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

Herein, the copper-catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B(2)pin(2)) or bis(neopentane glycolato)diboron (B(2)neop(2)) 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.

Automated summary

A copper-catalyzed borylation reaction is reported, which involves the reaction of acyl chlorides with boron esters to produce stable potassium acyltrifluoroborates. This reaction is conducted under mild conditions and can tolerate various functional groups. It is applicable to substrates with different carbon skeletons and can be scaled up for industrial use. It is also useful for the late-stage conversion of carboxylic acid-containing drugs into acylboron analogues.