Dataset Information

Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp3-sp2 Cross-Coupling of Oxalates with Aryl Halides.

ABSTRACT: Alkyl oxalates, prepared from their corresponding alcohols, are engaged for the first time as carbon radical fragments in metallaphotoredox catalysis. In this report, we demonstrate that alcohols, native organic functional groups, can be readily activated with simple oxalyl chloride to become radical precursors in a net redox-neutral Csp3-Csp2 cross-coupling with a broad range of aryl halides. This alcohol-activation coupling is successfully applied to the functionalization of a naturally occurring steroid and the expedient synthesis of a medicinally relevant drug lead.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5464990 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp3-sp2 Cross-Coupling of Oxalates with Aryl Halides.

Zhang Xiaheng X MacMillan David W C DWC

Journal of the American Chemical Society 20161017 42

Alkyl oxalates, prepared from their corresponding alcohols, are engaged for the first time as carbon radical fragments in metallaphotoredox catalysis. In this report, we demonstrate that alcohols, native organic functional groups, can be readily activated with simple oxalyl chloride to become radical precursors in a net redox-neutral Csp3-Csp2 cross-coupling with a broad range of aryl halides. This alcohol-activation coupling is successfully applied to ...[more]

PMID: 27718570

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Project description:In the past 50 years, cross-coupling reactions mediated by transition metals have changed the way in which complex organic molecules are synthesized. The predictable and chemoselective nature of these transformations has led to their widespread adoption across many areas of chemical research. However, the construction of a bond between two sp(3)-hybridized carbon atoms, a fundamental unit of organic chemistry, remains an important yet elusive objective for engineering cross-coupling reactions. In comparison to related procedures with sp(2)-hybridized species, the development of methods for sp(3)-sp(3) bond formation via transition metal catalysis has been hampered historically by deleterious side-reactions, such as ?-hydride elimination with palladium catalysis or the reluctance of alkyl halides to undergo oxidative addition. To address this issue, nickel-catalysed cross-coupling processes can be used to form sp(3)-sp(3) bonds that utilize organometallic nucleophiles and alkyl electrophiles. In particular, the coupling of alkyl halides with pre-generated organozinc, Grignard and organoborane species has been used to furnish diverse molecular structures. However, the manipulations required to produce these activated structures is inefficient, leading to poor step- and atom-economies. Moreover, the operational difficulties associated with making and using these reactive coupling partners, and preserving them through a synthetic sequence, has hindered their widespread adoption. A generically useful sp(3)-sp(3) coupling technology that uses bench-stable, native organic functional groups, without the need for pre-functionalization or substrate derivatization, would therefore be valuable. Here we demonstrate that the synergistic merger of photoredox and nickel catalysis enables the direct formation of sp(3)-sp(3) bonds using only simple carboxylic acids and alkyl halides as the nucleophilic and electrophilic coupling partners, respectively. This metallaphotoredox protocol is suitable for many primary and secondary carboxylic acids. The merit of this coupling strategy is illustrated by the synthesis of the pharmaceutical tirofiban in four steps from commercially available starting materials.

Dataset Information

Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp3-sp2 Cross-Coupling of Oxalates with Aryl Halides.

Publications

Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp<sup>3</sup>-sp<sup>2</sup> Cross-Coupling of Oxalates with Aryl Halides.

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