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

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 <b>2</b>, <b>6</b>, and <b>7</b> exclusively afforded mixtures of <i>exo</i> adducts. The product selectivity was highly dependent on the solvent of the reaction. In CH<sub>2</sub>Cl<sub>2</sub>, the kinetic products <b>3</b>, <b>8</b>, and <b>9</b> always predominated, whereas in hexane or toluene, less polar solvents, the thermodynamic adducts <b>4</b>, <b>10</b>, and <b>11</b> 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 <b>13</b>, bearing an open dienic component, was much less stereoselective, and a mixture of two <i>exo</i> and two <i>endo</i> 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.