A simple and efficient asymmetric synthesis of 3-alkyl-isoindolin-1-ones

A simple asymmetric access to 3-alkyl-isoindolin-1-ones was investigated through the diastereoselective alkylation of 2-[(1R)-2-hydroxy- 1-phenylethyl]-2,3-dihydro-1H-isoindolin-1-one 5. High diastereoselectivities were observed with LDA or LiHMDS while the isolated yields were modest (about 50%). In contrast the use of NaHMDS gave good isolated yields (up to 85%) but lowered diastereoselectivities. This methodology offers an efficient asymmetric synthesis of 3-alkylated isoindolin-1-ones. (C) 2002 Elsevier Science Ltd. All rights reserved.