Synlett 2014; 25(20): 2819-2826
DOI: 10.1055/s-0034-1379304
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© Georg Thieme Verlag Stuttgart · New York

Proton-Coupled Electron Transfer in Organic Synthesis: Novel Homolytic Bond Activations and Catalytic Asymmetric Reactions with Free Radicals

Hatice G. Yayla
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA   Email: rknowles@princeton.edu
,
Robert R. Knowles*
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA   Email: rknowles@princeton.edu
› Author Affiliations
Further Information

Publication History

Received: 15 August 2014

Accepted after revision: 20 September 2014

Publication Date:
16 October 2014 (online)

Abstract

Proton-coupled electron transfers (PCET) are unconventional redox processes in which an electron and proton are exchanged together in a concerted elementary step. While these mechanisms are recognized to play a central role in biological redox catalysis, their applications in synthetic organic chemistry have yet to be widely established. In this Account, we highlight two recent examples from our group outlining the use of concerted PCET as a platform for the development of catalytic and enantioselective reactions of neutral ketyl radicals. Central to this work was the recognition that PCET provides a mechanism for independent proton and electron donors to function jointly as a formal hydrogen atom donor competent to activate organic π systems that are energetically inaccessible using conventional H-atom transfer technologies. In addition, we found that neutral ketyls formed in the PCET event are remarkably strong hydrogen-bond donors and remain strongly associated to the conjugate base of the proton donor following the PCET event. When chiral proton donors are used, these successor H-bond complexes provide a basis for asymmetric induction in subsequent reactions of the ketyl radical.

1 Introduction

2 Concerted PCET and Effective Bond Strengths

3 Concerted PCET Activation of Ketones: A Catalytic Protocol for Ketyl–Olefin Coupling and Mechanistic Investigations

4 Enantioselective PCET Catalysis: Development of Catalytic Asymmetric Aza-pinacol Cyclizations

5 Conclusions

Supporting Information

 
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