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      Organic Synthesis: Wherefrom and Whither? (Some Very Personal Reflections)

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      Israel Journal of Chemistry
      Wiley

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          Abstract

          <p class="first" id="P1">This perspective represents a (highly personal) examination of the past, present and future of synthetic organic chemistry. The central thesis posits that the confluence of factors that led to the “Golden Age of Natural Product Synthesis” in the second half of the twentieth century can be traced back to the identification of the therapeutic potential of steroid hormones culminating in the introduction of oral contraceptives. The tremendous benefits of those activities to the development of organic synthesis as a vibrant discipline led to the exponential increase in strategies and methods and the ability to tackle, larger and larger molecules of greater and greater complexity. The existential challenge to the health of organic synthesis is whether a similarly dynamic future can be anticipated and if so, to what end and how. Musings on potential answers to those questions are presented. </p>

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          Most cited references75

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

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            Frustrated Lewis Pairs: Metal-free Hydrogen Activation and More

            Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form "classical" Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically "frustrated Lewis pairs (FLPs)" is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter- or intramolecular combinations of bulky phosphines or amines with strongly electrophilic RB(C(6)F(5))(2) components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H(+)/H(-) pairs (stabilized for example, in the form of the respective phosphonium cation/hydridoborate anion salts) serve as active metal-free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small molecules, including carbon dioxide, in cooperative three-component reactions, offering new strategies for synthetic chemistry.
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              Cascade reactions in total synthesis.

              The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.
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                Author and article information

                Journal
                Israel Journal of Chemistry
                Isr. J. Chem.
                Wiley
                00212148
                February 2018
                February 2018
                October 23 2017
                : 58
                : 1-2
                : 61-72
                Affiliations
                [1 ]Roger Adams Laboratory; University of Illinois at Urbana-Champaign; 600 South Mathews Avenue Urbana, IL 61801 USA
                Article
                10.1002/ijch.201700085
                6010076
                29937573
                a9a2ed58-6e21-4dc6-84d8-624b49564b28
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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