Asymmetric synthesis of 1-substituted 2-azaspiro[3.3]heptanes: important motifs for modern drug discovery.

Highly diastereoselective addition of ethyl cyclobutanecarboxylate anions to Davis-Ellman's imines is reported. This methodology afforded the preparation of enantiomerically and diastereomerically pure 1-substituted 2-azaspiro[3.3]heptanes. This three-step procedure proceeded efficiently (yield up to 90%) and diastereoselectively (dr values up to 98 : 2). This methodology is applicable to the synthesis of 1-substituted 2-azaspiro[3.4]octane and 1-substituted 2-azaspiro[3.5]nonane.