ALKYNE-CO-2(CO)(6) COMPLEXES IN THE SYNTHESIS OF FUSED TRICYCLIC BETA-LACTAM AND AZETIDINE SYSTEMS

A synthetic approach to racemic and enantiomerically pure, fused tricy clic 2-azetidinones and azetidines has been developed by using a Pauso n-Khand (P-K) reaction on monocyclic enyne-beta-lactams as the key syn thetic step. The access to cyclization precursors, monocyclic beta-lac tams 1-7, was achieved by Staudinger reaction of enyne imines 8 and 9 and D-glyceraldehyde imines 10 and (benzyloxy)- or phenoxyacetyl chlor ides. Enyne imines 8 and 9 formed cis-2-azetidinones 1 and 2 having th e required enyne moiety. cis-2-Azetidinones 11 were obtained as single diastereomers and transformed to enyne-2-azetidinones 3 and 5 by stan dard methodology. Alternatively, 4-formyl-2-azetidinones 14 were prepa red by cyclization of p-anisyl glyoxal diimine and (benzyloxy)acetyl c hloride and converted to racemic enyne-beta-lactams 4 and 6 by standar d reactions. Enyne-8-azetidinones 1-7 were reacted with Co-2(CO)(8) to quantitatively yield the corresponding alkyne-Co-2(CO)(6) complexes. Reaction of such complexes with different promoters, especially heat a nd TMANO, formed tricyclic 2-azetidinones 15-19 with the ring system f used to the C3-C4 and C4-N1 lactam bonds. Yields were usually high, an d the processes were highly diastereoselective. The exceptions were en yne-2-azetidinones 2 and 3a bearing N-propargyl moieties. These produc ts decomposed to mixtures of unidentifiable products. Inhibition of th e amide resonance was postulated as responsible for the failure of bet a-lactams 2 and 3a to form tricyclic systems. In fact, the analogous e nyne-azetidines 20a,b smoothly cyclized to form the corresponding tric yclic systems. This approach to tricyclic azetidines was extended to p repare different products. A new, unprecedented, N1-C2 bond breakage w as also observed in the azetidine ring. The results described show tha t the P-K reaction is a suitable approach to tricyclic 2-azetidinones and azetidines. These are the first examples reported for a P-K reacti on in with the enyne system is tethered to a strained heterocyclic fou r-membered ring.