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.

Frustrated Lewis pair chemistry of CO.

Transition metal species readily capture and react with CO as the metal can act both as an acceptor and donor of electron density. In contrast, such a situation is less common in the main group and thus far fewer examples of main group CO adducts and their subsequent reactivity have been studied. In this review, we focus on the application of the concept of Frustrated Lewis Pairs (FLPs) to develop main group chemistry of CO. Specifically, we address reactions of FLPs that illustrate the ability to capture CO in addition to subsequent reactivity involving reduction with a variety of reagents. These developments illustrate that the donation and acceptance of electron density provided by FLPs is an alternative strategy to advance the reactivity of CO. Such insights augur well for future advances in the homogeneous chemistry of CO.

Synthesis and Reactivity of the [NCCCO]- Cyanoketenate Anion.

Cyanoketene is a fundamental molecule that is actively being searched for in the interstellar medium. Its deprotonated form (cyanoketenate) is a heterocumulene that is isoelectronic to carbon suboxide whose structure has been the subject of debate. However, the investigation of cyanoketene and its derivatives is hampered by the lack of practical synthetic routes to these compounds. We report the first synthesis of the cyanoketenate anion in [K(18-crown-6)][NCCCO] (1) as a stable molecule on a multigram scale in excellent yields (>90 %). The structure of this molecule is probed crystallographically and computationally. We also explore the protonation of 1, and its reaction with triphenylsilylchloride and carbon dioxide. In all cases, anionic dimers are formed. The cyanoketene could be synthesized and crystallographically characterized when stabilized by a N-heterocyclic carbene. The cyanoketenate is a very useful unsaturated building block containing N, C and O atoms that can now be explored with relative ease and will undoubtedly unlock more interesting reactivity.

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.

Alkoxyphosphorane/Borane Cooperative Alkylations: A Frustrated Lewis Pair Version of the Mitsunobu Reaction.

The combination of the alkoxyphosphoranes, Ph2 P(OR)(O2 C6 Cl4 ) and the borane B(C6 F5 )3 generates the zwitterions 3 which act as FLP to effect the alkylation of several nucleophiles affording C-C, C-N, C-H and C-Cl coupling products. A DFT study shows the reaction proceeds via an FLP activation pathway generating an alkoxyphosphonium intermediate which effects the alkylation of the nucleophiles, akin to the Mitsunobu reaction.

Borane catalyzed transesterification of tert-butyl esters using α-aryl α-diazoesters.

The B(C6F5)3-catalyzed transesterification of a series of 3-alkenyl-oxindoles and other unsaturated tert-butyl esters with aryl-diazo esters is reported. This protocol is facile and generally high yielding proceeding under mild conditions and is remarkably chemoselective leaving the CC bonds intact.

B(C6F5)3-catalyzed hydrogermylation of enones: a facile route to germacycles.

Organogermacycles are important skeletons for medicinal chemistry and materials. Herein, we reported a B(C6F5)3 mediated domino hydrogermylation reaction of enones with dihydrogermanes, affording 21 variants of organogermacycle compounds. These germacyclic compounds were obtained in good to excellent yields (up to 99% yield) under mild reaction conditions.

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.

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.

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 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.

Ambiphilic Behavior of Ge(II)-Pseudohalides in Inter- and Intramolecular Frustrated Lewis Pair Alkyne Addition Reactions.

The reaction of the germylene chloride (NacNac)GeCl (1, NacNac = CH{(CMe)(2,6-iPr2C6H3N)}2), phenylacetylene, and B(C6F5)3 gives the intermolecular frustrated Lewis pair (FLP) addition product 2. In this case, the Ge(II) center acts as a base. In contrast, the analogous reaction of germylene thiocyanate 3 reacts independently with B(C6F5)3 to give the germylene cation salt [(NacNac)Ge][SCNB(C6F5)3] 4. Subsequent in the presence of alkynes, the Ge(II) cation and γ-C of 4 act as a Lewis acidic and basic center, respectively, to affect the addition of alkynes, affording products [(NacNac)Ge(RCCR')][SCNB(C6F5)3] 5 and 6. Compound 4 also reacts with Me3SiCN to give the cyanide-bridged Ge/B species 7, which also reacts with phenylacetylene to give CN abstraction and intramolecular addition yielding the salt [(NacNac)Ge(PhCCH)][NCB(C6F5)3] 8. Despite the similarity of 1 and 3, DFT calculations show that the highest occupied molecular orbital (HOMO) of 1 is mainly located at the more sterically hindered germylene center, while the HOMO of 3 is located on the less sterically hindered NCS group, prompting markedly different FLP addition products.

Catalyst-dependent chemoselective insertion of diazoalkanes into the N-H/C-H/O-H/C-O bonds of 2-hydroxybenzothiazoles.

The control of chemoselective insertions of diazoalkanes into 2-hydroxybenzothiazoles is challenging. Herein, the chemoselective N-H, O-H, C-O or C-H bond insertions of diazoalkanes into 2-hydroxybenzothiazoles are achieved using B(C6F5)3, Rh2(OAc)4 or TfOH as the catalyst. This affords routes to 54 benzothiazole derivatives. These protocols are scalable and demonstrate the complementary nature of Lewis acid, transition metal and Brønsted acid catalyses.

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.

Diverse Uses of the Reaction of Frustrated Lewis Pair (FLP) with Hydrogen.

The articulation of the notion of "frustrated Lewis pairs" (FLPs) emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered main group Lewis acids and bases. This has prompted numerous studies focused on various perturbations of the Lewis acid/base combinations and the applications to organic reductions. This Perspective focuses on the new directions and developments that are emerging from this FLP chemistry involving hydrogen. Three areas are discussed including new applications and approaches to FLP reductions, the reductions of small molecules, and the advances in heterogeneous FLP systems. These foci serve to illustrate that despite having its roots in main group chemistry, this simple concept of FLPs is being applied across the discipline.

Lewis Superacidic Catecholato Phosphonium Ions: Phosphorus-Ligand Cooperative C-H Bond Activation.

A series of catecholato phosphonium ions, including the first stable bis(catecholato)-substituted derivatives, are isolated and fully characterized. The cations rank among the most potent literature-known Lewis acids on the Gutmann-Beckett and ion affinity scales. In contrast to halogenated or multiply charged phosphorus cations, Lewis superacidity is imparted by structural constraints, as disclosed by energy decomposition analysis. The modular access provides a tunable scaffold while maintaining extreme affinity, demonstrated by the synthesis of a chiral Lewis superacid. The combination of electrophilic phosphorus and basic oxygen substituents leverages new reactivity modes by phosphorus-ligand cooperativity. With this, a phosphorus-mediated C-H bond activation is accomplished.

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.

The Reactivity of Isomeric Nitrenium Lewis Acids with Phosphines, Carbenes, and Phosphide.

Alkylation of spiro[fluorene-9,3'-indazole] at N(1) and N(2) with tBuCl affords the nitrenium cations [C6 H4 N2 (tBu)C(C12 H8 )][BF4 ], 1 and 2, respectively. Compound 1 converts to 2 over the temperature range 303-323 K with a free energy barrier of 28±5 kcal mol-1 . Reaction of 1 with PMe3 afforded the N-bound phosphine adduct [C6 H4 N(tBu)N(PMe3 )C(C12 H8 )]BF4 ] 3. However, phosphines attack 2 at the para-carbon atom of the aryl group with concurrent cleavage of N(2)-C(1) bond and proton migration to C(1) affording [(R3 P)C6 H3 NN(tBu)CH(C12 H8 )][BF4 ] (R=Me 4, nBu 5). Analogous reactions of 1 and 2 with the carbene SIMes prompt attack at the para-carbon with concurrent loss of H. affording the radical cation salts [(SIMes)C6 H3 N(tBu)NC(C12 H8 ). ][BF4 ] 6 and [(SIMes)C6 H3 NN(tBu)C(C12 H8 ). ][BF4 ] 7, whereas reaction of 2 with BAC gives the Lewis acid-base adduct, [C6 H4 N(BAC)N(tBu)C(C12 H8 )][BF4 ] 8. Finally, reactions of 1 and 2 with KPPh2 result in electron transfer affording (PPh2 )2 and the persistent radicals C6 H4 N(tBu)NC(C12 H8 ). and C6 H4 NN(tBu)C(C12 H8 ). . The detailed reaction mechanisms are also explored by extensive DFT calculations.

Bipyridinium and Phenanthrolinium Dications for Metal-Free Hydrodefluorination: Distinctive Carbon-Based Reactivity.

The development of novel Lewis acids derived from bipyridinium and phenanthrolinium dications is reported. Calculations of Hydride Ion Affinity (HIA) values indicate high carbon-based Lewis acidity at the ortho and para positions. This arises in part from extensive LUMO delocalization across the aromatic backbones. Species [C10 H6 R2 N2 CH2 CH2 ]2+ (R=H [1 a]2+ , Me [1 f]2+ , tBu [1 g]2+ ), and [C12 H4 R4 N2 CH2 CH2 ]2+ (R=H [2 a]2+ , Me [2 b]2+ ) were prepared and evaluated for use in the initiation of hydrodefluorination (HDF) catalysis. Compound [2 a]2+ proved highly effective towards generating catalytically active silylium cations via Lewis acid-mediated hydride abstraction from silane. This enabled the HDF of a range of aryl- and alkyl- substituted sp3 (C-F) bonds under mild conditions. The protocol was also adapted to effect the deuterodefluorination of cis-2,4,6-(CF3 )3 C6 H9 . The dications are shown to act as hydride acceptors with the isolation of neutral species C16 H14 N2 (3 a) and C16 H10 Me4 N2 (3 b) and monocationic species [C14 H13 N2 ]+ ([4 a]+ ) and [C18 H21 N2 ]+ ([4 b]+ ). Experimental and computational data provide further support that the dications are initiators in the generation of silylium cations.

Reactions of a Dilithiomethane with CO and N2 O: An Avenue to an Anionic Ketene and a Hexafunctionalized Benzene.

Synthesis of value-added products from simple C1 feedstocks is an attractive alternative avenue to traditional fossil fuels. Hexa-substituted benzene derivatives are highly useful molecules but are often challenging to prepare. Herein, we report that the lithium complex [(Ph2 P(S))2 CLi2 (THF)]2 1 reacts with CO lead to C-C bond formation and migration of a Ph2 P(S)-fragment affording 2. Subsequent reaction with N2 O results in oxidative cleavage of a P-C bond affording [Ph2 P(S)OLi(THF)2 ]2 4 and the anionic ketene-derivative Ph2 P(S)CCOLi(THF)2 5. Heating 5 prompts cyclotrimerization giving the hexa-substituted benzene derivative [Ph2 P(S)CCOLi(THF)2 ]3 6 regioselectively. This transition metal-free protocol to a hexa-substituted benzene is viable on a gram scale and permits the incorporation of 13 C labels. The mechanisms of these reactions are detailed via extensive DFT computations.