Selective formation of 1,3,4-Trisubstituted and 3,4-Disubstituted trans-β-lactams from Zinc enolates and imines

A new route for the high yield synthesis (better then 90% ) of exclusively trans-β-lactams (azetidin-2-ones) is reported which involves the 1:1 reaction of an α-aminoacid ester zinc enolate with an appropriate imine. The reaction can be carried out as a 'one-pot' synthesis as has been demonstrated for the synthesis of trans-3-diethylamino-4-phenyl azetidin-2-one (93% yield). The novel zinc enolates have most likely a Z-geometry as a result of intramolecular chelate coordination. Evidence has been obtained that in the first step these zinc enolates react with the imine in a highly diastereoselective manner providing the threo aldolate which in a subsequent step undergoes ring closure to the azetidin-2-one.