Studies on the synthesis of chiral oxetanes

Abstract

The key intermediates for the synthesis of chiral oxetanes (3,5-di-O-benzyl-D-xylofurano-1,4-lactone, 3,5-di-O-benzyl-D-ribofurano-1,4-lactone, 3,5-di-O-benzyl-D-lyxofurano-1,4-lactone, 3,5-di-O-benzyl-D-arabinofurano-1, 4-lactone, and enantiomers of the corresponding lactones) were prepared in good yields by using the well-known procedures. Each lactone was triflated and reacted with sodium methoxide to give the chiral oxetanes. Thus 3,5-di-O-benzyl-D-xylofurano-1,4-lactone and 3,5-di-Obenzyl-L-lyxofurano-1,4-lactone yielded a single oxetane, (2S, 3S, 4S)-2carbomethoxy-3-benzyloxy-4-benzyloxy methyl oxetane, in 92% and 82% yield, respectively. 3,5-Di-O-benzyl-L-xylofurano-1,4-lactone and 3,5-di-O-benzylL-lyxofurano-1,4-lactone also yielded a single oxetane, (2R, 3R, 4R)-2-carbomethoxy-3-benzyloxy-4-benzyloxymethyl-oxetnae, in 88% and 82% yield, respectively. 3,5-Di-O-benzyl-D-ribofurano-1,4-lactone produced ca. 8 : 1 mixture of (2R, 3R, 4S)-2-carbomethoxy-3-benzyloxy-4-benzyloxymethyl-oxetane and (2S,3R, 4S)-2-carbomethoxy-3-benzyloxy-4-benzyloxymethyl-oxetane in 77% yield. 3,5-Di-O-benzyl-D-arabinofurano-1,4-lactone gave ca. 20 : 1 mixture of the same products as above in 81% yield. 3,5-Di-O-benzyl-L-arabinofurano1,4-lactone gave ca. 20:1 mixture of (2S, 3S, 4R)-2-carbomethoxy-3-benzyloxy-4-benzyloxymethyl-oxetane and (2R, 3S, 4R)-2-carbomethoxy-3-benzyloxy4-benzyloxymethyl-oxetane in 79% yield. 3,5-Di-O-benzyl-L-ribofurano-1,4lactone also produced ca. 8:1 mixture of the same products as sbove in 72% yield. On the basis of the stereochemistry of the carbon which has a leaving group (triflyl), the above-mentioned results show that four lactones(D-xylo, L-xylo-, D-arabino-, L-arabino-) produce ``inversion`` oxetanes and the other four lactones(D-lyxo-, L-lyxo-, D-ribo-, L-ribo-) produce ``retention`` oxetanes predominantly. Therefore, the oxetane formation reaction appears not to be governed by the stereochemistry of the leaving group, but governed by the ster...