Recent advances and applications of iridium-catalysed asymmetric allylic substitution

Abstract

Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions have been developed into a broadly applicable tool for the synthesis of chiral building blocks via C-C and C-heteroatom bond formation. The remarkable generality of these reactions and the high levels of regio- and enantioselectivity that are usually obtained in favour of the branched products have been made possible by a thorough investigation of the catalyst system and its mode of action. Therefore, today the Ir-catalysed asymmetric allylic substitution is a powerful reaction in the organic chemist's repertoire and has been used extensively for several applications. This article aims to provide an overview of the development of iridium catalysts derived from an Ir salt and a chiral phosphoramidite and their application to the enantioselective synthesis of natural products and biologically relevant compounds.

Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

“…The initial experiment was performed with 2-hydroxypyridine (2 a) and cinnamyl methyl carbonate (3 a) in the presence of a well-developed iridium catalytic system [11,12] including [{Ir(cod)Cl} 2 ] (2 mol %) and the Feringa phosphoramidite (S,S,S a )-1 a (4 mol %) in tetrahydrofuran at 50 8C. By using Cs 2 CO 3 as the base, the desired N-alkylation process proceeded in 96 % conversion to give the branched product 4 aa in 84 % yield and 94 % ee without observation of the Oalkylation product (entry 1, Table 1).…”

“…To our delight, the reaction proceeded much more quickly with a significant increase in yield and enantioselectivity (entry 2) when the Alexakis ligand (S,S,S a )-1 b was used. In contrast, a stronger organic base such as DBU and various inorganic bases such as tBuOLi, K 3 PO 4 , K 2 CO 3 , and NaH could all be tolerated, thus affording the desired products in good yields and excellent enantioselectivity (entries [8][9][10][11][12]. However, the use of (R,R a )-1 d or (R a )-1 e afforded the desired product (4 aa) in moderate enantioselectivity but with disappointing yield and regioselectivity (entries 4 and 5).…”

Enantioselective Approach to Quinolizidines: Total Synthesis of Cermizine D and Formal Syntheses of Senepodine G and Cermizine C

“…33 The key C-N bond-forming event between allylic carbonate 31 and amine 30 would be facilitated through allylic amination chemistry developed by Hartwig and co-workers. 34 While we are unaware of an example using α-branched 2° amines for this transformation (e.g., 30 ), Helmchen and co-workers demonstrated some promising examples of utilizing this amination chemistry for the synthesis of a series of piperidinecontaining natural products. 35 Both of the proposed coupling partners for this reaction could be derived from a common intermediate 32 .…”

Computational Protein Engineering: Bridging the Gap between Rational Design and Laboratory Evolution

“…Due to their ubiquity, a great variety of artificial catalysts have been created to accelerate organic synthesis, from compounds using simple acid/base catalysis to organometallic catalysts using transition metals such as palladium [2], platinum [3], iridium [4], rhodium [5] or gold [6] as their metal centers. Particularly, the use of transition metals has permitted us to increase our ability to form carbon-carbon bonds [7–9], a process which forms the basic building block of almost all synthetic organic chemistry.…”