Oxetanes enantioselective synthesis

Scheme 7.32 Enantioselective synthesis of oxetanes in the PB reaction of glyoxylate derivatives.

A practical and efficient asymmetric synthesis of 2-substituted oxetane-3-ones 46 has been developed by Shipman and co-workers by lithiation of SAMP/RAMP hydrazones of oxetane-3-one 45, followed by interception of the putative azaenolate lithiated intermediate with a range of electrophiles that include alkyl, aUyl and benzyl halides, and an aldehyde (Scheme 13) (2013JOC12243). As for the bases, w-BuLi and <-BuLi were found to be the most suitable for the metalation step providing adducts 46 in good yields and enantioselectivities (up to 84% ee), whereas LDA was less effective. Conversion of hydrazones 46 to the enantiomerically enriched 2-substituted oxetane-3-ones 47 can be achieved without detectable racemization using aqueous oxaHc acid at room temperature. 

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