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. 2023 Sep 14;14(39):10971-10978.
doi: 10.1039/d3sc03987k. eCollection 2023 Oct 11.

Rh(iii)-catalyzed highly site- and regio-selective alkenyl C-H activation/annulation of 4-amino-2-quinolones with alkynes via reversible alkyne insertion

Naohiro Hirako  1 , Takeshi Yasui  1 , Yoshihiko Yamamoto  1
Affiliations

Rh(iii)-catalyzed highly site- and regio-selective alkenyl C-H activation/annulation of 4-amino-2-quinolones with alkynes via reversible alkyne insertion

Naohiro Hirako et al. Chem Sci. .

Abstract

3,4-Fused 2-quinolone frameworks are important structural motifs found in natural products and biologically active compounds. Intermolecular alkenyl C-H activation/annulation of 4-amino-2-quinolone substrates with alkynes is one of the most efficient methods for accessing such structural motifs. However, this is a formidable challenge because 4-amino-2-quinolones have two cleavable C-H bonds: an alkenyl C-H bond at the C3-position and an aromatic C-H bond at the C5-position. Herein, we report the Rh(iii)-catalyzed highly site-selective alkenyl C-H functionalization of 4-amino-2-quinolones to afford 3,4-fused 2-quinolones. This method has a wide substrate scope, including unsymmetrical internal alkynes, with complete regioselectivity. Several control experiments using an isolated key intermediate analog suggested that the annulation reaction proceeds via reversible alkyne insertion involving a binuclear Rh complex although alkyne insertion is generally recognized as an irreversible process due to the high activation barrier of the reverse process.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Site-selective C–H functionalization of aromatic compounds with two cleavable C–H bonds.
Scheme 2
Scheme 2. Substrate scope.
Scheme 3
Scheme 3. Analysis of hydrogen/deuterium exchange.
Fig. 1
Fig. 1. Temperature-dependence of the reaction. aYields are determined by 1H NMR. Isolated yields are shown in parentheses.
Fig. 2
Fig. 2. Mechanistic study involving rhodacycle intermediates.
Scheme 4
Scheme 4. Proposed reaction mechanism.
See this image and copyright information in PMC

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