Highly diastereoselective addition of N-Boc-pyrrolidin-2-yllithium to optically active ketimines -: Synthesis of enantiomerically pure 1,3-imidazolidin-2-ones and diamines

A highly diastereoselective addition of chiral N-Boc-pyrrolidin-2-yllithium to optically active bicyclic ketimines has been developed. For this purpose alkyl- and aryl-substituted chiral N-Boc-amino ketones 2 have been synthesized by addition of various Grignard reagents to an N-Boc-protected lactam 1. The resulting N-Boc-amino ketones 2 have been converted into bicyclic ketimines 3 after deprotection and intramolecular cyclization. A kinetic resolution of the racemic organolithium compound by the chiral substrate is discussed based on X-ray crystal structure analysis and experimental results. The influence of the substituent of the ketimine has been studied. Some of the obtained tetracyclic 1,3-imidazolidin-2-ones 4 have been converted into tetracyclic aminals 5 and these compounds have been hydrolysed to the desired diamines 6.