H14NaO2 (M+Na+) 261.0886, found 261.0886.

(Z)-5-Methoxy-2-styrylbenzaldehyde (27c) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (18.0 mg, 0.075 mmol, 82%). Rf (20% EtOAc/hexane) 0.38. IR (UATR): nmax 2937, 2840, 1688, 1497, 1034, 696 cm-1. 1H NMR (300 MHz, CDCl3): d 10.22 (s, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.22 – 7.11 (m, 4H), 7.09 – 7.01 (m, 3H), 6.91 (d, J = 12.1 Hz, 1H), 6.79 (d, J = 12.1 Hz, 1H), 3.86 (s, 3H). 13C NMR (75 MHz, CDCl3): d 191.7, 159.1, 136.0, 134.2, 133.9, 133.3, 131.8, 129.2, 128.3, 127.5, 125.8, 121.6,


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111.2, 55.5. LRMS (EI) m/z (rel intensity) 239 (M+, 16), 238 (100), 209 (23), 178 (72), 149 (55). TOF-HRMS calcd for C16H14NaO2 (M+Na+) 261.0886, found 261.0886.

(Z)-4,5-Dimethoxy-2-styrylbenzaldehyde (27d) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (166 mg, 0.62 mmol, 93%). Rf (20% EtOAc/hexane) 0.35. IR (UATR): nmax 2936, 1738, 1677, 1509, 1269, 1093, 696 cm-1. 1H NMR (300 MHz, CDCl3): d 10.16 (s, 1H), 7.40 (s, 1H), 7.20 – 7.14 (m, 3H), 7.09 (dd, J = 7.3, 2.5 Hz, 2H), 6.95 (d, J = 12.2 Hz, 1H), 6.83 (d, J = 12.1 Hz, 1H), 6.69 (s, 1H), 3.95 (s, 3H), 3.72 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 190.3, 153.8, 148.6, 136.2, 136.0, 133.6, 129.2, 128.8,

128.3, 127.6, 126.6, 125.6, 112.1, 109.3, 56.0, 56.0. LRMS (EI) m/z (rel intensity) 269 (M+, 17), 268 (100), 237 (25), 165 (57), 91 (31), 71 (19). TOF-HRMS calcd for C17H16NaO3 (M+Na+) 291.0992, found 291.0986.

General Procedure for the Synthesis of (Z)-(2-stilbenyl)methanol To a solution of (Z)-2-styrylbenzaldehyde (1.0 equiv) in dry ether at 0°C under argon atmosphere was added phenylmagnesium bromide (1.5 equiv). The reaction mixture was stirred at 0 °C and slowly warmed up to room temperature for overnight. The reaction mixture was stirred until all of the starting material was consumed as monitored by TLC before quenching with saturated NH4Cl. Water and EtOAc were added, and the two phases were separated. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was



further purified by column chromatography on silica (EtOAc/hexanes) to furnish the desired products.

(Z)-Phenyl(2-styrylphenyl)methanol (24a) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (316 mg, 1.11 mmol, 86%). Rf (20% EtOAc/hexane) 0.50. IR (UATR): nmax 3374, 2889, 1599, 1446, 1017, 697 cm-1. 1H NMR (300 MHz, CDCl3): d 7.52 (d, J = 7.8 Hz, 1H), 7.37 – 7.16 (m, 6H), 7.15 – 7.07 (m, 5H), 7.03 – 6.96 (m, 2H), 6.65 (d, J = 12.2 Hz, 1H), 6.60 (d, J = 12.3 Hz, 1H), 6.03 (s, 1H), 2.17 (s, 1H). 13C NMR (101 MHz, CDCl3): d 143.0, 141.4, 136.4, 136.0, 131.4, 129.4, 129.0, 128.6, 128.3, 128.1, 127.9, 127.6, 127.3, 127.2, 126.7, 73.2. LRMS (EI) m/z (rel intensity) 286 (M+, 2), 195 (100), 194 (64), 178 (32), 149 (26), 105 (30), 71 (29). TOF-HRMS calcd for C21H18NaO (M+Na+) 309.1249, found 309.1245.

(Z)-(4-Methoxy-2-styrylphenyl)(phenyl)methanol (24b) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (432 mg, 1.37 mmol, 88%). Rf (20% EtOAc/hexane) 0.37. IR (UATR): nmax 3400, 2937, 2834, 1602, 1231, 1031, 696 cm-1. 1H NMR (300 MHz, CDCl3): d 7.41 – 7.26 (m, 6H), 7.21 – 7.15 (m, 3H), 7.12 – 7.06 (m, 2H), 6.84 (dd, J = 8.6, 2.8 Hz, 1H), 6.70 (d, J = 2.8 Hz, 1H), 6.68 (d, J = 2.7 Hz, 2H), 6.03 (d, J = 3.3 Hz, 1H), 3.66 (s, 3H), 1.99 (d, J = 3.8 Hz, 1H).

13

C NMR (75 MHz, CDCl3): d 158.8, 143.4, 137.3,

136.4, 133.9, 131.5, 129.0, 128.5, 128.4, 128.2, 128.2, 127.3, 127.2, 126.5, 114.1, 113.8, 72.7,


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55.1. LRMS (EI) m/z (rel intensity) 316 (M+, 9), 298 (15), 225 (100), 194 (20), 105 (30), 91 (13), 71 (6). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1355, found 339.1352.

(Z)-(5-Methoxy-2-styrylphenyl)(phenyl)methanol (24c) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as yellow sticky gum (165 mg, 0.52 mmol, 89%). Rf (20% EtOAc/hexane) 0.37. IR (UATR): nmax 3421, 2938, 2835, 1605, 1493, 1031, 734 cm-1. 1H NMR (300 MHz, CDCl3): d 7.39 – 7.16 (m, 5H), 7.15 – 7.08 (m, 4H), 7.06 – 6.99 (m, 3H), 6.67 (dd, J = 8.5, 2.7 Hz, 1H), 6.55 (s, 2H), 6.00 (s, 1H), 3.77 (s, 3H), 2.19 (d, J = 3.3 Hz, 1H).

13

C

NMR (75 MHz, CDCl3): d 159.1, 143.0, 142.9, 136.7, 130.9, 130.7, 128.9, 128.5, 128.4, 128.2, 128.1, 127.4, 127.1, 126.8, 113.2, 111.9, 73.2, 55.2. LRMS (EI) m/z (rel intensity) 316 (M+, 12), 225 (100), 105 (16), 97 (5), 71 (7). TOF-HRMS calcd for C22H20NaO2 (M+Na+) 339.1355, found 339.1352.

(Z)-(4,5-Dimethoxy-2-styrylphenyl)(phenyl)methanol (24d) Following the general procedure and purification by column chromatography on silica (20% EtOAc /hexane), the product was obtained as orange sticky gum (64.0 mg, 0.19 mmol, 83%). Rf (20% EtOAc/hexane) 0.17. IR (UATR): nmax 3502, 2934, 1734, 1508, 1204, 1090, 697 cm-1. 1H NMR (400 MHz, CDCl3): d 7.42 – 7.19 (m, 5H), 7.15 (d, J = 6.6 Hz, 3H), 7.09 – 7.05 (m, 2H), 7.03 (s, 1H), 6.67 – 6.56 (m, 3H), 6.04 (s, 1H), 3.85 (s, 3H), 3.59 (s, 3H), 2.05 (s, 1H). 13C NMR (101 MHz, CDCl3): d 148.5, 148.0, 143.3, 136.7, 134.0, 131.1, 129.0, 128.3, 128.2, 128.1, 127.3, 127.2, 126.5, 112.3, 109.6, 72.7, 55.8, 55.7. LRMS (EI) m/z (rel intensity) 346 (M+, 32),



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255 (100), 224 (43), 105 (29), 91 (190, 71 (16). TOF-HRMS calcd for C23H22NaO3 (M+Na+) 369.1461, found 369.1446.

General procedure for the synthesis of indane via Lewis acid-mediated cyclization followed by nucleophilic transfer from the silyl reagents To a stirred solution of biaryl alcohol (1.0 equiv) in DCM -78, -30, -20, -10, 0 °C or room temperature was added triethylsilane or azidotrimethylsilane (1.5 equiv) before adding boron trifluoride diethyl etherate (1.5 equiv). The resulting mixture was stirred until the starting material was consumed as monitored by TLC. Water and EtOAc were added, and the two phases were separated. The aqueous layer was extracted with EtOAc 2 times, and the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product which was further purified by column chromatography on silica gel.

6-Methoxy-1,2-diphenyl-2,3-dihydro-1H-indene (30a) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as clear sticky gum (22.0 mg, 0.07 mmol, 85%). Rf (20% EtOAc/hexane) 0.62. IR (UATR): nmax 2935, 1606, 1492, 1282, 1032, 699 cm-1. 1H NMR (400 MHz, CDCl3): d 7.30 (d, J = 8.2 Hz, 1H), 7.06 – 6.98 (m, 6H), 6.88 – 6.75 (m, 3H), 6.68 (d, J = 2.5 Hz, 1H), 6.62 – 6.58 (m, 2H), 4.62 (d, J = 8.0 Hz, 1H), 4.02 (q, J = 8.1 Hz, 1H), 3.74 (s, 3H), 3.31 (dd, J = 15.4, 8.5 Hz, 1H), 3.18 (dd, J = 15.4, 7.5 Hz, 1H).

13

C NMR (101 MHz,

CDCl3): d 159.1, 146.8, 141.2, 140.6, 135.9, 129.1, 128.4, 127.6, 127.5, 126.0, 126.0, 124.8,


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110.5, 57.2, 55.4, 52.5, 36.1. LRMS (EI) m/z (rel intensity) 300 (M+, 84), 209 (72), 178 (100), 149 (63), 71 (47). TOF-HRMS calcd for C22H20O (M+) 300.1509, found 300.1518.

1-Azido-5-methoxy-2,3-diphenyl-2,3-dihydro-1H-indene (30b) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as pink sticky gum (23.0 mg, 0.067 mmol, 94%). Rf (20% EtOAc/hexane) 0.69. IR (UATR): nmax 2912, 2091, 1605, 1490, 1231, 1030, 698 cm-1. 1H NMR (300 MHz, CDCl3): d 7.46 (d, J = 8.3 Hz, 1H), 7.14 – 6.90 (m, 8H), 6.82 – 6.66 (m, 3H), 6.64 – 6.54 (m, 2H), 5.18 (d, J = 7.0 Hz, 1H), 4.78 (d, J = 8.0 Hz, 1H), 3.90 (t, J = 7.5 Hz, 1H), 3.77 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 160.9, 146.1 139.7, 138.2, 133.3, 129.1, 128.6,

127.9, 127.8, 126.8, 126.5, 125.1, 114.3, 110.8, 68.2, 59.3, 55.5, 55.1. LRMS (EI) m/z (rel intensity) 341 (M+, 5), 313 (26), 299 (100), 298 (23), 178 (61), 149 (56), 71 (49). TOF-HRMS calcd for C22H19O (M-N3+) 299.1430, found 299.1440.

5,6-Dimethoxy-1,2-diphenyl-2,3-dihydro-1H-indene (30c) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as clear sticky gum (7.00 mg, 0.021 mmol, 52%). Rf (20% EtOAc/hexane) 0.47. IR (UATR): nmax 2917, 1728, 1604, 1501, 1217, 1097, 698 cm-1. 1H NMR (300 MHz, CDCl3): d 7.09 – 6.98 (m, 6H), 6.94 (s, 1H), 6.85 – 6.77 (m, 2H), 6.66 (s, 1H), 6.62 – 6.55 (m, 2H), 4.60 (d, J = 8.1 Hz, 1H), 4.04 (q, J = 8.1 Hz, 1H), 3.95 (s, 3H), 3.78 (s, 3H), 3.32 (dd, J = 15.3, 8.8 Hz, 1H), 3.18 (dd, J = 15.3, 7.6 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 148.6, 148.5, 141.3, 141.1, 136.9, 135.5, 129.1, 128.5, 127.6, 127.5, 126.0, 126.0, 108.5, 107.4,



57.0, 56.1, 56.0, 52.5, 36.9. LRMS (EI) m/z (rel intensity) 330 (M+, 100), 299 (24), 239 (35), 208 (20). TOF-HRMS calcd for C23H22NaO2 (M+Na+) 353.1512, found 353.1517.

1-Azido-5,6-dimethoxy-2,3-diphenyl-2,3-dihydro-1H-indene (30d) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as yellow sticky gum (13.0 mg, 0.041 mmol, 41%). Rf (20% EtOAc/hexane) 0.40. IR (UATR): nmax 2953, 2093, 1605, 1503, 1453, 1221, 700 cm-1. 1H NMR (400 MHz, CDCl3): d 7.10 – 6.99 (m, 7H), 6.80 – 6.74 (m, 2H), 6.68 (s, 1H), 6.59 – 6.53 (m, 2H), 5.19 (d, J = 7.5 Hz, 1H), 4.73 (d, J = 8.1 Hz, 1H), 3.99 (s, 3H), 3.95 (t, J = 7.8 Hz, 1H), 3.81 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 150.4, 149.3, 140.2, 138.1, 136.1, 132.9, 128.9,

128.6, 127.9, 127.8, 126.8, 126.5, 108.3, 106.6, 68.8, 59.3, 56.2, 56.0, 54.9. LRMS (EI) m/z (rel intensity) 371 (M+, 7), 329 (100), 191 (21), 149 (18), 105 (18), 71 (25). TOF-HRMS calcd for C23H21N3NaO2 (M+Na+) 394.1526 found 394.1513.

(Z)-1-Benzyl-2-styrylbenzene (31a) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as clear sticky gum (13.0 mg, 0.048 mmol, 54%). Rf (20% EtOAc/hexane) 0.71. IR (UATR): nmax 2910, 1599, 1493, 1029, 694 cm-1. 1H NMR (400 MHz, CDCl3): d 7.27 – 7.11 (m, 11H), 7.10 – 7.00 (m, 3H), 6.64 (d, J = 12.2 Hz, 1H), 6.58 (d, J = 12.2 Hz, 1H), 4.00 (s, 2H).

13

C NMR (101 MHz, CDCl3): d 40.6, 138.9, 137.1, 136.8, 130.8,

130.1, 129.5, 129.3, 128.9, 128.3, 128.0, 127.6, 127.4, 127.0, 126.3, 125.9, 39.4. LRMS (EI) m/z (rel intensity) 270 (M+, 3), 178 (40), 149 (51), 71 (72), 57 (100). TOF-HRMS calcd for C14H11 (M-C7H7+) 179.0855, found 179.0859.


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(Z)-1-(Azido(phenyl)methyl)-2-styrylbenzene (31b) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as clear sticky gum (28.0 mg, 0.090 mmol, 69%). Rf (20% EtOAc/hexane) 0.68. IR (UATR): nmax 2923, 2095, 1695, 1494, 1452, 1243, 696 cm-1. 1H NMR (400 MHz, CDCl3): d 7.58 – 6.92 (m, 13H), 6.67 – 6.52 (m, 3H), 5.95 (s, 1H).

13

C NMR

(101 MHz, CDCl3): d 138.9, 137.4, 136.7, 136.3, 131.9, 129.8, 129.0, 128.6, 128.2, 128.1, 128.0, 128.0, 127.8, 127.6, 127.5, 127.4, 65.7. LRMS (EI) m/z (rel intensity) 311 (M+, 2), 283 (96), 206 (100), 178 (82), 97 (65), 71 (73). TOF-HRMS calcd for C21H18N3 (M+H+) 312.1495, found 312.1505.

(Z)-1-Benzyl-4-methoxy-2-styrylbenzene (31c) Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as pink sticky gum (23.0 mg, 0.077 mmol, 87%). Rf (20% EtOAc/hexane) 0.66. IR (UATR): nmax 2934, 1602, 1492, 1037, 694 cm-1. 1H NMR (300 MHz, CDCl3): d 7.27 – 7.03 (m, 11H), 6.78 – 6.68 (m, 2H), 6.59 (s, 2H), 3.92 (s, 2H), 3.59 (s, 3H).

13

C NMR (75 MHz, CDCl3): d 157.9, 141.1, 138.0, 136.8, 131.1, 130.9, 129.2, 128.9,

128.8, 128.3, 128.1, 127.1, 125.8, 114.2, 113.7, 55.1, 38.6. LRMS (EI) m/z (rel intensity) 300 (M+, 33), 209(100), 194(50), 178(43), 91(22), 71(13). TOF-HRMS calcd for C22H20NaO (M+Na+) 323.1406, found 323.1417.

(Z)-1-(Azido(phenyl)methyl)-4-methoxy-2-styrylbenzene (31d)



Following the general procedure and purification by column chromatography on silica (25% DCM/hexane), the product was obtained as green sticky gum (8.00 mg, 0.024 mmol, 31%). Rf (20% EtOAc/hexane) 0.62. IR (UATR): nmax 2931, 2097, 1703, 1602, 1027, 756 cm-1. 1H NMR (400 MHz, CDCl3): d 7.32 – 7.13 (m, 10H), 7.09 – 7.02 (m, 2H), 6.83 (dd, J = 8.7, 2.8 Hz, 1H), 6.70 (d, J = 2.8 Hz, 1H), 6.66 (d, J = 12.2 Hz, 1H), 6.59 (d, J = 12.2 Hz, 1H), 5.90 (s, 1H), 3.64 (s, 3H).

13

C NMR (101 MHz, CDCl3): d 159.1, 139.4, 138.1, 136.2, 132.0, 129.5, 129.1, 129.0,

128.5, 128.2, 127.9, 127.7, 127.5, 127.3, 114.4, 113.8, 65.1, 55.2. LRMS (EI) m/z (rel intensity) 341 (M+, 0.57), 311 (81), 238 (100), 178 (18), 97 (17), 71 (19). TOF-HRMS calcd for C22H20NO (M-N2+) 314.1540, found 314.1520.

5-Methoxy-1,2-diphenyl-2,3-dihydro-1H-indene (32c) Following the general procedure and purification by HPLC columns, reverse phase C18 (250 × 21.2 mm, 5 μm particle size; Luna®) was equilibrated with 100% solvent A (50% methanol in water) and 0% B (isopropanol) at a flow rate of 9 mL/min. The solvent was programmed as follows: a linear gradient from the starting solvent to 30% (vol/vol) B in 5 min; a linear gradient increasing from 30 to 55% (vol/vol) B for 35 min, holding for 10 min; increasing to 100% B in 1 min, holding for 10 min; and re-equilibrating at initial conditions for 30 min, the product was obtained as clear sticky (11.0 mg, 0.037 mmol, 58%). Rf (30% EtOAc/hexane) 0.38. IR (UATR):

nmax 1604, 1490, 1282, 1247, 1032 cm-1. 1H NMR (400 MHz, CDCl3): d 7.29 – 7.16 (m, 8H), 7.10 – 7.06 (m, 2H), 6.87 (d, J = 2.4 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.74 (dd, J = 8.3, 2.5 Hz, 1H), 4.35 (d, J = 9.1 Hz, 1H), 3.83 (s, 3H), 3.65 – 3.53 (m, 1H), 3.39 (dd, J = 15.8, 8.1 Hz, 1H), 3.22 (dd, J = 15.8, 9.8 Hz, 1H).

13

C NMR (101 MHz, CDCl3): d 159.2, 144.2, 143.8, 143.4,

138.1, 128.3, 127.5, 126.4, 126.4, 125.6, 112.7, 109.5, 59.1, 57.0, 55.5, 40.3. LRMS (EI) m/z (rel


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intensity) 300 (M+, 91), 209 (100). TOF-HRMS calcd for C22H20O (M+) 300.1509, found 300.1470.

3-Azido-5-methoxy-1,2-diphenyl-2,3-dihydro-1H-indene (32d) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as clear sticky (15.0 mg, 0.044 mmol, 87% (major:minor, 2.5:1)) Rf (20% EtOAc/hexane) 0.54. 1H NMR (300 MHz, CDCl3): d 7.40 – 7.17 (m, 16H), 7.16 – 7.12 (m, 2H), 7.10 – 7.02 (m, 2H), 7.02 – 6.96 (m, 2H), 6.92 – 6.88 (m, 2H), 6.86 (d, J = 1.5 Hz, 2H), 5.02 (d, overlapping, 1H, minor), 4.99 (d, J = 9.3 Hz, 1H, major), 4.77 (d, J = 9.7 Hz, 1H, minor), 4.33 (d, J = 9.6 Hz, 1H, major), 3.85 (s, 3H, major), 3.85 (s, 3H, minor), 3.80 (dd, J = 9.3, 6.0 Hz, 1H, minor), 3.47 (t, J = 9.3 Hz, 1H, major).

13

C NMR (75

MHz, CDCl3): d 159.8 (major), 159.4 (minor), 142.1(major), 141.94 (minor), 141.4 (major), 140.8 (minor), 139.5 (major), 138.8 (minor), 137.1 (minor), 136.2 (major), 129.2 (minor), 128.7, 128.5, 128.5, 128.4, 128.3, 128.3, 127.9, 127.3 (major), 127.2 (minor), 126.9 (major), 126.8 (minor), 126.3 (minor), 126.1 (major), 115.8 (minor), 115.6 (major), 109.7 (minor), 108.4 (major), 70.9 (major), 68.9 (minor), 64.3 (major), 60.9 (minor), 56.1 (major), 55.6 (major), 52.7. TOF-HRMS calcd for C22H18NO (M-N2H+) 312.1383, found 312.1387.

6-Methoxy-1,2-diphenyl-2,3-dihydro-1H-indene (32e) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as yellow sticky (20.3 mg, 0.067 mmol, 87% major:minor, 7.7:1). Rf (20% EtOAc/hexane) 0.47. IR (UATR): nmax 3394, 1689, 1602, 1490, 1279, 1030 cm-1. 1H NMR (300 MHz, CDCl3): d 7.31 – 7.14 (m, 12H), 7.10 – 7.05 (m, 2H), 7.04



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– 6.99 (m, 6H), 6.87 – 6.74 (m, 2H), 6.68 (d, J = 2.5 Hz, 1H, minor), 6.62 – 6.58 (m, 2H, minor), 6.46 (d, J = 1.5 Hz, 1H, major), 4.62 (d, J = 8.0 Hz, 1H, minor), 4.38 (d, J = 9.4 Hz, 1H, major), 4.02 (q, J = 8.1 Hz, 1H, minor), 3.73 (s, 3H, minor), 3.70 (s, 3H, major), 3.65 – 3.54 (m, 1H), 3.35 (dd, J = 15.4, 8.0 Hz, 2H), 3.16 (dd, J = 15.5, 9.7 Hz, 2H).

13


159.1 (major), 147.3 (major), 143.3 (major), 143.3 (major), 135.9 (major), 134.7 (major), 129.1 (minor), 128.4 (major), 128.4 (major), 128.3 (major), 127.6 (minor), 127.5 (major), 126.5 (major), 126.4 (major), 126.0 (minor), 126.0 (minor), 124.8 (minor), 124.7 (major), 113.3 (minor), 113.1 (major), 110.5 (minor), 110.3 (major), 59.9 (major), 57.1 (major), 55.4 (major), 52.5 (minor), 39.4 (major), 36.1 (minor). LRMS (EI) m/z (rel intensity) 300 (M+, 100), 225 (24). TOF-HRMS calcd for C22H20O (M+) 300.1509, found 300.1471.

1-Azido-5-methoxy-2,3-diphenyl-2,3-dihydro-1H-indene (32f) Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as yellow sticky (20.4 mg, 0.060 mmol, 84% (major:minor, 4.55:1)). Rf (20% EtOAc/hexane) 0.30. IR (UATR): nmax 3358, 2095, 1689, 1602, 1491 cm-1. 1H NMR (300 MHz, CDCl3): d 7.48 – 7.11 (m, 18H), 7.11 – 7.02 (m, 4H), 6.94 – 6.88 (m, 2H), 6.51 (d, J = 1.4 Hz, 1H, minor), 6.48 (d, J = 1.5 Hz, 1H, major), 5.02 (d, J = 6.0 Hz, 1H, minor), 4.97 (d, J = 8.4 Hz, 1H, major), 4.81 (d, J = 10.5 Hz, 1H, minor), 4.35 (d, J = 9.5 Hz, 1H, major), 3.88 – 3.81 (m, 1H, minor), 3.73 (s, 3H, minor), 3.72 (s, 3H, major), 3.53 – 3.40 (m, 1H, major). 13C NMR (75 MHz, CDCl3): d 161.0 (minor), 160.7 (major), 148.9 (minor), 146.1 (major), 141.7 (minor), 139.8 (major), 137.1 (minor), 132.2 (major), 131.7 (minor), 129.2, 128.7, 128.6, 128.5, 128.3, 127.8, 127.3, 127.2, 127.0, 125.6 (minor), 124.8 (major), 114.2 (major), 113.5 (minor), 110.7 (minor), 110.1 (major), 70.7 (major), 68.4 (minor), 64.1 (major),


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60.8 (minor), 56.9 (major), 55.5 (major), 53.4 (minor). LRMS (EI) m/z (rel intensity) 299 (MN3+, 58), 178 (27). TOF-HRMS calcd for C22H19N3NaO (M+Na+) 364.1420, found 364.1426.

1-Azido-5,6-dimethoxy-2,3-diphenyl-2,3-dihydro-1H-indene (32h) Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as clear sticky (17.3 mg, 0.047 mmol, 77% (major:minor, 5.88:1)). Rf (20% EtOAc/hexane) 0.38. IR (UATR): nmax 2094, 1702, 1603, 1501, 1215 cm-1. 1H NMR (300 MHz, CDCl3): d 7.37 – 7.18 (m, 17H), 7.10 – 7.04 (m, 3H), 6.99 (s, 1H, minor), 6.95 (s, 1H, major), 6.50 (s, 1H, minor), 6.45 (s, 1H, major), 5.01 (d (overlapping), 1H, minor), 4.97 (d, J = 8.2 Hz, 1H, major), 4.79 (d, J = 9.5 Hz, 1H, minor), 4.34 (d, J = 9.0 Hz, 1H, major), 3.95 (s, 3H, major), 3.94 (s, 3H, minor), 3.76 (s, 3H, minor), 3.75 (s, 3H, major), 3.44 (t, J = 8.6 Hz, 1H, major).

13

C NMR (75 MHz, CDCl3): d 150.5 (minor), 150.3 (major),

149.4 (major), 148.9 (minor), 142.3 (major), 142.0 (minor), 140.0 (major), 139.0 (minor), 137.2 (minor), 136.2 (major), 131.7 (major), 131.2 (minor), 129.2 (major), 128.7 (major), 128.6 (major), 128.3 (major), 127.8 (major), 127.3 (major), 126.9 (major), 126.9, 108.0 (minor), 107.7 (major), 107.3 (minor), 106.3 (major), 71.4 (major), 69.2 (minor), 64.3 (major), 61.4 (minor), 57.1 (major), 56.1 (major), 53.7 (minor). LRMS (EI) m/z (rel intensity) 371 (M+, 10), 329 (100), 252 (27). TOF-HRMS calcd for C23H21N3NaO2 (M+Na+) 394.1526, found 394.1524.

Supporting Information: The Supporting Information is available free of charge on the ACS Publications website. 1H and 13C NMR spectra for all products (PDF).

Acknowledgements



Page 100 of 110

Financial support from the Thailand Research Fund (BRG5980010, DBG6080010, and IRN58W0005 for P.P. and the Swedish Link for J.J.) and Mahidol University is gratefully acknowledged.

This article is dedicated in memory of the late Professor Gary H. Posner.

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Selective divergent synthesis of indanols, indanones, and indenes via

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