Palladium-Catalyzed Difluorocarbene Transfer Enabled Divergent Synthesis of γ-Butenolides and Ynones from Iodobenzene and Terminal Alkynes.

Herein, we report a ligand-controlled palladium-catalyzed method that enables the synthesis of ynones and γ-butenolides with excellent regioselectivity from the same set of readily available aryl iodides, aryl acetylenes, and BrCF2CO2K. In this reaction, the [PdII]═CF2 does demonstrate electrophilicity and can generate CO readily when reacting with H2O. It is environmentally friendly and safe compared to traditional methods, and the current protocol enables us to afford ynones and γ-butenolides in high yields with excellent functionality tolerance. Moreover, esters can also be obtained with corresponding phenols and alcohols utilizing this strategy. The success of late-stage functionalization of bioactive compounds further illustrates the synthetic utility of this protocol in material development and drug discovery.

Unlocking Diverse π-Bond Enrichment Frameworks by the Synthesis and Conversion of Boronated Phenyldiethynylethylenes.

The π-bond enrichment frameworks not only serve as a crucial building block in organic synthesis but also assume a pivotal role in the fields of materials science, biomedicine, photochemistry, and other related disciplines owing to their distinctive structural characteristics. The incorporation of various substituents into the C═C double bonds of tetrasubstituted alkenes is currently a highly significant research area. However, the synthesis of tetrasubstituted alkenes with diverse substituents on double bonds poses a significant challenge in achieving stereoselectivity. Here, we reported an efficient and convergent route of Cu-catalyzed borylalkynylation of both symmetrical and unsymmetrical 1,3-diynes, B2pin2, and acetylene bromide to the construction of boronated phenyldiethynylethylene (BPDEE) derivatives with excellent chemo-, stereo-, and regioselectivities. BPDEE derivatives could transform into novel tetrasubstituted organic π-conjugated gem-diphenyldiethynylethylene (DPDEE), vinylphenyldiethynylethylene (VPDEE), and phenyltriethynylethylene (PTEE) derivatives by a stepwise process, which provides a flexible platform for the synthesis of complex π-bond enrichment frameworks that were difficult to synthesize by previous methods. The initial optical characterization revealed that the synthesized molecules exhibited aggregation-induced emission (AIE) properties, which further establishes the groundwork for future applications and enriches and advances the field of functional π-conjugated frameworks research.

Unconventional Transformations of Difluorocarbene with Amines and Ethers.

ConspectusFluorine-containing compounds are extensively involved in various fields originating from intriguing and unique characteristics of fluorine atom; notably, in pharmaceuticals, the involvement of a fluorine atom or a fluorine-containing group is a chief technique for improving the pesticide effect and developing new drugs. Difluorocarbene, one of the most important and powerful fluorine-containing reagents, is widely employed and studied in many areas mainly to assemble gem-difluoromethyl molecules, including but not limited to the abundant reactions between difluorocarbene with nucleophilic substrates, Wittig reaction with ketones or aldehydes, cascade reaction with both a nucleophile and an electrophile, or [2+1] cycloaddition with alkenes or alkynes. However, its unconventional and intriguing protocols beyond as a difluoromethyl synthon have rarely been studied, and thus, it is highly desired given its abundance, inexpensiveness and peculiar properties. In this Account, we mainly discuss our discovery with unconventional transformations of difluorocarbene, instead of as a sole difluoromethyl source (different from other dihalocarbene), actually can serve as an electron acceptor to activate C-X bonds (X = N and O) and thus promote a myriad of fascinating transformations for the assembly of versatile valuable products with various aza-compounds (primary/secondary/tertiary amines as well as NH3 and NaNH2 and so on) and aliphatic ethers in the absence of transition metals and expensive ligands. Inspired by the electron-deficient characteristics of difluorocarbene, we first found that the isocyanides could be readily formed in situ when the unoccupied orbital of difluorocarbene meets the lone-pair of primary amines; in basic condition, a cascade defluorination and cyclizations could afford plethora of valuable N-containing heterocycles. Meanwhile, we disclosed that cyano anion could be accessible in situ as well when difluorocarbene and NaNH2 or NH3 were mixed up in suitable basic conditions, and thus a series of aryl nitrile compounds were obtained in the presence of Pd catalysis and ArI. Interestingly, when difluorocarbene encountered secondary amines, formamides were rendered under mild reactions. Of note, concomitant functionalizations of C and N moieties via cleavage of the unstrained C(sp3)-N bond in the absence of metal and oxidant are sparce, which indeed significantly add versatility and diversity to products. Gratifyingly, by uitilizing difluorocarbene and cyclic tertiary amines, we achieved difluorocarbene-mediated deconstructive functionalizations for the first time, showing successive C(sp3)-N bond scission of amines and simultaneous functionalization of C and N atoms which would be introduced into the products in the absence of transition metals and oxidants. This method provides a brand-new while very universal synthetic pathway to selectively cleave inert unactivated Csp3-N bonds, in which halodifluoromethyl reagents act as both C1 synthon and halo (Cl, Br, I) sources. Fascinatingly, nitrogen ylides are generated in situ from difluorocarbene and tertiary amines, and an intriguing and universal approach for deaminative arylation or alkenylation of tertiary amines was disclosed for the first time in appropriate basic conditions, which represents an intriguing reaction mode to lead to a formal transition-metal free Suzuki cross coupling. Besides, we also disclosed that difluorocarbene could proceed novel atom recombination to render meaningful 2-fluoroindoles or 3-(2,2-difluoroethyl)-2-fluoroindoles from ortho-vinylanilines, 3-fluorined oxindoles from 2-aminoarylketones, in which difluorocarbene acts as a C1 synthon and F1 source simultaneously. Last but not the least, we recently found that the lone-pair-electron of oxygen could trap difluorocarbene as well to form oxonium ylide, which eventually leads to C-O bond cleavage with the formation of difluoromethyl ethers.

"Homoleptic" Tetracoordinate Boron Compounds.

"Homoleptic" tetracoordinate boron compounds, in which the central boron atom links to four identical atoms, are a special and important family of boron compounds. During the past decades, they have been extensively employed in inorganic, organic, macromolecular, and materials chemistry. Many of them exhibit a diverse range of outstanding properties, and therefore, the synthesis and application of those compounds have emerged as a hot research topic in modern boron chemistry. This review summarizes and discusses the "homoleptic" tetracoordinate boron compounds, which are organized according to the kinds of atoms coordinated to the central boron.

N-Heterocycle-Editing to Access Fused-BN-Heterocycles via Ring-Opening/C-H Borylation/Reductive C-B Bond Formation.

Skeletal editing of N-heterocycles has recently received considerable attention, and the introduction of boron atom into heterocycles often results in positive property changes. However, direct enlargement of N-heterocycles through boron atom insertion is rarely reported in the literature. Here, we report a N-heterocyclic editing reaction through the combination boron atom insertion and C-H borylation, accessing the fused-BN-heterocycles. The synthetic potential of this chemistry was demonstrated by substrate scope and late-stage diversification of products.

Palladium-Catalyzed Atroposelective Kinetic C-H Olefination and Allylation for the Synthesis of C-B Axial Chirality.

The direct C-H functionalization of 1,2-benzazaborines, especially asymmetric version, remains a great challenge. Here we report a palladium-catalyzed enantioselective C-H olefination and allylation reactions of 1,2-benzazaborines. This asymmetric approach is a kinetic resolution (KR), providing various C-B axially chiral 2-aryl-1,2-benzazaborines and 3-substituted 2-aryl-1,2-benzazaborines in generally high yields with excellent enantioselectivities (selectivity (S) factor up to 354). The synthetic potential of this reaction is showcased by late-stage modification of complex molecules, scale-up reaction, and applications.

Tetracoordinate Boron Intermediates Enable Unconventional Transformations.

ConspectusOrganoboron compounds are a class of multifunctional reagents for the construction of carbon-carbon and carbon-heteroatom bonds in modern synthetic chemistry. The transformations of organoboron compounds are usually carried out through tetracoordinate boron intermediates and mainly include additions to unsaturated bonds, rearrangement reactions, transmetalation reactions, and so on. Although great progress has been achieved in improving tetracoordinate boron intermediates, there are still shortcomings, such as sparse activation modes, a paucity of reaction strategies and difficulties in stereoselective control. In this Account, we mainly discuss our recent advances in the development of unconventional transformations of organoboron compounds based on the design of tetracoordinate boron intermediates, including the following three topics: (1) the construction of C-B bonds; (2) the construction of C-C bonds; (3) the design and application of chiral tetracoordinate boron.The development of new strategies to build C-B bonds is of great interest for chemists. We have developed tandem reactions involving multiple tetracoordinate boron intermediates for the selective borylations of alkynes and the synthesis of stable tetracoordinate boron, including a domino-borylation-protodeboronation (DBP) strategy for selective borylations of alkynes, highly regio-, stereo-, and chemoselective Cu-catalyzed diborylation of ß-CF3-1,3-enynes and cascade B-Cl/C-B cross-metathesis and C-H bond borylation for the synthesis of tetracoordinate triarylboranes. We have also developed novel strategies involving tetracoordinate boron intermediates to form C-C bonds because the formation of C-C bonds is an enduring theme of organic chemistry. We disclosed long distance or multiple migration reactions and novel coupling partners in transmetalation reactions, such as long distance 1,4-migrations of tetracoordinate nitrile oxide boron and nitrilium boron intermediates, multiple migrations of tetracoordinate isocyanide boron intermediate, palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides, copper-catalyzed atroposelective Michael-type addition, and a palladium-catalyzed atroposelective Catellani reaction. Moreover, in terms of stereoselective control of the tetracoordinate boron intermediate, we found that a chiral tricoordinate boron complex could activate water to form a chiral tetracoordinate boron complex with Brønsted acidity, which has been successfully applied with high enantioselectivity to the asymmetric catalytic reduction of challenging indoles.This Account summarizes our recent efforts using unconventional transformations of organoboron compounds for the design of tetracoordinate boron intermediates, which not only achieved the precise construction of a wide range of diverse C-B bonds and C-C bonds but also developed a novel chiral Brønsted acid for the asymmetric catalytic reduction of challenging indoles.

Deaminative Arylation and Alkenyaltion of Aliphatic Tertiary Amines with Aryl and Alkenylboronic Acids via Nitrogen Ylides.

Transition-metal-catalyzed Suzuki-Miyaura coupling has significantly advanced C-C bond formation and has been well recognized in organic synthesis, pharmaceuticals, materials science and other fields. In this rapid development, cross coupling without transition metal catalyst is a big challenge in this field, and using widely existing tertiary amines as electrophiles to directly couple with boronic acids has great hurdles yet significant application prospects. Herein, we report an efficient and general deaminative arylation and alkenylation of tertiary amines (propargyl amines, allyl amines and 1H-indol-3-yl methane amines) with ary and alkenylboronic acids enabled by difluorocarbene under transition-metal-free conditions. Preliminary mechanism experiments suggest that in situ formed difluoromethyl quaternary amine salt, nitrogen ylide and tetracoordinate boron species are the key intermediates, the subsequent 1,2-metallate shift and protodeboronation complete the new coupling reaction.

Enantioselective Cobalt-Catalyzed Cascade Hydrosilylation and Hydroboration of Alkynes to Access Enantioenriched 1,1-Silylboryl Alkanes.

Enantioenriched 1,1-silylboryl alkanes possess silyl and boryl groups that are both connected to the same stereogenic carbon center at well-defined orientations. As these chiral multifunctionalized compounds potentially offer two synthetic handles, they are highly valued building blocks in asymmetric synthesis as well as medicinal chemistry. Despite the potential usefulness, efficient synthetic approaches for their preparation are scarce. Seeking to address this deficiency, an enantioselective cobalt-catalyzed hydrosilylation/hydroboration cascade of terminal alkynes has been realized. This protocol constitutes an impressive case of chemo-, regio-, and stereoselectivity wherein the two different hydrofunctionalization events are exquisitely controlled by a single set of metal catalyst and ligand, an operation which would usually require two separate catalytic systems. Downstream transformations of enantioenriched 1,1-silyboryl alkanes led to various valuable chiral compounds. Mechanistic studies suggest that the present reaction undergoes highly regioselective and stereocontrolled sequential hydrosilylation and hydroboration processes.

Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation.

Compared with the well-developed centrally chiral boron chemistry, C-B axially chiral chemistry remains elusive and challenging. Herein we report the first atroposelective Miyaura borylation of bromoarenes with unsymmetrical diboron reagents for the direct catalytic synthesis of optically active atropisomeric arylborons. This reaction features broad substrate scope and produces axially chiral arylborons with high yields and good enantioselectivities.

Recent progress on selective deconstructive modes of halodifluoromethyl and trifluoromethyl-containing reagents.

Halodifluoromethyl and trifluoromethyl-containing compounds are widely employed in organic chemistry, pharmaceuticals and materials science. Therefore, their applications and transformations have received significant attention during the past few decades. The single, double, triple and quadruple cleavage of halodifluoromethyl compounds and various deconstructive modes of trifluoromethyl-containing compounds could generate a variety of synthons to prepare more valuable products. Herein, we summarize the most significant achievements in this field with an intriguing focus on results from the last decade.

Elemental-Sulfur-Enabled Divergent Synthesis of Disulfides, Diselenides, and Polythiophenes from ß-CF3 -1,3-Enynes.

Divergent synthesis for precise constructions of cyclic unsymmetrical diaryl disulfides or diselenides and polythiophenes from CF3 -containing 1,3-enynes and S8 was developed when the ortho group is F, Cl, Br, and NO2 on aromatic rings. Meanwhile, disulfides (diselenides) were also quickly constructed when the ortho group is H. These transformations undergo cascade thiophene construction/selective C3-position thiolation process, featuring simple operations, divergent synthesis, broad substrate scope, readily available starting materials, and valuable products. A novel plausible radical annulation process was proposed and validated by DFT calculations for the first time. A series of derivatizations about the thiophene (TBT) and disulfides were also well-represented.

Michael Reaction Inspired Atroposelective Construction of Axially Chiral Biaryls.

The first copper-catalyzed atroposelective Michael-type addition between azonaphthalenes and arylboronic acids for the construction of biaryl atropisomers was established using a novel BINOL-derived phosphoramidite as a chiral ligand. A broad range of atropisomeric biaryls were obtained with good efficiency, and the practicality of this approach was verified by versatile transformations toward axially chiral ligands, catalysts, and other functional atropisomers. This set of catalytic systems successfully inhibited the routine 1,2-addition and promoted the formation of an aryl-aryl chiral axis. Meanwhile, this strategy bypassed the use of an oxidant as well as the harsh conditions normally necessary for transition-metal-mediated arene C-H coupling with arylboronic acids as an arylation counterpart, offering a straightforward alternative to access optically active biaryls.

Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles.

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This "designer acid catalyst", which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

Gold-Catalyzed Radical-Involved Intramolecular Cyclization of Internal N-Propargylamides for the Construction of 5-Oxazole Ketones.

An expedient strategy for the synthesis of 5-oxazole ketones was developed via homogeneous gold catalysis with 4-MeO-TEMPO as an oxidant. The desired 5-oxazole ketones were achieved in decent yields with an excellent functional group compatibility under mild conditions. The current protocol also represents the first example for merging a gold catalyst and radical chemistry in one-pot synthesis with internal N-propargylamides.

Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes.

Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.

Copper(I)-Catalyzed Chemoselective Reduction of Benzofuran-2-yl Ketones to Alcohols with B2pin2 via a Domino-Borylation-Protodeboronation Strategy.

A novel copper(I)-catalyzed chemoselective reduction of the carbonyls of benzofuran-2-yl ketones over furan rings with B2pin2 has been developed. This reaction proceeded under mild conditions. High valuable secondary alcohol derivatives of benzofurans were obtained in good to excellent yields with a broad substrate scope. The mechanistic studies suggested that a domino-borylation-protodeboronation pathway was involved in this reaction.

Umpolung of protons from H2O: a metal-free chemoselective reduction of carbonyl compounds via B2pin2/H2O systems.

H2O is routinely described as a proton donor, however, in the presence of diboron compounds, the umpolung reaction of H2O under metal-free conditions was successfully developed, which could afford hydride species, leading to a highly efficient and chemoselective reduction of C[double bond, length as m-dash]O bonds. This strategy exhibits excellent chemoselectivities toward carbonyl groups in the presence of ester, olefin, halogen, thioether, sulfonyl, cyano as well as heteroaromatic groups.

Gold(i)-catalyzed synthesis of 2-substituted indoles from 2-alkynylnitroarenes with diboron as reductant.

An efficient method for the synthesis of 2-substituted indoles via a diboron/base promoted tandem reductive cyclization of o-alkynylnitroarene under Au catalysis conditions has been disclosed. This reaction is efficient and convenient, affording 2-substituted indoles with broad functional groups tolerance and excellent yields.

Divergent Synthesis of Disulfanes and Benzenesulfonothioates Bearing 2-Aminofurans From N-Tosylhydrazone-Bearing Thiocarbamates.

An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade. Remarkably, the Ts anion released from N-tosylhydrazone further serves as a nucleophile, thus rendering the formation of benzenesulfonothioates under controlled conditions.