Iridium-Catalyzed Silylation of Aryl C–H Bonds

A method for the iridium-catalyzed silylation of aryl C–H bonds is described. The reaction of HSiMe­(OSiMe₃)₂ with arenes and heteroarenes catalyzed by the combination of [Ir­(cod)­(OMe)]₂ and 2,4,7-trimethylphenanthroline occurs with the aromatic compound as the limiting reagent and with high levels of sterically derived regioselectivity. This new catalytic system occurs with a much higher tolerance for functional groups than the previously reported rhodium-catalyzed silylation of aryl C–H bonds and occurs with a wide range of heteroarenes. The silylarene products are suitable for further transformations, such as oxidation, halogenation, and cross-coupling. Late-stage functionalization of complex pharmaceutical compounds was demonstrated

Enantioselective Functionalization of Allylic C–H Bonds Following a Strategy of Functionalization and Diversification

We report the enantioselective functionalization of allylic C–H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C–H bond functionalization, followed by the catalytic diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C–H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C–N, C–O, C–S, or C–C bond at the allylic position in good yield with a high branched-to-linear selectivity and excellent enantioselectivity (ee ≤97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,<i>n</i>)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated

Mechanistic Studies of Copper-Catalyzed Asymmetric Hydroboration of Alkenes

Mechanistic studies of the copper-catalyzed asymmetric hydroboration of vinylarenes and internal alkenes are reported. Catalytic systems with both DTBM-SEGPHOS and SEGPHOS as the ligands have been investigated. With DTBM-SEGPHOS as the ligand, the resting state of the catalyst, which is also a catalytic intermediate, for hydroboration of 4-fluorostyrene is a phen­ethyl­copper­(I) complex ligated by the bisphosphine. This complex was fully characterized by NMR spectroscopy and X-ray crystallography. The turnover-limiting step in the catalytic cycle for the reaction of vinylarenes is the borylation of this phenethylcopper complex with pinacolborane (HBpin) to form the boronate ester product and a copper hydride. Experiments showed that the borylation occurs with retention of configuration at the benzylic position. β-Hydrogen elimination and insertion of the alkene to reform this phenethylcopper complex is reversible in the absence of HBpin but is irreversible during the catalytic process because reaction with HBpin is faster than β-hydrogen elimination of the phenethylcopper complex. Studies on the hydroboration of a representative internal alkene, <i>trans</i>-3-hexenyl 2,4,6-trichloro­benzoate, which undergoes enantio- and regioselective addition of HBpin catalyzed by DTBM-SEGPHOS, KO<i>t</i>Bu, and CuCl, also was conducted, and these studies revealed that a DTBM-SEGPHOS-ligated copper­(I) dihydridoborate complex is the resting state of the catalyst in this case. The turnover-limiting step in the catalytic cycle for hydroboration of the internal alkene is insertion of the alkene into a copper­(I) hydride formed by reversible dissociation of HBpin from the copper dihydridoborate species. With SEGPHOS as the ligand, a dimeric copper hydride was observed as the dominant species during the hydroboration of 4-fluorostyrene, and this complex is not catalytically competent. DFT calculations provide a view into the origins of regio- and enantioselectivity of the catalytic process and indicate that the charge on the copper-bound carbon and delocalization of charge onto the aryl ring control the rate of the alkene insertion and the regioselectivity of the catalytic reactions of vinylarenes

Iridium-Catalyzed Regioselective and Enantioselective Allylation of Trimethylsiloxyfuran

We report the regio- and enantioselective allylation of an ester enolate, trimethylsiloxyfuran. This enolate reacts at the 3-position with linear aromatic allylic carbonates or aliphatic allylic benzoates to form the branched substitution products in the presence of a metallacyclic iridium catalyst. This process provides access to synthetically important 3-substituted butenolides in enantioenriched form. Stoichiometric reactions of the allyliridium intermediate suggest that the trimethylsiloxyfuran is activated by the carboxylate leaving group

PCI Express base specification

Mechanistic studies of the copper-catalyzed asymmetric hydroboration of vinylarenes and internal alkenes are reported. Catalytic systems with both DTBM-SEGPHOS and SEGPHOS as the ligands have been investigated. With DTBM-SEGPHOS as the ligand, the resting state of the catalyst, which is also a catalytic intermediate, for hydroboration of 4-fluorostyrene is a phen­ethyl­copper­(I) complex ligated by the bisphosphine. This complex was fully characterized by NMR spectroscopy and X-ray crystallography. The turnover-limiting step in the catalytic cycle for the reaction of vinylarenes is the borylation of this phenethylcopper complex with pinacolborane (HBpin) to form the boronate ester product and a copper hydride. Experiments showed that the borylation occurs with retention of configuration at the benzylic position. β-Hydrogen elimination and insertion of the alkene to reform this phenethylcopper complex is reversible in the absence of HBpin but is irreversible during the catalytic process because reaction with HBpin is faster than β-hydrogen elimination of the phenethylcopper complex. Studies on the hydroboration of a representative internal alkene, <i>trans</i>-3-hexenyl 2,4,6-trichloro­benzoate, which undergoes enantio- and regioselective addition of HBpin catalyzed by DTBM-SEGPHOS, KO<i>t</i>Bu, and CuCl, also was conducted, and these studies revealed that a DTBM-SEGPHOS-ligated copper­(I) dihydridoborate complex is the resting state of the catalyst in this case. The turnover-limiting step in the catalytic cycle for hydroboration of the internal alkene is insertion of the alkene into a copper­(I) hydride formed by reversible dissociation of HBpin from the copper dihydridoborate species. With SEGPHOS as the ligand, a dimeric copper hydride was observed as the dominant species during the hydroboration of 4-fluorostyrene, and this complex is not catalytically competent. DFT calculations provide a view into the origins of regio- and enantioselectivity of the catalytic process and indicate that the charge on the copper-bound carbon and delocalization of charge onto the aryl ring control the rate of the alkene insertion and the regioselectivity of the catalytic reactions of vinylarenes

A C–H Borylation Approach to Suzuki–Miyaura Coupling of Typically Unstable 2–Heteroaryl and Polyfluorophenyl Boronates

A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C–H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used <i>in situ</i>. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids

Iridium-Catalyzed Enantioselective Allylic Substitution of Enol Silanes from Vinylogous Esters and Amides

The enol silanes of vinylogous esters and amides are classic dienes for Diels–Alder reactions. Here, we report their reactivity as nucleophiles in Ir-catalyzed, enantioselective allylic substitution reactions. A variety of allylic carbonates react with these nucleophiles to give allylated products in good yields with high enantioselectivities and excellent branched-to-linear ratios. These reactions occur with KF or alkoxide as the additive, but mechanistic studies suggest that these additives do not activate the enol silanes. Instead, they serve as bases to promote the cyclometalation to generate the active Ir catalyst. The carbonate anion, which was generated from the oxidative addition of the allylic carbonate, likely activates the enol silanes to trigger their activity as nucleophiles for reactions with the allyliridium electrophile. The synthetic utility of this method was illustrated by the synthesis of the <i>anti</i>-muscarinic drug, fesoterodine

Iridium-Catalyzed C–H Borylation of Cyclopropanes

The borylation of cyclopropanes catalyzed by the combination of (η⁶-mes)­IrBpin₃ or [Ir­(COD)­OMe]₂ and a phenanthroline derivative is reported. The borylation occurs selectively at the methylene C–H bonds of the cyclopropane ring over methine or methyl C–H bonds. High diasteroselectivities were observed from reactions catalyzed by the combination of iridium and 2,9-Me₂phenanthroline. The cyclopropylboronate esters that are generated are versatile synthetic intermediates that can be converted to trifluoroborate salts, boronic acids, cyclopropylarenes, cyclopropylamines, and cyclopropanols

Ir-Catalyzed Enantioselective, Intramolecular Silylation of Methyl C–H Bonds

We report highly enantio­selective intramolecular, silylations of unactivated, primary C­(sp³)–H bonds. The reactions form dihydro­benzo­siloles in high yields with excellent enantio­selectivities by functionalization of enantio­topic methyl groups under mild conditions. The reaction is catalyzed by an iridium complex generated from [Ir­(COD)­OMe]₂ and chiral dinitrogen ligands that we recently disclosed. The C–Si bonds in the enantio­enriched dihydro­benzo­siloles were further transformed to C–Cl, C–Br, C–I, and C–O bonds in final products. The potential of this reaction was illustrated by sequential C­(sp³)–H and C­(sp²)–H silylations and functionalizations, as well as diastereo­selective C–H silylations of a chiral, natural-product derivative containing multiple types of C–H bonds. Preliminary mechanistic studies suggest that C–H cleavage is the rate-determining step

Mechanistic Studies on Rhodium-Catalyzed Enantioselective Silylation of Aryl C–H Bonds

Several classes of enantioselective silylations of C–H bonds have been reported recently, but little mechanistic data on these processes are available. We report mechanistic studies on the rhodium-catalyzed, enantioselective silylation of aryl C–H bonds. A rhodium silyl dihydride and a rhodium norbornyl complex were prepared and determined to be interconverting catalyst resting states. Kinetic isotope effects indicated that the C–H bond cleavage step is not rate-determining, but the C–H bond cleavage and C–Si bond-forming steps together influence the enantioselectivity. DFT calculations indicate that the enantioselectivity originates from unfavorable steric interactions between the substrate and the ligand in the transition state leading to the formation of the minor enantiomer