Alkyne-Co(2)(CO)(6) Complexes in the Synthesis of Fused Tricyclic beta-Lactam and Azetidine Systems(,)(1).
A synthetic approach to racemic and enantiomerically pure, fused tricyclic 2-azetidinones and azetidines has been developed by using a Pauson-Khand (P-K) reaction on monocyclic enyne-beta-lactams as the key synthetic step. The access to cyclization precursors, monocyclic beta-lactams 1-7, was achieved by Staüdinger reaction of enyne imines 8 and 9 and D-glyceraldehyde imines 10 and (benzyloxy)- or phenoxyacetyl chlorides. Enyne imines 8 and 9 formed cis-2-azetidinones 1 and 2 having the required enyne moiety. cis-2-Azetidinones 11 were obtained as single diastereomers and transformed to enyne-2-azetidinones 3 and 5 by standard methodology. Alternatively, 4-formyl-2-azetidinones 14 were prepared by cyclization of p-anisyl glyoxal diimine and (benzyloxy)acetyl chloride and converted to racemic enyne-beta-lactams 4 and 6 by standard reactions. Enyne-2-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 and TMANO, formed tricyclic 2-azetidinones 15-19 with the ring system fused to the C3-C4 and C4-N1 lactam bonds. Yields were usually high, and the processes were highly diastereoselective. The exceptions were enyne-2-azetidinones 2 and 3a bearing N-propargyl moieties. These products decomposed to mixtures of unidentifiable products. Inhibition of the amide resonance was postulated as responsible for the failure of beta-lactams 2 and 3a to form tricyclic systems. In fact, the analogous enyne-azetidines 20a,b smoothly cyclized to form the corresponding tricyclic systems. This approach to tricyclic azetidines was extended to prepare different products. A new, unprecedented, N1-C2 bond breakage was also observed in the azetidine ring. The results described show that the P-K reaction is a suitable approach to tricyclic 2-azetidinones and azetidines. These are the first examples reported for a P-K reaction in with the enyne system is tethered to a strained heterocyclic four-membered ring.
Alcaide
Benito
B
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, 28040-Madrid, Spain.
Polanco
Concepción
C
Sierra
Miguel A.
MA