Novel diethylaluminum chloride promoted reactions of the azetidine ring: Efficient and stereocontrolled entry to functionalized olefins, pyrrolidines, and pyrroles

The first examples of Lewis acid promoted fragmentation or rearrangement of the azetidine ring are reported. Azetidine precursors, cis-beta-lactams, w ere easily available as single cis-diastereoisomers by the Staudinger react ion. Both cis- and trans-4-formyl-beta-lactams react with the appropriate d ial or dithiol under acid catalysis to yield dioxolanes or dithiolanes, whi le reaction with trimethyl orthoformate or benzenethiol gave 4-acetal or th ioacetal beta-lactams, respectively. Azetidines were smoothly obtained by r eduction of easily available beta-lactams with monochloroalane (AlH2Cl), ge nerated in situ from LiAlH4/AlCl3. The chemical reactivity of azetidines wi th AlEt2Cl was further investigated. Different substituted azetidines showe d varied behavior on product formation during diethylaluminum chloride prom oted reactions. Azetidines having 4-methoxyphenyl or 2-furyl groups at C2 a nd a benzyl or allyl substituent at nitrogen efficiently reacted with AlEt2 Cl to give olefins stereoselectively through a fragmentation process, while acetal or thioacetal azetidines under the standard reaction conditions aff orded in a stereocontrolled manner pyrrolidines as the sole product. Furthe rmore, thioacetal azetidines bearing a substituent at C3 on the azetidine r ing that can promote aromatization (phenoxy or exocyclic double bond) gave pyrroles by reaction with AlEt2Cl.