A [3+2] AND [4+3] CYCLOADDITION APPROACH TO N-HETEROCYCLES VIA PD-CATALYZED TMM REACTIONS WITH IMINES

The question of cycloadditions of (trimethylenemethane)palladium complexes to heteroatom unsaturation is probed in the context of pyrrolidine syntheses. Whereas simple imines fail to react, imines possessing an electron-withdrawing group at either the carbon or nitrogen enhance the electrophilicity of the imine sufficiently to make it an excellent acceptor. Palladium(0) complexes catalyze cycloadditions of 2-((trimethylsilyl)methyl)allyl esters to N-tosyl- and N-nitroimines. The stronger electron-withdrawing nature of the nitro group permits nitrimines derived from relatively hindered ketones to participate. Conjugated cisoid imines lead to [4 + 3] cycloadditions-a process which constitutes an azepine synthesis. Substituted TMM precursors cycloadd with high regioselectivity. The results are consistent with a two-step addition process. Some of the simple examples explored to determine the scope and limitations of the process reveal simple syntheses of proline and nicotine analogues. The successful employment of imines as direct acceptors for TMM-PdL2 opens a new chapter on metal-catalyzed cycloadditions.