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      A robustness screen for the rapid assessment of chemical reactions

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      Nature Chemistry
      Springer Science and Business Media LLC

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          Abstract

          In contrast to the rapidity with which scientific information is published, the application of new knowledge often remains slow, and we believe this to be particularly true of newly developed synthetic organic chemistry methodology. Consequently, methods to assess and identify robust chemical reactions are desirable, and would directly facilitate the application of newly reported synthetic methodology to complex synthetic problems. Here, we describe a simple process for assessing the likely scope and limitations of a chemical reaction beyond the idealized reaction conditions initially reported. Using simple methods and common analytical techniques we demonstrate a rapid assessment of an established chemical reaction, and also propose a simplified analysis that may be reported alongside new synthetic methodology.

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          Most cited references18

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          The atom economy--a search for synthetic efficiency.

          B. Trost (1991)
          Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.
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            Atom Economy—A Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way

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              Discovery of an α-amino C-H arylation reaction using the strategy of accelerated serendipity.

              Serendipity has long been a welcome yet elusive phenomenon in the advancement of chemistry. We sought to exploit serendipity as a means of rapidly identifying unanticipated chemical transformations. By using a high-throughput, automated workflow and evaluating a large number of random reactions, we have discovered a photoredox-catalyzed C-H arylation reaction for the construction of benzylic amines, an important structural motif within pharmaceutical compounds that is not readily accessed via simple substrates. The mechanism directly couples tertiary amines with cyanoaromatics by using mild and operationally trivial conditions.
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                Author and article information

                Journal
                Nature Chemistry
                Nature Chem
                Springer Science and Business Media LLC
                1755-4330
                1755-4349
                July 2013
                June 9 2013
                July 2013
                : 5
                : 7
                : 597-601
                Article
                10.1038/nchem.1669
                23787750
                af496f8c-c320-4097-b023-9acf4a9deb11
                © 2013

                http://www.springer.com/tdm

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