Insights into the Molecular Recognition Process in Organocatalytic Chemoselective Monoacylation of 1,5-Pentanediol

Abstract

Monoacylation of long-chain linear diols often encounters difficulties associated with unavoidable overacylation affording the diacylate. However, several C1- and C2-symmetrical pyrrolidinopyridine (PPY) catalysts were found to effectively promote the chemoselective monoacylation of 1,5-pentanediol. The effects of catalyst structure on the performance for the monoacylation were investigated. The amide carbonyl group(s) in the pyrrolidine ring in both C1- and C2-symmetrical catalysts was(were) suggested to play the key role in selective monoacylation. On the other hand, the indolyl NH group in the amide side chain of the catalysts was found to be critically important for further increasing the chemoselectivity of monoacylation only when the catalyst has a C2-symmetrical structure. The effects of the catalyst structure on the chemoselective monoacylation were elucidated by DFT calculations, and the origin of the precise molecular recognition for 1,5-pentanediol by the catalysts and transition state (TS) stabilization effects by these functionalities were disclosed.