The development of flexible syntheses of A-ring precursors intermediates of vitamin D from (-)-quinic acid 24 was examined. The 1,4-dihydroxy-3,5-bis-silyl ether 75 was prepared from quinic acid, and treated with sodium hydride, carbon disulfide and methyl iodide to give the bis-xanthate 82 in which migration of the C-5 tert-butyldimethylsilyl group to C-4 took place. This product was submitted to pyrolysis and deoxygenation to give the αβ-unsaturated ester 91....[ Read more ]

The development of flexible syntheses of A-ring precursors intermediates of vitamin D from (-)-quinic acid 24 was examined. The 1,4-dihydroxy-3,5-bis-silyl ether 75 was prepared from quinic acid, and treated with sodium hydride, carbon disulfide and methyl iodide to give the bis-xanthate 82 in which migration of the C-5 tert-butyldimethylsilyl group to C-4 took place. This product was submitted to pyrolysis and deoxygenation to give the αβ-unsaturated ester 91.

Treatment of the 1,4-dihydroxy-3,5-bis-silyl ether 75 with phenylchlorothiocarbonate gave the 4-[(phenoxy)thiocarbonyl]oxy-3,5-bis(tert- butyldimethylsilyl ether 86 in god yield. Treatment of compound 86 with thionyl chloride gave the αβ-unsaturated esters 87 and 90 in a ratio of 4: 1. Treatment of the mixture with AIBN-tributyltin hydride in toluene resulted in conversion of the αβ-unsaturated ester 87 into the bicyclo[3.2.l]thia-octanone 92. On the other hand, sequential treatment of compound 86 with AIBN-tributyltin hydride in toluene followed by thionyl chloride gave the required αβ-unsaturated ester 73 in good yield. However, attempted. lithiation of 73 and its acid derivatives did not succeed. In an attempt to prepare the β-bromo-ester, treatment of the ester 73 with bromine provided a crude dibromide, but the latter compound was inert to attempted elimination, or decomposed under forcing conditions. The ester 73 was quite inert to conjugate addition with organocopper or thiol nucleophiles. It was concluded that the presence of the bulky tert-butyldimethylsilyl protecting groups provided a kinetic barrier to the addition reactions.