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Synlett 2007(3): 0387-0390  
DOI: 10.1055/s-2007-967935
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of 2,4-Disubstituted Thiochromans Using the ­Supported Reagent System ‘Na2CO3/SiO2-PPA/SiO2’

Tadashi Aoyama*a, Kazuyuki Okadaa, Hideaki Nakajimaa, Takuo Matsumotob, Toshio Takidoa, Mitsuo Kodomaric
a Department of Materials and Applied Chemistry, College of Science and Technology, Nihon University, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8308, Japan
Fax: +81(3)32590818; e-Mail: aoyama@chem.cst.nihon-u.ac.jp;
b Core Technology Research Laboratories, Sankyo Co., LTD., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
c Department of Applied Chemistry, Shibaura Institute of Technology, Toyosu, koto-ku, Tokyo 135-8548, Japan
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Publication History

Received 6 November 2006
Publication Date:
07 February 2007 (online)

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Abstract

A simple and efficient method has been developed for the stereoselective synthesis of 2,4-disubstituted thiochromans from arylthiols and α,β-unsaturated aldehydes by using an acid- and a base-supported reagent system, Na2CO3/SiO2-PPA/SiO2. Michael addition of arylthiol to α,β-unsaturated aldehydes was promoted by Na2CO3/SiO2, and then the product was cyclized in the presence of PPA/SiO2.

Key words

stereoselective synthesis - thiochroman - supported ­reagents

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Preparation of PPA/SiO 2 .
PPA (4.0 g) and CHCl3 (100 mL) were placed in the round-bottomed flask, and the mixture was stirred at 50 °C for 1 h. Then, SiO2 [Wakogel C-200 (Wako Pure Chemical Ind. Ltd.), 16.0 g], which was dried in vacuo (10 mmHg) at
160 °C for 2 h, was added to the mixture, and the mixture was stirred for another 1 h. The CHCl3 was removed with rotary evaporator and the resulting solid was dried in vacuo (10 mmHg) at r.t. for 3 h.

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Preparation of Na 2 CO 3 /SiO 2 . Silica gel [Wakogel C-200 (Wako Pure Chemical Ind. LTD.), 16.82 g] was added to a solution of Na2CO3 (30 mmol, 3.18 g) in distilled H2O (100 mL), and the mixture was stirred at r.t. for 0.5 h. Then, H2O was removed by rotary evaporator under reduced pressure, and the resulting reagent was dried in vacuo (10 mmHg) at 160 °C for 5 h.

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Typical Procedure. A mixture of arylthiols (4.20 mmol), α,β-unsaturated aldehydes (2.00 mmol), Na2CO3/SiO2 (1.88 mmol, 1.25 g) and PPA/SiO2 (20 wt%, 3.00 g) was stirred in PhCl (15 mL) at 80 °C for 4 h, and then the used supported reagents were removed by filtration. The filtrate was evaporated to leave crude product, which was purified by column chromatography eluted with hexane-EtOAc (300:1).

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Compound 3aa (trans:cis = 1.0:0.1): yellow solid; mp 59.4-60.1 °C (hexane-EtOAc). Anal. Calcd for C18H20S2: C, 71.95; H, 6.71. Found: C, 71.91; H, 6.79. HRMS (EI): m/z calcd for C18H20S2 [M+]: 300.1006; found: 300.0999. IR (neat): 3015, 1489, 1479, 818, 780 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.29 (0.27 H, d, J = 6.8 Hz), 1.31 (2.73 H, d, J = 6.8 Hz), 1.85 (0.91 H, ddd, J = 14.1, 11.7, 3.1 Hz), 1.99 (0.09 H, dt, J = 13.7, 10.7 Hz), 2.19 (0.91 H, dt, J = 14.1, 3.1 Hz), 2.22 (2.73 H, s), 2.27 (0.27 H, s), 2.32 (0.27 H, s), 2.35 (2.73 H, s), 2.50 (0.09 H, ddd, J = 13.7, 5.6, 2.9 Hz), 3.23-3.32 (0.09 H, m), 3.94-4.03 (0.91 H, m), 4.36 (0.09 H, dd, J = 10.7, 5.6 Hz), 4.47 (0.91 H, t, J = 3.1 Hz), 6.89-7.37 (7 H, m).
Compound 3ab (trans:cis = 1.0:0.04): white solid; mp 77-78 °C (EtOH). Anal. Calcd for C20H24S2: C, 73.12; H, 7.39. Found: C, 73.03; H, 7.36. HRMS (EI): m/z calcd for C20H24S2 [M+]: 328.1319; found: 328.1320. IR (neat): 3019, 1493, 1479, 814, 799 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.90 (0.12 H, t, J = 7.3 Hz), 0.95 (2.88 H, t, J = 7.3 Hz), 1.40-1.50 (2.00 H, m), 1.55-1.62 (2.00 H, m), 1.85 (0.96 H, ddd, J = 14.1, 11.7, 3.2 Hz), 1.99 (0.04 H, dt, J = 13.7, 11.0 Hz), 2.23 (0.96 H, dt, J = 14.1, 3.2 Hz), 2.23 (2.88 H, s), 2.27 (0.12 H, s), 2.33 (0.12 H, s), 2.36 (2.88 H, s), 2.53 (0.04 H, ddd, J = 13.7, 5.6, 3.7 Hz), 3.18-3.25 (0.04 H, m), 3.88-3.95 (0.96 H, m), 4.35 (0.04 H, dd, J = 11.0, 5.6 Hz), 4.46 (0.96 H, t, J = 3.3 Hz), 6.89-7.38 (7 H, m).
Compound 3ac (trans:cis = 1.0:0): white solid; mp 100-102 °C (acetone-hexane). Anal. Calcd for C23H22S2: C, 76.24; H, 6.19. Found: C, 76.19; H, 6.12. HRMS (EI): m/z calcd for C23H22S2 [M+]: 362.1163; found: 362.1163. IR (neat): 3034, 1598, 1492, 1479, 807 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.26 (3 H, s), 2.31 (3 H, s), 2.34-2.37 (2 H, m), 4.57 (1 H, t, J = 3.0 Hz), 5.10 (1 H, dd, J = 9.3, 5.4 Hz), 6.93-7.42 (12 H, m).
Compound 3ad: oil. HRMS (EI): m/z calcd for C17H18S2 [M+]: 286.0850; found: 286.0851. IR (neat): 3016, 1597, 1491, 1482, 810 cm-1. 1H NMR (400 MHz, CDCl3): δ = 2.07 (1 H, ddt, J = 14.1, 12.4, 3.2 Hz), 2.22 (3 H, s), 2.22-2.29 (1 H, m), 2.32 (3 H, s), 2.69-2.75 (1 H, m), 3.68 (1 H, td, J = 12.4, 3.2 Hz), 4.44 (1 H, t, J = 3.2 Hz), 6.87-7.36 (7 H, m).
Compound 3ae: oil. HRMS (EI): m/z calcd for C19H22S2 [M+]: 314.1163; found: 314.1164. IR (neat): 3018, 1597, 1491, 1475, 810 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.33 (3 H, s), 1.38 (3 H, s), 2.14-2.25 (2 H, m), 2.30 (3 H, s), 2.33 (3 H, s), 4.42 (1 H, dd, J = 10.0, 6.4 Hz), 6.92-6.99 (2 H, m), 7.09 (2 H, d, J = 7.8 Hz), 7.26-7.29 (2 H, m), 7.65 (1 H, s).