One-Pot Stereoselective Synthesis of Pyrano[3,2-c]benzothiopyrans: A New Generation and [4+2] Cycloaddition of ortho-Thioquinonemethides

Abstract

Pyrano[3,2-c]benzothiopyrans are synthesized from thiosalicylaldehyde derivatives and unsaturated alcohols in the presence of trimethyl orthoformate and a catalytic amount of p-toluenesulfonic acid with complete trans-stereoselectivity via intramolecular [4+2] cycloaddition of ortho-thioquinonemethides. A more efficient generation and cycloaddition of ortho-thioquinone­methides with Lewis acid is also described.

stereoselective synthesis - [4+2] cycloaddition - Lewis acid - sulfur - heterocycles

References

1a Ellis GP. Lockhart IM. In Chromans and Tocopherols   Vol. 36:  John Wiley and Sons; New York: 1981.  p.1-58  

1b Cinganek E. In Organic Reactions   Vol. 32:  Dauben WG. John Wiley and Sons; New York: 1984.  p.79 

1c Ingal AH. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Boulton AS. Mckillop A. Pergamon Press; Oxford: 1984.  p.773 

1d Talley JJ. J. Org. Chem.  1985,  50:  1695 

1e Hepworth JD. Heron BM. In Progress in Heterocyclic Chemistry   Vol. 15:  Gribble GW. Joule JA. Pergamon Press; Amsterdam: 2003.  p.360-384  

2a Boger DL. Weinreb SM. In Hetero Diels-Alder Methodology in Organic Synthesis   Academic Press; New York: 1987.  p.193-197  

2b Boger DL. Weinreb SM. In Hetero Diels-Alder Methodology in Organic Synthesis   Academic Press; New York: 1987.  p.225 

2c Inamoto N. Heteroat. Chem.  2001,  12:  183 

2d Okazaki R. Ishii F. Inamoto N. Bull. Chem. Soc. Jpn.  1978,  51:  309 

3a Kaye PT. Nocanda XW. Synthesis  2001,  2389 

3b Katritzky AR. Button MAC. J. Org. Chem.  2001,  66:  5595 

3c Kumar P. Bodas MS. Tetrahedron  2001,  57:  9755 

3d Ram VJ. Agarwal N. Saxena AS. Farhanullah S. Sharon A. Maulik PR. J. Chem. Soc., Perkin Trans. 1  2002,  1426 

4 Saito T. Horikoshi T. Otani T. Matsuda Y. Karakasa T. Tetrahedron Lett.  2003,  44:  6513 

5 Wermuth CG. The Practice of Medicinal Chemistry   Academic Press; London: 1996.  p.258 

6a Inoue S. Asami M. Honda K. Miyazaki H. Chem. Lett.  1996,  889 

6b Miyazaki H. Honda K. Asami M. Inoue S. J. Org. Chem.  1999,  64:  9507 

6c Miyazaki H. Honda Y. Honda K. Inoue S. Tetrahedron Lett.  2000,  41:  2643 

7 For a review of ortho-thioquinonemethide see: Inoue S. Honda K. Kagaku Kogyo  2004,  55:  212 ; Journal written in Japanese

8a Arnoldi A. Carughi M. Synthesis  1988,  155 

8b Kasmai HS. Mischke SG. Synthesis  1989,  763 

8c Toste FD. Lough AJ. Still IWJ. Tetrahedron Lett.  1995,  36:  6619 

8d Gallagher T. Pardoe DA. Porter RA. Tetrahedron Lett.  2000,  41:  5415 

9

Compound 5a: ¹H NMR (400 MHz, CDCl₃): δ = 1.21 (d, J = 6.1 Hz, 3 H), 1.45 (m, 1 H), 1.50 (s, 3 H), 1.71-1.80 (m, 2 H), 1.92 (m, 1 H), 2.47 (ddd, J = 2.9, 10.0, 11.5 Hz, 1 H), 3.42 (s, 3 H), 3.67 (dqd, J = 2.0, 6.1, 11.1 Hz, 1 H), 4.60 (m, 2 H), 4.85 (d, J = 11.2 Hz, 1 H), 4.93 (d, J = 11.2 Hz, 1 H), 4.95 (d, J = 10.0 Hz, 1 H), 7.21 (ddd, J = 1.7, 7.3, 7.6 Hz, 1 H), 7.23 (ddd, J = 1.5, 7.3, 7.6 Hz, 1 H), 7.43 (dd, J = 1.7, 7.6 Hz, 1 H), 7.56 (dd, J = 1.5, 7.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.4, 22.2, 30.7, 33.7, 48.5, 56.1, 74.4, 78.6, 79.5, 112.3, 127.2, 127.6, 128.0, 131.6, 135.5, 141.4, 145.8.

10

Compound 6 was purified by silica gel column chromatography, and was characterized by NMR.

11a Ishihara K. In Lewis Acid Reagents   Yamamoto H. Oxford University Press; New York: 1999.  p.31-64  

11b Lin GQ. Li YM. Chan ASC. In Principles and Applications of Asymmetric Synthesis   Wiley-Interscience; Great Britain: 2001.  p.267-330  

11c Hayashi Y. In Cycloaddition Reactions in Organic Synthesis   Kobayashi S. Jørgensen KA. Wiley-VCH; Weinheim (Germany): 2002.  p.5-56  

12a Okauchi T. Tanaka T. Minami T. J. Org. Chem.  2001,  66:  3924 

12b Yadav JS. Reddy BVS. Aruna M. Thomas M. Synthesis  2002,  217