Iridium-Catalyzed Asymmetric Allylic Substitutions

Iridium Complexes in Organic Synthesis. Edited by Luis A. Oro and Carmen Claver 

Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim 

---

Good fortune and design in the discovery of iridium-catalyzed asymmetric allylic substitution. 

A fourth focus of catalytic chemistry in our laboratory has been iridium-catalyzed asymmetric allylic substitution. Dr. Toshimichi Ohmura had been studying additions to rhodium and iridium allyl and benzyl complexes in hopes of developing... 

I 9 Iridium-Catalyzed Asymmetric Allylic Substitutions Table 9.2 Ir-catalyzed asymmetric allylic aminations. 

Work of the Helmchen group was focused on the iridium-catalyzed asymmetric allylic substitution, which was introduced by the group and developed into a broadly applicable tool for organic synthesis ... 

Scheme 1 Asymmetric allylic substitution catalyzed by metaiacyciic iridium-phosphoramidite complexes...

Asymmetric Iridium-Catalyzed Allylic Substitution A Survey of Ligands. 177... 

Although Helmchen et al. showed that asymmetric iridium-catalyzed allylic substitution could be achieved, the scope of the reactions catalyzed by iridium complexes of the PHOX ligands was limited. Thus, they evaluated reactions catalyzed by complexes generated from [lr(COD)Cl]2 and the dimethylamine-derived phosphoramidite monophos (Scheme 8) [45,51]. Although selectivity for the branched isomer from addition of malonate nucleophiles to allylic acetates was excellent, the highest enantiomeric excess obtained was 86%. This enantiomeric excess was obtained from a reaction of racemic branched allylic acetate. The enantiomeric excess was lower when linear allylic acetates were used. This system catalyzed addition of the hthium salts of A-benzyl sulfonamides to aUylic acetates, but the product of the reaction between this reagent and an alkyl-substituted linear aUylic acetate was formed with an enantiomeric excess of 13%. 

As an alternative, iridium complexes show exciting catalytic activities in various organic transformations for C-C bond formation. Iridium complexes have been known to be effective catalysts for hydrogenation [1—5] and hydrogen transfers [6-27], including in enantioselective synthesis [28-47]. The catalytic activity of iridium complexes also covers a wide range for dehydrogenation [48-54], metathesis [55], hydroamination [56-61], hydrosilylation [62], and hydroalkoxylation reactions [63] and has been employed in alkyne-alkyne and alkyne - alkene cyclizations and allylic substitution reactions [64-114]. In addition, Ir-catalyzed asymmetric 1,3-dipolar cycloaddition of a,P-unsaturated nitriles with nitrone was reported [115]. 

Up to date, numerous examples of nucleophilic substitution reactions on diverse allylic substrates catalyzed by Ir complexes have been published. Allylic or dienylic esters, carbonates, and phosphates are used as typical allyl donors. As an iridium source, no precatalyst better suited than [Ir(cod)Cl]2 (cod, 1,5-cyclooctadiene) has emerged, despite considerable work of several groups. The first Ir-catalyzed allylation was reported by Takeuchi in 1997 [146]. The first asymmetric version was then published by Janssen and Hebnchen (Scheme 12.64) [147]. Since then many further chiral ligands have been developed, providing regioselective access to branched substitution products with excellent enantioselectivities (Figure 12.4). 

---