Palladium-Catalyzed Formation of Substituted Tetrahydropyrans: Mechanistic Insights and Structural Revision of Natural Products

This work is dedicated to Professor Albert J. Kascheres for his guidance and positive example to one of us (R.A.P.).

Abstract

A comprehensive study on the stereochemical outcome of palladium-catalyzed formation of 2,4,6-trisubstituted tetrahydropyrans through cyclization of the corresponding allylic acetates using both Pd(0) and Pd(II) catalysts is presented. We have found that the stereochemical outcome of this cyclization is dependent not only on the ­stereochemistry of the acyclic precursor but also on the nature of the palladium catalyst. These results were applied to the total synthesis of the putative structure of cryptoconcatone H. Experimental and computational DP4+ NMR results were used to assess the structures proposed for cryptoconcatones K and L.

Key words

tetrahydropyran - palladium catalysis - DP4+ - structural revision - natural product synthesis

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