Understanding Rate Acceleration and Stereoinduction of an Asymmetric Giese Reaction Mediated by a Chiral Rhodium Catalyst

The surprising acceleration of the addition of electron-rich radicals to α,β-unsaturated 2-acyl imidazoles by a chiral-at-metal rhodium catalyst is investigated. M06/Lanl2DZ (Rh),6-31G­(d) calculations reproduce the observed rate acceleration and shed light on a catalyst design where a rigid chiral pocket with a steric interaction >5 Å from the chiral metal center leads to the observed high stereoinduction. Analysis of the molecular orbitals of two key addition transition states emphasize the role of the catalyst as a Lewis acid without significant charge transfer

Reductive Labilization of a Cyclometalating Ligand Applied to Auxiliary-Mediated Asymmetric Coordination Chemistry

(4<i>S</i>)-4-Isopropyl-2-(3-nitrophenyl)-4,5-dihydrooxazole ((<i>S</i>)-<b>Phox</b>) is introduced as a novel chiral auxiliary for the asymmetric synthesis of ruthenium polypyridyl complexes. A simply accessible (<i>S</i>)-<b>Phox</b>-bearing precursor serves as the starting point for diastereoselective coordination chemistry: The stereogenic carbon atom of the cyclometalating auxiliary controls the spatial arrangement of incoming 1,10-phenanthrolines during ligand substitution reactions (ratio Λ:Δ up to 14:1), and further precipitation affords diastereopure compounds. In the following key step, the labilization of the auxiliary ligand is achieved by reduction, thus permitting its replacement against a third polypyridyl ligand with complete retention of the configuration at the metal center (er > 99:1) under mildly acidic conditions, in contrast with previously developed systems that require strong acid. On the basis of results of NMR experiments and X-ray analysis obtained for intermediate compounds, mechanistic considerations for the formation of diastereomeric complexes were made, revealing a Δ → Λ isomerization as the reason for the observed limitations in selectivity optimization. This work expands the pool of methods available for the asymmetric synthesis of tris-heteroleptic ruthenium polypyridyl complexes and additionally may serve as an inspiration for the synthesis of other nonracemic octahedral chiral-at-metal compounds

Catalytic, Enantioselective Addition of Alkyl Radicals to Alkenes via Visible-Light-Activated Photoredox Catalysis with a Chiral Rhodium Complex

An efficient enantioselective addition of alkyl radicals, oxidatively generated from organotrifluoroborates, to acceptor-substituted alkenes is catalyzed by a bis-cyclometalated rhodium catalyst (4 mol %) under photoredox conditions. The practical method provides yields up to 97% with excellent enantioselectivities up to 99% ee and can be classified as a redox neutral, electron-transfer-catalyzed reaction

Catalytic Enantioselective Synthesis of Key Propargylic Alcohol Intermediates of the Anti-HIV Drug Efavirenz

The catalytic, enantioselective synthesis of key propargylic alcohol intermediates toward the synthesis of the anti-HIV drug efavirenz is reported. Using a recently reported chiral-at-ruthenium catalyst (J. Am. Chem. Soc. 2017, 139, 4322), catalytic enantioselective alkynylations of 1-(2,5-dichloro­phenyl)-2,2,2-trifluoro­ethanone (99% yield, 95% ee) and 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoro­ethanone (97% yield, 99% ee) are achieved using catalyst loadings of merely 0.2 mol % (ca. 500 TON)

Enantioselective 2‑Alkylation of 3‑Substituted Indoles with Dual Chiral Lewis Acid/Hydrogen-Bond-Mediated Catalyst

A chiral-at-metal bis-cyclometalated iridium complex combines electrophile activation via metal coordination with nucleophile activation through hydrogen bond formation. This new bifunctional chiral Lewis acid/hydrogen-bond-mediated catalyst permits the challenging enantioselective 2-alkylation of 3-substituted indoles with α,β-unsaturated 2-acyl imidazoles in up to 99% yield and with up to 98% enantiomeric excess at a catalyst loading of 2 mol %. As an application, the straightforward synthesis of a chiral pyrrolo­[1,2-<i>a</i>]­indole is demonstrated

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

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% <i>ee</i>) 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

DNA Mismatch Recognition by a Hexacoordinate Silicon Sandwich–Ruthenium Hybrid Complex

The diastereoselective synthesis of two dinuclear Ru–Si complexes is reported, in which silicon­(IV) is coordinated in an octahedral fashion by two 1,10-phenanthrolines and one 4,5-pyrenediolato ligand and additionally η⁶-coordinated to a (η⁵-pentamethylcyclopentadienyl)­ruthenium­(II) moiety through one fused benzene ring of the pyrene ligand. One of these Ru–Si hybrid complexes was found to selectively stabilize DNA duplexes that contain cytosine–cytosine or cytosine–thymine mismatches, and it is proposed that this occurs by a novel dual insertion/intercalation binding mode in which the entire ruthenium sandwich unit is introduced into the DNA π-stacking at the site of the DNA mismatch

Polymer-Supported Chiral-at-Metal Lewis Acid Catalysts

The covalent immobilization of a chiral-at-metal bis-cyclometalated iridium­(III) catalyst on a solid support is reported, and its catalytic activity has been investigated. As a catalyst immobilization strategy, a catalyst precursor was tethered to polystyrene macrobeads through an ester or amide linkage and subsequently converted to the immobilized active chiral Lewis acid by treatment with a Brønsted acid. The amide-linked catalyst displays high robustness and can be recycled multiple times without deterioration of enantioselectivity and only a gradual loss of catalytic activity. Chiral Lewis acid activity was demonstrated as an example for the enantioselective Friedel–Crafts alkylation of indole with an α,β-unsaturated 2-acyl imidazole and for the enantioselective Diels–Alder reactions of an α,β-unsaturated 2-acyl imidazole with 2,3-dihydrofuran or isoprene

Enantioselective, Catalytic Trichloromethylation through Visible-Light-Activated Photoredox Catalysis with a Chiral Iridium Complex

An enantioselective, catalytic trichloromethylation of 2-acyl imidazoles and 2-acylpyridines is reported. Several products are formed with enantiomeric excess of ≥99%. In this system, a chiral iridium complex serves a dual function, as a catalytically active chiral Lewis acid and simultaneously as a precursor for an <i>in situ</i> assembled visible-light-triggered photoredox catalyst

Asymmetric Catalysis with Organic Azides and Diazo Compounds Initiated by Photoinduced Electron Transfer

Electron-acceptor-substituted aryl azides and α-diazo carboxylic esters are used as substrates for visible-light-activated asymmetric α-amination and α-alkylation, respectively, of 2-acyl imidazoles catalyzed by a chiral-at-metal rhodium-based Lewis acid in combination with a photoredox sensitizer. This novel proton- and redox-neutral method provides yields of up to 99% and excellent enantioselectivities of up to >99% ee with broad functional group compatibility. Mechanistic investigations suggest that an intermediate rhodium enolate complex acts as a reductive quencher to initiate a radical process with the aryl azides and α-diazo carboxylic esters serving as precursors for nitrogen and carbon-centered radicals, respectively. This is the first report on using aryl azides and α-diazo carboxylic esters as substrates for asymmetric catalysis under photoredox conditions. These reagents have the advantage that molecular nitrogen is the leaving group and sole byproduct in this reaction