6-Methyl-2,4-pyrimidyl Diesters. A Highly Efficient Acylating Agent for the Synthesis of Unsymmetrical Ketones

摘要

It is well known that the reaction of organometallics with carboxylic acid derivatives is a useful method for the synthesis of ketones. The reaction of acid chlorides with Grignard reagents gives ketones, but yields are low to moderate due to the formation of the corresponding tertiary alcohols. To overcome these drawbacks the reaction of in situ formed acyl triphenyl-phosphonium ions from acid chlorides and Bu3P with Grignard reagents has been developed, but the separation of Bu3P is tedious. Alternatively, the coupling of acid chlorides with terminal alkynes or organostannanes in the presence of palladium catalyst and alkynyldimethylaluminum reagents, derived from Et3N-catalyzed alumination of terminal alkynes, leads to the aromatic ketones or ynones at reflux temperature. Although thiol esters are also coupled with organozinc or organoboron reagents in the presence of PdCl2(PPh3)2 to afford ketones including aldehyde, ester, and halide functional groups, these methods are exclusively limited to the synthesis of aliphatic ketones.