Asymmetric Synthesis of 2‐Mono‐ and 2,3‐trans‐Disubstituted Azetidines

Abstract

AbstractA versatile and efficient asymmetric synthesis of 2‐mono‐ and 2,3‐trans‐disubstituted azetidines with excellent diastereomeric (de = 93 to ⩾ 96%) and enantiomeric excesses (ee ⩾ 96%) in good overall yields is described. Virtually stereoisomerically pure differently N,O‐protected 3‐amino‐1‐alkanols were prepared as intermediates. Key steps are a diastereoselective α‐alkylation of aldehyde SAMP‐hydrazones with benzyloxymethyl chloride as the electrophile, and a nucleophilic 1,2‐addition of various organocerium reagents to the hydrazone CN double bond. An epimerisation‐free reductive removal of the auxiliary gave O‐benzyl‐protected 3‐amino‐1‐alkanols. After N‐tosylation and hydrogenolytic cleavage of the benzylic protecting group, ring closure to the corresponding N‐tosylazetidines was achieved in good yields under Mitsunobu conditions. Detosylation was easily accomplished employing sodium/naphthalene. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)