Pd/NHC-Controlled Regiodivergent Defluorinative Allylation of gem-Difluorocyclopropanes with Allylboronates

Abstract

Controlling the selectivity of synthetically useful reactions has been a longstanding objective of organic chemistry. Wereport a regiodivergent synthetic protocol allowing access to diversefluorinated 1,5-dienes through Pd/NHC-catalyzed ring-openingallylation ofgem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transitionstates provided critical insight into the design of the NHC ligand for switching regioselectivity. Consistent with the DFT predictions,N-heterocyclic carbene (NHC) ligands with bulkyorthosubstituents favored branched allylation, with the IHept ligand providing >20:1 branched/linear regioselectivity. NHC ligands with less hinderedorthosubstituents such as IMes favored thethermodynamically more stable linear products. We were able to carry out late-stage modification of various complex moleculesusing this protocol. Our ligand-controlled approach provides efficient access to regioisomericfluorinated 1,5-dienes from the samestarting materials and constitutes a valuable addition to the toolbox of diversity-oriented synthesis.

Publisher

American Chemical Society

Publication Date

6-3-2022

Publication Title

ACS Catalysis

Department

Chemistry and Biochemistry

Document Type

Article

DOI

10.1021/acscatal.2c01391

Keywords

C-F bond clevage, Gem-difluorocyclopropane, Allylic alkylation, PEPPSI catalyst, Regioselectivity

Language

English

Format

text

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