Reinvestigation of the alkylation of pyroglutamate ester urethanes

Article abstract of DOI:10.1016/S0040-4039(98)00174-9

Previous studies by several groups on the alkylation of pyroglutamic acid derivatives have led to a consensus that the stereoselectivity of alkylation at C-4 is invariably trans to the ester group at C-2. We have now discovered that this generalisation is not invariably correct and that, although for S(N)1-type electrophiles stereoselectivity is in fact trans, S(N)2-type electrophiles can give the thermodynamically less stable cis products with high diastereoselectivity. Use of the bulky proton source 2,6- di-tert-butylphenol to quench these reactions yields cis isomers as the only products in good yield, thus making direct alkylation of pyroglutamic acid derivatives a useful starting point for the synthesis of homochiral target compounds.