Abstract
Aryl carboxylic acids are among the most abundant substrates in chemical synthesis and represent a perfect example of a traceless directing group that is central to many processes in the preparation of pharmaceuticals, natural products and polymers. Herein, we describe a highly selective method for the direct step-down reduction of carboxylic acids to arenes, proceeding via well-defined Pd(0)/(ii) catalytic cycle. The method shows a remarkably broad substrate scope, enabling to direct the classical acyl reduction towards selective decarbonylation by a redox-neutral mechanism. The utility of this reaction is highlighted in the direct defunctionalization of pharmaceuticals and natural products, and further emphasized in a range of traceless processes using removable carboxylic acids under mild, redox-neutral conditions orthogonal to protodecarboxylation. Extensive DFT computations were conducted to demonstrate preferred selectivity for the reversible oxidative addition and indicated that a versatile hydrogen atom transfer (HAT) pathway is operable.
Highlights
The reduction of carboxylic acid derivatives represents one of the most fundamental transformations in synthetic chemistry and catalysis.[1]
We proposed that the direct reduction of carboxylic acids[9,10] to hydrocarbons via a heretofore unknown redox-neutral, decarbonylative[11,12,13,14,15] Pd(0)-catalyzed pathway could enable to use ubiquitous carboxylic acids as traceless activating groups, offering high level of predictability5a,b and functional group tolerance5e–g under redox-neutral conditions orthogonal to protodecarboxylation.[16]
A er extensive optimization, we found that the reduction of 4-Ph-benzoic acid in the presence of Pd(OAc)[2] (1 mol%), dppb (2 mol%, dppb 1⁄4 1,4-bis(diphenylphosphino)butane), piv2O (1.5 equiv., piv 1⁄4 2,2-dimethylpropanoyl), Et3N (1.5 equiv.) and Et3SiH (1.5 equiv.) as a hydride source afforded the desired reduction product in 97% yield on gram scale, attesting to the scalability of the method
Summary
The reduction of carboxylic acid derivatives represents one of the most fundamental transformations in synthetic chemistry and catalysis.[1]. Aryl carboxylic acids are among the most abundant substrates in chemical synthesis and represent a perfect example of a traceless directing group that is central to many processes in the preparation of pharmaceuticals, natural products and polymers. We describe a highly selective method for the direct step-down reduction of carboxylic acids to arenes, proceeding via well-defined Pd(0)/(II) catalytic cycle.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
