Mechanism of the Stereoselective α-Alkylation of Aldehydes Driven by the Photochemical Activity of Enamines
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Open Access
- 16 June 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 138 (25), 8019-8030
- https://doi.org/10.1021/jacs.6b04871
Abstract
Herein we describe our efforts to elucidate the key mechanistic aspects of the previously reported enantioselective photochemical α-alkylation of aldehydes with electron-poor organic halides. The chemistry exploits the potential of chiral enamines, key organocatalytic intermediates in thermal asymmetric processes, to directly participate in the photoexcitation of substrates either by forming a photoactive electron donor-acceptor complex or by directly reaching an electronically excited state upon light absorption. These photochemical mechanisms generate radicals from closed-shell precursors under mild conditions. At the same time, the ground-state chiral enamines provide effective stereochemical control over the enantioselective radical-trapping process. We use a combination of conventional photophysical investigations, nuclear magnetic resonance spectroscopy, and kinetic studies to gain a better understanding of the factors governing these enantioselective photochemical catalytic processes. Measurements of the quantum yield reveal that a radical chain mechanism is operative, while reaction-profile analysis and rate-order assessment indicate the trapping of the carbon-centered radical by the enamine, to form the carbon-carbon bond, as rate-determining. Our kinetic studies unveil the existence of a delicate interplay between the light-triggered initiation step and the radical chain propagation manifold, both mediated by the chiral enamines.Keywords
Funding Information
- European Research Council (278541)
- Ministerio de Economía y Competitividad (CTQ2013-45938-P, SEV-2013-0319)
- Agència de Gestió d’Ajuts Universitaris i de Recerca (2014 SGR 1059)
- Institut Català d'Investigació Química
- Ministerio de Educación, Cultura y Deporte (FPU13/02402)
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