Highly Enantioselective Intramolecular 1,3-Dipolar Cycloaddition: A Route to Piperidino-Pyrrolizidines

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. So selective: A highly enantioselective intramolecular 1,3‐dipolar cycloaddition alone or in tandem with a highly diastereoselective intermolecular 1,3‐dipolar cycloaddition provides efficient access to complex natural‐product‐inspired polycyclic scaffolds. Piperidino‐pyrrolizidines with up to seven contiguous stereocenters were thus obtained.