Highly Selective Monomethylation Of Primary Amines Through Host-guest Product Sequestration

摘要

Secondary amines are an important class of organic compounds whose synthesis is one of the most studied in organic chemistry. N-monomethylated amines, in particular, are present in a broad range of biologically active compounds, and they are widely utilized as intermediates in the preparation of Pharmaceuticals and dyes. Traditional methods for direct N-methylation of primary amines are still problematic despite the use of catalysts, solid bases, and nonconventional methylating agents. Harsh reaction conditions, poor yields, and low selectivity are the major limitations. To control reaction output, supramolecular protection constitutes a possible alternative to catalysis or to the introduction of hindered protecting groups. To date, supramolecular structures have been used as catalysts, promoters, and nanovessels to direct reactivity, regioselectivity, and chemoselectivity of organic reactions. A still unexplored approach to reaction control involves the sequestration of the desired product to avoid subsequent unwanted reactions. Herein, we report the exclusive N-monomethylation of primary amines through specific sequestration of the intermediate product by a suitable host, therefore avoiding further methylation in situ.