Synthesis of (R)-[1-2H,1-3H]- and [1,1,10,10-2H4]-decane: inverse isotope effects in the protonation of anions from 1,3-dithians

Abstract

A protocol for applying substrates with chiral methyl groups to determine the stereochemistry of enzymic hydroxylation of methyl groups is discussed. Efficient methods are described for the synthesis of (R)-[1-²H,1-³H]- and [1,1,10,10-²H₄]-decane from decanal and diethyl sebacate, respectively. Decanal was converted via the 2-anion of 2-nonyl-1,3-dithian to [1-³H]decanal which was reduced to (S)-[1-³H]decan-1-ol by NADH–liver alcohol dehydrogenase. Tosylation of the decanol, followed by reduction with Li[Al²H₄] gave (R)-[1-²H,1-³H]-decane (specific activity 0.095 Ci mol^–1). Diethyl sebacate was reduced with Li[Al²H₄] to [1,1,10,10-²H₄] decane-1,10-diol. Conversion of the diol to its ditosylate and reduction with Li[AlH₄] gave [1,1,10,10-²H₄]-decane. Although these procedures are essentially adaptations of literature methods, several significant improvements are described. The protonation (deuteriation, tritiation) of the 2-anion of 2-nonyl-1,3-dithian shows an inverse isotope effect, the magnitude of which has been explored for 2-anions of several 2-alkyl- and 2-aryl-1,3-dithianes (see Table).