The Overman rearrangement on a diacetone-D-glucose template: Kinetic and theoretical studies on the chirality transcription

Article abstract of DOI:10.1016/S0040-4020(01)81282-5

A divergent and highly enantioselective synthetic methodology for both enantiomers of α-amino acids and chirally deuterated glycine was developed based upon the chirality transcription approach using a versatile chiral template, diacetone-D-glucos-3-ulose 1. An acetylenic C₃ starting unit was introduced into the chiral template 1 and was transformed into (E)-allylic trichloroacetamidate 5a and (Z)-counterpart 5b via stereospecific reduction and condensation with trichloroacetonitrile. The Overman's thermal rearrangement of 5a and 5b underwent with high diastereoselectivity to afford (Z)-allylic trichloroacetamide 6a and 6b, which in turn were converted to L- and D-alanine, respectively, by oxidative cleavage of the double bond and acid hydrolysis. The effectiveness of the present approach was assessed by using the simplest allylic alcohol system, i.e. (Z)- and (E)-monodeuterated allylic trichloroacetimidates 10a and 10b. Both enantiomers of chirally deuterated glycine were prepared stereoselectively in a similar sequence of reactions. Kinetic analyses of the template-based diastereoselective rearrangement of 5a and 5b were carried out along with theoretical studies of the transition states using the semi-empirical molecular orbital calculations, PM3-MNDO, which allowed us to deduce the mechanism of chirality transcription on the versatile chiral template 1.