Concerning the generation and the character of thiocarbonyl ylides in cycloaddition reactions.

Abstract

These studies clarified numerous aspects of thiocarbonyl ylide cycloaddition methodology. Through acid catalysis, a phenyl-stabilized thiocarbonyl ylide has been generated from trimethylsilylmethyl (trimethylsilyloxy)benzyl sulfide to undergo successful dipolar cycloadditions with doubly activated dipolarophiles forming various substituted tetrahydrothiophenes. Both the stabilized (aromatic and ester) and nonstabilized (alkyl) thiocarbonyl ylides have been generated through the thermal decarboxylation of various 2-substituted 1,3-oxathiolan-5-ones. This was followed by successful intermolecular cycloaddition reactions between both the stabilized and nonstabilized thiocarbonyl ylides with numerous doubly activated dipolarophiles to form monocyclic and bicyclic sulfur heterocycles in high yield and with moderate to excellent stereoselectivity. The intermolecular cycloadditions were extended to their intramolecular variants through the use of a tether. The studies found that these new bicyclic systems were formed between nonstabilized thiocarbonyl ylides and monoactivated dipolarophiles consisting of double and triple bonds, both of which are unsuccessful when conducted intermolecularly. The presence of intermediates through nonsynchronous bond formation in cycloadditions represents the second nonconcerted thiocarbonyl ylide cycloaddition reaction. The nonstereospecificity of the cycloadducts violated Woodward and Hoffmann's conservation of orbital symmetry rules. The decarboxylative methodology was applied to the synthesis of the tetrahydrothiophene-ring nucleus of a natural product, biotin. This represents the first application of thiocarbonyl ylide cycloaddition methodology for the synthesis of the sulfur-ring nucleus of biotin. In a model study, diamine formation through the double rearrangements of a cyclic dicarboxylic acid employing a modified Curtius rearrangement provided an invaluable method for the synthesis of the nitrogen-ring nucleus of biotin.