Josef Stawitz

Pyrroles from 1,2‐Cyclopropanediamines and Aldehydes

Mechanistic investigations by means of proton spectroscopy detected intermediates and uncovered the course of reactions in acetate-buffered [D4]methanol of primary cyclopropanediamines cis- and trans-2a with benzaldehyde (3a) or 2,2-dimethylpropanal (3b), of secondary cyclopropanediamines cis- and trans-2b with 3b, and of the ring-methylated cyclopropanediamine trans-14a and the aromatic aldehydes 3a and c. This study provided the basis of an expedient synthesis of pyrroles which takes place under exceptionally mild conditions. Irrespective of the configuration, primary (2a·2HBr) and secondary cyclopropanediammonium dibromides 2b and c·2HBr that are devoid of ring substituents react with aromatic aldehydes 3a, e–h, cinnamic aldehyde (3i), and 3b to afford 2-substituted (8a, b) and 1,2-disubstituted pyrroles (8c–i), respectively. The 3-substituted secondary trans-cyclopropanediammonium dibromides 24·2HBr furnish 1,2,4-trisubstituted pyrroles 25. While the primary 1-methylcyclopropanediammonium dibromide trans-14a·2HBr reacts regioselectively with 3a and c to produce only 2,3-substituted pyrroles 19a, c, the corresponding secondary dibromide trans-14c·2HBr gives rise to the formation of mixtures of 1,2,3- (22) and 1,2,5-trisubstituted pyrroles 23. The key step of pyrrole formation from 1,2-cyclopropanediamines and aldehydes is the ring expansion of intermediate monoiminium ions of type 5 via azomethine ylides (E, Z)-6 to yield dihydropyrrolium ions 7.