Dept. of Chemistry
Oregon Graduate Center
3-(2'-Tetrahydropyranylthio) indole, VI, was synthesized from 3-thioindole, X, by treatment with 2-chlorotetrahydropyran, VIII, under basic conditions. This compound was used as a model system to study the feasibility of synthesizing biologically important C-nucleosides by first connecting the sugar to the base through a bridging sulfur atom and then extruding the sulfur atom with formation of the required carbon-carbon bond. The hemithioketal, VI, is inert to phosphines and phosphites under a variety of conditions. Treatment of the hemithioketal with silver perchlorate in tetrahydrofuran produced a silver complex as evidenced by thin-layer chromatography analysis. Treatment of the complex with hydrochloric acid to precipitate the silver yielded a complex reaction mixture from which was isolated the starting hemithioketal, VI, 3-thioindole, X, and the disulfide of 1-(2'-tetrahydropyranylthio) indole, XVa. When the silver complex was treated with methyl iodide and the resulting reaction mixture was subjected to thin-layer chromatography, 3-methylthioindole, XVI, 1-(2â-tetrahydropyranyl)-3-methylthioindole, XVIII, and the bis-tetrahydropyranyl derivative, XVII, were isolated. It is apparent that carbon sulfur bond cleavage results in the formation of the carbonium ion of tetrahydropyran, XXI, which alkylates an indole nucleus in the one position to produce XV, XVII and XVIII. There is no evidence to indicate that the desired rearrangement to 3-(2â-tetrahydropyranyl) indole, VII, has occurred.
Lee, Terry Dwight, "Some chemistry of 3-(2'-tetrahydropyranylthio)indole: a model study in sulfur extrusion" (1971). Scholar Archive. 24.