Regiospecific Synthesis of the C and D Rings of Viridin

Abstract

An eight-step regiospecific synthesis of the C and D rings of viridin is reported using an intramolecular Diels-Alder reaction of a furan diene as the key step.

Key words

intramolecular Diels-Alder reaction - furans - furano­steroids - viridin

References and Notes

• 1 Hanson JR. Nat. Prod. Rep.  1995,  12:  381 
• 2 Wipf P. Halter RJ. Org. Biomol. Chem.  2005,  3:  2053 
• 3 Brian PW. McGowan JC. Nature (London)  1945,  156:  144 
• 4 Anderson EA. Alexanian EJ. Sorensen EJ. Angew. Chem. Int. Ed.  2004,  43:  1998 
• 5a Sessions EH. Jacobi PA. Org. Lett.  2006,  8:  4125 
• 5b Wright DL. Robotham CV. Aboud K. Tetrahedron Lett.  2002,  43:  943 
• 5c Boynton J. Hanson JR. Kiran I. J. Chem. Res., Synop.  1999,  638 
• 5d Souza FES. Rodrigo R. Chem. Commun.  1999,  1947 
• 5e Carlina R. Higgs K. Older C. Randhawa S. Rodrigo R. J. Org. Chem.  1997,  62:  2330 
• 5f Yasuchika Y. Kenji H. Kanemastsu K. J. Chem. Soc., Chem. Commun.  1987,  515 
• 5g Moffatt JS. J. Chem. Soc. C  1966,  734 ; and references therein
• 6a Maddaford SP. Andersen NG. Cristofoli WA. Keay BA. J. Am. Chem. Soc.  1996,  118:  10766 
• 6b Keay BA. Maddaford SP. Cristofoli WA. Andersen NG. Passafaro MS. Wilson NS. Nieman JA. Can. J. Chem.  1997,  75:  1163 
• 6c Miyazaki F. Uotso K. Shibasaki M. Tetrahedron  1998,  54:  13073 
• 7 Loewenthal HJE. Schatzmiller S. J. Chem. Soc., Perkin Trans. 1  1975,  2149 
• 8 Loewenthal HJE. Schatzmiller S. Tetrahedron Lett.  1972,  31:  3115 
• 9 Kametani T. Hirai Y. Kajiwara T. Kukumoto K. Chem. Pharm. Bull.  1975,  23:  2634 
• 10 Moreno A. Gomez MV. Vazquez E. de la Hoz A. Diaz-Ortiz A. Prieto P. Mayoral JA. Piers E. Synlett  2004,  1259 
• 11a Cauwberghs S. De Clercq PJ. Tetrahedron Lett.  1988,  29:  2493 
• 11b Sternbach DD. Rossana DM. Tetrahedron Lett.  1985,  26:  591 
• 11c Sternbach DD. Rossana DM. Tetrahedron Lett.  1982,  23:  303 
• 12 Padwa A. Brodney MA. Liu B. Satake K. Wu T. J. Org. Chem.  1999,  64:  3595 
• 13 Muller KM. M.Sc. Thesis   University of Calgary; Canada: 2003. 
• 14 Ramos AC. Peláez R. López JL. Caballero E. Medarde M. San Feliciano A. Tetrahedron  2001,  57:  3963 
• 15 Houghton TJ. Choi S. Rawal VH. Org. Lett.  2001,  3:  3615 
• 16 Taschner MJ. Kraus GA. J. Org. Chem.  1978,  43:  4235 
• 17 For similar equilibria with dithiane-derived anions of thiadiazoles and oxadiazoles, see: Meyers AI. Knaus GN. J. Am. Chem. Soc.  1973,  95:  3408 
• 18 Keay BA. Hunt IR. In Advances in Cycloaddition   Vol. 6:  Harmata M. JAI Press; Stanford, USA: 1999.  p.173 ; and references therein

19

Experimental Procedure for the Preparation of 10: Compound 12 (0.394 g, 1.33 mmol) was dissolved in CH₂Cl₂ (25 mL) and the solution was cooled to -78 °C. Dimethylaluminum chloride (1.50 equiv) was added slowly to the solution, and the mixture was stirred overnight, warming to r.t. The reaction was then placed in an ice-bath and H₂O (10 mL) was slowly added to the reaction. The aqueous layer was shaken gently with CHCl₃ (3 × 15 mL) to prevent the formation of an emulsion. The organic layers were combined, dried over MgSO₄, filtered, and concentrated in vacuo to provide a brown solid. The crude product was purified by flash chromatography (hexanes-EtOAC, 20:1) to provide phenol 10 as a white solid (0.213 g, 0.720 mmol, 54.1%); mp 137-139 °C. IR (KBr): 3113 (OH), 1669 (C=O), 1222 (CO) cm^-1. ¹H NMR (400 MHz): δ = 1.95 (m, 1 H), 2.14 (m, 1 H), 2.86 (m, 4 H), 3.16 (t, J = 8.0 Hz, 2 H), 3.30 (t, J = 6.0 Hz, 2 H), 3.94 (s, 3 H), 6.95 (d, J = 8.5 Hz, 1 H), 7.59 (d, J = 8.5 Hz, 1 H), 11.24 (s, 1 H). ¹³C NMR (100 MHz): δ = 25.0, 29.2, 32.9, 43.0, 52.2, 58.4, 109.8, 117.0, 131.2, 136.5, 145.7, 163.3, 171.3. MS: m/z (relative intensity, %) = 296.1 (11.82) [M⁺]. HRMS: m/z calcd for C₁₄H₁₆O₃S₂: 296.0555; found: 296.0541.