Reactivity of Frustrated Lewis Pair: Carbocation versus Radical Intermediates.

Recent reports of radical formation within frustrated Lewis pairs (FLPs) suggested that single-electron transfer (SET) could play an important role in their chemistry especially for C-C coupling. In sharp contrast, our extensive dispersion-corrected DFT calculations show that although reactive benzhydryl radical along with phosphine radical cation species can be kinetically generated from bulky phosphines and benzhydryl cation, direct P-C hetero-coupling may lead to bulky phosphonium cation as reactive carbocation transfer reagents to styrene substrates, which is kinetically much more favorable than the recently proposed radical C-C coupling between benzhydryl radical and styrene. Similarly, meta-stable radical cation Mes3 P+ ⋅ salt is also kinetically accessible via SET reactions of Mes3 P and B(C6 F5 )3 with 0.5 equivalent of p-O2 C6 Cl4 .

Fluorination/Dearomatization of C6F5 Groups: An FLP Route to an Electrophilic Borane and Non-Coordinating Anions.

B(C6F5)3 and the corresponding anion [B(C6F5)4]- are ubiquitous in main group and transition metal chemistry. Known derivatives are generally limited to the incorporation of electron donating substituents. Herein we describe electrophilic fluorination and dearomatization of such species using XeF2 in the presence of BF3 or Lewis acidic cations. In this fashion the anions [HB(C6F5)3]-, [B(C6F5)4]- and [(C6F5)3BC≡NB(C6F5)3]-, are converted to [FB(C6F7)3]-, [B(C6F7)4]-, and [(C6F7)3BC≡NB(C6F7)3]-, respectively. Similarly, the borane adducts (L)B(C6F7)3 (L=MeCN, OPEt3) are produced. These rare examples of electrophilic attack of electron deficient rings proceed as [XeF][BF4] acts as a frustrated Lewis pair effecting fluorination and dearomatization of C6F5 rings.

AlCl3-Promoted Intramolecular Indolinone-Quinolone Rearrangement of Spiro[indoline-3,2'-quinoxaline]-2,3'-diones: Easy Access to Quinolino[3,4-b]quinoxalin-6-ones.

A facile and direct intramolecular indolinone-quinolone rearrangement was developed for the synthesis of quinolino[3,4-b]quinoxalin-6-ones from spiro[indoline-3,2'-quinoxaline]-2,3'-diones, which are readily available with use of isatines, malononitrile, and 1,2-phenylenediamines under quite mild conditions. This efficient approach provides excellent yields and could potentially be used for the construction of a diverse library of quinolino[3,4-b]quinoxalin-6-ones for high-throughput screening in medicinal chemistry. The reaction mechanism is explored by extensive DFT calculations.

Stereoconvergent Approach to the Enantioselective Construction of α-Quaternary Alcohols by Radical Epoxide Allylation.

We describe a highly stereoconvergent radical epoxide allylation towards diastereomerically and enantiomerically enriched α-quaternary alcohols in two steps from olefins. Our approach combines the stereospecifity and enantioselectivity of the Shi epoxidation with the unprecedented Ti(III)-promoted intramolecular radical group transfer allylation of epoxides. A directional isomerization step via configurationally labile radical intermediates enables the selective preparation of all-carbon quaternary stereocenters in a unique fashion.

Diazene Chemistry: Metal-Free Models of N2 Reduction Intermediates.

Interest in main group chemistry related to the Haber-Bosch process has drawn less attention than that of transition metal species. Herein, we show that the steric demands in (tBuO2CN)2 block initial interaction of B(C6F5)3 with nitrogen and prompt loss of methylpropene and CO2 to diazene (N2H2) borane adduct 1 and the analogous hydrazine (N2H4) adduct 2. These species react with basic phosphines to give anions of 3 and 5 containing N2H and N2H3 fragments, respectively. While these species are not derived directly from N2, they represent metal-free species containing N2Hn (n = 1-4) fragments, which model plausible intermediates in the reduction of N2.

Calcium Hydride Cation Dimer Catalyzed Hydrogenation of Unactivated 1-Alkenes and H2 Isotope Exchange: Competitive Ca-H-Ca Bridges and Terminal Ca-H Bonds.

Recently, it was shown that the double Ca-H-Ca bridged calcium hydride cation dimer complex [LCaH2 CaL]2+ (macrocyclic ligand L=NNNN-tetradentate Me4 TACD) exhibited remarkable activity in catalyzing the hydrogenation of unactivated 1-alkenes as well as the H2 isotope exchange under mild conditions, tentatively via the terminal Ca-H bond of cation monomer LCaH+ . In this DFT mechanistic work, a novel substrate-dependent catalytic mechanism is disclosed involving cooperative Ca-H-Ca bridges for H2 isotope exchange, competitive Ca-H-Ca bridges and terminal Ca-H bonds for anti-Markovnikov addition of unactivated 1-alkenes, and terminal Ca-H bonds for Markovnikov addition of conjugation-activated styrene. THF-coordination plays a key role in favoring the anti-Markovnikov addition while strong cation-π interactions direct the Markovnikov addition to terminal Ca-H bonds.

Photoredox Catalyzed Single C-F Bond Activation of Trifluoromethyl Ketones: A Solvent Controlled Divergent Access of gem-Difluoromethylene Containing Scaffolds.

Selective defluorinative functionalization of trifluoromethyl ketones is a long-standing challenge owing to the exhaustive mode of the process. To meet the demands for the installation of the gem-difluoromethylene unit for the construction of the molecular architectures of well-known pharmaceuticals and agrochemicals, a distinct pathway is thereby highly desirable. Here, a protocol is introduced that allows the divergent synthesis of gem-difluoromethylene group containing tetrahydrofuran derivatives and linear ketones via single C-F bond activation of trifluoromethyl ketones using visible-light photoredox catalysis in the presence of suitable olefins as trapping partner. The choice of appropriate solvent and catalyst plays a significant role in controlling the divergent behavior of this protocol. Highly reducing photo-excited catalysts are found to be responsible for the generation of α,α-difluoromethyl ketone (DFMK) radicals as the key intermediate via a SET process. This protocol also results in a high diastereoselectivity towards the formation of partially fluorinated cyclic ketal derivatives with simultaneous construction of one C-C and two C-O bonds. State-of-the-art DFT calculations are performed to address the origin of diastereoselectivity as well as the divergence of this protocol.

PI and PIII Ions Supported by BZIMPY Ligands.

We report a class of compounds in which both PIII -X and PI forms featuring the same ligand are stable and readily cycled with each other. A series of PIII -X (X=Cl, Br, I) dicationic triflate salts supported by benzyl- and allyl-substituted 2,6-bis(benzimidazole-2-yl)pyridine (BZIMPY) ligands is synthesized. Surprisingly, treatment of these with R3 PO (R=Et, Oct) results in reduction to BZIMPY-ligated PI monocationic triflate salts while treatment with Ph3 P reduces but also substitutes the compound to produce Ph3 P-BZIMPY-ligated PI dicationic triflate salts. The mechanisms of these surprising reductions are probed experimentally and rationalized computationally. The PIII -X dications are shown to be strong Lewis acids both experimentally and computationally and to readily behave as X+ , PX, and P+ transfer agents in reactions with phosphines, NHCs, and diazabutadienes. The PI mono- and dications are shown to be very effective P+ transfer agents when treated similarly. Oxidation from a monocationic PI salt back to the dicationic PIII -X (X=Cl, Br) salt was achieved by treatment with N-chlorosuccinimide (NCS) or N-bromosuccinimide (NBS). Full characterization is reported using multinuclear nuclear magnetic resonance spectroscopy, elemental analysis, and single-crystal X-ray diffractometry where suitable crystals were isolated.

Divergent Synthesis of 3-(Indol-2-yl)quinoxalin-2-ones and 4-(Benzimidazol-2-yl)-3-methyl(aryl)cinnolines via Polyphosphoric Acid (PPA)-Mediated Intramolecular Rearrangements of 3-(Methyl/aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones.

Herein, we report a polyphosphoric acid (PPA)-mediated divergent metal-free operation to access a diverse collection of 3-(indol-2-yl)quinoxalin-2-ones and 4-(benzimidazol-2-yl)-3-methylcinnolines in moderate to excellent overall yields. The described process involves two distinct, and competing rearrangements of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, namely [3,3]-sigmatropic Fischer rearrangement with the formation of an indole ring to produce 3-(indol-2-yl)-quinoxalin-2-ones, and Mamedov rearrangement with simultaneous construction of benzimidazole and cinnoline rings to form the new biheterocyclic system─4-(benzimidazol-2-yl)-3-methylcinnolines. The reaction mechanism of both rearrangement channels is explored by extensive dispersion-corrected DFT calculations. It is partcularly remarkable that when 3-(aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones is used, instead of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, reactions proceed regioselectively with the formation of only rearrangement products─4-(benzimidazol-2-yl)-3-arylcinnolines with high yields. This operationally simple protocol enables a rapid access to these scaffolds and is compatible with a wide scope of starting materials. In addition, the new rearrangement found features a promising approach for the design of unique compound libraries for drug design and discovery programs.

Phosphino-Phosphination Reactions: Frustrated Lewis Pair Reactivity of Phosphino-Phosphonium Cations with Alkynes.

The phosphino-phosphonium cations of the form [R3 PPR'2 ]+ are labile and provide access to the constituent Lewis acidic and Lewis basic fragments. This permits frustrated Lewis pair-type addition reactions to alkynes, affording unprecedented phosphino-phosphination reactions and giving cations of the form [cis-R3 PCHC(R'')PR'2 ]+ . This reactivity is further adapted to prepare several examples of a rare class of dissymmetric cis-olefin-linked bidentate phosphines.

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.

A Nuclearity-Dependent Enantiodivergent Epoxide Opening via Enthalpy-Controlled Mononuclear and Entropy-Controlled Dinuclear (Salen)Titanium Catalysis.

A nuclearity-dependent enantiodivergent epoxide opening reaction has been developed, in which both antipodes of chiral alcohol products are selectively accessed by mononuclear (salen)TiIII complex and its self-assembled oxygen-bridged dinuclear counterparts within the same stereogenic ligand scaffold. Kinetic studies based on the Eyring equation revealed an enthalpy-controlled enantio-differentiation mode in mononuclear catalysis, whereas an entropy-controlled one in dinuclear catalysis. DFT calculations outline the origin of the enantiocontrol of the mononuclear catalysis and indicate the actual catalyst species in the dinuclear catalytic system. The mechanistic insights may shed a light on a strategy for stereoswichable asymmetric catalysis utilizing nuclearity-distinct transition-metal complexes.

Reactions of Diethylazo-Dicarboxylate with Frustrated Lewis Pairs.

Reactions of PAr3 /B(C6 F5 )3 (Ar=o-Tol, Mes, Ph) FLPs with diethyl azodicarboxylate (DEAD) afford the corresponding FLP addition products 1-3 in which P-N and B-O linkages are formed. In contrast, the reaction of BPh3 , PPh3 and DEAD gave product 4 where P-N and N-B linkages were confirmed. In all cases, other binding modes were computed to be both higher in energy and readily distinguishable by 31 P and 11 B NMR parameters. These data illustrate the influence of steric demands and electronic structures on the nature of the products of FLP reactions with DEAD.

The Non-Ancillary Nature of Trimethylsilylamide Substituents in Boranes and Borinium Cations.

The known boranes (R(Me3 Si)N)2 BF (R=Me3 Si 1, tBu 2, C6 F5 3, o-tol 4, Mes 5, Dipp 6) and borinium salts (R(Me3 Si)N)2 B][B(C6 F5 )4 ] (R=Me3 Si 7, tBu 8) are prepared and fully characterized. Compound 7 is shown to react with phosphines to generate [R3 PSiMe3 ]+ and [R3 PH]+ (R=Me, tBu). Efforts to generate related borinium cations via fluoride abstraction from (R(Me3 Si)N)2 BF (R=C6 F5 3, o-tol 4, Mes 5) gave complex mixtures suggesting multiple reaction pathways. However for R=Dipp 6, the species [(µ-F)(SiMe2 N(Dipp))2 BMe][B(C6 F5 )4 ] was isolated as the major product, indicating methyl abstraction from silicon and F/Me exchange on boron. These observations together with state-of-the-art DFT mechanistic studies reveal that the trimethylsilyl-substituents do not behave as ancillary subsitutents but rather act as sources of proton, SiMe3 and methyl groups.

The Varied Frustrated Lewis Pair Reactivity of the Germylene Phosphaketene (CH{(CMe)(2,6-i Pr2 C6 H3 N)}2 )GePCO.

The germylene species (CH{(CMe)(2,6-iPr2 C6 H3 N)}2 )GePCO 1 is shown to react with the Lewis acids (E(C6 F5 )3 E=B, Al). Nonetheless, 1 participates in FLP chemistry with electron deficient alkynes or olefins, acting as an intramolecular FLP. In contrast, in the presence of B(C6 F5 )3 and an electron rich alkyne, 1 behaves as Ge-based nucleophile to effect intermolecular FLP addition to the alkyne. This reactivity demonstrates that the reaction pathway is controlled by the nature of the electrophile and nucleophile generated in solution, as revealed by extensive DFT calculations.

Catalyst-free CO2 hydrogenation with BH3NH3 in water: DFT mechanistic insights.

Extensive DFT calculations show that BH3NH3 may transfer dihydrogen as separated hydride and proton to CO2 rather than HCO3- in water over a barrier of 25.9 kcal mol-1, followed by faster hydride transfer from borate anions to either electrophilic CO2 or protic H2O or HCO2H, leading to competitive formate production and H2 release.

Intermolecular Carbosilylation of α-Olefins with C(sp3 )-C(sp) Bond Formation Involving Silylium-Ion Regeneration.

A regioselective addition of alkynylsilanes across unactivated, terminal alkenes is reported. The reaction is initiated by the capture of a sterically unhindered silylium ion by a silylated phenylacetylene derivative to form a bis(silylated) ketene-like carbocation. This in situ-generated key intermediate is the actual catalyst that maintains the catalytic cycle by a series of electrophilic addition reactions of silylium ions and ß-silicon-stabilized carbocations. The computed reaction mechanism is fully consistent with the experimental findings. This unprecedented two-component carbosilylation establishes a C(sp3 )-C(sp) bond and a C(sp3 )-Si bond in atom-economic fashion.

HFIP-Assisted Single C-F Bond Activation of Trifluoromethyl Ketones using Visible-Light Photoredox Catalysis.

A visible light photoredox catalytic method for the selective cleavage of single strong C-F bond in trifluoromethyl ketones is reported. Single electron reduction of trifluoromethyl ketones generates difluoromethyl radicals which can be engaged in intermolecular C-C bond formation with N-methyl-N-arylmethacrylamides to furnish fluorine-containing oxindole derivatives in good yields. The reaction shows excellent chemoselectivity with good functional group tolerance under mild conditions. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) as a solvent plays a critical role for the selective single C-F bond cleavage. High-level DFT calculations are depicted to shed light on the mechanism.

Reactions of Frustrated Lewis Pairs with Chloro-Diazirines: Cleavage of N=N Double Bonds.

The reactions of FLPs with diazomethanes leads to the rapid loss of N2 . In contrast, in this work, we reported reactions of phosphine/borane FLPs with chlorodiazirines which led to the reduction of the N=N double bond, affording linked phosphinimide/amidoborate zwitterions of the general form R3 PNC(Ar)NR'BX(C6 F5 )2 . A detailed DFT mechanistic study showed that these reactions proceed via FLP addition to the N=N bond, followed by subsequent group transfer reactions to nitrogen and capture of the halide anion.

Lithium Dicyclohexylamide in Transition-Metal-Free Fischer-Tropsch Chemistry.

Lithium dicyclohexylamide (Cy2NLi) reacts with syn-gas or CO to generate transient intermediates with carbene character, which are capable of reacting further with CO or H2, effecting sequential C-C and C-H bond formations from CO or H2, thus providing a transition-metal-free avenue to the fundamental reactions of the Fischer-Tropsch process. Further experimental and computational data indicate that reactions with CO and H2 are thermodynamically accessible, with a kinetic bias toward CO homologation.