GLYCOSYLSULFENYL AND (GLYCOSYLTHIO)SULFENYL HALIDES (HALOGENO-1-THIOGLYCOSIDES AND HALOGENOTHIO-1-THIOGLYCOSIDES, RESP) - PREPARATION AND REACTION WITH ALKENES

The disulfides 11-17 and 20 were prepared from 7, 9, and 18 via the dithiocarbonates 8, 10, and 19, respectively (Scheme 2). The structure of 11 and of 13 was established by X-ray analysis. Chlorolysis (SO2Cl2) of 11 gave mostly the sulfenyl chloride 24, characterized as the sulfenamide 26, a small amount of 21, characterized as the (glycosylthio)sulfenamide 23, and the glycosyl chloride 27 (Scheme 3). Bromolysis of 11 followed by treatment of the crude with PhNH2 yielded only 28. Chlorolysis of the diglycosyl disulfide 13, however, gave mostly the (glycosylthio)sulfenyl chloride 21 and 27, besides 24. Bromolysis of 13 (--> 22 and traces of 25) followed by treatment with PhNH2 gave an even higher proportion of 23. Similarly, 20 led to 29 and hence to 30. In solution (CH2Cl2), the sulfenyl chloride 24 decomposes faster than the (thio)sulfenyl chloride 21, and both interconvert. Addition of crude 24 to styrene (-78-degrees) yielded the chloro-sulfide 31 and some 37, both in low yields. The product of the addition of 24 to 1-methylcyclohexene was transformed into the triol 32. Silyl ethers of allylic alcohols reacted with 24 only at room temperature, yielding, after desilylation, isomer mixtures 33 and 34, and pure 35. Much higher yields were achieved for the addition of (thio)sulfenyl halides yielding halogeno-disulfides. Good diastereoselectivities were only obtained with 21, its cyclohexylidene-protected analogue, and 22, and this only in the addition to styrene (--> 36, 37, 38), to (E)-disubstituted alkenes (--> 46, 48, 49a/b, 50a/b, 53), and to trisubstituted alkenes (--> 47, 51, 52, 54, 55). Other monosubstituted alkenes (--> 41-45) and (Z)-hex-2-ene (--> 49c/d, 50c/d) reacted with low diastereoselectivities. Where structurally possible, a stereospecific trans-addition was observed; regioselectivity was observed in the addition to mono- and trisubstituted alkenes and to derivatives of allyl alcohols. The absolute configuration of the 2-chloro-disulfides was either established by X-ray analysis (47a) or determined by transforming (LiAlH4) the chloro-disulfides into known thiiranes (Scheme 5). Thus, 37, 48, and the mixture of 49a/b and 50a/b gave the thiiranes 56, 61, and 64, respectively, in good-to-acceptable yields (Scheme 5). Harsher conditions transformed 56 into the thiols 57 and 58. Similarly, 61 gave 62. The enantiomeric excesses of these thiols were determined by GC analysis of their esters obtained with (-)-camphanoyl chloride. Addition of 21 to {[(E)-hex-2-enyl]oxy}trimethylsilane, followed by LiAlH4 reduction and desilylation, gave the known 66 (63%, e.e. 74%). The diastereoselectivity of the addition of 21 to trans-disubstituted and trisubstituted alkenes is rationalized by assuming a preferred conformation of the (thio)sulfenyl chloride and destabilizing steric interactions with one of the alkene substituents, while the diastereoselectivity of the addition to styrene is explained by postulating a stabilizing interaction between the phenyl ring and the C(1)-S substituent (Fig. 4).