Directing the Regioselectivity of the Alkylation of Pyroglutamate Carbamates by Formation of a Stable Counter-ion Complex

Abstract

A l k y l a t i o n o f P y r o g l u t a m a t e C a r b a m a t e s v i a a C o u n t e r -i o n C o m p l e x Abstract: The alkylation of benzyl N-Boc pyroglutamate was carried out using chloroformates in order to introduce an activating group at the 4-position. Deprotonation with three equivalents of LiHMDS followed by alkylation with different electrophiles lead to 2-alkylated pyroglutamates. The directing effect of the alkylation to the 2-position can be accounted for by the formation of a counterion complex.

Straightforward Ring Expansion of Pyroglutamates to Perhydro-1,3-diazepine-2,4-diones

“…During our research on pyroglutamates for the development of agrochemicals and pharmaceutically interesting azaheterocyclic skeletons, we found that when the sodium salt of an alkylpyroglutamate 5 is treated with 1 equiv of an isocyanate, reaction occurs both on the N-atom and on the C2-atom resulting in a complex mixture of different compounds. However, when a mixture of 5 with an isocyanate is treated with NaH in diethyl ether, a precipitate is formed during the reaction, which after workup proved to be the sodium salt of the expected carbamoyllactam 6 in high purity (Scheme ).…”

Synthesis ofN(3),N‘(3)-Polymethylene-bis-hydantoins and Their Macrocyclic Derivatives

“…Starting from pyroglutamates would avoid the problem of N(3)selectivity and also allows the synthesis of highly functionalized derivatives since pyroglutamates can easily be derivatized. 16,[21][22][23][24]…”

“…The problem with this reaction is the need for N(3)-selective alkylation and the yield which is usually quite low. Starting from pyroglutamates would avoid the problem of N(3)-selectivity and also allows the synthesis of highly functionalized derivatives since pyroglutamates can easily be derivatized. ,− …”