Copper-Catalyzed Borylation of Acyl Chlorides with an Alkoxy Diboron Reagent: A Facile Route to Acylboron Compounds

Abstract

Herein, the copper-catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B2pin2) or bis(neopentane glycolato)diboron (B2neop2) is reported, which provides stable potassium acyltrifluoroborates (KATs) in good yields from the acylboronate esters. A variety of functional groups are tolerated under the mild reaction conditions (room temperature) and substrates containing different carbon-skeletons, such as aryl, heteroaryl and primary, secondary, tertiary alkyl are applicable. Acyl N-methyliminodiacetic acid (MIDA) boronates can also been accessed by modification of the workup procedures. This process is scalable and also amenable to the late-stage conversion of carboxylic acid-containing drugs into their acylboron analogues, which have been challenging to prepare previously. A catalytic mechanism is proposed based on in situ monitoring of the reaction between p-toluoyl chloride and an NHC-copper(I) boryl complex as well as the isolation of an unusual lithium acylBpinOBpin compound as a key intermediate.