Asymmetric Catalysis with Substitutionally Labile yet Stereochemically Stable Chiral-at-Metal Iridium(III) Complex

Abstract

A metal-coordination-based high performance asymmetric catalyst utilizing metal centrochirality as the sole element of chirality is reported. The introduced substitutionally labile chiral-at-metal octahedral iridium(III) complex exclusively bears achiral ligands and effectively catalyzes the enantioselective Friedel-Crafts addition of indoles to α,β-unsaturated 2-acyl imidazoles (19 examples) with high yields (75%-99%) and high enantioselectivities (90-98% ee) at low catalyst loadings (0.25-2 mol %). Counterintuitively, despite its substitutional lability, which is mechanistically required for coordination to the 2-acyl imidazole substrate, the metal-centered chirality is maintained throughout the catalysis. This novel class of reactive chiral-at-metal complexes will likely be of high value for a large variety of asymmetric transformations.

Merger of Visible Light Induced Oxidation and Enantioselective Alkylation with a Chiral Iridium Catalyst

“…[7] We were wondering if this class of chiral iridium photocatalysts would also be capable of catalyzing asymmetric photoredox processes which instead proceed through oxidative chemistry and we chose the well-established oxidation of a-silylamines as our model system. [8][9][10][11][12] To start with, 2-phenylacetyl-1-methylimidazole (1 a'') was treated with N,N-diphenyl-N-(trimethylsilyl)methylamine (2 a) in the presence of the enantiomerically pure iridium complex L-IrO [13] (2 mol %), while exposed to air. Encouragingly, irradiation with visible light in the form of a standard 12 W energy saving household lamp for 20 h afforded the expected aminoalkylation product 3 a'' with 91 % ee, albeit with a low yield of just 34 % (Table 1, entry 1).…”

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

“…However, we found that the catalyst loading could be reduced to 0.5 mol% while still providing a satisfactory reaction time of 24 hours for complete conversion at room temperature with a diastereoselectivity of 2:1 and 95% e.e. for each diastereomer at the optimized concentration of 1.0 M (entries [8][9][10][11]. A further reduction of the catalyst loading to 0.2 mol% resulted in an undesirable drop in stereoselectivities (entry 12).…”

“…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.…”

Exploiting Octahedral Stereocenters: From Enzyme Inhibition to Asymmetric Photoredox Catalysis

“…Two achiral 5-tert-butyl-2-phenylbenzoxazole or analogous phenylbenzothiazole ligands cyclometalate a central iridium or rhodium center in a propeller-type and configurationally inert fashion; these are complemented by two additional, labile acetonitrile ligands ( Figure 5). [27][28][29] In this design, the metal serves as both the reactive center and the only stereogenic center. A related "chiral-only-at-metal" polypyridine complex of ruthenium was reported by Fontecave and co-workers but provided only very low enantioselectivities in the oxidation of organic sulfides to sulfoxides.…”

“…[15a] In contrast, to our delight, these biscyclometalated iridium and rhodium complexes turned out to be highly versatile chiral catalysts for a variety of transformations, such as enantioselective Friedel-Crafts reactions, Michael reactions, cycloadditions, cross-dehydrogenative couplings, and even asymmetric radical addition reactions. [27][28][29][30][31][32] Most of these reactions can be classified as either conjugate additions or enolate reactions in which one substrate is activated by two-point binding to the metal center. However, other mechanisms have also been realized, for example, in asymmetric transfer hydrogenations, which supposedly proceed through an iridium-hydride intermediate with an ancillary pyrazole ligand forming a crucial hydrogen bond to the ketone substrate ( Figure 5).…”