General synthesis of homochiral trisubstituted γ-butyrolactones

Abstract

The synthetically useful keto ester methyl 2-deoxy-2-(2-ethoxy-2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-ribo-hexopyranosid-3-ulose can be prepared exclusively by reaction of the potassium enolate of methyl 2-deoxy-4,5-O-(phenylmethylene)-α-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)-α-D-ribo-hexopyranosid-3-ulose and subsequent cyclisation led to methyl 2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-α-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)-α-D-allopyranoside 2′,3 lactone, methyl 5′-(R)-2-deoxy-5′-(1-hexyl)-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-α-D-allopyranoside 2′,3 lactone and methyl 5′-(R)-2-deoxy-2-(2-oxoethyl)-4,6-O-(phenylmethylene)-5′-(2-propenyl)-α-D-allopyranos-ide 2′,3 lactone derivatives. This method provides a convenient and high-yielding route to homo-chiral γ-butyrolactones, thereby offering an opening into a wide range of enantiomerically pure γ-lactones. The work described provides another solution to the ‘off-template’ problem.