Transition Metal Catalyzed Enantioselective Allylic Substitution in Organic Synthesis

Table of Contents

1. Frontmatter

2. Selectivity in Palladium-Catalyzed Allylic Substitution

   Giovanni Poli, Guillaume Prestat, Frédéric Liron, Claire Kammerer-Pentier

   Abstract

   The present chapter introduces the basic fundaments of the palladium-catalyzed allylic substitution reaction. After a brief introduction, the reaction is explored into the different steps of the catalytic cycle in a chronological order. Formation of the crucial η ³-allyl palladium complexes is first commented, followed by a brief description of the static isomerism and dynamic features related to these compounds. Synthetic opportunities to intercept these complexes are then presented. Selectivity is then addressed with a first focus on regioselectivity and memory effects. Finally, selected examples of enantioselective versions are presented and classified according to the position of the enantiodiscriminating step in the catalytic cycle.

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3. Computational Insights into Palladium-Mediated Allylic Substitution Reactions

   Jonatan Kleimark, Per-Ola Norrby

   Abstract

   Allyl palladium complexes have a rich chemistry. Many aspects of their structure and reactivity have been studied computationally. This chapter gives an overview of the history in this field, from structural studies and the effect of ligands and substituents, to the rich reactivity of the title complexes. The latter includes complex formation, reactions with nucleophiles and electrophiles, and dynamic equilibria. An important focus area has been the TsujiIt1;ndash;Trost reaction, in particular asymmetric versions thereof. A brief overview of computational methods, aimed at modeling novices, can be found in the introduction.

4. Palladium-Catalyzed Enantioselective Allylic Substitution

   Ludovic Milhau, Patrick J. Guiry

   Abstract

   Abstract

   Palladium-catalyzed allylic substitution is one of the main reactions for testing new chiral ligands. The most relevant examples from the work published in the period 2007 to mid-2010 are reviewed. The vast majority of the work published within this timeframe relies upon the application of chiral ligands for asymmetric induction. The recent advances in the development and applications of new chiral P–P, P–N, P–O, P–S, N–N, N–S, S–S, and NHC ligands are covered and are the main focus of this chapter. Other aspects of enantioselective palladium allylic alkylations are discussed in the subsequent sections, for example, heterogeneous catalysis, the use of chiral salt additives, and recent applications in kinetic resolution.

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5. Iridium-Catalyzed Asymmetric Allylic Substitutions

   Wen-Bo Liu, Ji-Bao Xia, Shu-Li You

   Abstract

   Ir-catalyzed asymmetric allylic substitution reactions have been reviewed. This chapter discusses respectively the mechanistic investigation, reaction scope, and synthetic application of Ir-catalyzed allylic substitution reactions. The reaction scope is classified according to different types of nucleophiles such as C, N, O, and S.

6. Molybdenum-Catalyzed and Tungsten-Catalyzed Enantioselective Allylic Substitutions

   Christina Moberg

   Abstract

   Asymmetric allylic substitutions catalyzed by molybdenum and tungsten complexes provide branched chiral products from unsymmetrically substituted allylic reagents. Highly selective chiral ligands are available for both types of reactions, but for the tungsten-catalyzed substitutions, enantioselective reactions are only possible starting from achiral linear allylic substrates. A variety of stabilized carbanions can be used as nucleophiles. The molybdenum-catalyzed reaction has been applied to the synthesis of several biologically active compounds.

7. Copper-catalyzed Enantioselective Allylic Substitution

   Jean-Baptiste Langlois, Alexandre Alexakis

   Abstract

   The efficiency of organocopper reagents in the displacement of allylic leaving groups has been well established during the past five decades. In sharp contrast, catalytic asymmetric version of this reaction using a chiral catalyst is a more recent field of research. This chapter presents an overview of tremendous studies towards the development of an It1;ldquo;ideallyIt1;rdquo; active catalyst achieving high regio- and enantioselectivities. The comparative reactivity and generality of peptides, phosphorus, as well as N-heterocyclic carbenes based catalysts are discussed in the first part. Then, relevant scope and synthetic applications are reviewed. Noteworthily, this chapter is restricted to CIt1;ndash;C bond formation processes, excluding CIt1;ndash;B and CIt1;ndash;Si bond formations.

8. Allylic Substitutions Catalyzed by Miscellaneous Metals

   Jeanne-Marie Begouin, Johannes E. M. N. Klein, Daniel Weickmann, Bernd Plietker

   Abstract

   Allylic substitutions catalyzed by miscellaneous metals have recently been uncovered as useful alternatives to the established corresponding transition metal catalyzed transformations. In particular, the interesting regioselectivity course of the allylic substitutions is of synthetic interest. In this chapter, we summarize the most recent findings in the field of group 8–10 metal (Fe, Ru, Co, Rh, Ni, Pt) catalyzed substitutions with a strong emphasis on the substrate range and the regioselectivity.

9. Enantioselective Allylic Substitutions in Natural Product Synthesis

   Barry M. Trost, Matthew L. Crawley

   Abstract

   Enantioselective transition metal-cataylzed allylic substitution reactions constitute a broad and deep methodology that has expanded to incorporate ever more metals and ligands. The utility of these processes is reflected in the wide range of natural product and drug target total syntheses that incorporate asymmetric allylic alkylations as the key step or steps.

10. Backmatter