Palladium-catalyzed $α$-arylation for the addition of small rings to aromatic compounds

He, Zhi-Tao; Hartwig, John F.

doi:10.1038/s41467-019-12090-z

Palladium-catalyzed $$α$$-arylation for the addition of small rings to aromatic compounds

Journal Article · Mon Sep 09 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-12090-z· OSTI ID:1572052

He, Zhi-Tao ^[1]; ^[1]

Univ. of California, Berkeley, CA (United States)

Small, strained rings have rigid, defined conformations and unique electronic properties. For these reasons, many groups seek to use these subunits to form biologically active molecules. We report a generally applicable approach to attach small rings to a wide range of aromatic compounds by palladium-catalyzed α-arylation of cyclopropyl, cyclobutyl and azetidinyl esters. The direct α-arylation of cyclopropyl esters and cyclobutyl esters is achieved in high yield by ensuring that the rate of coupling exceeds the rate of Claisen condensation. The $$α$$-arylation of azetidines is achieved without ring opening of the strained saturated heterocycle by conducting the reactions with an azetidine derivative bearing a benzyl protecting group on nitrogen. Mechanistic studies show that the α-arylation of small rings is challenging because of the weak acidity of α C-H bond (cyclopropanes), strong sensitivity of the strained esters to Claisen condensation (cyclobutatanes), or facile decomposition of the enolates (azetidinyl esters).

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1572052

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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