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Cite This: J. Org. Chem. 2017, 82, 11594-11602

H2SO4‑Mediated Stereocontrolled Annulation of Oxygenated Naphthalenes and 4‑Alkenols: One-Pot Synthesis of Tetanthrenes Meng-Yang Chang* and Yu-Ting Hsiao Department of Medicinal and Applied Chemistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan S Supporting Information *

ABSTRACT: H2SO4-mediated one-pot stereocontrolled (4 + 2) annulation of 4-alkenols and oxygenated naphthalenes provided tetanthrenes in CH2Cl2 at 25 °C for 10 h. The use of various Brønsted acids or Lewis acids was investigated for a facile and efficient transformation. A plausible mechanism has been proposed.

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(DOS).6 A substituted tetanthrene ring system is a key core skeleton for bioactive molecules,7a natural products,7b and functionalized building blocks.7c−e A considerable number of attempts have been made to determine the synthetic routes for a tricyclic skeleton. As a result, new methods for the route’s preparation still represent a continuing need in organic fields.

INTRODUCTION Brønsted acids or Lewis acids that mediated the stepwise Friedel−Crafts-type annulation reactions of oxygenated arenes have attracted significant attention for the formation of a variety of hetero- and carbocyclic aromatic ring skeletons.1,2 In the past decade, continuous efforts have been made in the field of synthetic organic chemistry due to successful construction of valuable polycyclic arene frameworks. Among the core structures, functionalized naphthalenes are the key components of naturally occurring compounds which possess various biological activities.3 Compared with oxygenated benzenes, substituted naphthols as aromatic synthons are reported less for the formation of naphthalenes, especially 1-naphthols.4,5 In particular, all these examples are limited to the C2−C bond formation of a 1-naphthol donor and diversified acceptors (e.g., aziridines, aldimines, glyoxal hydrates, ketimines, or aldehydes) mediated by the expensive metal complexes or complicated organocatalysts (Scheme 1). Thus, the development of a new, single-step route for the direct simultaneous C3,4−C bond linkages of 1-naphthols and 4-alkenols to ring construction of diversified tetrahydrophenanthrenes (tetanthrenes) from easily available promoters is highly desired from the point-of-view of diversity-oriented synthesis

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RESULTS AND DISCUSSION Continuing our research on synthetic applications of βketosulfones 1,8 herein, we present various Brønsted acid or Lewis acid mediated synthesis of sulfonyl tetanthrene 4 via onepot stereocontrolled (4 + 2) annulation of sulfonyl 4-alkenol 2 with oxygenated naphthalene 3, as shown in Scheme 2. Scheme 2. Our Synthetic Route of 4

According to previous works,8 the starting materials, sulfonyl 4alkenols 2, were prepared in high yields by two-step routes via the K2CO3-mediated α-allylation of β-ketosulfones 1 followed by the NaBH4-promoted stereoselective reduction of the resulting α-allyl-β-ketosulfones (by the Felkin-Anh model). Also, another starting material, oxygenated naphthalene 3, was obtained from the O-alkylation of commercially available naphthols. The initial study commenced with the treatment of model substrates 3a (Y = H, P = H, 0.5 mmol) and 2a (Ar = Ph, R = Tol, 0.5 mmol) with H2SO4 in CH2Cl2 at 25 °C for 10 h. As summarized in Table 1, the use of 3, 5, and 6 equiv of H2SO4 gave 4a in 60, 78, and 69% yields, respectively (entries 1−3). An almost quantitative transformation (based on the 1-

Scheme 1. Friedel−Crafts Reactions of 1-Naphthols

Received: September 11, 2017 Published: September 21, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

Article

The Journal of Organic Chemistry Table 1. Reaction Conditionsa

entry

acids (equiv)

solvent

temp (°C)

time (h)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

H2SO4 (3) H2SO4 (5) H2SO4 (6) H2SO4 (5) H2SO4 (5) H2SO4 (5) H2SO4 (5) H3PO4 (5) CF3CO2H (5) TfOH (5) TfOH (1) TfOH (0.5) Tf2NH (5) Tf2NH (1) Tf2NH (0.5) AgOTf (5) Cu(OTf)2 (5) Bi(OTf)3 (5) BF3·OEt2 (5) BF3·OEt2 (1) BF3·OEt2 (0.5)

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 benzene toluene CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2

25 25 25 40 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25

10 10 10 10 15 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10 10

60 78 69 37 77 42 38 c c 74 63 33 18d 30d 36d 50 62 73 78 60 48

concluded that H2SO4 (5 equiv)/CH2Cl2 (10 mL) provided optimal conditions (25 °C and 10 h) for synthesizing 4a via one-pot tandem (4 + 2) cyclization. For the diastereoselectivity of the one-pot reaction, we found that only one stereoisomer was isolated, and no other diastereomers were detected. The related configuration of 4a was confirmed through single-crystal X-ray crystallography analysis. 9 On the basis of the experimental results, a plausible mechanism for the formation of 4a is illustrated in Scheme 3. Initially, H2SO4-mediated Scheme 3. Plausible Mechanism

protonation of the hydroxyl group of 2a yields A. By the intermolecular addition of A with 1-naphthol (3a), B could be afforded via a C4−C bond formation (blue). Following the intramolecular annulation of the in situ formed B, the C3 position of 1-naphthol attacks the secondary carbon of olefin motif via the C3−C bond formation. Subsequently, the construction of 4a is furnished via H2SO4-mediated one-pot stereocontrolled (4 + 2) annulation by the Felkin-Anh model. To study the scope and limitations of this one-pot approach, 2 and 3 were reacted with H2SO4 to afford diversified 4, as shown in Table 2. With optimal conditions established (Table 1, entry 2) and a plausible mechanism proposed (Scheme 3), we found that this route allowed a direct (4 + 2) annulation under mild conditions in moderate to good yields (56−83%). Besides 4d (Ar = 4-MeOC6H4) and 4e (Ar = 4-CF3C6H4), the efficient formation of 4a−4c and 4f−4ah showed that the substituents (Ar and R) did not affect the yield changes (entries 1−34). For the electronic nature of aryl substituents (Ar) of 2, stronger electron-donating groups (for 4d) and electronwithdrawing groups (for 4e) were inappropriate. For entries 4 and 5, complex results were observed, and no detection of the desired 4d,e was observed. In particular, when the reaction of 2g and 3a was treated with H2SO4, 4g was isolated in a 69% yield along with a 10% yield of 4g-1 under the optimal condition (entry 7). The structures of 4a, 4b, 4g-1, 4k, 4q, 4ab, 4ac, and 4af were determined by single-crystal X-ray crystallography.9 For the sulfonyl substituents (R) of 2, both the aliphatic and aromatic groups were well-tolerated. For the Y and P substituents of 3, different positions of the oxygenated groups (Y = 5-MeO, 6-MeO, 6-nBuO, 7-MeO, 2-MeO, and 2MeO-7-Ph; P = 1-HO, 1-MeO, and 1-nBuO) could be wellapplied for the generation of 4y−4z and 4ab−4ah (entries 25, 26, and 28−34). When the 2-aceto group was examined, 4aa afforded a slightly poorer yield of 67% (entry 27). For the generation of 4af, the unsymmetrical 1,5-oxygenated 3i produced a sole isomer 4af in a 73% yield via regio- and stereoselective annulation (entry 32). This is unexpected result. For 3e and 3i,

a The reactions were run on a 0.5 mmol scale with 2a, 3a (1 equiv), and solvent (10 mL). bIsolated yields. cNo reaction. dMajor complex products were isolated.

naphthol 3a nucleophile) to the annulated product was achieved, and no isolation of 2a was detected by TLC under the above conditions. With the results in hand, 5 equiv of H2SO4 was first chosen as the reaction promoter to screen the following reaction conditions: elevate the reaction temperature (25 → 40 °C) and decrease the yield of 4a (37%, entry 4). When the reaction time was lengthened (10 → 15 h), the yield of 4a was maintained (77%, entry 5). When reaction solvents were changed, benzene or toluene provided similar results (42 and 38%, entries 6 and 7). Subsequently, some Brønsted acids with different catalytic and stoichiometric amounts (0.5, 1, and 5 equiv) were studied, such as weaker acids (H3PO4, CF3CO2H, for entries 8 and 9) and stronger acids (for entries 10−12, TfOH; for entries 13−15, Tf2NH). However, none of them obtained higher yields of 4a than H2SO4. From the results, we found that weaker acids did not trigger reactions, and stronger acid caused a complex reaction. Obviously, the reactions were highly sulfonic-acid-dependent with better yields obtained in H2SO4 and TfOH, respectively (entries 2 and 10). Furthermore, Lewis acids with triflate ligand screening were studied with the addition of stoichiometric amounts of different metal triflates (AgOTf, Cu(OTf)2, Bi(OTf)3, entries 16−18). However, the isolated yields of 4a were not enhanced (50, 62, and 73%) compared with those of H2SO4. Changing the metal triflates to BF3·OEt2 produced 4a in a 78% yield (entry 19). When the equivalents of BF3·OEt2 were adjusted to 1 and 0.5, the yields of 4a were decreased to 60 and 48% yields, respectively (entries 20 and 21). Considering economic and environmental issues, H2SO4 was used as the promoter to investigate the substrate’s scope. From these observations, we 11595

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

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The Journal of Organic Chemistry Table 2. Synthesis of 4a

Scheme 4. Reactions of 2a with 5a−5c

entry

2, Ar, R

3, P, Y

4, %b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

2a, Ph, Tol 2b, 4-FC6H4, Tol 2c, Tol, Tol 2d, 4-MeOC6H4, Tol 2e, 4-CF3C6H4, Tol 2f, 3,4-Cl2C6H4, Tol 2g, 4-PhC6H4, Tol 2h, 2-naphthyl, Tol 2i, Ph, Ph 2j, Ph, 3-MeC6H4 2k, Ph, 4-EtC6H4 2l, Ph, 4-iPrC6H4 2m, Ph, 4-nBuC6H4 2n, Ph, 4-tBuC6H4 2o, Ph, 4-FC6H4 2p, Ph, 4-MeOC6H4 2q, Ph, Me 2r, Ph, nBu 2s, 4-FC6H4, Ph 2t, 4-PhC6H4, Me 2u, 4-FC6H4, Me 2v, 4-PhC6H4, Ph 2w, Tol, Ph 2x, Tol, Me 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol 2a, Ph, Tol

3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3a, H, H 3b, Me, H 3c, nBu, H 3d, H, 2-C(O)Me 3e, Me, 5-OMe 3f, Me, 6-OMe 3g, nBu, 6-OnBu 3h, Me, 7-OMe 3i, H, 5-OMe 3j, Me, 2-OMe 3k, Me, 2-Me-7-Ph

4a, 78 4b, 80 4c, 80 4dc 4ec 4f, 56 4g, 69d 4h, 73 4i, 79 4j, 81 4k, 80 4l, 76 4m, 73 4n, 74 4o, 80 4p, 76 4q, 76 4r, 78 4s, 82 4t, 80 4u, 82 4v, 83 4w, 83 4x, 78 4y, 78 4z, 80 4aa, 67 4ab, 75 4ac, 82 4ad, 76 4ae, 73 4af, 74 4ag, 76 4ah, 78

Scheme 5. Reactions of 2a with 5d−5f

yielded. The plausible reason could be that a nitrogen atom blocked the proton such that the Friedel−Crafts reaction could not be initiated. Then, by controlling 3a as the nucleophile donor, different acceptors 2y−2aa with α-prenyl, α-styryl, or α-methallyl were examined (Scheme 6). Unfortunately, 8a (76%) and 8b (80%) Scheme 6. Reactions of 2y−2aa with 3a

a The reactions were run on a 0.5 mmol scale with 2, 3 (1 equiv), and CH2Cl2 (10 mL), 10 h, 25 °C. bIsolated yields. cComplex mixture. d 10% of 4g-1 was isolated.

the 5-methoxy group with the factor of steric hindrance did not affect the formation of 4ab and 4af. Table 2 shows that sulfonyl tetanthrenes 4 were prepared by one-pot stereocontrolled (4 + 2) annulation of 4-alkenols 2a−2x and oxygenated naphthalenes 3a−3k. As an extension of the one-pot annulation, the synthesis of 2a with other bicyclic arenes was explored next (Scheme 4, eqs 1−3). Under the above conditions, treatment of 2a with sulfurated naphthalene 5a produced 4ai in a 73% yield. However, no detection of tricyclic 4aj−4ak was observed by the H2SO4-mediated annulation of 2a with oxygenated quinoline 5b and indole 5c. After the bicyclic arenes were changed to benzenes 5d,e (Scheme 5), only intermolecular adducts 6a,b were generated, and no desired cyclized products 7a,b were detected via a H2SO4-mediated reaction of 2a with anisole (5d) and thioanisole (5e). When 2a was treated with dimethylaminobenzene (5f), no isolation of 6c and 7c was

with a monocycle displaced the desired 9a and 9b with the tricyclic ring system. This implies that the intramolecular ring closure of 2y or 2z is faster than the intermolecular addition of 3a. Next, when 2aa was treated with these conditions, 68% of 9c was isolated along with trace amounts of 8c. Compared with different results from 2z, 2y, and 2aa, the reason could be that 2z could provide a more stable in situ formed tertiary phenyl carbocation than 2y or 2aa such that intramolecular annulation is ideal to proceed. By a less steric hindrance, 2y having a longer arm could make intramolecular cyclization to a six-membered ring easier than 2aa under an acidic process. In summary, we have developed a synthesis of sulfonyl tetanthrenes in moderate to good yields by H2SO4-mediated one-pot stereocontrolled (4 + 2) annulation of 4-alkenols and oxygenated naphthalenes in CH2Cl2 at 25 °C for 10 h. The one-pot process provides a cascade pathway of C4−C and then 11596

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

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The Journal of Organic Chemistry

system, space group P1̅, a = 7.7512(6) Å, b = 11.6780(9) Å, c = 13.0912(10) Å, V = 1126.04(15) Å3, Z = 2, dcalcd = 1.358 g/cm3, F(000) = 484, 2θ range 1.807−26.382°, R indices (all data) R1 = 0.0363, wR2 = 0.0841. 1-Methyl-3-(toluene-4-sulfonyl)-4-p-tolyl-1,2,3,4-tetrahydrophenanthren-9-ol (4c): Yield = 80% (182 mg); colorless solid; mp = 212−213 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C29H29O3S 457.1837; found 457.1838; 1 H NMR (400 MHz, CDCl3) δ 8.22−8.19 (m, 1H), 7.84−7.81 (m, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.38−7.33 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 6.99−6.89 (m, 5H), 5.56 (d, J = 2.8 Hz, 1H), 4.04−3.99 (m, 1H), 2.92−2.87 (m, 1H), 2.37 (s, 3H), 2.28−2.15 (m, 2H), 2.24 (s, 3H), 1.91−1.83 (m, 1H), 1.34 (d, J = 2.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.2, 144.7, 141.2, 139.9, 135.8, 134.3, 132.4, 129.7 (2×), 129.2 (2×), 128.7 (2×), 127.4 (2×), 126.6, 124.0, 123.8, 123.0, 122.8, 122.2, 105.9, 68.5, 38.0, 31.9, 30.5, 21.4, 20.8, 19.4. 4-(3,4-Dichlorophenyl)-1-methyl-3-(toluene-4-sulfonyl)-1,2,3,4tetrahydrophenanthren-9-ol (4f): Yield = 56% (143 mg); colorless solid; mp = 224−225 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H25Cl2O3S 511.0902; found 511.0908; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.44−7.40 (m, 1H), 7.36−7.32 (m, 3H), 7.14 (s, 1H), 7.11 (d, J = 8.8 Hz, 2H), 6.85−6.81 (m, 2H), 6.51 (s, 1H), 5.47 (s, 1H), 4.53 (d, J = 10.0 Hz, 1H), 3.76−3.69 (m, 1H), 3.66−3.57 (m, 1H), 2.95−2.89 (m, 1H), 2.41 (s, 3H), 2.25−2.16 (m, 1H), 1.57 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.3, 144.3, 141.4, 136.8, 136.6, 132.4, 132.3, 131.7, 131.4, 130.1, 129.7, 129.4 (2×), 127.8, 127.6 (2×), 125.9, 125.6, 123.0, 121.8, 121.0, 119.7, 65.5, 47.0, 30.0, 28.6, 22.0, 21.6. 4-Biphenyl-4-yl-1-methyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4g): Yield = 69% (179 mg); colorless solid; mp = 239−240 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C34H31O3S 519.1994; found 519.1996; 1 H NMR (400 MHz, CDCl3) δ 8.19−8.17 (m, 1H), 7.85−7.83 (m, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.48−7.40 (m, 2H), 7.40−7.28 (m, 7H), 7.24 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.89 (s, 1H), 6.49 (br s, 1H), 5.61 (d, J = 3.2 Hz, 1H), 4.05−3.99 (m, 1H), 2.94− 2.89 (m, 1H), 2.38 (s, 3H), 2.23−2.17 (m, 1H), 1.90−1.82 (m, 1H), 1.37 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.2, 144.8, 143.4, 140.5, 140.1, 139.2, 134.4, 132.5, 129.7 (2×), 128.9 (2×), 128.6 (2×), 128.1 (2×), 127.3 (2×), 127.1, 126.84, 126.80 (2×), 124.2, 123.8, 123.1, 122.9, 122.2, 105.9, 68.5, 38.2, 32.1, 30.7, 21.5, 19.5. 4-[1-Biphenyl-4-yl-2-(toluene-4-sulfonyl)-pent-4-enyl]-naphthalen-1-ol (4g-1): Yield = 10% (26 mg); colorless solid; mp = 228−229 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C34H31O3S 519.1994; found 519.1995; 1H NMR (400 MHz, CDCl3+DMSO-d6) δ 8.91 (br s, 1H), 8.25−8.20 (m, 2H), 7.52−7.48 (m, 1H), 7.42−7.37 (m, 1H), 7.35−7.23 (m, 8H), 7.20 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 1H), 5.92−5.81 (m, 1H), 5.27−5.25 (m, 1H), 4.85 (d, J = 10.4 Hz, 1H), 4.54 (d, J = 16.8 Hz, 1H), 4.35−4.30 (m, 1H), 2.79− 2.74 (m, 2H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 152.2, 142.9, 140.4, 139.5, 138.9, 137.7, 134.0, 132.4, 129.2 (2×), 129.0 (2×), 128.5 (2×), 128.2, 127.5 (2×), 127.0, 126.6 (2×), 126.5, 126.4 (2×), 125.3, 124.7, 124.4, 122.9, 122.7, 117.9, 107.7, 68.8, 44.5, 31.6, 21.2. Single-crystal X-ray diagram: crystal of compound 4g-1 was grown by slow diffusion of EtOAc into a solution of compound 4g-1 in CH2Cl2 to yield colorless prisms. The compound crystallizes in the orthorhombic crystal system, space group Pca21, a = 11.4491(5) Å, b = 11.7989(6) Å, c = 26.9170(11) Å, V = 5485.2(4) Å3, Z = 8, dcalcd = 1.256 g/cm3, F(000) = 2192, 2θ range 1.144−26.409°, R indices (all data) R1 = 0.1093, wR2 = 0.1854. 1-Methyl-4-naphthalen-2-yl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4h): Yield = 73% (180 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H29O3S 493.1837; found 493.1841; 1H NMR (400 MHz, CDCl3+DMSO-d6) δ 8.91 (br s, 1H), 8.20−8.16 (m, 1H), 7.75−7.72 (m, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.67−7.62 (m, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.49−7.45 (m, 1H), 7.33−7.24 (m, 4H), 7.19−7.15 (m, 4H), 6.95 (s, 1H), 5.57 (d, J = 3.2 Hz, 1H), 3.95−3.90 (m, 1H), 2.99−2.93 (m, 1H), 2.34 (s, 3H),

C3−C bond formations. The use of various Brønsted acids or Lewis acids was investigated for a facile and efficient transformation. Related, plausible mechanisms have been proposed. The structures of the key products were confirmed by X-ray crystallography. Further investigations regarding the synthetic application of β-ketosulfones will be conducted and published in due course.

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EXPERIMENTAL SECTION

General Methods. All reagents and solvents were obtained from commercial sources and used without further purification. Reactions were routinely carried out under an atmosphere of dry nitrogen with magnetic stirring. Products in organic solvents were dried with anhydrous magnesium sulfate before concentration in vacuo. Purity was determined by NMR and melting point. Melting points were determined with an SMP3 melting apparatus. 1H and 13C NMR spectra were recorded on a Varian spectrometer operating at 400 and 100 MHz, respectively. Chemical shifts (δ) are reported in parts per million (ppm), and the coupling constants (J) are given in hertz. Highresolution mass spectra (HRMS) were measured with a mass spectrometer microTOF-Q by ESI using a hybrid ion-trap. X-ray crystal structures were obtained with a diffractometer (CAD4, Kappa CCD). Representative Synthetic Procedure of Skeleton 4a. Oxygenated naphthalenes (3, 0.5 mmol) were added to a solution of sulfonyl 4-alkenols (2, 0.5 mmol) in CH2Cl2 (8 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 5 min. H2SO4 (245 mg, 2.5 mmol) in CH2Cl2 (2 mL) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at 25 °C for 10 h. The residue was diluted with water (20 mL), and the mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/EtOAc = 8/1−1/ 1) afforded 4. 1-Methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4a): Yield = 78% (172 mg); colorless solid; mp = 242−243 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C28H27O3S 443.1681; found 443.1688; 1 H NMR (400 MHz, CDCl3) δ 8.14−8.12 (m, 1H), 7.79−7.76 (m, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.40−7.35 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.15−7.07 (m, 3H), 6.96 (d, J = 8.4 Hz, 2H), 6.84 (s, 1H), 5.51 (d, J = 2.8 Hz, 1H), 3.96−3.90 (m, 1H), 2.93−2.87 (m, 1H), 2.40 (s, 3H), 2.32 (br s, 1H), 2.19−2.13 (m, 1H), 1.86−1.78 (m, 1H), 1.41 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 150.8, 144.6, 144.3, 140.0, 134.7, 132.6, 129.7 (2×), 129.0 (2×), 128.7 (2×), 127.7 (2×), 127.0, 126.4, 124.4, 123.6, 123.5, 123.3, 121.9, 105.9, 68.4, 38.5, 32.1, 30.7, 21.6, 19.6. Single-crystal X-ray diagram: crystal of compound 4a was grown by slow diffusion of EtOAc into a solution of compound 4a in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal system, space group P1̅, a = 7.7884(7) Å, b = 11.6933(11) Å, c = 12.7018(11) Å, V = 1109.35(17) Å3, Z = 2, dcalcd = 1.325 g/cm3, F(000) = 468, 2θ range 1.790−26.492°, R indices (all data) R1 = 0.0403, wR2 = 0.0895. 4-(4-Fluorophenyl)-1-methyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4b): Yield = 80% (184 mg); colorless solid; mp = 188−189 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H26FO3S 461.1587; found 461.1580; 1H NMR (400 MHz, CDCl3) δ 8.16−8.14 (m, 1H), 7.77− 7.73 (m, 3H), 7.36−7.32 (m, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.98−6.94 (m, 2H), 6.86 (s, 1H), 6.83−6.78 (m, 2H), 6.60 (br s, 1H), 5.53 (d, J = 3.6 Hz, 1H), 3.92−3.87 (m, 1H), 2.86−2.81 (m, 1H), 2.37 (s, 3H), 2.16−2.09 (m, 1H), 1.80 (q, J = 10.8 Hz, 1H), 1.32 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 161.2 (d, J = 244.1 Hz), 151.3, 144.9, 140.2 (d, J = 3.0 Hz), 140.0, 134.3, 132.3, 129.8 (2×), 129.3 (d, J = 7.6 Hz, 2×), 128.8 (2×), 126.9, 124.2, 123.8, 123.0, 122.9, 122.2, 115.3 (d, J = 20.5 Hz, 2×), 105.8, 68.6, 37.8, 32.3, 30.7, 21.5, 19.5. Single-crystal X-ray diagram: crystal of compound 4b was grown by slow diffusion of EtOAc into a solution of compound 4b in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal 11597

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

Article

The Journal of Organic Chemistry

(100 MHz, CDCl3) δ 151.0, 149.6, 144.3, 140.1, 134.7, 132.6, 129.1 (2×), 129.0 (2×), 128.6 (2×), 127.6 (2×), 126.9, 126.4, 124.3, 123.7, 123.23, 123.16, 122.0, 105.9, 68.5, 38.6, 35.5, 33.1, 32.0, 30.6, 22.2, 19.6, 13.8. 3-(4-t-Butylbenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4n): Yield = 74% (179 mg); colorless solid; mp = 233−234 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C31H33O3S 485.2150; found 485.2154; 1 H NMR (400 MHz, CDCl3) δ 8.13−8.11 (m, 1H), 7.79−7.76 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.38−7.34 (m, 2H), 7.13−7.05 (m, 3H), 6.92 (d, J = 8.4 Hz, 2H), 6.82 (s, 1H), 5.73 (s, 1H), 5.52 (d, J = 3.2 Hz, 1H), 4.00−3.95 (m, 1H), 2.91−2.86 (m, 1H), 2.28−2.21 (m, 1H), 1.89−1.80 (m, 1H), 1.39 (d, J = 6.8 Hz, 3H), 1.29 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 157.6, 150.9, 144.2, 140.1, 134.5, 132.7, 128.9 (2×), 128.6 (2×), 127.7 (2×), 126.9, 126.4 126.0 (2×), 124.3, 123.6, 123.4, 123.2, 122.0, 105.8, 68.5, 38.7, 35.1, 32.0, 31.0 (3×), 30.6, 19.5. 3-(4-Fluorobenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4o): Yield = 80% (178 mg); colorless solid; mp = 250−251 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C27H24FO3S 447.1430; found 447.1433; 1H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 8.17−8.14 (m, 1H), 7.77−7.73 (m, 2H), 7.68−7.65 (m, 1H), 7.31−7.25 (m, 2H), 7.08−6.99 (m, 5H), 6.90 (d, J = 7.2 Hz, 2H), 6.86 (s, 1H), 5.41 (d, J = 3.2 Hz, 1H), 3.89−3.84 (m, 1H), 2.86−2.79 (m, 1H), 2.13−2.07 (m, 1H), 1.74−1.66 (m, 1H), 1.35 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.5 (d, J = 254.7 Hz), 152.4, 144.1, 140.0, 133.6 (d, J = 3.1 Hz), 132.3, 131.6, 131.5, 128.4 (2×), 127.5 (2×), 126.5, 126.2, 124.1, 123.6, 122.6 (d, J = 9.1 Hz, 2×), 121.4, 116.1 (d, J = 22.8 Hz, 2×), 105.4, 68.5, 38.4, 31.9, 30.5, 19.5. 3-(4-Methoxybenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4p): Yield = 76% (174 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H27O4S 459.1630; found 459.1627; 1H NMR (400 MHz, CDCl3) δ 8.16−8.13 (m, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.37−7.32 (m, 2H), 7.16−7.07 (m, 3H), 6.98 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.84 (s, 1H), 6.40 (br s, 1H), 5.53 (d, J = 2.8 Hz, 1H), 3.99−3.94 (m, 1H), 3.78 (s, 3H), 2.89−2.84 (m, 1H), 2.22−2.16 (m, 1H), 1.85−1.77 (m, 1H), 1.35 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 163.6, 151.1, 144.2, 140.1, 132.6, 131.0 (2×), 128.8, 128.6 (2×), 127.7 (2×), 126.8, 126.4, 124.2, 123.7, 123.1, 123.0, 122.1, 114.2 (2×), 105.9, 68.7, 55.6, 38.6, 32.1, 30.6, 19.5. 3-Methanesulfonyl-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4q): Yield = 76% (139 mg); colorless solid; mp = 246−247 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C22H23O3S 367.1368; found 367.1372; 1 H NMR (400 MHz, CDCl3+DMSO-d6) δ 9.31 (s, 1H), 8.14−8.11 (m, 1H), 7.69−7.66 (m, 1H), 7.25−7.19 (m, 2H), 7.07−7.04 (m, 2H), 7.00−6.96 (m, 3H), 6.90 (s, 1H), 8.35 (d, J = 3.6 Hz, 1H), 3.72−3.67 (m, 1H), 2.86−2.80 (m, 1H), 2.45 (s, 3H), 2.38−2.32 (m, 1H), 1.63− 1.54 (m, 1H), 1.35 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 152.6, 143.8, 140.3, 132.2, 128.4 (2×), 127.5 (2×), 126.6, 125.3, 124.1, 123.6, 122.5, 122.4, 121.1, 105.3, 67.4, 38.4, 37.4, 32.5, 30.5, 19.2. Single-crystal X-ray diagram: crystal of compound 4q was grown by slow diffusion of EtOAc into a solution of compound 4q in CH2Cl2 to yield colorless prisms. The compound crystallizes in the orthorhombic crystal system, space group P212121, a = 8.3650(3) Å, b = 14.5526(5) Å, c = 15.0103(4) Å, V = 1827.24(10) Å3, Z = 4, dcalcd = 1.332 g/cm3, F(000) = 776, 2θ range 1.949−26.383°, R indices (all data) R1 = 0.0327, wR2 = 0.0742. 3-(n-Butane-1-sulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4r): Yield = 78% (159 mg); colorless solid; mp = 194−195 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C25H29O3S 409.1837; found 409.1839; 1 H NMR (400 MHz, CDCl3) δ 8.21−8.18 (m, 1H), 7.88−7.86 (m, 1H), 7.36−7.31 (m, 2H), 7.21−7.11 (m, 4H), 6.96 (s, 1H), 6.73 (br s, 1H), 5.57 (d, J = 4.0 Hz, 1H), 3.89−3.84 (m, 1H), 3.00−2.94 (m, 1H), 2.83−2.71 (m, 2H), 2.47−2.41 (m, 1H), 1.83−1.63 (m, 3H), 1.41 (d, J = 6.8 Hz, 3H), 1.34−1.22 (m, 3H), 0.79 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 151.4, 144.3, 140.2, 132.5, 128.7

2.20−2.12 (m, 1H), 1.84−1.75 (m, 1H), 1.42 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 152.4, 144.5, 141.9, 140.2, 134.8, 133.1, 132.5, 131.9, 129.6 (2×), 128.8 (2×), 128.3, 127.7, 127.2, 126.5, 126.2, 125.9, 125.8, 125.5, 124.3, 123.7, 122.9, 122.5, 121.8, 105.6, 68.2, 38.8, 31.9, 30.8, 21.4, 19.7. 3-Benzenesulfonyl-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4i): Yield = 79% (169 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C27H25O3S 429.1524; found 429.1528; 1H NMR (400 MHz, CDCl3) δ 8.21−8.19 (m, 1H), 7.92− 7.90 (m, 2H), 7.86−7.84 (m, 1H), 7.59−7.55 (m, 1H), 7.52−7.28 (m, 8H), 7.04 (d, J = 8.0 Hz, 2H), 6.89 (s, 1H), 5.62 (d, J = 3.2 Hz, 1H), 4.06−4.01 (m, 1H), 2.95−2.90 (m, 1H), 2.23−2.17 (m, 1H), 1.92− 1.83 (m, 1H), 1.37 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.3, 143.3, 140.4, 140.1, 137.5, 133.6, 132.5, 129.1, 128.9, 128.6, 128.0, 127.3, 127.1, 126.9, 126.8 (2×), 124.2, 123.9, 123.1, 122.8, 122.2, 105.9, 68.4, 38.2, 32.0, 30.7, 19.5. 1-Methyl-4-phenyl-3-(toluene-3-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4j): Yield = 81% (179 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H27O3S 443.1681; found 443.1685; 1H NMR (400 MHz, CDCl3) δ 8.17−8.15 (m, 1H), 7.80− 7.77 (m, 2H), 7.68−7.65 (m, 1H), 7.61 (br s, 1H), 7.39−7.29 (m, 3H), 7.16−7.07 (m, 3H), 6.99−6.97 (m, 2H), 6.84 (s, 1H), 6.29 (br s, 1H), 5.58 (d, J = 3.2 Hz, 1H), 4.04−3.99 (m, 1H), 2.89−2.84 (m, 1H), 2.25 (s, 3H), 2.23−2.16 (m, 1H), 1.86−1.77 (m, 1H), 1.34 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.1, 144.1, 140.1, 139.4, 137.2, 134.4, 132.5, 129.1, 128.8, 128.6 (2×), 127.6 (2×), 126.9, 126.4, 126.1, 124.2, 123.7, 123.01, 122.98, 122.1, 105.8, 68.4, 38.5, 31.9, 30.5, 21.1, 19.4. 3-(4-Ethylbenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4k): Yield = 80% (182 mg); colorless solid; mp = 185−186 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C29H29O3S 457.1837; found 457.1843; 1 H NMR (400 MHz, CDCl3) δ 8.18−8.16 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.68 (br s, 1H), 7.32−7.27 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.08−6.99 (m, 3H), 6.89−6.87 (m, 3H), 5.43 (d, J = 3.2 Hz, 1H), 3.89−3.84 (m, 1H), 2.89−2.83 (m, 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.16−2.10 (m, 1H), 1.80−1.71 (m, 1H), 1.38 (d, J = 7.2 Hz, 3H), 1.18 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 152.2, 150.6, 144.5, 140.1, 134.8, 132.4, 128.9 (2×), 128.4 (4×), 127.6 (2×), 126.4, 126.1, 124.2, 123.6, 122.9, 122.5, 121.8, 105.5, 68.4, 38.4, 32.0, 30.6, 28.6, 19.6, 14.9. Single-crystal X-ray diagram: crystal of compound 4k was grown by slow diffusion of EtOAc into a solution of compound 4k in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal system, space group P1̅, a = 7.6290(4) Å, b = 11.9937(7) Å, c = 13.0614(6) Å, V = 1144.01(10) Å3, Z = 2, dcalcd = 1.325 g/cm3, F(000) = 484, 2θ range 1.628−26.393°, R indices (all data) R1 = 0.0348, wR2 = 0.0922. 3-(4-Isopropylbenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4l): Yield = 76% (179 mg); colorless solid; mp = 232−233 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H31O3S 471.1994; found 471.1996; 1H NMR (400 MHz, CDCl3) δ 8.13−8.11 (m, 1H), 7.79− 7.77 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.39−7.35 (m, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.14−7.05 (m, 3H), 7.92 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 5.52 (d, J = 3.2 Hz, 1H), 3.99−3.94 (m, 1H), 2.96−2.87 (m, 2H), 2.26−2.19 (m, 1H), 1.88−1.80 (m, 1H), 1.40 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 155.3, 150.8, 144.2, 140.0, 134.9, 132.64 129.2 (2×), 128.6 (2×), 127.7 (2×), 127.1 (2×), 126.9, 126.4, 124.3, 123.6, 123.5, 123.3, 122.0, 105.8, 68.5, 38.7, 34.2, 32.0, 30.7, 23.59, 23.57, 19.55. 3-(4-n-Butylbenzenesulfonyl)-1-methyl-4-phenyl-1,2,3,4-tetrahydrophenanthren-9-ol (4m): Yield = 73% (177 mg); colorless solid; mp = 202−203 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H33O3S 485.2150; found 485.2145; 1H NMR (400 MHz, CDCl3) δ 8.13−8.11 (m, 1H), 7.78− 7.75 (m, 3H), 7.38−7.33 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.14−7.06 (m, 3H), 7.93 (d, J = 8.0 Hz, 2H), 6.83 (s, 1H), 5.52 (d, J = 2.8 Hz, 1H), 3.98−3.93 (m, 1H), 2.91−2.86 (m, 1H), 2.64 (t, J = 8.0 Hz, 2H), 2.23−2.17 (m, 1H), 1.88−1.80 (m, 1H), 1.61−1.53 (m, 2H), 1.38 (d, J = 7.2 Hz, 3H), 1.36−1.27 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H); 13C NMR 11598

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

Article

The Journal of Organic Chemistry

(m, 1H), 2.45 (s, 3H), 2.41−2.35 (m, 1H), 2.13 (s, 3H), 1.65−1.57 (m, 1H), 1.38 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 152.6, 140.7, 140.3, 135.9, 132.3, 129.1 (2×), 127.4 (2×), 126.6, 124.1, 123.7, 122.6, 122.5, 121.4, 105.3, 67.7, 38.3, 37.4, 32.5, 30.6, 20.6, 19.2. 9-Methoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthrene (4y): Yield = 78% (178 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C29H29O3S 457.1837; found 457.1839; 1H NMR (400 MHz, CDCl3) δ 8.28−8.24 (m, 1H), 7.80−7.77 (m, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.42−7.36 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.17−7.09 (m, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.84 (s, 1H), 5.53 (d, J = 3.2 Hz, 1H), 4.03 (s, 3H), 3.97−3.93 (m, 2H), 3.03−2.97 (m, 1H), 2.39 (s, 3H), 2.25−2.20 (m, 1H), 1.94−1.86 (m, 1H), 1.52 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.6, 144.5, 144.3, 139.7, 134.8, 132.4, 129.6 (2×), 128.9 (2×), 128.6 (2×), 128.1, 127.6 (2×), 126.9, 126.3, 124.9, 124.3, 123.0, 122.2, 101.2, 68.3, 55.3, 38.6, 31.8, 31.0, 21.5, 19.8. 9-n-Butoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthrene (4z): Yield = 80% (199 mg); colorless solid; mp = 105−106 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H35O3S 499.2307; found 499.2312; 1H NMR (400 MHz, CDCl3) δ 8.31−8.29 (m, 1H), 7.80− 7.78 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.42−7.36 (m, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.17−7.09 (m, 3H), 7.00 (d, J = 8.4 Hz, 2H), 6.84 (s, 1H), 5.53 (d, J = 3.6 Hz, 1H), 4.20 (t, J = 6.4 Hz, 2H), 3.98−3.93 (m, 1H), 3.02−2.97 (m, 1H), 2.39 (s, 3H), 2.26−2.19 (m, 1H), 1.99−1.86 (m, 3H), 1.70−1.61 (m, 2H), 1.52 (d, J = 6.8 Hz, 3H), 1.08 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.1, 144.44, 144.38, 139.8, 134.8, 132.4, 129.6 (2×), 128.9 (2×), 128.5 (2×), 127.7 (2×), 126.8, 126.3, 125.0, 124.2, 123.0, 122.7, 122.3, 101.9, 68.3, 67.6, 38.6, 31.8, 31.4, 31.0, 21.5, 19.8, 19.5, 13.9. 1-[10-Hydroxy-8-methyl-5-phenyl-6-(toluene-4-sulfonyl)-5,6,7,8tetrahydrophenanthren-9-yl]ethanone (4aa): Yield = 67% (162 mg); colorless solid; mp = 174−175 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H29O4S 485.1787; found 485.1791; 1H NMR (400 MHz, CDCl3) δ 13.89 (br s, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.8 Hz, 1H), 7.76 (s, 1H), 7.67−7.62 (m, 1H), 7.52−7.48 (m, 1H), 7.33 (d, J = 8.8 Hz, 2H), 7.16−7.13 (m, 2H), 7.01−6.97 (m, 4H), 5.16 (d, J = 9.6 Hz, 1H), 4.64−4.60 (m, 1H), 4.23−4.19 (m, 1H), 2.68 (s, 3H), 2.44−2.38 (m, 1H), 2.32 (s, 3H), 1.78−1.72 (m, 1H), 1.03 (d, J = 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 204.5, 161.4, 143.6, 140.4, 136.9, 135.8, 130.5, 129.2 (2×), 128.9 (2×), 128.3 (2×), 127.9 (2×), 126.9, 126.6, 125.7, 125.6, 125.23, 125.19, 123.2, 112.6, 66.4, 65.2, 46.4, 36.0, 26.9, 24.2, 21.4. 5,9-Dimethoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4tetrahydrophenanthrene (4ab): Yield = 75% (182 mg); colorless solid; mp = 176−177 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H31O4S 487.1943; found 487.1948; 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 1.2, 8.4 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.29−7.25 (m, 1H), 7.16−7.05 (m, 5H), 6.92 (d, J = 7.6 Hz, 2H), 6.79 (s, 1H), 6.76 (dd, J = 0.8, 8.4 Hz, 1H), 6.67 (d, J = 1.2 Hz, 1H), 4.06−4.01 (m, 1H), 4.00 (s, 3H), 3.62 (s, 3H), 2.89−2.83 (m, 1H), 2.36−2.29 (m, 1H), 2.30 (s, 3H), 1.87− 1.78 (m, 1H), 1.42 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.0, 154.2, 145.2, 144.0, 140.5, 134.6, 129.2 (2×), 129.1 (2×), 128.2 (2×), 127.4 (2×), 127.0, 125.6, 125.5, 124.4, 123.6, 114.8, 107.3, 101.5, 68.7, 55.54, 55.45, 40.5, 32.7, 30.6, 21.5, 19.3. Single-crystal Xray diagram: crystal of compound 4ab was grown by slow diffusion of EtOAc into a solution of compound 4ab in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal system, space group P1̅, a = 8.1348(5) Å, b = 13.0188(7) Å, c = 15.4944(9) Å, V = 1424.63(15) Å3, Z = 2, dcalcd = 1.134 g/cm3, F(000) = 516, 2θ range 1.440−26.387°, R indices (all data) R1 = 0.0620, wR2 = 0.1752. 6,9-Dimethoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4tetrahydrophenanthrene (4ac): Yield = 82% (199 mg); colorless solid; mp = 172−173 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H31O4S 487.1943; found 487.1947; 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 9.2 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.17−7.00 (m,

(2×), 127.9 (2×), 127.0, 126.6, 124.3, 123.9, 123.13, 123.11, 122.2, 105.8, 66.8, 50.1, 38.8, 32.3, 31.1, 23.1, 21.6, 19.5, 13.3. 3-Benzenesulfonyl-4-(4-fluorophenyl)-1-methyl-1,2,3,4-tetrahydrophenanthren-9-ol (4s): Yield = 82% (183 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C27H24FO3S 447.1430; found 447.1432; 1H NMR (400 MHz, CDCl3) δ 8.17−8.14 (m, 1H), 7.88−7.86 (m, 2H), 7.76−7.73 (m, 1H), 7.59−7.55 (m, 1H), 7.47− 7.43 (m, 2H), 7.37−7.33 (m, 2H), 6.96−6.91 (m, 3H), 6.85 (s, 1H), 6.83−6.78 (m, 2H), 5.54 (d, J = 4.0 Hz, 1H), 3.93−3.88 (m, 1H), 2.88−2.82 (m, 1H), 2.16−2.08 (m, 1H), 1.85−1.76 (m, 1H), 1.34 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 161.2 (d, J = 244.1 Hz), 151.3, 140.2 (d, J = 3.1 Hz), 140.0, 137.5, 133.7, 132.4, 129.3 (d, J = 8.3 Hz, 2×), 129.1 (2×), 128.8 (2×), 126.9, 124.3, 123.9, 123.0, 122.9, 122.2, 115.4 (d, J = 21.2 Hz, 2×), 105.8, 68.6, 37.8, 32.2, 30.7, 19.6. 4-Biphenyl-4-yl-3-methanesulfonyl-1-methyl-1,2,3,4-tetrahydrophenanthren-9-ol (4t): Yield = 80% (177 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H27O3S 443.1681; found 443.1689; 1H NMR (400 MHz, CDCl3) δ 8.23−8.19 (m, 1H), 7.93− 7.90 (m, 1H), 7.50−7.37 (m, 8H), 7.32−7.28 (m, 1H), 7.20 (d, J = 8.0 Hz, 2H), 6.97 (s, 1H), 5.70 (br s, 1H), 5.59 (d, J = 3.2 Hz, 1H), 3.94− 3.89 (m, 1H), 3.04−2.98 (m, 1H), 2.60 (s, 3H), 2.57−2.50 (m, 1H), 1.81−1.72 (m, 1H), 1.50 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.2, 142.7, 140.5, 139.7, 132.7, 128.7 (2×), 128.2 (2×), 127.52 (2×), 127.50, 127.3, 126.9 (2×), 124.8, 124.1, 123.7, 123.2, 123.1, 122.2, 105.9, 67.8, 38.6, 37.6, 33.0, 30.8, 19.4. 4-(4-Fluorophenyl)-3-methanesulfonyl-1-methyl-1,2,3,4-tetrahydrophenanthren-9-ol (4u): Yield = 82% (157 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H22FO3S 385.1274; found 385.1278; 1H NMR (400 MHz, CDCl3) δ 8.22−8.19 (m, 1H), 7.82−7.79 (m, 1H), 7.40−7.36 (m, 2H), 7.12−7.07 (m, 2H), 6.95 (s, 1H), 6.90−6.85 (m, 2H), 6.43 (br s, 1H), 5.53 (d, J = 3.2 Hz, 1H), 3.85−3.80 (m, 1H), 2.95−2.89 (m, 1H), 2.63 (s, 3H), 2.51−2.45 (m, 1H), 1.74 (q, J = 11.8 Hz, 1H), 1.43 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 161.42 (d, J = 244.1 Hz), 151.6, 140.3, 139.5 (d, J = 3.1 Hz), 132.4, 129.4 (d, J = 8.3 Hz, 2×), 127.4, 124.6, 123.8, 122.8, 122.7, 122.3, 115.6 (d, J = 21.2 Hz, 2×), 105.8, 67.9, 38.0, 37.6, 33.0, 30.8, 19.3. 3-Benzenesulfonyl-4-biphenyl-4-yl-1-methyl-1,2,3,4-tetrahydrophenanthren-9-ol (4v): Yield = 83% (209 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C33H29O3S 505.1837; found 505.1838; 1H NMR (400 MHz, CDCl3) δ 8.17−8.15 (m, 1H), 7.90− 7.87 (m, 2H), 7.84−7.82 (m, 1H), 7.60−7.56 (m, 1H), 7.47−7.26 (m, 11H), 7.02 (d, J = 8.8 Hz, 2H), 6.86 (s, 1H), 5.85 (s, 1H), 5.59 (d, J = 2.8 Hz, 1H), 4.03−3.98 (m, 1H), 2.96−2.91 (m, 1H), 2.23−2.16 (m, 1H), 1.90−1.81 (m, 1H), 1.41 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.0, 143.3, 140.5, 140.1, 139.3, 137.7, 133.6, 132.6, 129.1 (2×), 129.0 (2×), 128.7 (2×), 128.1 (2×), 127.4 (2×), 127.2, 127.0, 126.9 (2×), 124.4, 123.7, 123.3, 123.2, 122.1, 105.9, 68.4, 38.2, 32.0, 30.7, 19.6. 3-Benzenesulfonyl-1-methyl-4-p-tolyl-1,2,3,4-tetrahydrophenanthren-9-ol (4w): Yield = 83% (183 mg); colorless solid; mp = 202−204 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C28H27O3S 443.1681; found 443.1684; 1 H NMR (400 MHz, CDCl3) δ 8.14−8.12 (m, 1H), 7.87−7.85 (m, 2H), 7.79−7.77 (m, 1H), 7.59−7.55 (m, 1H), 7.46−7.42 (m, 2H), 7.38−7.33 (m, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.83 (s, 1H), 6.82 (d, J = 8.0 Hz, 2H), 6.04 (s, 1H), 5.50 (d, J = 2.8 Hz, 1H), 3.99−3.94 (m, 1H), 2.91−2.86 (m, 1H), 2.21 (s, 3H), 2.20−2.14 (m, 1H), 1.88−1.79 (m, 1H), 1.37 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 151.0, 141.2, 139.9, 137.6, 136.0, 133.6, 132.6, 129.3 (2×), 129.1 (2×), 128.9 (2×), 127.5 (2×), 126.9, 124.3, 123.7, 123.3, 123.1, 122.0, 105.9, 68.5, 38.1, 31.8, 30.6, 20.8, 19.6. 3-Methanesulfonyl-1-methyl-4-p-tolyl-1,2,3,4-tetrahydrophenanthren-9-ol (4x): Yield = 78% (148 mg); colorless solid; mp = 232−234 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C23H25O3S 381.1524; found 381.1530; 1 H NMR (400 MHz, CDCl3+DMSO-d6) δ 9.21 (s, 1H), 8.16 (d, J = 10.0 Hz, 1H), 7.72 (d, J = 10.0 Hz, 1H), 7.28−7.23 (m, 2H), 6.92− 6.88 (m, 5H), 5.35 (d, J = 3.6 Hz, 1H), 3.74−3.69 (m, 1H), 2.89−2.83 11599

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

Article

The Journal of Organic Chemistry 7H), 6.70 (s, 1H), 5.37 (d, J = 4.0 Hz, 1H), 4.00 (s, 3H), 3.92−3.87 (m, 1H), 3.77 (s, 3H), 3.02−2.97 (m, 1H), 2.41 (s, 3H), 2.20−2.14 (m, 1H), 1.90−1.82 (m, 1H), 1.49 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 158.4, 154.8, 144.6, 144.5, 140.5, 135.0, 133.9, 129.6 (2×), 128.9 (2×), 128.6 (2×), 127.9 (2×), 126.4, 123.9, 122.4, 120.0, 116.1, 102.8, 99.3, 68.5, 55.3, 55.1, 39.2, 32.2, 31.4, 21.6, 19.9. Singlecrystal X-ray diagram: crystal of compound 4ac was grown by slow diffusion of EtOAc into a solution of compound 4ac in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P21/n, a = 9.3547(4) Å, b = 15.8152(7) Å, c = 16.7422(8) Å, V = 2472.76(19) Å3, Z = 4, dcalcd = 1.307 g/cm3, F(000) = 1032, 2θ range 1.773−26.415°, R indices (all data) R1 = 0.0606, wR2 = 0.1156. 6,9-Di-n-butoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)1,2,3,4-tetrahydrophenanthrene (4ad): Yield = 78% (222 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C36H43O4S 571.2882; found 571.2886; 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.8 Hz, 1H), 8.14 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.17−7.00 (m, 7H), 6.68 (s, 1H), 5.37 (d, J = 2.4 Hz, 1H), 4.15 (t, J = 6.4 Hz, 2H), 4.05−3.99 (m, 1H), 3.93−3.82 (m, 2H), 3.00−2.95 (m, 1H), 2.40 (s, 3H), 2.19−2.13 (m, 1H), 1.96−1.49 (m, 9H), 1.48 (d, J = 6.8 Hz, 3H), 1.05 (t, J = 7.2 Hz, 3H), 0.99 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.9, 154.3, 144.7, 144.5, 140.4, 134.9, 133.9, 129.6 (2×), 128.9 (2×), 128.5 (2×), 127.9 (2×), 126.3, 123.9, 122.1, 120.0, 116.5, 103.4, 99.9, 68.5, 67.6, 67.5, 39.2, 32.3, 31.4, 31.3, 31.1, 21.5, 19.9, 19.5, 19.2, 13.9, 13.8. 7,9-Dimethoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4tetrahydrophenanthrene (4ae): Yield = 73% (177 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H31O4S 487.1943; found 487.1940; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 9.2 Hz, 1H), 7.54 (d, J = 2.8 Hz, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.16−7.04 (m, 4H), 6.96 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 5.46 (d, J = 3.2 Hz, 1H), 4.03 (s, 3H), 3.93−3.88 (m, 1H), 3.90 (s, 3H), 2.98−2.95 (m, 1H), 2.41 (s, 3H), 2.22−2.16 (m, 1H), 1.91−1.83 (m, 1H), 1.50 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 156.7, 153.7, 144.5, 137.2, 134.9, 129.7 (2×), 128.9 (2×), 128.6 (2×), 128.1, 127.7 (2×), 126.5, 126.3, 125.9, 124.8, 123.2, 119.1, 101.8, 100.7, 68.4, 55.3, 55.2, 38.7, 32.0, 30.8, 21.5, 19.9. 5-Methoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)-1,2,3,4-tetrahydrophenanthren-9-ol (4af): Yield = 74% (175 mg); colorless solid; mp = 155−156 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C29H29O4S 473.1787; found 473.1786; 1H NMR (400 MHz, CDCl3) δ 9.08 (br s, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.06 (t, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.94 (d, J = 7.6 Hz, 1H), 6.89−6.86 (m, 1H), 6.76 (s, 1H), 6.69 (d, J = 7.2 Hz, 2H), 6.57 (d, J = 7.6 Hz, 1H), 6.47 (d, J = 1.2 Hz, 1H), 3.82−3.77 (m, 1H), 3.45 (s, 3H), 2.66−2.61 (m, 2H), 2.17 (s, 3H), 2.12−2.06 (m, 1H), 1.61−1.53 (m, 1H), 1.20 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 156.5, 151.7, 145.2, 143.8, 140.6, 134.2, 128.9 (2×), 128.5 (2×), 127.8 (2×), 126.9 (2×), 126.0, 125.2, 125.1, 123.3, 121.7, 115.0, 106.5, 105.6, 68.3, 55.1, 39.7, 32.2, 29.9, 21.1, 19.0. Single-crystal X-ray diagram: crystal of compound 4af was grown by slow diffusion of EtOAc into a solution of compound 4af in CH2Cl2 to yield colorless prisms. The compound crystallizes in the triclinic crystal system, space group P1,̅ a = 8.1394(6) Å, b = 9.4166(7) Å, c = 19.4343(15) Å, V = 1380.39(18) Å3, Z = 2, dcalcd = 1.325 g/cm3, F(000) = 584, 2θ range 1.069−26.515°, R indices (all data) R1 = 0.0417, wR2 = 0.0893. 9,10-Dimethoxy-1-methyl-4-phenyl-3-(toluene-4-sulfonyl)1,2,3,4-tetrahydrophenanthrene (4ag): Yield = 76% (185 mg); colorless solid; mp = 198−199 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C30H31O4S 487.1943; found 487.1948; 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.0 Hz, 2H), 7.50−7.47 (m, 3H), 7.36− 7.32 (m, 1H), 7.20−7.16 (m, 1H), 7.05−7.02 (m, 3H), 6.42−6.39 (m, 2H), 5.13 (s, 1H), 4.08 (s, 3H), 4.02 (s, 3H), 3.56−3.49 (m, 2H), 2.57 (s, 3H), 2.52 (d, J = 15.2 Hz, 1H), 2.35−2.28 (m, 1H), 1.70 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 147.3, 146.0, 144.8, 144.6, 136.6, 135.5, 130.1 (2×), 129.2, 128.90, 128.87 (2×), 128.7 (2×),

127.2 (2×), 126.6, 125.2, 124.9, 124.5, 123.8, 121.7, 66.3, 60.73, 60.71, 39.8, 26.7, 24.3, 22.7, 21.8. 9,10-Dimethoxy-1-methyl-4,7-diphenyl-3-(toluene-4-sulfonyl)1,2,3,4-tetrahydrophenanthrene (4ah): Yield = 78% (219 mg); colorless solid; mp = 230−231 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C36H35O4S 563.2256; found 563.2255; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 1.2 Hz, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 7.2 Hz, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.48−7.43 (m, 3H), 7.36−7.33 (m, 1H), 7.08−7.06 (m, 3H), 7.48−7.46 (m, 2H), 5.16 (s, 1H), 4.11 (s, 3H), 4.05 (s, 3H), 3.58−3.51 (m, 2H), 2.57 (s, 3H), 2.56−2.53 (m, 1H), 2.38−2.31 (m, 1H), 1.73 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 147.7, 146.2, 144.73, 144.66, 141.1, 137.6, 136.5, 135.6, 130.1 (2×), 129.2, 128.9 (2×), 128.7 (4×), 128.3, 127.3 (2×), 127.22, 127.20 (2×), 126.6, 124.8, 124.44, 124.42, 119.6, 66.2, 60.8, 60.7, 39.9, 26.8, 24.3, 22.7, 21.8. 1-Methyl-9-methylsulfanyl-4-phenyl-3-(toluene-4-sulfonyl)1,2,3,4-tetrahydrophenanthrene (4ai): Yield = 73% (172 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C29H29O2S2 473.1609; found 473.1605; 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.47−7.39 (m, 3H), 7.23 (d, J = 8.0 Hz, 2H), 7.17−7.08 (m, 3H), 6.97 (d, J = 8.4 Hz, 2H), 5.58 (d, J = 2.8 Hz, 1H), 3.98−3.93 (m, 1H), 3.01−2.96 (m, 1H), 2.59 (s, 3H), 2.40 (s, 3H), 1.91−1.83 (m, 2H), 1.52 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 144.6, 143.8, 139.3, 135.0, 134.7, 131.8, 131.0, 129.7 (2×), 129.2, 128.9 (2×), 128.7 (2×), 127.7 (2×), 126.8, 126.5, 125.3, 124.8, 123.9, 121.5, 68.2, 38.8, 31.9, 30.8, 21.5, 19.7, 16.5. Representative Synthetic Procedure of Compounds 6a,b. Anisole (5a, 54 mg, 0.5 mmol) or thioanisole (5b, 62 mg, 0.5 mmol) was added to a solution of 2a (158 mg, 0.5 mmol) in CH2Cl2 (8 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 5 min. H2SO4 (245 mg, 2.5 mmol) in CH2Cl2 (2 mL) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at 25 °C for 10 h. The residue was diluted with water (20 mL), and the mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford crude product under reduced pressure. Purification on silica gel (hexanes/ EtOAc = 8/1−1/1) afforded 6a,b. 5-(4-Methoxyphenyl)-5-phenyl-4-(toluene-4-sulfonyl)-1-pentene (6a): Yield = 90% (183 mg); colorless solid; mp = 145−146 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C25H27O3S 407.1681; found 407.1684; 1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.07−6.97 (m, 7H), 6.78 (d, J = 8.8 Hz, 2H), 5.89−5.78 (m, 1H), 4.98 (dd, J = 1.2, 10.4 Hz, 1H), 4.78 (dd, J = 1.2, 17.2 Hz, 1H), 4.49 (d, J = 10.0 Hz, 1H), 4.09−4.04 (m, 1H), 3.74 (s, 3H), 2.74−2.68 (m, 1H), 2.64−2.57 (m, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.4, 143.4, 141.4, 137.4, 133.9, 133.4, 129.5 (2×), 129.2 (2×), 128.3 (2×), 128.2 (2×), 128.0 (2×), 126.4, 118.0, 114.0 (2×), 68.0, 55.2, 50.6, 31.7, 21.5. 5-Phenyl-5-(4-thiomethoxyphenyl)-4-(toluene-4-sulfonyl)-1-pentene (6b): Yield = 93% (196 mg); colorless gum; HRMS (ESI-TOF) m/z [M + H]+ calcd for C25H27O2S2 423.1453; found 423.1458; 1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 7.17−7.11 (m, 4H), 7.07−6.97 (m, 7H), 5.91−5.80 (m, 1H), 5.00 (dd, J = 1.6, 10.0 Hz, 1H), 4.79 (dd, J = 1.6, 17.2 Hz, 1H), 4.51 (d, J = 10.0 Hz, 1H), 4.12−4.07 (m, 1H), 2.76−2.70 (m, 1H), 2.64−2.57 (m, 1H), 2.42 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.4, 140.9, 138.1, 137.4, 137.0, 133.7, 129.2 (2×), 128.9 (2×), 128.3 (2×), 128.2 (2×), 128.0 (2×), 126.7 (2×), 126.5, 118.2, 67.6, 50.9, 31.7, 21.4, 15.8. Representative Synthetic Procedure of Compounds 8a,b and 9c. 1-Naphthol (3a, 72 mg, 0.5 mmol) was added to a solution of 2y−2aa (0.5 mmol) in CH2Cl2 (8 mL) at 25 °C. The reaction mixture was stirred at 25 °C for 5 min. H2SO4 (245 mg, 2.5 mmol) in CH2Cl2 (2 mL) was added to the reaction mixture at 25 °C. The reaction mixture was stirred at 25 °C for 10 h. The residue was diluted with water (20 mL), and the mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford crude product under reduced 11600

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

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pressure. Purification on silica gel (hexanes/EtOAc = 8/1−1/1) afforded 8a,b and 9c. 2,2-Dimethyl-6-phenyl-5-(toluene-4-sulfonyl)tetrahydropyran (8a): Yield = 76% (131 mg); colorless solid; mp = 148−150 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C20H25O3S 345.1524; found 345.1526; 1H NMR (400 MHz, CDCl3) δ 7.22−7.20 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.09− 7.06 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H), 5.09 (d, J = 2.8 Hz, 1H), 3.56− 3.54 (m, 1H), 2.80−2.76 (m, 1H), 2.30 (s, 3H), 2.25−2.12 (m, 2H), 1.50−1.46 (m, 1H), 1.42 (s, 3H), 1.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.8, 138.7, 138.4, 128.9 (2×), 127.6 (2×), 127.5 (2×), 126.8, 126.1 (2×), 72.8, 71.0, 62.8, 31.3, 31.1, 21.5, 21.4, 21.3. 2-Methyl-2,5-diphenyl-4-(toluene-4-sulfonyl)tetrahydrofuran (8b): Yield = 80% (157 mg); colorless solid; mp = 173−174 °C (recrystallized from hexanes and EtOAc); HRMS (ESI-TOF) m/z [M + H]+ calcd for C24H25O3S 393.1524; found 393.1530; 1H NMR (400 MHz, CDCl3) δ 7.42−7.39 (m, 4H), 7.30−7.16 (m, 8H), 7.07 (d, J = 8.0 Hz, 2H), 5.12 (d, J = 8.0 Hz, 1H), 3.99 (q, J = 8.0 Hz, 1H), 2.88 (dd, J = 1.2, 8.4 Hz, 2H), 2.37 (s, 3H), 1.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.3, 143.8, 136.3, 135.7, 129.4 (2×), 128.6 (2×), 128.5 (2×), 128.1, 127.8 (2×), 127.6 (2×), 127.2, 124.5 (2×), 83.8, 79.5, 67.6, 40.1, 30.3, 21.5. 4′,4′-Dimethyl-2′-(toluene-4-sulfonyl)-1′,2′,3′,4′-tetrahydro[1,1′]binaphthalenyl-4-ol (9c): Yield = 68% (155 mg); colorless solid; mp = 234−238 °C (recrystallized from hexanes and EtOAc); HRMS (ESITOF) m/z [M + H]+ calcd for C29H29O3S 457.1837; found 457.1839; 1 H NMR (400 MHz, CDCl3+DMSO-d6) δ 9.09 (s, 1H), 8.48 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 7.2 Hz, 1H), 7.27− 7.24 (m, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.92 (dt, J = 0.8, 8.0 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 6.72 (dt, J = 1.2, 7.6 Hz, 1H), 6.59 (d, J = 7.6 Hz, 1H), 6.31 (br s, 1H), 5.49 (d, J = 4.0 Hz, 1H), 5.11 (s, 1H), 3.72 (ddd, J = 2.0, 3.2, 13.6 Hz, 1H), 2.70 (s, 3H), 2.22 (t, J = 13.2 Hz, 1H), 1.66 (d, J = 13.2 Hz, 1H), 1.33 (s, 3H), 1.02 (s, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 152.0, 143.3, 142.4, 138.3, 134.1, 133.1, 129.4 (2×), 128.4 (2×), 127.5 (2×), 126.9, 126.2, 125.9, 125.8, 125.5, 124.4, 124.0, 123.6, 121.9, 106.9, 62.5, 36.9, 36.7, 34.2, 31.9, 30.8, 20.9. Single-crystal X-ray diagram: crystal of compound 9c was grown by slow diffusion of EtOAc into a solution of compound 9c in CH2Cl2 to yield colorless prisms. The compound crystallizes in the monoclinic crystal system, space group P21/c, a = 12.4191(8) Å, b = 13.6805(10) Å, c = 15.3389(11) Å, V = 2535.1 (3) Å3, Z = 4, dcalcd = 1.194 g/cm3, F(000) = 964, 2θ range 1.686−26.494°, R indices (all data) R1 = 0.0479, wR2 = 0.1032.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02291. X-ray analysis data of 4a, 4b, 4g-1, 4k, 4q, 4ab, 4ac, 4af, and 9c (CIF) Scanned photocopies of NMR spectral data for all compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

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

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors would like to thank the Ministry of Science and Technology of the Republic of China for financial support (MOST 106-2628-M-037-001-MY3). 11601

DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602

Article

The Journal of Organic Chemistry Cambridge CB2 1EZ, UK; fax: 44−1223−336033; e-mail: deposit@ ccdc.cam.ac.uk).

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DOI: 10.1021/acs.joc.7b02291 J. Org. Chem. 2017, 82, 11594−11602