Diversified Synthesis of All-Carbon Quaternary gem-Difluorinated Cyclopropanes via Copper-Catalyzed Cross-Coupling

Abstract

The construction of all-carbon quaternary centers in small-ring systems is important but challenging in organic synthesis. Herein, by taking gem-difluorocyclopropyl bromides (DFCBs) as a type of general and versatile building block, we developed a practical method for building all-carbon quaternary centers in gem-difluorinated cyclopropanes (DFCs). The reaction relies on the involvement of a gem-difluorocyclopropyl radical intermediate, which can couple with a wide range of nucleophiles under copper catalysis.Letter pubs.acs.org/OrgLett

Recent Advances in Nonprecious Metal Catalysis

“…Xia and co-workers developed a method for generating allcarbon quaternary centers in gem-difluorinated cyclopropane scaffolds using Cu catalysis. 14 Suzuki−Miyaura-type couplings of gem-difluorocyclopropyl bromides (DFCBs) with arylboronic acids were demonstrated using CuI (10 mol %) and tButerPy (10 mol %) and gave the desired products in moderate to good yields (Scheme 12). A range of substituted phenylboronic acids were tolerated in the reaction (e.g., methyl, methoxy, fluoro, chloro, trifluoromethyl, ester).…”

High‐Valent Copper Catalysis Enables Regioselective Fluoroarylation of Gem‐Difluorinated Cyclopropanes

“…[ 2 ] In this context, gem ‐difluorinated cyclopropanes ( gem ‐DFCPs), owing to their facile availability (for selected reviews and reports on the synthesis of gem ‐DFCPs, see ref. [ 3 ]) and unique reactivity [ 4 ] ( Scheme 1 a , left), have emerged as highly versatile building blocks for the synthesis of fluorine‐containing molecules. In recent years, the utilization of transition‐metal (TM) catalysts renders the cross‐coupling reactions of gem ‐DFCPs with various nucleophiles (for reviews, see ref.…”

Sterically demanding Csp2(ortho-substitution)–Csp3(tertiary) bond formation via carboxylate-directed Mizoroki-Heck reaction under extra-ligand-free conditions

“…Over the past decade, although a plethora of interesting new approaches have emerged allowing for versatile access to tertiary Csp 2 –Csp 3 bonds intermolecularly, only a few of them could tolerate ortho -substitution on the sp 2 coupling partner, including the Friedel–Crafts reaction, 3 directed Mizoroki-Heck reaction 4 and C–H functionalization, 5 redox-relay Heck reaction, 6 and the widely studied cross-coupling reactions. 7 Of these approaches, the directing group strategy is particularly highly reliable and shows adequate regio- and stereo-chemical control. 8 For example, the amine-directed intermolecular Mizoroki-Heck reaction developed by Hallberg was used to construct a Csp 2 ( o S)–Csp 3 (T) bond efficiently in a highly regio- and enantio -selective manner (Fig.…”