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Published December 13, 2017 | Accepted Version + Supplemental Material
Journal Article Open

Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides

Abstract

Despite the long history of S_N2 reactions between nitrogen nucleophiles and alkyl electrophiles, many such substitution reactions remain out of reach. In recent years, efforts to develop transition-metal catalysts to address this deficiency have begun to emerge. In this report, we address the challenge of coupling a carbamate nucleophile with an unactivated secondary alkyl electrophile to generate a substituted carbamate, a process that has not been achieved effectively in the absence of a catalyst; the product carbamates can serve as useful intermediates in organic synthesis as well as bioactive compounds in their own right. Through the design and synthesis of a new copper-based photoredox catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be activated upon irradiation by blue-LED lamps, we can achieve the coupling of a range of primary carbamates with unactivated secondary alkyl bromides at room temperature. Our mechanistic observations are consistent with the new copper complex serving its intended role as a photoredox catalyst, working in conjunction with a second copper complex that mediates C–N bond formation in an out-of-cage process.

Additional Information

© 2017 American Chemical Society. Received: October 12, 2017; Published: December 4, 2017. Support has been provided by the National Institutes of Health (National Institute of General Medical Sciences, grant R01-GM109194), the Natural Sciences and Engineering Research Council of Canada (graduate research fellowship for J.M.A.), the National Science Foundation (support of the Caltech EPR Facility (NSF-1531940)), and the Arnold and Mabel Beckman Foundation (support of the Beckman Institute Laser Resource Center). We thank Kareem I. Hannoun, Lawrence M. Henling, Dr. Brian C. Sanders, Dr. Jonas Schwaben, Dr. Michael K. Takase, and Dr. Haolin Yin for assistance and helpful discussions. The authors declare no competing financial interest.

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Accepted Version - nihms978053.pdf

Supplemental Material - ja7b10907_si_001.pdf

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