Lithiation and stereoselective transformations of 3-aroyl-2,2,4,4-tetramethyloxazolidines (TMO amides), a new class of acid-labile atropisomeric amides.

Arom. amides 4 (3-aroyl-2,2,4,4-tetramethyloxazolidines or TMO amides) derived by acylation of 2,2,4,4-tetramethyloxazolidine undergo ortho- and lateral lithiation reactions. Given sufficient steric hindrance to bond rotation, they exhibit atropisomerism about the Ar-CO bond and the Ar-CO axis is able to control the atroposelective formation of new stereogenic centers. For example, an 85:15 ratio of syn and anti isomers of 3-(2'-(1-hydroxypropyl)-1'-naphthoyl)-2,2,4,4-tetramethyloxazolidine (15a) was obtained from lithiated 3-(1'-naphthoyl)-2,2,4,4-tetramethyloxazolidine and EtCHO. Unlike amides derived from hindered secondary amines such as diisopropylamine, the 3-aroyl-2,2,4,4-tetramethyloxazolidines are acid-sensitive, and treatment with methanesulfonic acid gives lactones or lactams by cyclization onto the amide group. For example, 15a gave I in 62% yield. The crystal and mol. structures of 3-(2-bromo-5-methoxybenzoyl)-2,2,4,4-tetramethyloxazolidine and (Ra*,S*)-3-(2'-(.alpha.-hydroxybenzyl)-1'-naphthoyl)-2,2,4,4-tetramethyloxazolidine were detd. by x-ray crystallog. [on SciFinder (R)]