Amides, 3-keto-2- cycloaddition reactions

A concise synthesis of biologically important Vinca alkaloid ( )-3H-epivincamine was accomplished. A central step in the synthesis consists of rhodium-catalyzed intramolecular [3-l-2]-cycloaddition of a-diazo amide 223 which provides the cycloadduct 224, which has the core skeleton of the natural product, in excellent yield with complete diastereoselectivity (Scheme 70). Further, a reductive ring opening of the cyclo adduct followed by a decar-boethoxylation reaction and a base-induced keto-amide ring contraction reaction furnished ( )-3H -epivincamine (225) [171]. 

The proposed reaction pathway invokes initial formation of carbonyl ylide 100 by intramolecular cyclization of the intermediate keto carbenoid onto the oxygen atom of the amide. Subsequent isomerization to the azomethine ylide is followed by 1,3-dipolar cycloaddition to DMAD to furnish the intermediate cycloadduct 101, which undergoes in situ alkoxy 1,3-shift to the final drhydropyrrolizine 102 (Scheme 3.28). 

Rh-catalysed intramolecular insertion into thiophene. 59, 204 cycloaddition to uracils, 55, 1% Carbene, 5,6-cycloadduct with 2H-thiopyran, 59, 225 Carbenes, a-keto-perfluoroalkyl-, generation, trapping. 60, 40 Carbenes, Fischer, reaction with N-(hexafluoroisopropylidene) amides,... 

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