A Novel Method for the Stereoselective Synthesis of Tetralins and Indanes

Abstract

Heavily-substituted 1-aryltetralins and 1-arylindanes were prepared in a highly stereoselective manner using a two-step sequence. Addition of t-butyl benzyl sulfoxides to unsaturated carbonyl compounds gave conjugate adducts with high diastereoselectivity. Treatment of the adducts with SnCl₄ generated benzyl carbocations which reacted intramolecularly with suitably-positioned aromatic rings to give tetralins and indanes, again with high diastereoselectivity.

carbocations - diastereoselectivity - natural products - lignans - sulfoxides

References

1 Ward RS. Nat. Prod. Rep.  1999,  16:  75 ; and earlier reviews in the series

2a Casey M. Manage AC. Nezhat L. Tetrahedron Lett.  1988,  29:  5821 

2b Casey M. Manage AC. Gairns RS. Tetrahedron Lett.  1989,  30:  6919 

2c Casey M. Gairns RS. Geraghty GM. Kelly CJ. Murphy PJ. Walker AJ. Synlett  2000,  1721 

3 Nakamura S. Watanabe Y. Toru T. J. Org. Chem.  2000,  65:  1758 ; and references therein

4 Angle SR. Arnaiz DO. J. Org. Chem.  1992,  57:  5937 ; and references therein

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6 Casey M. Manage AC. Murphy PJ. Tetrahedron Lett.  1992,  33:  965 

7

The t-butyl, p-tolyl and 2-pyridyl sulfoxides 1a,b,c,e,f were prepared by reacting the thiols with the benzyl halides in refluxing acetone in the presence of K₂CO₃, and oxidising the resulting sulfides using NaIO₄ in aq methanol. The 2,4-dimethoxyphenyl p-methoxybenzyl sulfoxide 1d was obtained from the reaction of p-methoxybenzylmagnesium chloride with 2,4-dimethoxybenzenesulfinyl chloride, [25] in THF at 0 °C.

8 Dauksas V. Gaidelis P. Petrauskas O. Udrenaite S. Gasperaviciene G. Ragoutiene N. Khim. Farm. Zh.  1987,  21:  569 

9

Typical Procedure for Conjugate Addition: A solution of the sulfoxide 1b (0.50 g, 2.22 mmol) in THF (12 mL) at
-78 °C was added dropwise via cannula to a solution of LDA, formed from diisopropylamine (0.76 mL, 5.42 mmol) and 2.5 M BuLi in hexanes (2.08 mL, 5.2 mmol) in THF (20 mL), at -78 °C. After 15 min, a solution of the ester 11a (1.09 g, 5.34 mmol) in THF (4 mL) at -78 °C was added, also via cannula. After a further 30 min, the reaction was quenched with sat. aq NH₄C1 (7 mL) and the mixture was warmed to r.t. The suspension was poured into water (10 mL) and extracted with CH₂Cl₂ (3 × 30 mL). The combined extracts were dried over MgSO₄ and concentrated in vacuo. The crude product was purified using flash column chromatography on silica (1:1 petrol:ethyl acetate) to give (RS)-ethyl 3-[(lSR, SRS)-tert-butylsulfinyl-(4-methoxy-phenyl)methyl]-5-phenylpentanoate 12a, as an off white solid (0.72 g, 1.68 mmol, 74%), mp 95-96 °C. IR (KBr): 2941, 1732, 1610, 1511, 1258, 1177, 1039 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.06 (s, 9 H, t-Bu), 1.23 (t, J = 7.2 Hz, 3 H, OEt), 1.60-1.80 (m, 2 H, H-4), 2.06 (dd, J = 10.8, 16.2 Hz, 1 H, H-2), 2.70-2.79 (m, 2 H, H-5), 2.94 (dd, J = 3.5, 16.2 Hz, 1 H, H-2), 2.94-3.02 (m, partially obscured, 1 H, H-3), 3.80 (s, 3 H, OMe), 4.04 (d, J = 3.5 Hz, 1 H, SCH), 4.09-4.13 (m, 2 H, OEt), 6.86 (d, J = 8.8 Hz, 2 H, H3′,H5′), 7.13-7.27 (m, 7 H, Ar-H). ¹³C NMR (CDCl₃, 67.5 MHz): δ = 14.22 (OEt), 23.85 (C(CH₃)₃), 33.57 (C-5), 33.80, 35.56, 36.03 (C-3), 55.27 (OCH₃), 55.70 (CMe₃), 60.52 (OEt), 61.96 (SCH), 114.19 (C-3′,C-5′), 125.93 (C_Ar), 126.15 (C_Ar), 128.37 (C_Ar), 128.41 (C_Ar), 131.02 (C-2′, C-6′), 141.87 (C_Ar), 159.31 (C-4′), 172.35 (C=O). Anal. Calcd for C₂₅H₃₄O₄S: C, 69.77; H, 7.91; S, 7.44. Found: C, 69.85; H, 7.97; S, 7.80.

10a Ohno A. Higaki M. Rev. Heteroatom. Chem.  1995,  13:  1 

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13

Typical Procedure for Cyclisation: A solution of the sulfoxide 12a (1.31 g, 3.04 mmol) in nitromethane (32 mL) was cooled to 0 °C under N₂. Tin tetrachloride (0.44 mL, 3.79 mmol) was added dropwise and the solution was heated at 50 °C for 90 min. Aq NaOH (5%, 15 mL) was added, the solution was extracted with CH₂Cl₂ (2 × 100 mL), and the combined organic extracts were washed with water (2 × 80 mL). The organic layer was dried over MgSO₄ and con-centrated in vacuo. The crude product was purified using flash column chromatography on silica (80:20 petrol:ethyl acetate) to give (1RS, 2SR)-ethyl l-(4-methoxyphenyl)-l,2,3,4-tetrahydro-2-naphthaleneacetate 13a, as a yellow solid (705 mg, 2.18 mmol, 72%), mp 84-85 °C. IR (KBr): 2912, 1727, 1513, 1240, 1124, 1021, 809 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 1.22 (t, J = 7.0 Hz, 3 H, OEt), 1.57-1.62 (m, 1 H, H-3), 2.02-2.08 (m, 1 H, H-3), 2.17 (dd, J = 10.0, 16.7 Hz, 1 H, CHCO₂Et), 2.36-2.43 (m, 2 H, H-2, CHCO₂Et), 2.90-2.99 (m, 2 H, H-4), 3.74 (d, J = 8.5 Hz,
1 H, H-1), 3.78 (s, 3 H, OCH₃), 4.07 (q, J = 7.0 Hz, 2 H, OEt), 6.74 (d, J = 7.6 Hz, 1 H, H-8), 6.82 (d, J = 8.8 Hz, 2 H, H-3′, H-5′), 6.96-7.04 (m, 3 H, H-5, H-2′, H-6′), 7.06-7.11 (m, 2 H, H-6, H-7). ¹³C NMR (CDCl₃, 75 MHz): δ = 14.25 (OEt), 27.06 (C-3), 28.51 (C-4), 38.94 (CH₂CO₂Et), 39.14 (C-2), 50.56 (C-1), 55.22 (OCH₃), 60.21 (OEt), 113.76, 125.79, 125.83, 128.64, 130.33, 130.48, 136.58, 137.52, 139.17, 158.13, 172.99 (C=O). Anal. Calcd for C₂₁H₂₄O₃: C, 77.78; H, 7.41. Found: C, 77.72; H, 7.53. MS (EI): m/z (rel. intensity) = 324 (9) [M⁺], 236 (100), 201 (8), 121 (13), 29 (8).
(1 SR , 2 RS , 3 SR )-Methyl 7,8-dimethoxy-1-(3,4-dimethoxyphenyl)-2-benzyloxymethyl-1,2,3,4-tetra-hydronaphthalene-3-carboxylate(16): IR absorption: IR (KBr): 3010, 2930, 1730, 1244, 1027 cm^-1. ¹H NMR (CDCl₃, 500 MHz): δ = 2.75 (1 H, m, H-2), 2.92 (ddd, J = 3.0 5.5, 9.0 Hz, 1 H, H-3), 2.98-3.00 (m, 2 H, H₂-4), 3.40-3.50 (m, 2 H, CH₂OBn), 3.55 (s, 3 H, OCH₃), 3.71 (s, 3 H, OCH₃), 3.80 (s, 3 H, OCH₃), 3.84 (s, 3 H, OCH₃), 3.88 (s, 3 H, OCH₃), 4.19 (d, J = 3.2 Hz, 1 H, H-1), 4.45 (d, J = 12.1 Hz, 1 H, OCH₂Ph), 4.47 (d, J = 12.1 Hz, 1 H, OCH₂Ph), 6.41 (dd, J = 2.1, 8.4 Hz, 1 H, Ar-H), 6.42 (1 H, s, H-9), 6.61 (d, J = 2.1 Hz, 1 H, Ar-H), 6.64 (1 H, s, H-6), 6.73 (d, J = 8.4 Hz, 1 H, Ar-H). Anal. Calcd for C₃₀H₃₄O₇: C, 71.2; H, 6.7. Found: C, 71.4; H, 6.4. MS (EI): m/z (rel. intensity) = 506 (7) [M⁺], 385 (22), 325 (12), 91 (100).
(1 RS, 2 SR, 3 RS )-Methyl 3-(4-methoxyphenyl)-2-phenylindan-1-carboxylate(19): IR (KBr): 2946, 1735, 1512, 1246, 1169, 1034, 744 cm^-1. ¹H NMR (CDCl₃, 300 MHz): δ = 3.75 (s, 3 H, OMe), 3.76 (s, 3 H, OMe), 3.98 (apparent t, J = 10.3 Hz, 1 H, H-2), 4.35 (d, J = 10.0 Hz, 1 H, H-3), 4.38 (d, J = 10.3 Hz, 1 H, H-1), 6.79 (d, J = 8.8 Hz, 2 H, Ar-H), 6.89 (dd, J = 1.2, 7.3 Hz, 1 H, H-7). 7.02 (d, J = 8.8 Hz, 2 H, Ar-H), 7.20-7.30 (m, 7 H, Ar-H), 7.38 (1 H, dd, J = 1.2, 7.0 Hz, Ar-H). ¹³C NMR (CDCl₃, 75 MHz): δ = 52.39 (C-2) 55.43 (OMe), 56.92 (OMe), 58.21, 59.78, 114.10, 124.06, 125.46, 127.14, 127.65, 128.2, 128.33, 128.73, 129.88, 134.61, 140.02, 141.21 146.05, 172.99.

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15 Unsaturated ester 11b was prepared by Wittig reaction of the substituted cinnamaldehyde, obtained according to: Browder CC. Marmsaeter FP. West FG. Org. Lett.  2001,  3:  3033 

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For examples:

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