Enantioselective catalytic intermolecular 1,3-dipolar cycloadditions are powerful methods for the synthesis of heterocycles. In contrast, intramolecular enantioselective 1,3-dipolar cycloadditions are virtually unexplored. A highly enantioselective synthesis of natural-product-inspired pyrrolidino-piperidines by means of an intramolecular 1,3-dipolar cycloaddition with azomethine ylides is now reported. The method has a wide scope and yields the desired cycloadducts with four tertiary stereogenic centers with up to 99% ee. Combining the enantioselective catalytic intramolecular 1,3-dipolar cycloaddition with a subsequent diastereoselective intermolecular 1,3-dipolar cycloaddition yielded complex piperidino-pyrrolizidines with very high stereoselectivity in a one-pot tandem reaction.
Keywords: asymmetric catalysis; biology-oriented synthesis; cycloaddition; pyrrolidino-piperidines; pyrrolizidines.
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