Experimental and Theoretical Studies of the Internal Stereodifferentiation Occurring During the Lithiation of β‐Stereogenic Alkyl Carbamates. Kinetic Resolutions by (‐)‐Sparteine‐Mediated Deprotonation

Abstract

Abstract The deprotonation of β‐stereogenic alkyl carbamates 8 with sec ‐butyllithium/TMEDA proceeds kinetically controlled with differentiation between the diastereotopic protons at the α‐methylene group. The lithium intermediates 9A and 9B are trapped by electrophiles to give carboxylic acid esters 10A / B and stannanes 11A / B , 13A / B . The diastereomeric ratio of A to B is independent of the electrophile. The highest efficiency is achieved with β‐aryl‐β‐alkyl‐substituted starting compounds 8d – f . The trends in the experimentally observed diastereoselectivities are reflected by the results of semiempirical PM3 calculations on the transition states of the deprotonation reaction. — As a result of double stereodifferentiation, application of the chiral base sec ‐butyllithium/(‐)‐sparteine gives rise to efficient kinetic resolution of racemic alkyl carbamates.