Diversity-Oriented Metal-Free Synthesis of Nitrogen-Containing Heterocycles Using Atropaldehyde Acetals as a Dual C3/C2-Synthon

Abstract

A highly efficient and elegant diversity-oriented reaction paradigm employing atropaldehyde acetals as new dual C2/C3 synthons was developed under metal-free conditions using glycine esters as the counterpart reagents, which allowed rapid synthesis of two important nitrogen-containing heterocycles, pyrrolo[1,2-a]quinolines and 3,5-diarylpyridines. The divergent products are subtly controlled by the manipulation of the substitutional groups of glycine esters. When a N-arylglycine ester was used, pyrrolo[1,2-a]quinolines can be formed through cascade oxidative C-C cleavage/multiple cyclization. Instead, N-benzylglycine ester as the counter-reagent led to the synthesis of 3,5-diarylpyridines via two key C-N cleavages. Mild conditions, broad substrate scope, scalability and environmentally acceptable organic solvents rendered this method practical and attractive.

Keywords: atropaldehyde acetals; diversity-oriented synthesis; dual C3/C2-synthon; metal-free catalysis; nitrogen-containing heterocycles.