A study on the stereoselectivity of C,O bond formation in esterification of cyclic thiohydroxamic acids

Esterification of cyclic thiohydroxamic acids, for example, N-hydroxypyridine-2(1H)-thione, N-hydroxy-4-methylthiazole-2(3H)-thione, and N-hydroxy-4-(p-chlorophenyl)-thiazole-2(3H)-thione, occurred with inversion of configuration at the attacked stereocenter, as evident from the use of chiral alcohols, alkyl p-toluene sulfonates, and cyclic sulfates. Stereochemical analysis of enantiomerically pure O-alkyl thiohydroxamates was performed on the basis of CD-spectroscopy and chemical derivatization. The assignment of the relative configuration in cyclic O-esters was feasible via NMR spectroscopy, whereas chiral aliphatic glycolato monoesters required hydroxyl group derivatization with chloro-(4R,5R)-bis[(1R,2S,5R)-menth-1-yloxycarbonyl)]-1,3,2-dioxaphospholane for this purpose.

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(S)-N-(Oct-2-yloxy)-pyridine-2(1H)-thioneC13H21NOS[α]D25=+28.3 (c 1.27, EtOH)Absolute configuration: (S)Source of chirality: (s)-2-octanol

(S)-N-(Oct-2-yloxy)-4-methylthiazole-2(3H)-thioneC12H21NOS2[α]D25=+34.7 (c 1.47, EtOH)Absolute configuration: (S)Source of chirality: (s)-2-octanol

(S)-N-(Oct-2-yloxy)-4-(p-chlorophenyl)-thiazole-2(3H)-thioneC17H22ClNOS2[α]D25=+30.5 (c 0.93, CHCl3)Absolute configuration: (S)Source of chirality: (s)-2-octanol

N-[(5S,6R)-6-Hydroxydecyl-5-oxy]-4-methylthiazole-2(3H)-thioneC14H25O2NS2[α]D25=-26.8 (c 1.01, EtOH)Absolute configuration: (5S,6R)Source of chirality: asymmetric dihydroxylation