25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Alcohols as alkylating agents in heteroarene C–H functionalization

      research-article
      1 , 1
      Nature

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage 1 . One of the core principles that underlies DNA biosynthesis is the radical-mediated elimnation of H 2O to deoxygenate ribonucleotides, an example of ‘spin-center shift’ (SCS) 2 , during which an alcohol C–O bond is cleaved, resulting in a carbon-centered radical intermediate. While SCS is a well-understood biochemical process, it is underutilized by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylations using alcohols as radical precursors. Considering traditional radical-based alkylation methods require the use of stoichiometric oxidants, elevated temperatures, or peroxides 37 , the development of a mild protocol using simple and abundant alkylating agents would have significant utility in the synthesis of diversely functionalized pharmacophores. In this manuscript, we describe the successful execution of this idea via the development of a dual catalytic alkylation of heteroarenes using alcohols as mild alkylating reagents. This method represents the first broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer (HAT) catalysis. The utility of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: not found
          • Article: not found

          Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Visible light photoredox catalysis: applications in organic synthesis.

            The use of visible light sensitization as a means to initiate organic reactions is attractive due to the lack of visible light absorbance by organic compounds, reducing side reactions often associated with photochemical reactions conducted with high energy UV light. This tutorial review provides a historical overview of visible light photoredox catalysis in organic synthesis along with recent examples which underscore its vast potential to initiate organic transformations.
              Bookmark
              • Record: found
              • Abstract: found
              • Book: not found

              Free Radicals in Biology and Medicine

              Free Radicals in Biology and Medicine has become a classic text in the field of free radical and antioxidant research since its first publication in 1985. <br> This latest edition has been comprehensively rewritten and updated (over 80% of the text is new), while maintaining the clarity of its predecessor. There is expanded coverage of isoprostanes and related compounds, mechanisms of oxidative damage to DNA and proteins (and the repair of such damage), the free radical theory of aging and the roles played by reactive species in signal transduction, cell death, human reproduction, and other important biological events. Greater emphasis has also been placed on the methods available to measure reactive species and oxidative damage (and their potential pitfalls), as well as the importance of antioxidants in the human diet. <br> This book is recommended as a comprehensive introduction to the field for students, clinicians and researchers, and an invaluable companion to all those interested in the role of free radicals in the life and biomedical sciences.
                Bookmark

                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                8 July 2015
                26 August 2015
                3 September 2015
                03 March 2016
                : 525
                : 7567
                : 87-90
                Affiliations
                [1 ]Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, USA
                Author notes
                Correspondence and requests for materials should be addressed to: D.W.C.M. ( dmac-mill@ 123456princeton.edu )
                Article
                NIHMS703713
                10.1038/nature14885
                4560617
                26308895
                73a297db-0ea8-494f-8e8a-df858682fb9c

                Reprints and permissions information is available at www.nature.com/reprints.

                History
                Categories
                Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article