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Thermal and Lewis Acid Catalyzed Diastereoselective Intramolecular Diels−Alder Reaction on α,β-Unsaturated Amides Derived from (−)-8-Aminomenthol
journal contribution
posted on 1999-06-11, 00:00 authored by Celia Andrés, María García-Valverde, Javier Nieto, Rafael PedrosaStereochemical 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.