Dedicated to Professor Aleksandar V. Teodorović with sentiments of gratitude and respect
An efficient strategy for a four-step synthesis of angularly fused tricyclic hydantoins
as suitable precursors of cis-fused bicyclic α-amino acids is developed by combining a highly diastereoselective
Bucherer–Bergs reaction of 2-alkenylcycloalkanones and a regiospecific selenium-induced
closure of pyrrolidine ring. This methodology was applied in a five-step synthesis
of bicycloproline derivatives in high overall yield. The method could be used for
the multigram preparation of free conformationally constrained bicyclic α-amino acids
with two points of diversity (size of cycloalkyl ring and substituent at the pyrrolidine
ring).
Key words
amino acids - cyclization - fused ring systems - heterocycles - regioselectivity -
selenium
