Thermal and Lewis Acid Catalyzed Diastereoselective Intramolecular Diels−Alder Reaction on α,β-Unsaturated Amides Derived from (−)-8-Aminomenthol

• Published in: Journal of organic chemistry 1999-07, Vol.64 (14), p.5230-5236
• Main Authors: Andrés, Celia, García-Valverde, María, Nieto, Javier, Pedrosa, Rafael
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9904462

Stereochemical aspects of the intramolecular Diels−Alder reaction on perhydro-1,3-benzoxazines derived from (−)-8-aminomenthol bearing α,β-unsaturated amides and the dienic component attached at C-2 are described. The thermal cyclization of 2-(2‘-furyl) derivatives 2, 6, and 7 exclusively afforded mixtures of exo adducts. The product selectivity was highly dependent on the solvent of the reaction. In CH2Cl2, the kinetic products 3, 8, and 9 always predominated, whereas in hexane or toluene, less polar solvents, the thermodynamic adducts 4, 10, and 11 were formed as major diastereoisomers. In cyclizations catalyzed with equimolar or 2-fold excess of Lewis acid, the kinetic stereiosomers were predominant. Some Lewis acids catalyzed the reaction, but diethylaluminum chloride was the most effective. The cyclization on the perhydro-1,3-benzoxazine 13, bearing an open dienic component, was much less stereoselective, and a mixture of two exo and two endo possible stereoisomers were formed. Elimination of the menthol appendage in two steps by reductive ring opening of the N,O-acetal moiety and oxidation−elimination yielded enantiomerically pure tetrahydroisoindoline derivatives.