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

A 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)