Metal-templated chiral Brønsted base organocatalysis

Abstract

Inert octahedral chiral-at-metal complexes are an emerging class of asymmetric catalysts that exploit the globular, rigid nature and stereochemical options of octahedral compounds. While the central transition metal serves as a structural anchorpoint and provides metal centrochirality, catalysis is mediated through the organic ligand sphere, thereby merging the branches of transition metal catalysis and organocatalysis. Here we report the development of inert octahedral 3-aminopyrazolato iridium(III) complexes as novel chiral Brønsted base catalysts and demonstrate their merit with applications to highly effective asymmetric sulfaMichael and aza-Henry reactions, permitting catalyst loadings down to 0.02 and 0.25 mol%, respectively. The observed high stereocontrol can be rationalized by a bifunctional mode of action in which the iridium catalyst, after the initial proton transfer, controls a ternary complex through defined hydrogen bonding interactions. This work reveals the potential of octahedral metal complexes as chiral scaffolds for the design of high-performance asymmetric catalysts.

Octahedral Chiral‐at‐Metal Iridium Catalysts: Versatile Chiral Lewis Acids for Asymmetric Conjugate Additions

“…On the other hand, we do not have an explanation for the failing or sluggish conversion of some of the other substrates such as the 2‐oxazolidinone 9 i ,28 2‐thiazolidinethione 9 j ,29 phosphonate 9 m ,31 and Weinreb amide 9 o 33. However, we believe that the addition to α,β‐unsaturated ketoesters,32 α,β‐unsaturated N ‐acyl pyrazoles,30 α,β‐unsaturated 2‐acyl thiazoles26, 8c and α,β‐unsaturated 2‐acyl imidazoles34 are particularly useful substrates since they are easily converted to a variety of different carbonyl compounds.…”

Chiral Cobalt(III) Complexes as Bifunctional Brønsted Acid–Lewis Base Catalysts for the Preparation of Cyclic Organic Carbonates

“…Recently, we introduced a new class of stereochemically inert coordinatively saturated chiral complexes of cobalt(III) as promoters of asymmetric carbon–carbon bond forming reactions . The use of chiral octahedral complexes, where the metal ion is not involved in the catalytic act and only serves to position and activate organic groups of a ligand, is a fast evolving new field of research . An efficient group of such catalysts developed by our group are cationic complexes of cobalt(III) and Schiff bases obtained from substituted salicylic aldehydes and ( R,R )‐ or ( S,S )‐cyclohexane diamine (Figure ) .…”

Asymmetric Friedel–Crafts alkylation of indoles with 2-nitro-3-arylacrylates catalyzed by a metal-templated hydrogen bonding catalyst

“…We recently introduced a convenient auxiliary-mediated methodology for the synthesis of chiral octahedral metal complexes which only contain achiral ligands and therefore draw their chirality exclusively from the metal center, [4][5][6][7][8] and we demonstrated that such chiral-only-at-metal complexes could serve as highly powerful catalysts for a variety of asymmetric transformations. [9][10][11][12][13][14][15] As an example, we developed a hydrogen-bond-mediated chiral iridium(III) complex as a very efficient catalyst for the Friedel-Crafts alkylation of indoles with β-nitroacrylates, thereby implementing all-carbon quaternary stereocenters with excellent enantioselectivities. 10 We were then wondering if related catalysts would be suitable for α-nitroacrylate substrates, thereby creating two consecutive stereocenters.…”