Diels-Alder Reactions of Imino Dienophiles

Heintzelman, Geoffrey R.; Meigh, Ivona R.; Mahajan, Yogesh R.; Weinreb, Steven M.


In comparison to all carbon [4 + 2] cycloadditions, Diesl-Alder reactions are still in their infancy. The last four decades, however, have seen intensive research in this area. The results if that synthetic organic chemists now have a powerful tool at their disposal for rapid construction of highly functionalized six-membered nitrogen heterocycles, often in a regio-, diastereo-, and enantioselective manner.

This chapter encompasses the topic of imine[4 + 2] cycloaddition reactions, of which there are a number of variants. This chapter is limited exclusively to imine and iminium ion dienophiles that undergo inter- and intramolecular Diels-Alder reactions with acylic and cyclic all-carbon 1,3-dienes affording 1,2,5,6-tetrahydropyridines as the initial cycloadducts. In situations where there is a mechanistic ambiguity, such as reactions that proceed via Mannich reactions, these mechanisms are included since it is difficult to know where to draw the line on coverage.

A comprehensive discussion of each structural type of imino dienophiles covers the literature up to the middle of 2004. A general overview of mechanistic, regiochemical, and sterochemical considerations is also presented. Specific relevant exo/endo issues, remote diasteroselectivity and the use of chiral auxiliaries are discussed under each separate imine type. Separate sections have also been included that describe intramolecular reactions, as well as more recent advances in enantioselective cycloadditions involving chiral catalysts.