Ring Contraction of Saturated Cyclic Amines and Rearrangement of Acyclic Amines Through Their Corresponding Hydroxylamines.

Compared to modifications at the molecular periphery, skeletal adjustments present greater challenges. Within this context, skeletal rearrangement technology stands out for its significant advantages in rapidly achieving structural diversity. Yet, the development of this technology for ring contraction of saturated cyclic amines remains exceedingly rare. While most existing methods rely on specific substitution patterns to achieve ring contraction, there is a persistent demand for a more general strategy for substitution-free cyclic amines. To address this issue, we report a B(C6F5)3-catalyzed skeletal rearrangement of hydroxylamines with hydrosilanes. This methodology, when combined with the N-hydroxylation of amines, enables the regioselective ring contraction of cyclic amines and proves equally effective for rapid reorganization of acyclic amine skeletons. By this, the direct scaffold hopping of drug molecules and the strategic deletion of carbon atoms are achieved in a mild manner. Based on mechanistic experiments and density functional theory calculations, a possible mechanism for this process is proposed.

Cationic Bis(hydrosilane)-Coinage Metal Complexes: Synthesis, Characterization, and Use as Catalysts for Outer-Sphere C=O Hydrosilylation Not Involving Metal Hydrides.

The preparation of cationic bis(hydrosilane)-coinage-metal complexes by chloride abstraction from the neutral metal chloride precursors with Na[BArF4] is described. Unlike previously reported hydrosilane-stabilized copper and silver complexes, the presented complexes are cationic and feature two bidentate ortho-(silylphenyl)phosphine ligands. These complexes were fully characterized by NMR spectroscopy and X-ray diffraction analysis, revealing that both Si-H bonds are activated by the Lewis acidic cationic metal center. The new complexes were found to be effective in catalytic carbonyl hydrosilylation, leading to the corresponding silyl ethers under mild conditions without the addition of an external base. Combined mechanistic control experiments and quantum chemical calculations support an ionic outer-sphere mechanism, in which a neutral metal alkoxide species instead of a metal hydride is the key intermediate that interacts with the silylcarboxonium ion to generate the silyl ether.

Enantioselective Dearomatization of Pyridinium Salts by Copper-Catalyzed C4-Selective Addition of Silicon Nucleophiles.

A copper-catalyzed C4-selective addition of silicon nucleophiles released from an Si-B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)-Ph-BPE (1,2-bis[(2R,5R)-2,5-diphenylphospholan-1-yl]ethane) as the chiral ligand. A carbonyl group at C3 is required for this, likely acting a weak donor group to preorganize and direct the nucleophilic attack towards C4. The resulting 4-silylated 1,4-dihydropyridines can be further converted into functionalized piperidine derivatives.

Copper-catalyzed silylation of aryl and alkenyl triflates with silylboronic esters avoiding base-mediated borylation.

Silylation of aryl and alkenyl triflates is found to occur readily with silylboronic esters as a silicon source under copper catalysis. The silyl moieties are exclusively installed into the organic frameworks through the preferential generation of a silylcopper species, wherein base-mediated direct borylation is totally suppressed. The combined use of tri-n-butylphosphine and 4,4'-diphenyl-2,2'-bipyridine as a ligand combination turned out to be indispensable for achieving the high catalytic activity.

Electrophilic Activation of S-Si Reagents by Silylium Ions for Their Regio- and Diastereoselective Addition Across C-C Multiple Bonds.

A regioselective silylium-ion-promoted thiosilylation of internal C-C triple bonds with control over the double bond geometry is described. Both a C(sp2)-S and a C(sp2)-Si bond are formed with a trans relationship in this two-component reaction of an alkyne and a thiosilane. The resulting orthogonally functionalized C-C double bond can be chemoselectively defunctionalized or further processed by cross-coupling reactions with the alkene configuration retained. The procedure is also applicable to the regio- and diastereoselective thiosilylation of terminal allenes to arrive at allylic thioethers containing a vinylsilane unit. These reactions involve the electrophilic activation of the S-Si reagent, both a silylated thiophenol and even alkylthiol derivative, by an in situ-generated carbocation intermediate. The catalytic cycle is maintained by a bissilylated aryl- or alkylsulfonium ion as a shuttle for the cationic silicon electrophile. Its independent preparation and structural characterization by X-ray diffraction are also reported.

Ligand-Controlled On-Off Switch of a Silicon-Tethered Directing Group Enabling the Regiodivergent Hydroalkylation of Vinylsilanes under Ni-H Catalysis.

A regiodivergent Ni-H-catalyzed hydroalkylation of vinylsilanes is described. Depending on the ancillary ligand at the nickel catalyst, the regioselectivity can be steered by a directing group attached to the silicon atom. The mild protocols allow for the selective synthesis of either branched or linear alkylsilanes. An example of a vinylgermane is also reported. The method features a broad scope with high functional-group tolerance and follows a radical mechanism.

Chiral Carborane Acids Decorated with Binol-Based Phosphonates: Synthesis, Characterization, and Application.

The syntheses of hexabrominated closo-carborates decorated with different chiral Binol-derived phosphonates and their conjugate acids are described. X-ray diffraction analysis reveals a polymeric structure for the sodium salt with the anionic units connected by [B-Br-Na-O═P]+ linkages. For the acid, coordination of the proton to the phosphonate's P═O oxygen atom is assumed. The pKa value was estimated by combining experiments and computations. Application of these Brønsted acids as chiral catalysts in an imino-ene and a Mukaiyama-Mannich reaction was moderately successful.

Bond-Forming Processes Enabled by Silicon-Masked Aryl- and Alkyl-Substituted Diazenes.

Aryl- and alkyldiimides (R-N═NH with R = aryl or alkyl) are elusive intermediates of valuable synthetic use, as they are assumed to be transient species in processes involving both carbon (with concomitant loss of N2) and nitrogen nucleophiles (with conservation of the N═N moiety). The actual compounds are fragile and as such not bench stable which is why they have not yet found the attention they deserve. Conversely, early contributions showed that the stability of the parent diimide is significantly increased by replacing the hydrogen atom by a silyl group, but the synthetic applicability of these silicon-protected aryl- and alkyldiazenes has been far less explored, in part due to the absence of general procedures for their preparation. This Perspective provides an overview of the underexplored diazene chemistry that has witnessed considerable progress in recent years and highlights the potential of this motif in a range of synthetically useful (catalytic) transformations. The rediscovered silicon-masked diazenes constitute a versatile platform possessing enhanced stability and tamed reactivity in comparison to the parent hydrogen-substituted diimides. Aryl, diazenyl, and alkyl anionic key intermediates can be selectively generated in situ under Lewis base or transition metal catalysis, giving rise to novel synthetic approaches as viable alternatives to the already existing methodologies.

Arenium-ion-catalysed halodealkylation of fully alkylated silanes.

'Organic silicon' is not found in nature but modern chemistry is hard to imagine without silicon bound to carbon. Although silicon-containing commodity chemicals such as those emerging from the 'direct process'1-4 look simple, it is not trivial to selectively prepare aryl-substituted and alkyl-substituted (functionalized) silicon compounds, known as silanes. Chlorosilanes such as Me4-nSiCln (n = 1-3) as well as SiCl4 (n = 4) are common starting points for the synthesis of silicon-containing molecules. Yet these methods often suffer from challenging separation problems5. Conversely, silanes with four alkyl groups are considered synthetic dead ends. Here we introduce an arenium-ion-catalysed halodealkylation that effectively converts Me4Si and related quaternary silanes into a diverse range of functionalized derivatives. The reaction uses an alkyl halide and an arene (co)solvent: the alkyl halide is the halide source that eventually engages in a Friedel-Crafts alkylation with the arene to regenerate the catalyst6, whereas the arenium ion acts as a strong Brønsted acid for the protodealkylation step7. The advantage of the top-down halodealkylation methodology over reported bottom-up procedures is demonstrated, for example, in the synthesis of a silicon drug precursor. Moreover, chemoselective chlorodemethylation of the rather inert Me3Si group attached to an alkyl chain followed by oxidative degradation is shown to be an entry into Tamao-Fleming-type alcohol formation8,9.

Dehydrative Coupling of 1,1-Diarylalkenes and Cyclohexa-2,5-diene-1-carbaldehyde Derivatives Induced by a B(C6F5)3-Initiated [1,2]-Alkyl Migration.

A four-step formal ipso allylation of benzoic acid derivatives involving a B(C6F5)3-initiated and proton-catalyzed [1,2]-alkyl shift as part of a dehydrative coupling of cyclohexa-2,5-diene-1-carbaldehyde derivatives and 1,1-diarylalkenes is reported. By this, a series of allyl arenes can be regioselectively obtained from readily available benzoic acids in good yields.

Fluoride-Catalyzed Arylation of α-(Trifluoromethyl)styrene Derivatives with Silicon-Masked, Functionalized Aryl Pronucleophiles.

An operationally simple transition-metal-free protocol for the arylation of α-(trifluoromethyl)styrene derivatives with silicon-protected functionalized aryl pronucleophiles is disclosed. Catalytic amounts of an anionic Lewis base such as fluoride trigger the release of the aryl nucleophile from N-aryl-N'-silyldiazenes by desilylation along with denitrogenation. The thus-generated carbon nucleophiles engage in an allylic displacement with α-(trifluoromethyl)styrene electrophiles to afford the corresponding geminal difluoroalkenes.

Regioselective Hydroalkylation of Vinyl- and Allylsilanes as Well as Vinylgermanes under Ni-H Catalysis.

A Ni-H-catalyzed hydroalkylation of vinylsilanes and -germanes as well as allylsilanes with unactivated alkyl iodides is reported. Unlike related reactions of styrene or vinyl boronate esters, the addition across the C-C double bond proceeds with anti-Markovnikov selectivity to deliver the linear regioisomer. Mechanistic control experiments support a radical mechanism, and a competition experiment reveals that the chemoselectivity is in favor of the vinyl over the allyl group.

Atom-economic and stereoselective catalytic synthesis of fully substituted enol esters/carbonates of amides in acyclic systems enabled by boron Lewis acid catalysis.

Carboacyloxylation of internal alkynes is emerging as a powerful and straightforward strategy for enol ester synthesis. However, the reported examples come with limitations, including the utilization of noble metal catalysts, the control of regio- and Z/E selectivity, and an application in the synthesis of enol carbonates. Herein, a boron Lewis acid-catalyzed intermolecular carboacyloxylation of ynamides with esters to access fully substituted acyclic enol esters in high yield with generally high Z/E selectivity (up to >96 : 4) is reported. Most importantly, readily available allylic carbonates are also compatible with this difunctionalization reaction, representing an atom-economic, catalytic and stereoselective protocol for the construction of acyclic ß,ß-disubstituted enol carbonates of amides for the first time. The application of the carboacyloxylation products to decarboxylative allylations provided a ready access to enantioenriched α-quaternary amides. Moreover, experimental studies and theoretical calculations were performed to illustrate the reaction mechanism and rationalize the stereochemistry.

Discrimination of the Enantiotopic Faces of Structurally Unbiased Carbenium Ions Employing a Cyclohexadiene-Based Chiral Hydride Source.

An enantioselective reduction of simple carbenium ions with cyclohexadienes containing a hydridic C-H bond at an asymmetrically substituted carbon atom is disclosed. The net reaction is a transfer hydrogenation of alkenes (styrenes) only employing chiral cyclohexadienes as dihydrogen surrogates. The trityl cation is used to initiate a Brønsted acid-promoted process, in which a delicate intermolecular capture of a carbenium-ion intermediate by the aforementioned chiral hydride source is enantioselectivity determining. Exclusively non-covalent interactions are rendering one of the transition states energetically more favored, giving the reduction products in good enantiomeric ratios. The computed reaction mechanism supports the present findings as well as previous results obtained from studies on other transfer-hydrogenation methods involving the cyclohexadiene platform.

Atroposelective Silylation of 1,1'-Biaryl-2,6-diols by a Chiral Counteranion Directed Desymmetrization Enhanced by a Subsequent Kinetic Resolution.

A desymmetrizing silylation of aromatic diols is reported. The previously unknown asymmetric silyl ether formation of phenol derivatives is achieved by applying List's counteranion directed silylation technique. A silylium-ion-like silicon electrophile generated from an allylic silane paired with an imidodiphosphorimidate (IDPi) enables enantioselective discrimination of achiral 1,1'-biaryl-2,6-diols. The enantioselectivity of that desymmetrization is further improved by a downstream kinetic resolution, converting the monosilylated minor enantiomer into the corresponding, again achiral bissilylated diol.

Intramolecular 7-endo-dig-Selective Carbosilylation of Internal Alkynes Involving Silylium-Ion Regeneration.

A catalytic silylium-ion-promoted intramolecular alkyne carbosilylation reaction is reported. The ring closure is initiated by electrophilic activation of the C-C triple bond by a silylium ion, and the catalytic cycle is then maintained by the protodesilylation of a stoichiometrically added allylsilane reagent. Exclusive 7-endo-dig selectivity is seen, leading to a series of silylated benzocycloheptene derivatives with a fully substituted vinylsilane. Control experiments showed that the catalytically active silylium ion can also be regenerated by protodesilylation of the vinylsilane product.

Enantio- and Regioconvergent Synthesis of γ-Stereogenic Vinyl Germanes and Their Use as Masked Vinyl Halides.

A nickel-catalyzed enantio- and regioconvergent alkylation of regioisomeric mixtures of racemic germylated allylic electrophiles with alkyl nucleophiles is reported. Key to success is a newly developed hept-4-yl-substituted Pybox ligand that enables accessing various chiral γ-germyl α-alkyl allylic building blocks in excellent yields and enantioselectivities. The reason for the regioconvergence is the steering effect of the bulky germyl group. The resulting vinyl germanes can be easily halodegermylated without racemization of the allylic stereocenter to afford synthetically valuable γ-stereogenic vinyl halides.

Catalytically Generated Meerwein's Salt-Type Oxonium Ions for Friedel-Crafts C(sp2)-H Methylation with Methanol.

A catalytic protocol for a Friedel-Crafts-type direct C(sp2)-H methylation of various arenes with methanol is disclosed. The reaction is initiated by counteranion-stabilized silylium or arenium ions, which form Meerwein's salt-like oxonium ions with methanol as the active methylating agents. The silylated methyloxonium ions are stronger electrophiles than their protonated congeners, allowing the Friedel-Crafts alkylation to proceed more efficiently and at a lower reaction temperature. The regeneration of these superelectrophiles within the catalytic cycle is accomplished by the addition of a tetraorganosilane additive, i.e., trimethyl(phenyl)silane or tetraethylsilane, that releases a silylium ion through protodesilylation by the Brønsted acidic Wheland intermediate, thereby acting as a productive "proton-into-silylium ion" generator. By this method, even the C-H methylation of electronically deactivated aryl halides with methanol is achieved. The protocol is also applicable to nonactivated primary as well as π-activated benzylic alcohols. Dialkyl ethers are also competent alkylating agents in the presence of the quaternary phenylsilane additive.

The [3]Dendralene Motif as an Entry into Nazarov Cyclizations by Silylium-Ion Initiation.

Geminal alkenes bearing an aryl and an allenyl group contain the motif of [3]dendralenes. The central alkene double bond in these cross-conjugated polyenes can be reacted with a silylium ion, thereby initiating a Nazarov cyclization. The cationic intermediate emerging from the electrocyclic ring closure is captured by hydride in the presence of excess hydrosilane. The resulting benzannulated methylenecyclopentene derivatives bearing a silylalkyl group then engage in silylium-ion regeneration followed by an unusual endo-selective intramolecular hydrosilylation. This cascade eventually leads to the formation of a silicon-containing bicyclo[3.2.1]octane skeleton.

B(C6 F5 )3 -Catalyzed Regioselective Ring Opening of Cyclic Amines with Hydrosilanes.

Opening the ring of cyclic amines by regioselective fission of one of the carbon-nitrogen bonds greatly expands the repertoire of available nitrogen-containing skeletons. Unlike approaches starting from cyclic tertiary amines, methods that can directly open secondary amines are still scarce. The present work discloses an efficient reductive ring opening of either of these cyclic amines using PhSiH3 under B(C6 F5 )3 catalysis. By this, the direct transformation of unstrained cyclic amines into the corresponding acyclic amines is achieved in a simple one-pot operation. A stepwise mechanism proceeding through the intermediacy of silylammonium ions followed by reductive cleavage of a carbon-nitrogen bond was experimentally verified.