Selective Divergent Synthesis of Indanols, Indanones, and Indenes via

Article Cite This: J. Org. Chem. 2018, 83, 13184−13210

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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*,†,‡,§

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†

Program in Chemical Biology, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand ‡ Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand § Centre of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand S Supporting Information *

ABSTRACT: Starting from bromo/iodobenzaldehyde derivatives, the corresponding (Z)- and (E)-(2-stilbenyl)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 low temperatures furnished the 2,3trans-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 was employed as a nucleophile; 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.

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osteoporosis, or inflammation11 has 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

INTRODUCTION An indane skeleton, a cyclopentane ring fused with a benzene ring, together with indenes, 1-indanols, 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 hypertension,1−3 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 1,2disubstituted indene,6 while sulindac (4), a synthetic 2,3disubstituted indene, is a nonsteroidal anti-inflammatory agent.7 Paucifloral F (5), a trans-2,3-diaryl-1-indanone secondary metabolite, was reportedly isolated from the stem bark of Vatica paucif lora.8 In addition, daphenylline as well as rubriflordilactones A and B are complex natural products containing indane as their core.9,10 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, © 2018 American Chemical Society

Received: July 27, 2018 Published: October 11, 2018 13184

DOI: 10.1021/acs.joc.8b01921 J. Org. Chem. 2018, 83, 13184−13210

Article

The Journal of Organic Chemistry

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-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 1,2- and 2,3-disubstituted indenes (e.g., 8 and 9) as byproducts. Thus, the 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 conditions. 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). From Table 1, PTS-Si was the best mediator to affect the selective formation of indanol 15, 1,2-disubstituted indene 16, and 2,3-disubstituted indene 17 using CH2Cl2 or toluene as a 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 a short reaction time, while both indenes 16 and 17 required either longer reaction times and/or elevated temperatures. It was anticipated that, under acidic conditions, 15 was one of the intermediates that could subsequently lead to the indene product(s). In addition, between the two possible indene products, the 1,2disubstituted 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

Figure 1. Representative examples of natural and synthetic indanecontaining compounds.

of common secondary bisbenzylic and indanyl-type carbocations 10 and 11, respectively (Scheme 1). In addition, some (Z)-(2-stilbenyl)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.

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RESULTS AND DISCUSSION Based on the previously reported chemistry, starting from 2bromobenzaldehyde derivatives, the corresponding (E)-(2stilbenyl)methanols could be straightforwardly prepared via the Pd-catalyzed 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)

Scheme 1. Strategy Toward Selective Formation of 6−9 via 10 and 11

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the selective synthesis of the corresponding 2,3-trans-diaryl-1indanols 15 and 19aγ, 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 21aγ (Figure 3). The presence of two methoxy groups at the 3- and 5-positions 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 4position 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 18xγ, 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 19xγ). The corresponding 1,2-disubstituted indenes (22l−q and 22xγ) were obtained instead. This could be due to the electron-donating property via resonance of the 5-methoxy group that facilitated the regeneration of the indanyl cations from the elusive indanols; such indanyl cations then eventually underwent the subsequent loss of a proton to furnish the 1,2disubstituted indenes. Thus, without the indanols, the corresponding indanones (21l−q and 21xγ) could not be obtained. The substrates 18r−w, with two methoxy groups on the 4- and 6-positions of the fused aromatic ring, gave the corresponding indanols 19r−w, 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%). 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 four steps from the corresponding benzaldehyde and styrene derivatives via Heck reaction, ArLi addition, PTS-Si-mediated cyclization, and DMP oxidation in a 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 18aγ were treated with PTS-Si at temperatures up to 40 °C as well as reaction times up to 18 h as indicated for each substrate in Figure 4. Moderate to good yields of the desired products 22aγ 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-positions 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 22γ). As shown in Figure 5, the corresponding 2,3-disubstituted indenes 23aγ 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 6positions 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

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 2 3c 4c 5 6e,f 7e 8e 9g 10e 11e,f 12e

PTS-Si PTS-Si PTS-Si PTS-Si p-TsOH La(OTf)3 Bi(OTf)3 InCl3 PtCl4 PtCl4 PtCl4 PtCl4

rt rt 80 80 80 0 or rt rt rt rt rt 0 40

0.25 18 6 18 18 18 18 18 6 48 18 18

80 0 0 0 0 0 50 35 87 53 0 0

0 85 78 0 76 0 35 65 0 h 0 85

0 0 17 88d 7 0 0 0 0 0 0 0

a Unless otherwise noted, the reactions were performed in CH2Cl2 as a solvent at the final concentration of 0.1 M in the presence of 1.1 equiv of the mediator. bIsolated yields. cThe reaction was run in toluene. dA similar yield was also obtained when the reaction was performed in the presence of 20 equiv of methanol. eA catalytic amount (10 mol %) of the mediator was employed. fThe alcohol 14 was fully recovered. gSubstoichiometric amount (0.4 equiv) of PtCl4 was used. hCompound 16 was contaminated with other impurities; thus, its exact yield could not be determined.

°C for 18 h produced 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 a 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). The 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 a substoichiometric amount (40 mol %) of PtCl4 gave 15 in 87% yield (entry 9), which was slightly better than using a stoichiometric amount of PTS-Si (entry 1), but the reaction using PtCl4 required a longer reaction time. A 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 (18aγ; 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 2-bromobenzaldehydes via the two-step reactions of Heck and ArLi/ArMgBr addition in yields up to 98%. Interestingly, 2-bromo-5methoxybenzaldehyde A underwent the Heck reaction under various conditions to not only provide the expected (E)-5methoxy-2-styrylbenzaldehydes B and C (41 and 32% yields) but also, surprisingly, provide the (E)-4-methoxy-2-styrylbenzaldehydes B′ and C′ (34 and 31% yields) as shown in Scheme 2.18 Selective Synthesis of Indanols, Indenes, and Indanones. The (E)-(2-stilbenyl)methanols 14 and 18aγ were subjected to cyclization using PTS-Si at low temperatures (0 °C or rt) for 13186


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Figure 2. Scope of substrates bearing different numbers and patterns of methoxy groups; R = OMe. (Footnote a) Numbers in parentheses refer to yields from Heck and ArLi/ArMgBr reactions, respectively.

Scheme 2. Heck Reactions of A Yielding Products B, B′, C, and C′

of two methoxy groups at the 3- and 5-positions on the Ar1 also lowered the yields of the corresponding products. 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 crosscoupling reactions20 between 2-bromo- or 2-iodobenzalde-

hydes 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 13187


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Figure 3. 2,3-trans-Diaryl-1-indanols 15 and 19aγ, each obtained as ca. 1:1 mixture of diastereomers at C1, from the reactions of 14 and 18aγ and the subsequent oxidation by Dess−Martin periodinane (DMP) to furnish 20 and 21aγ; R = OMe. Dichloromethane was used as a solvent for all reactions. (Footnote a) These indanols appeared to be rather unstable under reaction conditions or toward 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. (Footnote b) These 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.

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). 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 a 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 toward the formation of the corresponding indane derivatives (30a−d) as the products in moderate to excellent yields (41−94%). More importantly, all of the products were obtained as single diastereomers with

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 reinstalled the requisite aldehyde functional group and furnished 27a−d 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 (Z)-24a would lead to an indanol product similar to 15, 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 13188


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

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. 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). 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 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 π electrons of the (E)-geometry could achieve a better alignment with the empty p orbital of the carbocation 33 via σ bond rotation ((E)-s-trans and the (E)-s-cis),22 leading to cyclization, 13189


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

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 5-methoxy 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 the 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 a 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

which then afforded the indane derivatives upon nucleophilic addition to the 2,3-trans-indanyl cation 34. On the other hand, in the case of 24a,b, due to the steric factor that restricted the σ bond rotation from (Z)-s-trans to (Z)-s-cis to achieve the appropriate alignment for cyclization,22 the intermolecular nucleophilic addition by hydride/azide to the carbocation 35 prevailed over the intramolecular addition by the π electrons of the (Z)-olefin. As a result, the diarylmethanes were obtained instead of the indanes. This type of preferential mode 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 π electrons of the (Z)olefin, thus facilitating the intramolecular cyclization over the intermolecular nucleophilic addition and providing the indane products over the diarylmethanes. 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 18xγ for the (E)-substrates and 24c for the (Z)-substrate), did not 13190


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The Journal of Organic Chemistry Scheme 3. Preparation of (Z)-(2-Stilbenyl)methanols 24a− d

Scheme 4. Modes of Acid-Mediated Cyclization of (Z)- and (E)-(2-Stilbenyl)methanolsc

intermolecular quenching of water to the corresponding indanyl cation.23

a

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These 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. c Compounds 32a, 32b, and 32g were previously reported.15

CONCLUSION A selective divergent process that converted the common intermediate 2-stilbenylmethanols into the corresponding distinct products (diarylmethanes, indanols, 1,2-, and 2,3disubstituted 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 π electrons of the olefin with the empty p orbital of the initial carbocation. The (E)-olefin provided a 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 toward 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 byproduct, 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

Figure 6. Selected NOE data for indane derivatives 30a, 30b, and 30d with 2,3-cis relationship and 32h with 2,3-trans relationship.

labeling, 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 1,2-disubstituted indenes as the products. Heating the reactions to approximately 40 °C also helped direct them toward the formation of the kinetically favored 1,2disubstituted indenes, while heating to 80−110 °C would favor the formation of the thermodynamic 2,3-disubstituted 13191


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The Journal of Organic Chemistry Scheme 5. Mechanistic Understanding of the BF3·Et2OMediated Cyclization/Nucleophilic Transfer of (Z)- and (E)-(2-Stilbenyl)methanols

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

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 toward the synthesis of other biologically active compounds and their biological evaluations will be reported in due course.

reported in wavenumbers (cm−1). Low-resolution (LRMS) mass spectra were obtained either using electron ionization (EI) or time-offlight (TOF), while high-resolution (HRMS) mass spectra were obtained using time-of-flight (TOF) via the atmospheric pressure 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) were added styrene (2 equiv), sodium carbonate (Na2CO3, 2 equiv), and bis(triphenylphosphine)palladium(II) for i1−6, 9, and 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 Celite followed by the addition of 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).

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EXPERIMENTAL SECTION

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 a 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, δ) downfield from tetramethylsilane. Splitting patterns are described as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), broad (br), doublet of doublet (dd), doublet of triplet (dt), and doublet of doublet of doublet (ddd). Resonances for infrared (IR) spectra were

(E)-2-Styrylbenzaldehyde (i1). Following the general procedure and purification by column chromatography on silica (10% EtOAc/ hexane), the product was obtained as a yellow oil (854 mg, 4.105 mmol, 68%). Rf (20% EtOAc/hexane): 0.50. IR (UATR): νmax 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, 13192


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NMR (300 MHz, CDCl3): δ 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): δ 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

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 a yellow solid (2.03 g, 8.54 mmol, 99%). Mp: 83−84 °C. Rf (10% EtOAc/hexane): 0.25. IR (UATR): νmax 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). 13C 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

(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 a yellow solid (399 mg, 1.49 mmol, 32%). Mp: 93−95 °C. Rf (30% EtOAc/ hexane): 053. IR (UATR): νmax 3453, 1685, 1606, 1510, 1249 cm−1. 1 H NMR (300 MHz, CDCl3): δ 10.31 (s, 1H), 7.71 (d, J = 16.1 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.48−7.40 (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). 13C NMR (75 MHz, CDCl3): δ 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)-4-Methoxy-2-styrylbenzaldehyde (i3). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a yellow sticky residue (436 mg, 1.83 mmol, 78%). Rf (20% EtOAc/hexane): 0.37. IR (UATR): νmax 1682, 1592, 1290, 1234 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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)-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 a yellow solid (267 mg, 0.998 mmol, 82%). Mp: 75−76 °C. Rf (20% EtOAc/ hexane): 0.33. IR (UATR): νmax 1669, 1589, 1340, 1203, 1149 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 190.5, 164.9, 164.6, 142.8, 137.1, 132.4, 128.6, 127.9, 127.8, 127.0, 116.2, 103.7, 97.2, 55.8, 55.5. LRMS (EI): m/z (rel intensity) 268 (M+, 100), 161 (51). TOF-HRMS: calcd for C17H16NaO3 (M + Na+), 291.0992; found, 291.0997.

(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 a yellow solid (1.19 g, 4.43 mmol, 63%). Mp: 79−80 °C. Rf (20% EtOAc/ hexane): 0.26. IR (UATR): νmax 1677, 1593, 1509, 1248, 1173 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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). TOFHRMS: calcd for C17H16NaO3 (M + Na+), 291.0992; found, 291.0993. These spectroscopic data were identical to those reported previously.25

(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 a brown solid (542 mg, 1.82 mmol, 74%). Mp: 115−118 °C. Rf (20% EtOAc/hexane): 0.25. IR (UATR): νmax 1667, 1591, 1510, 1246, 1151 cm−1. 1H NMR (300 MHz, CDCl3): 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). 13C NMR (75 MHz, CDCl3): δ 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). TOF-HRMS: calcd for C18H18NaO4 (M + Na+), 321.1097; found, 321.1104. These spectroscopic data were identical to those reported previously.26

(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 a yellow sticky residue (380 mg, 1.60 mmol, 34%). Rf (20% EtOAc/hexane): 0.37. IR (UATR): νmax 3422, 1768, 1687, 1602, 1495, 1264, 1028 cm−1. 1H

(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 a yellow solid 13193


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The Journal of Organic Chemistry (226 mg, 0.84 mmol, 69%). Mp: 133−134 °C. Rf (30% EtOAc/ hexane): 0.39. IR (UATR): νmax 1663, 1589, 1508, 1272, 1097 cm−1. 1 H NMR (400 MHz, CDCl3): δ 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): δ 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

(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). Following the general procedure B and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a yellow sticky residue (631 mg, 1.82 mmol, 81%). Rf (20% EtOAc/hexane): 0.22. IR (UATR): νmax 3416, 1596, 1460, 1203, 1154 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a pale yellow solid (386 mg, 1.22 mmol, 88%). Mp: 79− 80 °C. Rf (20% EtOAc/hexane): 0.45. IR (UATR): νmax 3421, 3029, 1605, 1510, 1248, 1175, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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). TOFHRMS: 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). Following the general procedure A and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as a yellow sticky residue (182 mg, 0.53 mmol, 83%). Rf (30% EtOAc/hexane): 0.24. IR (UATR): νmax 3482, 1606, 1509, 1246, 1173 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a yellow sticky residue (167 mg, 0.44 mmol, 99%). Rf (30% EtOAc/hexane): 0.37. IR (UATR): νmax 3451, 1595, 1510, 1248, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a white solid (187 mg, 0.59 mmol, 94%). Mp: 101−102 °C. Rf (20% EtOAc/hexane): 0.20. IR (UATR): νmax 3421, 1602, 1493, 1279 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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). TOFHRMS: 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

(E)-4,5-Dimethoxy-2-(4-methoxystyryl)benzaldehyde (i10). Following the general procedure and purification by column chromatography on silica (30% EtOAc/hexane), the product was obtained as a yellow solid (235 mg, 0.79 mmol, 65%). Mp: 122−124 °C. Rf (30% EtOAc/hexane): 0.33. IR (UATR): νmax 2933, 1669, 1593, 1509, 1268, 1099 cm−1. 1H NMR (300 MHz, CDCl3): δ 10.29 (s, 1H), 7.72 (d, J = 16.1 Hz, 1H), 7.50−7.43 (m, 2H), 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): δ 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). TOF-HRMS: calcd for C18H18NaO4 (M + Na+), 321.1097; found, 321.1095. General Procedure for the Synthesis of (E)-(2-Stilbenyl)methanol. Procedure A is as follows: to a stirred solution of 0.1 M (1 equiv) (E)-2-styrylbenzaldehyde in dry ether for phenylmagnesium bromide or dry THF for 4-methoxyphenyl magnesium bromide at 0 °C under an 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. Procedure B is as follows: to a stirred solution of 0.1 M (2 equiv) 1bromo-3,5-dimethylbenzene in dry THF at −78 °C under an argon atmosphere was added tert-Butyllithium (3 equiv). The reaction mixture was stirred at −78 °C for 30 min, and then (E)-2styrylbenzaldehyde (1 equiv) was added. The mixture was stirred at −78 °C for 30 min before warming to room temperature, and then the mixture was 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 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 a white solid (580 mg, 2.03 mmol, 91%). Mp: 110−111 °C. Rf (20% EtOAc/hexane): 0.33. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a pale yellow sticky residue (622 mg, 1.97 mmol, 84%). Rf (20% EtOAc/ hexane): 0.22. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 13194


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hexane): 0.26. IR (UATR): νmax 3428, 2925, 1605, 1496, 1450 cm−1. H NMR (400 MHz, CDCl3): δ 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): δ 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 a pale yellow sticky residue (528 mg, 1.53 mmol, 91%). Rf (20% EtOAc/hexane): 0.19. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (182 mg, 0.48 mmol, 41%). Rf (20% EtOAc/hexane): 0.15. IR (UATR): νmax 3445, 1595, 1462, 1203, 1153 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a pale yellow solid (487 mg, 1.41 mmol, 94%). Mp: 81− 88 °C. Rf (20% EtOAc/hexane): 0.15. IR (UATR): νmax 3462, 1606, 1509, 1248, 1174, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a pale yellow sticky residue (325 mg, 0.87 mmol, 93%). Rf (20% EtOAc/hexane): 0.10. IR (UATR): νmax 3461, 3001, 1607, 1509, 1246, 1174, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (559 mg, 1.38 mmol, 74%). Rf (20% EtOAc/hexane): 0.10. IR (UATR): νmax 3480, 1606, 1511, 1462, 1248, 1154, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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

obtained as a pale yellow sticky residue (573 mg, 1.66 mmol, 95%). Rf (20% EtOAc/hexane): 0.17. IR (UATR): νmax 3461, 2835, 1602, 1509, 1281, 1246, 1170, 1032 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (535 mg, 1.42 mmol, 84%). Rf (20% EtOAc/hexane): 0.12. IR (UATR): νmax 3462, 1595, 1457, 1288, 1203, 1152, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a white solid (469 mg, 1.35 mmol, 91%). Mp: 116−117 °C. Rf (40% EtOAc/hexane): 0.50. IR (UATR): νmax 3422, 1602, 1510, 1283, 1249, 1174, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a light yellow sticky residue (448 mg, 1.19 mmol, 99%). Rf (20% EtOAc/hexane): 0.19. IR (UATR): νmax 3482, 1601, 1509, 1246, 1172, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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+, 8), 358 (25), 255 (63), 121 (100). TOFHRMS: 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 a yellow sticky residue (454 mg, 1.12 mmol, 60%). Rf (40% EtOAc/hexane): 0.41. IR (UATR): νmax 3482, 1598, 1510, 1462, 1284, 1249, 1153, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (391 mg, 1.24 mmol, 98%). Mp: 84−85 °C. Rf (20% EtOAc/

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The Journal of Organic Chemistry (rel intensity) 406 (M+, 41), 285 (47), 253 (38). TOF-HRMS: 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 a white solid (210 mg, 0.61 mmol, 97%). Mp: 113−115 °C. Rf (20% EtOAc/hexane): 0.23. IR (UATR): νmax 3526, 1598, 1449, 1200, 1144 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (530 mg, 1.41 mmol, 92%). Rf (20% EtOAc/hexane): 0.17. IR (UATR): νmax 3526, 1598, 1508, 1244, 1143 cm−1. 1H NMR (400 MHz, CDCl3): δ 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, 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). 13C NMR (101 MHz, CDCl3): δ 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 a yellow sticky residue (419 mg, 1.03 mmol, 66%). Rf (30% EtOAc/hexane): 0.32. IR (UATR): νmax 3502, 1595, 1456, 1425, 1312, 1201, 1147 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a yellow solid (370 mg, 0.98 mmol, 72%). Mp: 115−117 °C. Rf (20% EtOAc/hexane): 0.20. IR (UATR): νmax 3526, 1598, 1510, 1452, 1247, 1143 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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)(4methoxyphenyl)methanol (18v). Following the general procedure A and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a pale yellow solid (622 mg, 1.53 mmol, 75%). Mp: 98−100 °C. Rf (20% EtOAc/hexane): 0.17. IR (UATR): νmax 3545, 1599, 1509, 1244, 1172, 1144, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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)(3,5dimethoxyphenyl)methanol (18w). Following the general procedure B and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a yellow solid (326 mg, 0.75 mmol, 62%). Mp: 151−152 °C. Rf (20% EtOAc/hexane): 0.11. IR (UATR): νmax 3510, 1595, 1456, 1309, 1201 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 160.4, 159.7, 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 a yellow solid (447 mg, 1.29 mmol, 90%). Mp: 119−121 °C. Rf (40% EtOAc/hexane): 0.44. IR (UATR): νmax 3502, 1597, 1508, 1273, 1096 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a yellow sticky residue (325 mg, 0.87 mmol, 95%). Rf (30% EtOAc/hexane): 0.24. IR (UATR): νmax 3510, 1606, 1508, 1247 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a light yellow sticky residue (413 mg, 1.02 mmol, 91%). Rf (30% EtOAc/hexane): 0.24. IR (UATR): νmax 3490, 1595, 1509, 1462, 1273 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13 C NMR (101 MHz, CDCl3): δ 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 (18α). Following the general procedure A and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as a yellow solid (191 mg, 0.51 mmol, 99%). Mp: 124−126 °C. Rf (40% EtOAc/hexane): 0.23. IR (UATR): νmax 3503, 1606, 1510, 1247, 1174, 1096 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.43−7.33 (m, 6H), 7.31−7.20 (m, 2H), 7.10 (s, 1H), 7.04 (s, 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): δ 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. 13196


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MHz, CDCl3): δ 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 a pale yellow sticky residue (33.2 mg, 0.11 mmol, 60%). Rf (20% EtOAc/hexane): 0.26. 1H NMR (300 MHz, CDCl3): δ 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 C NMR (75 MHz, CDCl3): δ 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. TOFHRMS: 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 a pale yellow sticky residue (23.5 mg, 0.075 mmol, 87%). Rf (10% EtOAc/hexane): 0.21. IR (UATR): νmax 3030, 1713, 1603, 1511, 1248, 1177 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a clear sticky residue (8.00 mg, 0.023 mmol, 47%). Rf (20% EtOAc/hexane): 0.26. IR (UATR): νmax 3422, 1595, 1457, 1204, 1154 cm−1. 1H NMR (300 MHz, CDCl3): δ 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 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): δ 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 a clear sticky residue (9.90 mg, 0.029 mmol, 91%). Rf (20% EtOAc/hexane): 0.32. IR (UATR): νmax 2936, 1714, 1594, 1457, 1153, 1065 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a clear sticky residue (27.9 mg, 0.089 mmol, 70%). Rf (20% EtOAc/hexane): 0.18. IR (UATR): νmax 3394, 3028, 1611,

(E)-(4,5-Dimethoxy-2-(4-methoxystyryl)phenyl)(4methoxyphenyl)methanol (18β). Following the general procedure A and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a white solid (489 mg, 1.20 mmol, 97%). Mp: 84−85 °C. Rf (20% EtOAc/hexane): 0.10. IR (UATR): νmax 3503, 1607, 1510, 1247, 1174 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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)(3,5dimethoxyphenyl)methanol (18γ). Following the general procedure B and purification by column chromatography on silica (30% EtOAc/ hexane), the product was obtained as a pale yellow sticky residue (326 mg, 0.75 mmol, 74%). Rf (30% EtOAc/hexane): 0.33. IR (UATR): νmax 3482, 1703, 1592, 1461, 1296 cm−1. 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): δ 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. TOF-HRMS: calcd for C26H28NaO6 (M + Na+), 459.1778; found, 459.1761. General Procedure for the Synthesis of Indanols or Endocyclic Indenes. To a stirred solution of 0.1 M (1 equiv) (E)-(2-stilbenyl)methanol in dichloromethane (DCM), dichloroethane (DCE), or toluene 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 and then concentrated 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 of 0.025 M (1 equiv) 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 a pale yellow sticky residue (20.1 mg, 0.07 mmol, 81%). Rf (20% EtOAc/hexane): 0.31. 1H NMR (300 MHz, CDCl3): δ 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, J = 10.1, 8.4 Hz, 1H), 2.30 (s, 1H), 1.62 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 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. TOF-HRMS: calcd for 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 a yellow sticky residue (75.4 mg, 0.27 mmol, 99%). Rf (20% EtOAc/hexane): 0.43. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 13197


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The Journal of Organic Chemistry 1512, 1247, 1178, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a pale yellow sticky residue (16.0 mg, 0.051 mmol, 99%). Rf (20% EtOAc/hexane): 0.38. IR (UATR): νmax 1714, 1513, 1250, 1179,1031 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a white sticky residue (35.3 mg, 0.102 mmol, 61%). Rf (20% EtOAc/ hexane): 0.16. IR (UATR): νmax 3447, 1611, 1511, 1245, 1032 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 an orange sticky residue (26.5 mg, 0.077 mmol, 82%). Rf (20% EtOAc/hexane): 0.29. IR (UATR): νmax 1714, 1609, 1509, 1246, 1177, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 3-(3,5-Dimethoxyphenyl)-2-(4-methoxyphenyl)-2,3-dihydro-1Hinden-1-one (21e). Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as an orange sticky residue (22.5 mg, 0.06 mmol, 41%). Rf (20% EtOAc/hexane): 0.42. IR (UATR): νmax 1715, 1595, 1460, 1248 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a 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): νmax 3420, 1610, 1489, 1265 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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), 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 an orange sticky residue (17.0 mg, 0.054 mmol, 95%). Rf (20% EtOAc/ hexane): 0.48. IR (UATR): νmax 3028, 1709, 1488, 1279, 1026 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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-1Hinden-1-ol (19g). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a pale yellow sticky residue (18.6 mg, 0.054 mmol, 67%). Rf (20% EtOAc/hexane): 0.16. IR (UATR): νmax 3421, 2835, 1610, 1509, 1246, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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-1Hinden-1-one (21g). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a yellow sticky residue (14.3 mg, 0.042 mmol, 92%). Rf (20% EtOAc/hexane): 0.26. IR (UATR): νmax 1709, 1610, 1511, 1489, 1279 1246, 1027 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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-1Hinden-1-ol (19h). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a clear sticky residue (6.40 mg, 0.017 mmol, 43% (major/minor, 1.28:1)). Rf (20% EtOAc/hexane): 0.08. IR (UATR): 13198


Article

The Journal of Organic Chemistry νmax 3462, 1594, 1489, 1457, 1203, 1148 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 160.8 (minor), 160.7 (major), 159.7 (major), 159.5 (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-1Hinden-1-one (21h). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a yellow sticky residue (15.8 mg, 0.042 mmol, 38% (2 steps)). Rf (20% EtOAc/hexane): 0.28. IR (UATR): νmax 1709, 1594, 1489, 1278, 1026 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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). TOFHRMS: calcd for C24H22NaO4 (M + Na+), 397.1410; found, 397.1402. 6-Methoxy-2-(4-methoxyphenyl)-3-phenyl-2,3-dihydro-1Hinden-1-ol (19i). Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as a 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): νmax 3421, 1611, 1513, 1489, 1248, 1178, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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-1Hinden-1-one (21i). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a white solid (21.7 mg, 0.063 mmol, 88%). Mp: 137−138 °C. Rf (40% EtOAc/hexane): 0.54. IR (UATR): νmax 2932, 1712, 1609, 1512, 1281, 1248 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.35−7.15 (m, 6H), 7.12−6.97 (m, 4H), 6.89−6.82 (m, 2H), 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): δ 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). Following the general procedure and purification by column chromatography on silica (40% EtOAc/hexane), the product was obtained as a clear sticky residue (20.9 mg, 0.056 mmol, 73% (major/ minor, 2.0:1)). Rf (40% EtOAc/hexane): 0.28. IR (UATR): νmax 3462, 1610, 1510, 1244, 1176 cm−1. 1H NMR (300 MHz, CDCl3): δ

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). 13C NMR (75 MHz, CDCl3): δ 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-1one (21j). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as an orange sticky residue (17.7 mg, 0.047 mmol, 75%). Rf (20% EtOAc/hexane): 0.30. IR (UATR): νmax 1709, 1610, 1511, 1488, 1280, 1243, 1027 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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)-2,3dihydro-1H-inden-1-one (21k). Following the general procedure and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a pale orange sticky residue (10.8 mg, 0.027 mmol, 48% (2 steps)). Rf (30% EtOAc/hexane): 0.41. IR (UATR): νmax 1709, 1595, 1245, 1154, 1027, 829 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (21.6 mg, 0.063 mmol, 54% (2 steps)). Mp: 147−149 °C. Rf (20% EtOAc/hexane): 0.37. IR (UATR): νmax 1713, 1614, 1493, 1359, 1306, 1149 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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. LRMS (EI): m/z (rel intensity) 344 (M+, 100), 253 (13). TOFHRMS: 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-1Hinden-1-one (21s). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a 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): δ 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): 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. 13199


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solid (19.0 mg, 0.064 mmol, 65%). Mp: 171−173 °C. Rf (20% EtOAc/hexane): 0.56. IR (UATR): νmax 2930, 1509, 1248, 1176, 1033 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (10.4 mg, 0.032 mmol, 54%). Mp: 99−101 °C. Rf (20% EtOAc/ hexane): 0.49. IR (UATR): νmax 2937, 1592, 1457, 1202, 1153, 1063 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 160.9, 149.5, 148.6, 143.2, 142.3, 135.0, 128.4, 128.1, 127.3, 127.0, 126.5, 125.4, 123.6, 121.0, 106.0, 98.3, 56.3, 55.2. LRMS (EI): m/z (rel intensity) 328 (M+, 100), 178 (18). TOF-HRMS: calcd for C23H20NaO2 (M + Na+), 351.1356; found, 351.1344. 2-(4-Methoxyphenyl)-1-phenyl-1H-indene (22c). Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as a pale red solid (18.7 mg, 0.063 mmol, 82%). Mp: 175−177 °C. Rf (20% EtOAc/hexane): 0.54. IR (UATR): νmax 2932, 1716, 1603, 1511, 1249, 1178, 1032 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (24.7 mg, 0.075 mmol, 65%). Mp: 125−126 °C. Rf (20% EtOAc/ hexane): 0.43 IR (UATR): νmax 1607, 1508, 1246, 1176, 1032 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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): δ 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). TOFHRMS: 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 an orange solid (8.90 mg, 0.025 mmol, 44%). Mp: 144− 147 °C. Rf (20% EtOAc/hexane): 0.41. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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 a white solid (14.4 mg, 0.048 mmol, 61%). Mp: 162−164 °C. Rf (20% EtOAc/hexane): 0.39. IR (UATR): νmax 1613, 1466, 1235, 1033 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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).

3-(3,5-Dimethoxyphenyl)-4,6-dimethoxy-2-phenyl-2,3-dihydro1H-inden-1-one (21t). Following the general procedure and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a pale yellow sticky residue (6.30 mg, 0.016 mmol, 27% (2steps)). Rf (20% EtOAc/hexane): 0.29. IR (UATR): νmax 1712, 1593, 1455, 1302, 1202, 1150 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 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-1Hinden-1-one (21u). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a yellow sticky residue (23.2 mg, 0.062 mmol, 67% (2 steps)). Rf (20% EtOAc/hexane): 0.30. IR (UATR): νmax 1711, 1610, 1509, 1492, 1304, 1248, 1148, 1030 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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-inden1-one (21v). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a white solid (15.6 mg, 0.039 mmol, 42% (2 steps)). Mp: 172−174 °C. Rf (20% EtOAc/hexane): 0.26. IR (UATR): νmax 1712, 1610, 1509, 1303, 1245, 1032 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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). TOFHRMS: calcd for C25H24NaO5 (M + Na+), 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 a clear sticky residue (31.1 mg, 0.072 mmol, 46% (2 steps)). Rf (40% EtOAc/hexane): 0.33. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 a white solid (30.0 mg, 0.112 mmol, 85%). Mp: 176−177 °C. Rf (20% EtOAc/hexane): 0.62. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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 an orange 13200


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The Journal of Organic Chemistry 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 a white solid (19.6 mg, 0.060 mmol, 74%). Mp: 134−137 °C. Rf (20% EtOAc/hexane): 0.54. IR (UATR): νmax 1607, 1509, 1247, 1032 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 159.2, 158.2, 151.4, 144.4, 141.9, 135.1, 132.2, 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 a white solid (11.5 mg, 0.032 mmol, 41%). Mp: 122−123 °C. Rf (20% EtOAc/hexane): 0.38. IR (UATR): νmax 1594, 1457, 1203, 1152, 1064 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a pale red solid (14.8 mg, 0.045 mmol, 44%). Mp: 148−150 °C. Rf (60% DCM/hexane): 0.62. IR (UATR): νmax 1603, 1509, 1473, 1250, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a pale red solid (8.80 mg, 0.025 mmol, 46%). Mp: 131−133 °C. Rf (60% DCM/ hexane): 0.38. IR (UATR): νmax 1602, 1508, 1464, 1247, 1176, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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)-1Hindene (22k). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a red solid (11.2 mg, 0.029 mmol, 47%). Mp: 135− 137 °C. Rf (20% EtOAc/hexane): 0.39. IR (UATR): νmax 1592, 1509, 1462, 1249, 1151 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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, 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 a white solid (16.7 mg, 0.065 mmol, 78%). Mp: 160−161 °C. Rf (20% EtOAc/hexane): 0.64. IR (UATR): νmax 1596, 1490, 1283, 1220 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 a white solid (17.0 mg, 0.052 mmol, 62%). Mp: 136−137 °C. Rf (20% EtOAc/hexane): 0.47. IR (UATR): νmax 1596, 1509, 1283, 1247, 1220, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.49− 7.42 (m, 2H), 7.32−7.19 (m, 4H), 7.16−7.09 (m, 1H), 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): δ 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. 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 a pale orange solid (19.8 mg, 0.060 mmol, 64%). Mp: 130−132 °C. Rf (80% DCM/hexane): 0.67. IR (UATR): νmax 1608, 1508, 1477, 1279, 1249, 1221, 1179 cm−1. 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): δ 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 a red sticky residue (19.8 mg, 0.055 mmol, 82%). Rf (20% EtOAc/hexane): 0.51. IR (UATR): νmax 1610, 1509, 1247, 1171, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a white solid (11.7 mg, 0.036 mmol, 76%). Mp: 154−157 °C. Rf (20% EtOAc/ hexane): 0.55. IR (UATR): νmax 1597, 1339, 1209, 1140, 1101 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (13.1 mg, 0.037 mmol, 39%). Mp: 154−156 °C. Rf (20% EtOAc/hexane): 0.40. IR (UATR): νmax 1598, 1508, 1246, 1139, 1104, 1035 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.51− 7.43 (m, 2H), 7.28−7.10 (m, 4H), 7.10−7.02 (m, 2H), 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). 13C NMR (75 MHz, CDCl3): δ 161.0, 157.8, 155.8, 152.3, 145.5, 135.0, 131.0, 13201


Article


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 a white foam (33.6 mg, 0.094 mmol, 62%). Rf (20% EtOAc/hexane): 0.27. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a brown sticky residue (9.00 mg, 0.023 mmol, 25%). Rf (40% EtOAc/hexane): 0.39. IR (UATR): νmax 1704, 1592, 1455, 1298, 1204, 1154 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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. TOF-HRMS: calcd for C25H25O4 (M + H+), 389.1747; found, 389.1746. 5,6-Dimethoxy-2-(4-methoxyphenyl)-1-phenyl-1H-indene (22α). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a red solid (22.4 mg, 0.063 mmol, 75%). Mp: 146−148 °C. Rf (20% EtOAc/hexane): 0.39. IR (UATR): νmax 1703, 1604, 1489, 1214 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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). TOFHRMS: 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 a deep red sticky residue (18.8 mg, 0.049 mmol, 66%). Rf (40% EtOAc/ hexane): 0.31. IR (UATR): νmax 1604, 1509, 1490, 1248 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a 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): δ 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 a yellow sticky residue (20.5 mg, 0.069 mmol, 67%). Rf (20% EtOAc/hexane): 0.57. IR (UATR): νmax 3059, 1705, 1509, 1460, 1247, 1176, 1029 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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;

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 a white foam (5.10 mg, 0.013 mmol, 17%). Rf (20% EtOAc/hexane): 0.33. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow solid (14.1 mg, 0.039 mmol, 43%). Mp: 173− 175 °C. Rf (20% EtOAc/hexane): 0.44. IR (UATR): νmax 1599, 1510, 1255, 1140 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a pale red solid (13.2 mg, 0.034 mmol, 47%). Mp: 135−137 °C. Rf (20% EtOAc/hexane): 0.36. IR (UATR): νmax 1598, 1509, 1464, 1250 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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, 53.2. LRMS (EI): m/z (rel intensity) 388 (M+, 100), 373 (21), 178 (18). TOFHRMS: 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 a pale yellow sticky residue (6.20 mg, 0.015 mmol, 29%). Rf (20% EtOAc/hexane): 0.24. IR (UATR): νmax 1594, 1461, 1340, 1253, 1203 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a white solid (6.90 mg, 0.021 mmol, 68%). Mp: 139−141 °C. Rf (20% EtOAc/ hexane): 0.34. IR (UATR): νmax 1702, 1597, 1488, 1312, 1214 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 13202


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NMR (300 MHz, CDCl3): δ 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): δ 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 a red sticky residue (8.90 mg, 0.027 mmol, 72%). Rf (60% DCM/ hexane): 0.67. IR (UATR): νmax 1702, 1601, 1510, 1282, 1248 cm−1. 1 H NMR (300 MHz, CDCl3): δ 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): δ 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 a red sticky residue (10.3 mg, 0.029 mmol, 52%). Rf (20% EtOAc/hexane): 0.49. IR (UATR): νmax 1607, 1513, 1465, 1283, 1246, 1176 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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)-1Hindene (23k). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as a red sticky residue (11.2 mg, 0.029 mmol, 59%). Rf (20% EtOAc/hexane): 0.44. IR (UATR): νmax 1705, 1591, 1456, 1247 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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). Following the general procedure and purification by column chromatography on silica (10% EtOAc/hexane), the product was obtained as a white solid (9.10 mg, 0.0.31 mmol, 39%). Mp: 139−142 °C. Rf (20% EtOAc/hexane): 0.57. IR (UATR): νmax 1702, 1600, 1475, 1285, 1221 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a white foam (22.2 mg, 0.068 mmol, 73%). Rf (60% DCM/hexane): 0.65. IR (UATR): νmax 1604, 1508, 1474, 1283, 1245, 1032 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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.

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 a yellow sticky residue (9.70 mg, 0.030 mmol, 49%). Rf (20% EtOAc/hexane): 0.53. IR (UATR): νmax 2936, 1708, 1588, 1458, 1204, 1154, 1062 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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, 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 an orange sticky residue (17.6 mg, 0.059 mmol, 78%). Rf (20% EtOAc/hexane): 0.59. IR (UATR): νmax 3008, 1598, 1510, 1250, 1177, 1026 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a red sticky residue (32.5 mg, 0.099 mmol, 93%). Rf (20% EtOAc/hexane): 0.41. IR (UATR): νmax 1705, 1504, 1245, 1028 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 an orange sticky residue (16.1 mg, 0.045 mmol, 42%). Rf (20% EtOAc/hexane): 0.46. IR (UATR): νmax 1587, 1459, 1248, 1154 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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 a red sticky residue (9.70 mg, 0.033 mmol, 73%). Rf (20% EtOAc/hexane): 0.63. IR (UATR): νmax 1596, 1226, 1031 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 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 a deep red sticky residue (22.0 mg, 0.067 mmol, 58%). Rf (20% EtOAc/ hexane): 0.57. IR (UATR): νmax 1607, 1509, 1246, 1031 cm−1. 1H 13203


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The Journal of Organic Chemistry LRMS (EI): m/z (rel intensity) 328 (M+, 100), 313 (24). TOFHRMS: 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 a clear sticky residue (26.9 mg, 0.075 mmol, 51%). Rf (20% EtOAc/hexane): 0.50. IR (UATR): νmax 1592, 1463, 1285, 1204, 1154 cm−1. 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): δ 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 an orange solid (15.1 mg, 0.046 mmol, 55%). Mp: 135−137 °C. Rf (40% DCM/hexane): 0.43. IR (UATR): νmax 1601, 1511, 1474, 1285, 1248, 1027 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 an orange solid (13.0 mg, 0.036 mmol, 68%). Mp: 139−140 °C. Rf (20% EtOAc/hexane): 0.49. IR (UATR): νmax 1602, 1504, 1474, 1289, 1244, 1175, 1028 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 159.1, 158.8, 158.5, 148.8, 141.8, 137.9, 134.3, 130.5, 129.3, 128.4, 123.8, 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). TOFHRMS: calcd for C24H23O3 (M + H+), 359.1642; found, 359.1656. 3-(3,5-Dimethoxyphenyl)-5-methoxy-2-(4-methoxyphenyl)-1Hindene (23q). Following the general procedure and purification by column chromatography on silica (20% EtOAc/hexane), the product was obtained as an orange sticky residue (14.4 mg, 0.037 mmol, 59%). Rf (20% EtOAc/hexane): 0.5. IR (UATR): νmax 1599, 1463, 1286, 1248, 1204, 1153 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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). TOF-HRMS: 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 a pale red sticky residue (19.1 mg, 0.053 mmol, 46%). Rf (20% EtOAc/hexane): 0.28. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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. TOFHRMS: 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 a brown sticky residue (6.00 mg, 0.016 mmol, 21%). Rf (40% EtOAc/hexane): 0.38. IR (UATR): νmax 1702, 1590, 1454, 1303, 1204 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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 a red sticky residue (20.9 mg, 0.058 mmol, 67%). Rf (60% DCM/hexane): 0.24. IR (UATR): νmax 1702, 1598, 1493, 1293, 1248 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a deep red sticky residue (13.9 mg, 0.036 mmol, 59%). Rf (20% EtOAc/ hexane): 0.23. IR (UATR): νmax 1604, 1487, 1290, 1245, 1176, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.33−7.23 (m, 2H), 7.22−7.15 (m, 2H), 7.11 (s, 1H), 7.01−6.93 (m, 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): δ 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 the Sonogashira Reaction. 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/starting material 0.1 g) in tetrahydrofuran (THF) was stirred under argon gas at room temperature. The solution was flushed to remove other gases and substituted by degassing with 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 aldehyde starting material as indicated by TLC. The reaction mixture was filtered under a vacuum to remove the 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 a pale yellow oil (262 mg, 1.27 mmol, 97%). Rf (20% EtOAc/hexane): 0.41. IR (UATR): νmax 2839, 2215, 1695, 1265, 755 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a black sticky gum (846.00 mg, 3.5847 mmol, 96%). Rf (20% EtOAc/hexane): 0.55. IR (UATR): νmax 2840, 1771, 1677, 1596, 1239, 1027, 692 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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+), 13204


Article


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 a yellow sticky gum (175 mg, 0.83 mmol, 88%). Rf (20% EtOAc/hexane): 0.65. IR (UATR): νmax 3334, 2877, 1445, 1028, 778 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a clear sticky gum (31.0 mg, 0.13 mmol, 76% (2steps)). Rf (20% EtOAc/hexane): 0.20. IR (UATR): νmax 3358, 2936, 1602, 1233, 1033, 695 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.27 (s, 1H), 7.12−6.98 (m, 5H), 6.72 (dd, J = 8.4, 2.7 Hz, 1H), 6.68−6.54 (m, 3H), 4.46 (s, 2H), 3.55 (s, 3H), 1.78 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 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). TOF-HRMS: 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 a yellow sticky gum (32.0 mg, 0.13 mmol, 84%). Rf (20% EtOAc/hexane): 0.20. IR (UATR): νmax 3363, 2935, 2835, 1606, 1030, 694 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 an orange sticky gum (64.0 mg, 0.24 mmol, 59% (2steps)). Rf (20% EtOAc/hexane): 0.06. IR (UATR): νmax 3485, 2935, 1603, 1509, 1208, 1093, 695 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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. General Procedure for Oxidation by PCC. A solution of alcohol 29a and 29b (1.0 equiv) in DCM was stirred at room temperature. Pyridinium chlorochromate (PCC) (1.5 equiv) and Celite (2× 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 of 0.025 M (1 equiv) 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.

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 a yellow solid (884 mg, 3.73 mmol, 80%). Mp: 77−79 °C. Rf (20% EtOAc/hexane): 0.54. IR (UATR): νmax 2840, 1771, 1677, 1596, 1239, 1027, 692 cm−1. 1H NMR (300 MHz, CDCl3): δ 10.59 (s, 1H), 7.56−7.47 (m, 3H), 7.40 (d, J = 2.8 Hz, 1H), 7.38−7.32 (m, 3H), 7.11 (dd, J = 8.6, 2.8 Hz, 1H), 3.84 (s, 3H). 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 an orange solid (664 mg, 2.50 mmol, 96%). Mp: 120−123 °C. Rf (20% EtOAc/ hexane): 0.23. IR (UATR): νmax 2937, 2835, 2377, 1734, 1734, 1680, 1589, 1506, 1218, 1089, 756 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 the 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 the 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 a pale yellow solid (664 mg, 0.73 mmol, 82%). Mp: 60−64 °C. Rf (20% EtOAc/hexane): 0.65. IR (UATR): νmax 3325, 2917, 2867, 2323, 1490, 1027, 755 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.58−7.45 (m, 4H), 7.41−7.29 (m, 5H), 4.92 (s, 2H), 2.08 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 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 a white solid (196 mg, 0.82 mmol, 85%). Mp: 95−97 °C. Rf (20% EtOAc/hexane): 0.21. IR (UATR): νmax 3340, 2914, 2212, 1745, 1494, 1222, 1040, 757 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 General Procedure for Hydrogenation. 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 a H2 atmosphere (300 psi). The mixture was stirred for 4 h, the palladium catalyst was removed by filtration through Celite, and the filtrate was 13205


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The Journal of Organic Chemistry (Z)-2-Styrylbenzaldehyde (27a). Following the general procedure and purification by column chromatography on silica (20% EtOAc/ hexane), the product was obtained as a yellow sticky gum (263 mg, 1.26 mmol, 96%). Rf (20% EtOAc/hexane): 0.58. IR (UATR): νmax 2925, 1771, 1692, 1192, 779, 659 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a yellow sticky gum (26.0 mg, 0.11 mmol, 88%). Rf (20% EtOAc/hexane): 0.38. IR (UATR): νmax 2940, 2839, 1682, 1242, 1029, 695 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 a yellow sticky gum (18.0 mg, 0.075 mmol, 82%). Rf (20% EtOAc/hexane): 0.38. IR (UATR): νmax 2937, 2840, 1688, 1497, 1034, 696 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 191.7, 159.1, 136.0, 134.2, 133.9, 133.3, 131.8, 129.2, 128.3, 127.5, 125.8, 121.6, 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 a yellow sticky gum (166 mg, 0.62 mmol, 93%). Rf (20% EtOAc/hexane): 0.35. IR (UATR): νmax 2936, 1738, 1677, 1509, 1269, 1093, 696 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 an argon atmosphere was added phenylmagnesium bromide (1.5 equiv). The reaction mixture was stirred at 0 °C and slowly warmed up to room temperature 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 a yellow sticky gum (316 mg, 1.11 mmol, 86%). Rf (20% EtOAc/hexane): 0.50. IR (UATR): νmax 3374, 2889, 1599, 1446, 1017, 697 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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 a yellow sticky gum (432 mg, 1.37 mmol, 88%). Rf (20% EtOAc/hexane): 0.37. IR (UATR): νmax 3400, 2937, 2834, 1602, 1231, 1031, 696 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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, 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 a yellow sticky gum (165 mg, 0.52 mmol, 89%). Rf (20% EtOAc/hexane): 0.37. IR (UATR): νmax 3421, 2938, 2835, 1605, 1493, 1031, 734 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 an orange sticky gum (64.0 mg, 0.19 mmol, 83%). Rf (20% EtOAc/ hexane): 0.17. IR (UATR): νmax 3502, 2934, 1734, 1508, 1204, 1090, 697 cm−1. 1H NMR (400 MHz, CDCl3): δ 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): δ 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), 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 at −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 a clear sticky gum (22.0 mg, 0.07 mmol, 85%). Rf (20% EtOAc/hexane): 0.62. IR (UATR): νmax 2935, 1606, 1492, 1282, 1032, 699 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 159.1, 146.8, 141.2, 140.6, 135.9, 129.1, 128.4, 13206


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(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 a pink sticky gum (23.0 mg, 0.077 mmol, 87%). Rf (20% EtOAc/hexane): 0.66. IR (UATR): νmax 2934, 1602, 1492, 1037, 694 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.27−7.03 (m, 11H), 6.78−6.68 (m, 2H), 6.59 (s, 2H), 3.92 (s, 2H), 3.59 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 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 a green sticky gum (8.00 mg, 0.024 mmol, 31%). Rf (20% EtOAc/hexane): 0.62. IR (UATR): νmax 2931, 2097, 1703, 1602, 1027, 756 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 mm × 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% (v/v) B in 5 min; a linear gradient increasing from 30 to 55% (v/v) 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 a clear sticky residue (11.0 mg, 0.037 mmol, 58%). Rf (30% EtOAc/hexane): 0.38. IR (UATR): νmax 1604, 1490, 1282, 1247, 1032 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 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 a clear sticky residue (15.0 mg, 0.044 mmol, 87% (major/ minor, 2.5:1)). Rf (20% EtOAc/hexane): 0.54. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (20.3 mg, 0.067 mmol, 87% major/minor, 7.7:1). Rf

127.6, 127.5, 126.0, 126.0, 124.8, 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 a pink sticky gum (23.0 mg, 0.067 mmol, 94%). Rf (20% EtOAc/hexane): 0.69. IR (UATR): νmax 2912, 2091, 1605, 1490, 1231, 1030, 698 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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 a clear sticky gum (7.00 mg, 0.021 mmol, 52%). Rf (20% EtOAc/ hexane): 0.47. IR (UATR): νmax 2917, 1728, 1604, 1501, 1217, 1097, 698 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13 C NMR (75 MHz, CDCl3): δ 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 a yellow sticky gum (13.0 mg, 0.041 mmol, 41%). Rf (20% EtOAc/hexane): 0.40. IR (UATR): νmax 2953, 2093, 1605, 1503, 1453, 1221, 700 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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 a clear sticky gum (13.0 mg, 0.048 mmol, 54%). Rf (20% EtOAc/hexane): 0.71. IR (UATR): νmax 2910, 1599, 1493, 1029, 694 cm−1. 1H NMR (400 MHz, CDCl3): δ 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). 13C NMR (101 MHz, CDCl3): δ 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. (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 a clear sticky gum (28.0 mg, 0.090 mmol, 69%). Rf (20% EtOAc/hexane): 0.68. IR (UATR): νmax 2923, 2095, 1695, 1494, 1452, 1243, 696 cm−1. 1H NMR (400 MHz, CDCl3): δ 7.58−6.92 (m, 13H), 6.67− 6.52 (m, 3H), 5.95 (s, 1H). 13C NMR (101 MHz, CDCl3): δ 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. 13207


Article

The Journal of Organic Chemistry (20% EtOAc/hexane): 0.47. IR (UATR): νmax 3394, 1689, 1602, 1490, 1279, 1030 cm−1. 1H NMR (300 MHz, CDCl3): δ 7.31−7.14 (m, 12H), 7.10−7.05 (m, 2H), 7.04−6.99 (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). 13C NMR (75 MHz, CDCl3): δ 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 a yellow sticky residue (20.4 mg, 0.060 mmol, 84% (major/minor, 4.55:1)). Rf (20% EtOAc/hexane): 0.30. IR (UATR): νmax 3358, 2095, 1689, 1602, 1491 cm−1. 1H NMR (300 MHz, CDCl3): δ 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): δ 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), 60.8 (minor), 56.9 (major), 55.5 (major), 53.4 (minor). LRMS (EI): m/z (rel intensity) 299 (M − N3+, 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 a clear sticky residue (17.3 mg, 0.047 mmol, 77% (major/ minor, 5.88:1)). Rf (20% EtOAc/hexane): 0.38. IR (UATR): νmax 2094, 1702, 1603, 1501, 1215 cm−1. 1H NMR (300 MHz, CDCl3): δ 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). 13C NMR (75 MHz, CDCl3): δ 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.

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ORCID

Poonsakdi Ploypradith: 0000-0003-2893-1598 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS 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.

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DEDICATION This article is dedicated in memory of the late Professor Gary H. Posner. (1) Keylor, M. H.; Matsuura, B. S.; Stephenson, C. R. J. Chemistry and Biology of Resveratrol-Derived Natural Products. Chem. Rev. 2015, 115, 8976−9027 and references cited therein. . (2) For the original isolation of caraphenol B from Caragana sinica, see: (a) Luo, H.-F.; Zhang, L.-P.; Hu, C.-Q. Five Novel Oligostilbenes from the Roots of Caragana sinica. Tetrahedron 2001, 57, 4849−4854. For reisolation, see: (b) Choi, C. W.; Choi, Y. H.; Cha, M.-R.; Yoo, D. S.; Kim, Y. S.; Yon, G. H.; Choi, S. U.; Kim, Y. H.; Ryu, S. Y. New Glycoside of Resveratrol Dimer from Stem Bark of Vitis vinifera. Bull. Korean Chem. Soc. 2010, 31, 3448−3450. For a biological activity evaluation, see: (c) Jin, Q. J.; Han, X. H.; Hong, S. S.; Lee, C.; Choe, S.; Lee, D.; Kim, Y.; Hong, J. T.; Lee, M. K.; Hwang, B. Y. Antioxidative Oligostilbenes from Caragana sinica. Bioorg. Med. Chem. Lett. 2012, 22, 973−976. (d) Meng, Q.; Niu, Y.; Roubin, R. H.; Hanrahan, J. R.; Niu, X. Ethnobotany, Phytochemistry and Pharmacology of the genus Caragana used in Traditional Chinese Medicine. J. Ethnopharmacol. 2009, 124, 350−368 and references cited therein. . (3) For the synthesis of caraphenol B, see: Snyder, S. A.; Brill, Z. G. Structural Revision and Total Synthesis of Caraphenol B and C. Org. Lett. 2011, 13, 5524−5527. (4) (a) Askin, D. The Synthesis of Indinavir and Other Clinically Useful HIV-1 Protease Inhibitors. Curr. Opin. Drug Discovery Devel. 1998, 1, 338−348. and references cited therein. (b) Plosker, G. L.; Noble, S. Indinavir: a Review of Its Use in the Management of HIV Infection. Drugs 1999, 58, 1165−1203 and references cited therein. . (5) For the original synthesis, see: (a) Dorsey, B. D.; Levin, R. B.; McDaniel, S. L.; Vacca, J. P.; Guare, J. P.; Darke, P. L.; Zugay, J. A.; Emini, E. A.; Schleif, W. A.; Quintero, J. C.; Lin, J. H.; Chen, I.-W.; Holloway, M. K.; Fitzgerald, P. M. D.; Axel, M. G.; Ostovic, D.; Anderson, P. S.; Huff, J. R. L-735,524: The Design of a Potent and Orally Bioavailable HIV Protease Inhibitor. J. Med. Chem. 1994, 37, 3443−3451. For solid-phase synthesis, see: (b) Cheng, Y.; Lu, Z.; Chapman, K. T.; Tata, J. R. Solid Phase Synthesis of Indinavir and Its Analogues. J. Comb. Chem. 2000, 2, 445−446. For a study of crystal structure of indinavir and HIV-1 protease, see: (c) Liu, F.; Boross, P. I.; Wang, Y.-F.; Tozser, J.; Louis, J. M.; Harrison, R. W.; Weber, I. T. Kinetic, Stability, and Structural Changes in High-Resolution Crystal Structures of HIV-1 Protease with Drug-Resistant Mutations L24I, I50V, and G73S. J. Mol. Biol. 2005, 354, 789−800. (6) For the original isolation, see: Aknin, M.; Miralles, J.; Kornprobst, J.-M.; Faure, R.; Gaydou, E.-M.; Boury-Esnault, N.; Kato, Y.; Clardy, J. Trikentramine, an Unusual Pyrrole Derivative from the Sponge Trikentrion loeve Carter. Tetrahedron Lett. 1990, 31, 2979−2982. (7) (a) Shuman, R. F.; Pines, S. H.; Shearin, W. E.; Czaja, R. F.; Abramson, N. L.; Tull, R. A Sterically Efficient Synthesis of (Z)-5Fluoro-2-methyl-1-(p-methylthiobenzylidene)-3-indenylacetic acid and Its S-Oxide, Sulindac. J. Org. Chem. 1977, 42, 1914−1919. (b) Barreiro, E. J.; Lima, M. E. F. The Synthesis and AntiInflammatory Properties of a New Sulindac Analogue Synthesized

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Selective Divergent Synthesis of Indanols, Indanones, and Indenes via

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