Cv. Stevens et al., Directing the regioselectivity of the alkylation of pyroglutamate carbamates by formation of a stable counter-ion complex, SYNLETT, (10), 2001, pp. 1519-1522
The alkylation of benzyl N-Boc pyroglutamate was carried out using chlorofo
rmates in order to introduce an activating group at the 4-position. Deproto
nation with three equivalents of LiHMDS followed by alkylation with differe
nt electrophiles lead to 2-alkylated pyroglutamates. The directing effect o
f the alkylation to the 2-position can be accounted for by the formation of
a counterion complex.