Enantioselective Route to 5-Methyl- and 5,7-Dimethyl-6,7-dihydro-5<i>H</i>-dibenz[<i>c</i>,<i>e</i>]azepine: Secondary Amines with Switchable Axial Chirality

Abstract

(-)-5-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine 4, a new secondary amine featuring an axis-center stereochemical relay, was prepared enantioselectively from 2'-acetylbiphenyl-2-carboxylic acid, using (R)-2-phenylglycinol as an auxiliary for the control of both elements of chirality. The biaryl axis in 4 preferentially adopts the aS-configuration, with the methyl substituent pseudoequatorial, but conversion into the corresponding N-Boc derivative locks the axis into the aR-configuration, as predicted on the basis of molecular mechanics calculations.