GENERAL-SYNTHESIS OF HOMOCHIRAL TRISUBSTITUTED GAMMA-BUTYROLACTONES

The synthetically useful keto ester methyl 2-deoxy-2-(2-ethoxy-2-oxoethyl)-4,6-O-(phenylmethylene)-alpha-D-ribo-hexopyranosid-3-ulose can be prepared exclusively by reaction of the potassium enolate of methyl 2-deoxy-4,5-O-(phenylmethylene)-alpha-D-erythro-hexopyranosid-3-ulose and ethyl iodoacetate in toluene in 74% yield. Reduction of methyl 2-deoxy-2-(2-ethoxy-2-oxoethyl)-4,6-O-(phenylmethylene)-alpha-D-ribo-hexopyranosid-3-ulose and subsequent cyclisation led to methyl 2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-alpha-D-allopyranoside 2',3 lactone, whose lithium enolate reacted with high stereoselectivity to give exclusively (> 95% d.r.) methyl 5'-(R)-2-deoxy-5'-methyl-2-(2-oxoethyl)4,6-O-(phenylmethylene)-alpha-D-allopyranoside 2',3 lactone, methyl 5'-(R)-2-deoxy-5'-(1-hexyl)-2-(2-oxoethyl-4,6-O-(phenylmethylene)-alpha-D-allopyranoside 2',3 lactone and methyl 5'-(R)-2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-5'-(2-propenyl)-alpha-D-allopyranoside 2',3 lactone derivatives. This method provides a convenient and high-yielding route to homochiral gamma-butyrolactones, thereby offering an opening into a wide range of enantiomerically pure gamma-lactones. The work described provides another solution to the 'off-template' problem.