Issue 47, 2021

Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

Abstract

Modulating the reaction selectivity is highly attractive and pivotal to the rational design of synthetic regimes. The defluorinative functionalization of gem-difluorocyclopropanes constitutes a promising route to construct β-vinyl fluorine scaffolds, whereas chemo- and regioselective access to α-substitution patterns remains a formidable challenge. Presented herein is a robust Pd/NHC ligand synergistic strategy that could enable the C–F bond functionalization with exclusive α-regioselectivity with simple ketones. The key design adopted enolates as π-conjugated ambident nucleophiles that undergo inner-sphere 3,3′-reductive elimination warranted by the sterically hindered-yet-flexible Pd-PEPPSI complex. The excellent branched mono-defluorinative alkylation was achieved with a sterically highly demanding IHept ligand, while subtly less bulky SIPr acted as a bifunctional ligand that not only facilitated α-selective C(sp3)–F cleavage, but also rendered the newly-formed C(sp2)–F bond as the linchpin for subsequent C–O bond formation. These examples represented an unprecedented ligand-controlled regioselective and chemodivergent approach to various mono-fluorinated terminal alkenes and/or furans from the same readily available starting materials.

Graphical abstract: Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

Supplementary files

Article information

Article type
Edge Article
Submitted
04 Okt. 2021
Accepted
07 Nov. 2021
First published
08 Nov. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 15511-15518

Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

L. Lv, H. Qian, Y. Ma, S. Huang, X. Yan and Z. Li, Chem. Sci., 2021, 12, 15511 DOI: 10.1039/D1SC05451A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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