Hendrik F. T. Klare

Cooperative Catalytic Activation of Si―H Bonds by a Polar Ru―S Bond: Regioselective Low-Temperature C—H Silylation of Indoles under Neutral Conditions by a Friedel—Crafts Mechanism

Merging cooperative Si-H bond activation and electrophilic aromatic substitution paves the way for C-3-selective indole C-H functionalization under electronic and not conventional steric control. The Si-H bond is heterolytically split by the Ru-S bond of a coordinatively unsaturated cationic ruthenium(II) complex, forming a sulfur-stabilized silicon electrophile. The Wheland intermediate of the subsequent Friedel-Crafts-type process is assumed to be deprotonated by the sulfur atom, no added base required. The overall catalysis proceeds without solvent at low temperature, only liberating dihydrogen.

C(sp3)-F bond activation of CF3-substituted anilines with catalytically generated silicon cations: spectroscopic evidence for a hydride-bridged Ru-S dimer in the catalytic cycle.

Heterolytic splitting of the Si-H bond mediated by a Ru-S bond forms a sulfur-stabilized silicon cation that is sufficiently electrophilic to abstract fluoride from CF(3) groups attached to selected anilines. The ability of the Ru-H complex, generated in the cooperative activation step, to intramolecularly transfer its hydride to the intermediate carbenium ion (stabilized in the form of a cationic thioether complex) is markedly dependent on the electronic nature of its phosphine ligand. An electron-deficient phosphine thwarts the reduction step but, based on the Ru-S catalyst, half of an equivalent of an added alkoxide not only facilitates but also accelerates the catalysis. The intriguing effect is rationalized by the formation of a hydride-bridged Ru-S dimer that was detected by (1)H NMR spectroscopy. A refined catalytic cycle is proposed.

Catalytic dehydrogenative Si–N coupling of pyrroles, indoles, carbazoles as well as anilines with hydrosilanes without added base

A base-free, catalytic protocol for the dehydrogenative Si-N coupling of weakly nucleophilic N-H groups of heteroarenes or aryl-substituted amines with equimolar amounts of hydrosilanes is reported. Cooperative Si-H bond activation at a Ru-S bond generates a silicon electrophile that forms a Si-N bond prior to the N-H deprotonation by an intermediate Ru-H complex, only releasing H(2).

Catalytic 1,4-Selective Hydrosilylation of Pyridines and Benzannulated Congeners†

Radically different! The hydrosilylation of pyridines and quinolines is strictly 1,4-selective and likely involves an ionic one-step rather than the established radical two-step hydride transfer from a ruthenium(II) hydride complex onto the respective pyridinium and quinolinium ion intermediates (see scheme; Ar(F) =3,5-(CF3)2C6H3). Even 4-substituted substrates react highly regioselectively. Isoquinolines yield the 1,2-reduced heterocycles.

Base-Free Dehydrogenative Coupling of Enolizable Carbonyl Compounds with Silanes

A dehydrogenative coupling between enolizable carbonyl compounds and equimolar amounts of triorganosilanes catalyzed by a tethered ruthenium complex with a Ru-S bond is reported. The complex is assumed to fulfill a dual role by activating the Si-H bond to release a silicon electrophile and by abstracting an α-proton from the intermediate silylcarboxonium ion, only liberating dihydrogen as the sole byproduct. Reaction rates are exceedingly high at room temperature with very low loadings of the ruthenium catalyst.

Insight into the mechanism of carbonyl hydrosilylation catalyzed by Brookhart's cationic iridium(III) pincer complex.

New experimental findings suggest partial revision of the currently accepted mechanism of the carbonyl hydrosilylation catalyzed by the iridium(III) pincer complex introduced by Brookhart. Employing silicon-stereogenic silanes as a stereochemical probe results in racemization rather than inversion of the configuration at the silicon atom. The degree of the racemization is, however, affected by the silane/carbonyl compound ratio, and inversion is seen with excess silane. Independently preparing the silylcarboxonium ion intermediate and testing its reactivity then helped to rationalize that effect. The stereochemical analysis together with these control experiments, rigorous multinuclear NMR analysis, and quantum-chemical calculations clearly prove that another silane molecule participates in the hydride transfer. The activating role of the silane is unexpected but, in fact, vital for the catalytic cycle to close.

Brønsted Acid-Promoted Formation of Stabilized Silylium Ions for Catalytic Friedel–Crafts C–H Silylation

A counterintuitive approach to electrophilic aromatic substitution with silicon electrophiles is disclosed. A strong Brønsted acid that would usually promote the reverse reaction, i.e., protodesilylation, was found to initiate the C-H silylation of electron-rich (hetero)arenes with hydrosilanes. Protonation of the hydrosilane followed by liberation of dihydrogen is key to success, fulfilling two purposes: to generate the stabilized silylium ion and to remove the proton released from the Wheland intermediate.

Friedel-Crafts-Type Intermolecular C-H Silylation of Electron-Rich Arenes Initiated by Base-Metal Salts.

An electrophilic aromatic substitution (SE Ar) with a catalytically generated silicon electrophile is reported. Essentially any commercially available base-metal salt acts as an initiator/catalyst when activated with NaBAr(F)4. The thus-generated Lewis acid then promotes the SE Ar of electron-rich arenes with hydrosilanes but not halosilanes. This new C-H silylation was optimized for FeCl2/NaBAr(F)4, affording good yields at catalyst loadings as low as 0.5 mol %. The procedure is exceedingly straightforward and comes close to typical Friedel-Crafts methods, where no added base is needed to absorb the released protons.

Direct Catalytic Access to N‐Silylated Enamines from Enolizable Imines and Hydrosilanes by Base‐Free Dehydrogenative SiN Coupling

A procedure for the synthesis of otherwise difficult-to-make N-silylated enamines, that is masked enamines derived from primary amines, is reported. The approach is based on formation of a silyliminium ion and subsequent abstraction of the acidified α-proton rather than α-deprotonation of the enolizable imine followed by reaction with an electrophilic silicon reagent. The silicon electrophile, stabilized by a sulfur atom, is generated by cooperative activation of an Si-H bond at the Ru-S bond of a tethered ruthenium(II) thiolate complex. After transfer of the silicon cation onto the imine nitrogen atom, the remaining ruthenium(II) hydride fulfills the role of the base. Deprotonation and release of dihydrogen close the catalytic cycle. The net reaction is a dehydrogenative Si-N coupling of enolizable imines and hydrosilanes.

Asymmetric Ring‐Closing Metathesis with a Twist

A double flip! The catalyst shown, with a molybdenum stereocenter and monodentate ligands (Si = SitBuMe(2)), promotes asymmetric ring-closing metathesis of a broad range of substrates. Its unprecedented activity originates from its structural fluxionality, which enables double inversion at the metal center in the course of a single catalytic cycle. The catalyst passed the test in a metathesis reaction en route to (+)-quebrachamine (see scheme).