DIASTEREOSELECTIVE ROUTES TO A 1-BETA-METHYLCARBAPENEM KEY INTERMEDIATE - SCOPE OF ATE COMPLEX-FORMATION BETWEEN ESTER ENOLATES AND ORGANOBORANES AND ORGANOALANES

Two diastereoselective syntheses of the 1-beta-methylcarbapenem key intermediate 5 are described. Triethylborane-mediated epimerization of the alpha-methyl diastereomer 4 proceeds with high stereoselectivity to give pure 5 in good yield. Triethylaluminum-mediated methylation of the desmethyl analogue 3 gives 5 with modest stereoselectivity. Low-temperature FT-IR studies of reaction intermediates demonstrated that the epimerization proceeds via an ate complex, while the methylation does not involve ate complex formation. The scope of ate complex formation with trialkylboranes and trialkylalanes was thus more clearly defined, with the IR data providing a rough indication of the extent to which trialkylaluminum ate complexes are less stable than the trialkylborane analogs. The IR studies also provided useful information about enolate aggregation and the effects of cations, amines, HMPA and temperature on ate complex formation.