Cyclic (Alkyl)(Amino)Carbene-Iminoboryl Compounds with Three Formal Oxidation States.

BN/CC isosterism is an effective strategy to build hybrid functional molecules with unique properties. In contrast to the alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes (CAACs) that feature only one reversible reduction wave, the isoelectronic cationic CAAC-iminoboryl adducts could be singly and doubly reduced smoothly. Both the resultant neutral radical and anionic azaborataallenes bear NBC-mixed allenic structures. The former radical has a high spin-density of 0.55e at CCAAC carbon, yet exhibits formal boron-centered radical reactivity. The latter azaborataallenes feature the nucleophilic CCAAC center and polar N(δ-)═B(δ+)═C(δ-) unit, and readily undergo nucleophilic substitution, isocyanide insertion, dipolar addition and cycloaddition reactions etc. The N-substituents have been shown to have a significant influence on the solid-state structure, thermal stability, and reactivity of azaborataallenes. This work showcases the allenic BN-unsaturated species as versatile building blocks in organic synthesis.

Palladium-Catalyzed Regioselective B(3,5)-Dialkenylation and B(4)-Alkenylation of o-Carboranes.

Picolyl group directed B(3,5)-dialkenylation and B(4)-monoalkenylation of o-carboranes has been developed with a very low palladium catalyst loading. The degree of substitution is determined by the cage C(2)-substituents due to steric reasons. On the basis of experimental results, a plausible mechanism is proposed including electrophilic palladation and alkyne insertion followed by protonation.

Catalyst-Free Regioselective Diborylation of Aryllithium with Tetra(o-tolyl)diborane(4).

A catalyst-free 1,2-diborylation of aryllithium with tetra(o-tolyl)diborane(4) has been achieved, giving a series of 1,2-diborylaryl lithium species in excellent yields under mild reaction conditions, which leads to 1,2-di(tolyl)borylarenes in 60-91 % yields upon treatment with the hydride-abstracting reagent. In these transformations, one sp2 C-H of arene is activated and both boryl units are utilized to build two new (sp2 )C-B bonds. This represents a new strategy for selective arene diborylation. Density functional theory (DFT) calculations suggest that an aromatic nucleophilic substitution is a key step in the formation of the products.

Functionalization of o-carboranes via carboryne intermediates.

Carborynes (1,2-dehydro-o-carborane and 1,3-dehydro-o-carborane), three-dimensional analogues of benzyne, can be generated in situ from the precursors 1-X-2-Li-1,2-C2B10H10 (X = Br, I, OTs, OTf), or 1-Me3Si-2-[IPh(OAc)]-1,2-C2B10H10 or [1-Li-3-N2-1,2-C2B10H10][BF4]. They are a class of very useful synthons for the synthesis of a large variety of functionalized carborane derivatives for potential application in medicine, materials science and organometallic/coordination chemistry. The experimental data demonstrate that there is a correspondence between the reactions of carborynes and those of benzyne with alkenes, dienes, alkynes, aromatics or heteroaromatics in a pericyclic reaction fashion. On the other hand, carborynes have unique properties of their own owing to their steric/electronic features. They undergo regioselective sp2/sp3 C-H bond and N-Li bond insertion reactions, which has not been observed for benzyne. This review provides a comprehensive overview of recent advances in this interesting research field with considerable attention devoted to the reaction modes and the mechanisms involved.

Visible-Light-Promoted Nickel-Catalyzed Cross-Coupling of Iodocarboranes with (Hetero)Arenes via Boron-Centered Carboranyl Radicals.

A general strategy for the generation of hypervalent boron-centered carboranyl radicals at the B(3), B(4), and B(9) positions has been developed for the first time via visible-light-promoted iodine atom abstraction from iodo-o-carboranes by low-valent nickel complex. These radicals react with various (hetero)arenes to afford a wide range of cage B-arylated carborane derivatives at room temperature in very good to excellent yields with a broad substrate scope. Their electrophilicities are dependent on the vertex charges of the cage and follow the order B(3) > B(4) > B(9). Both visible light and nickel catalyst are proved critical to the generation of boron-centered carboranyl radicals. The involvement of boron radicals is supported by control experiments. A reaction mechanism associated with these reactions is also proposed. This strategy offers a new protocol for the generation of boron-centered carboranyl radicals at the selected boron vertex, leading to a facile synthesis of a large class of cage boron substituted carborane molecules.

A Strategy for Selective Catalytic B-H Functionalization of o-Carboranes.

Carboranes are a class of polyhedral carbon-boron molecular clusters featuring three-dimensional aromaticity, which are often considered as 3D analogues of benzene. Their unique structural and electronic properties make them invaluable building blocks for applications ranging from functional materials to versatile ligands to pharmaceuticals. Thus, selective functionalization of carboranes has received tremendous research interest. In earlier days, the vast majority of the works in this area were focused on cage carbon functionalization via facile deprotonation of cage CH, followed by reaction with electrophiles. On the contrary, cage B-H activation is very challenging since the 10 B-H bonds on o-carborane are very similar, and how to achieve the desired transformation at specific boron vertex is a long-standing issue.As carbon is considered more electronegative than boron, this property results in different vertex charges on the o-carborane cage, which follow the order B(3,6)-H ≪ B(4,5,7,11)-H < B(8,10)-H < B(9,12)-H. We thought that this difference may trigger the favorite interaction of a proper transition metal complex with a specific B-H bond of carborane, which could be utilized to solve the selectivity issue. Accordingly, our strategy is described as follows: (1) electron-rich transition metal catalysts are good for the activation of the most electron-deficient B(3,6)-H bonds (connected to both cage C-H vertices); (2) electron-deficient transition metal catalysts are good for the activation of the relatively electron-rich B(8,9,10,12)-H bonds (with no bonding to either cage C-H vertices); and (3) directing-group-assisted transition metal catalysis is appropriate for the activation of the B(4,5,7,11)-H bonds (connected to only one cage C-H vertex), whose vertex charges lie in the middle of the range for the 10 B-H bonds. This strategy has been successfully applied by our laboratory and other groups in the development of a series of synthetic routes for catalytic selective activation of B-H bonds of the carborane cage, resulting in the synthesis of a large number of cage-boron-functionalized carborane derivatives in a regioselective and catalytic fashion. Subsequently, significant progress in this emerging area has been made.In 2013 we reported the selective tetrafluorination of o-carboranes at the B(8,9,10,12)-H bonds using an electron-deficient Pd(II) salt, [Pd(MeCN)4][BF4], as the catalyst. In 2014 we disclosed the first example of carboxy-directed alkenylation of o-carboranes at the B(4) vertex promoted by an Ir(III) catalyst. Subsequently, in 2017 we presented an electron-rich Ir(I)-catalyzed diborylation of o-carboranes at the B(3,6)-H bonds. We also uncovered the first example of Pd-catalyzed asymmetric synthesis of chiral-at-cage o-carboranes in 2018. These proof-of-principle studies have greatly stimulated research activities in selective B-H activation of carboranes and boron clusters enabled by transition metal catalysts. We have so far developed a toolbox of synthetic methods for selective catalytic cage B-olefination, -arylation, -alkenylation, -alkynylation, -oxygenation, -sulfenylation, -borylation, -halogenation, and -amination. We have recently expanded our research to base metal catalysis. As the field progresses, we expect that other methods for regioselective cage B-H activation will be invented, and the results detailed in this Account will promote these efforts.

N-Ligand-Enabled Aromatic Nucleophilic Amination of 1,2-Diaryl-o-Carboranes with (R2 N)2 Mg for Selective Synthesis of 4-R2 N-o-Carboranes and 2-R2 N-m-Carboranes.

The nucleophilic aromatic BH substitution reaction of carboranes is uncommon, compared to the electrophilic one. This work reported a pyridine-enabled transition-metal-free regioselective nucleophilic aromatic cage B(4)-H amination of 1,2-diaryl-o-carboranes with magnesium bisamides, giving a series of B(4)-aminated o-carboranes. DFT calculations showcased a stepwise B-N formation/B-H cleavage process, in which Mg-H formation/cage closure is the rate-determining step. Unprecedentedly, in the presence of 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbpy), a tandem B(4)-amination/cage isomerization reaction of o-carboranes was discovered for the facile preparation of B(2)-aminated m-carboranes. Control experiments indicated that magnesium complex, bidentate ligand (dtbpy) and reaction temperature were crucial in the cage isomerization process. This direct nucleophilic aromatic cage B-H amination reaction offers an alternative strategy for selective amination of o- and m-carboranes.

Ir-Catalyzed Selective B(3)-H Amination of o-Carboranes with NH3.

Ammonia gas, NH3, is a cheap and widely used industrial feedstock, which has received tremendous research interests in its functionalization. This work reports a breakthrough in catalytic selective cage B(3)-H amination of o-carboranes with NH3 via Ir-catalyzed B-H/N-H dehydrocoupling, offering convenient and efficient access to a series of 3-NH2-o-carborane derivatives in moderate to high isolated yields with a broad substrate scope. The employment of readily available NH3 gas as the aminating reagent with H2 as the sole byproduct endows the protocol economy, practicability, and environmental friendliness. A plausible reaction mechanism is proposed on the basis of control experiments.

Iridium-Catalyzed Annulation of o-Carboranyl Carboxylic Acids with Alkynes: Synthesis of Carborano-Isocoumarins.

An efficient iridium-catalyzed formal [4+2] annulation of carboranyl carboxylic acids with alkynes is developed, resulting in the facile synthesis of a new class of carborano-isocoumarin derivatives. The carboxyl group not only serves as a directing group to control the regioselectivity but also ingeniously becomes a part of the final products. The reaction mechanism involves sequential carboxyl-directed B(4)-H metalation, alkyne insertion, and reductive elimination.

Synthesis, Structure, and Reactivity of Acid-Free Neutral Oxoborane.

An efficient synthesis of an acid-free neutral oxoborane of the type carboranyl-B(carbene)=O has been developed via a serendipitous discovery from the reaction of 1,2-[BBr(carbene)]-o-carborane with AgOTf. This represents a new type of oxoborane. The stabilization of this oxoborane may be attributed to 1) kinetic stabilization provided by a bulky 3D carboranyl ligand and 2) thermodynamic stabilization offered by a carbene ligand. Crystallographic analyses support the presence of the shortest terminal B=O double bond ever reported thus far. Its reactivity has also been examined.

Transition-Metal-Free Cross-Coupling Reaction of Iodocarboranes with Terminal Alkynes Enabled by UV Light: Synthesis of 1-Alkynyl-o-Carboranes and Carborane-Fused Cyclics.

A transition-metal-free coupling protocol between iodocarboranes and terminal alkynes enabled by light at room temperature has been developed, leading to the synthesis of a variety of 1-alkynyl-o-carboranes. Moreover, following this strategy, the introduction of 1-I-3-aryl-o-carboranes or 1-I-2-aryl-o-carboranes results in the formation of o-carborane-fused cyclics. Interestingly, when 1-I-3-(p-R-C6H4)-o-carboranes are chosen as coupling partners, unexpected R-group migration products are also isolated. On the basis of the results of control experiments and isolation of the key intermediates, a possible reaction mechanism is then proposed, involving the formation of spiro radical species.

Copper-Catalyzed Electrochemical Selective B-H Oxygenation of o-Carboranes at Room Temperature.

Copper-catalyzed electrochemical selective cage B-H oxygenation of o-carboranes has been achieved for the first time. Under a constant electric current (4.0 mA) at room temperature, copper-catalyzed cross-coupling of carboranyl amides with lithium phenolates results in the formation of B(4,5)-diphenolated o-carboranes via direct B-H activation, whereas the use of lithium tert-butoxide affords B(4)-monooxygenated products. This reaction does not require any additional chemical oxidants and generates H2 and a lithium salt as byproducts. Control experiments indicated that a high-valent Cu(III) species is likely involved in the reaction process.

Iridium-Catalyzed Regioselective B(3)-Alkenylation/B(3,6)-Dialkenylation of o-Carboranes by Direct B-H Activation.

Invited for the cover of this issue is the group of Zaozao Qiu and Zuowei Xie at the Shanghai Institute of Organic Chemistry, CAS. The image depicts the cis- and trans-o-carborane products reported in this work. Read the full text of the article at 10.1002/chem.202000549.

Iridium-Catalyzed Regioselective B(3)-Alkenylation/B(3,6)-Dialkenylation of o-Carboranes by Direct B-H Activation.

Iridium-catalyzed formal alkyne hydroboration with cage B-H of o-carborane has been achieved, leading to the controlled synthesis of a series of 3,6-[trans-(AlkCH=CH)]2 -o-carboranes (Alk=alkyl), 3-cis-(ArCH=CH)-o-carboranes (Ar=aryl), and 3-cis-(ArCH=CH)-6-trans-(AlkCH=CH)-o-carboranes in high yields with excellent regio- and very good cis-trans selectivity. The most electron-deficient B(3,6)-H vertices favor oxidative addition on electron-rich metal centers, which is responsible for the regioselectivity. On the other hand, the configuration of the resultant olefinic units is dominated by alkyne substituents. Alkyl groups lead to a trans-configuration whereas bulky aryl substitutions result in cis-configuration.

Controlled functionalization of o-carborane via transition metal catalyzed B-H activation.

Carboranes, a class of carbon-boron molecular clusters, are often viewed as three-dimensional analogues of benzene. They are finding increasing applications as useful functional building blocks in materials science, medicine, organometallic/coordination chemistry and more. Thus, functionalization of carboranes has received considerable attention. In comparison with the weakly acidic cage C-H bonds that can be readily functionalized, selective cage B-H functionalization among ten chemically similar BH vertices in o-carboranes is very challenging. Only in the recent few years, considerable progress has been made in transition metal catalyzed vertex-specific BH functionalization. This review summarizes recent advances in this research area.

Pd-Catalyzed Selective Bifunctionalization of 3-Iodo-o-Carborane by Pd Migration.

A palladium-catalyzed highly selective 3,4-bifunctionalization of 3-I-o-carborane has been developed, leading to the preparation of 3-alkenyl-4-R-o-carboranes (R=alkyl, alkynyl, aryl, allyl, CN, and amido) in high to excellent yields. This protocol combines the sequential activation of cage B(3)-I and B(4)-H bonds by Pd migration from exo-alkenyl sp2 C to cage B(4), which is driven by thermodynamic force. This represents a brand-new strategy for selective bifunctionalization of carboranes with two different substituents.

Catalytic Regioselective Cage B(8)-H Arylation of o-Carboranes via "Cage-Walking" Strategy.

A proof-of-concept example of catalytic regioselective cage B(8)-H functionalization of o-carboranes has been disclosed for the first time. Under the help of an acylamino directing group at cage B(3), a series of B(8)-arylated, B(4,7,8)-triarylated and B(4,7,8)-trifluorinated o-carborane derivatives were conveniently prepared. On the basis of isolation of a key intermediate, deuterium labeling experiments and DFT calculations, a reaction mechanism involving a high-valent palladium induced "cage-walking" from B(4) to B(8) vertex is proposed to account for the regioselective B(8)-H activation.

Catalytic Cascade Dehydrogenative Cross-Coupling of BH/CH and BH/NH: One-Pot Process to Carborano-Isoquinolinone.

A proof-of-principle study of cascade dehydrogenative cross-coupling of carboranyl carboxylic acid with readily available benzamide has been achieved, resulting in the facile synthesis of previously inaccessible carborano-isoquinolinone derivatives in a simple one-pot process, in which two cage B-H, one aryl C-H, and one N-H bond were sequentially activated to construct efficiently new B-C and B-N bonds, respectively. Under suitable reaction conditions, such cascade cyclization can be stopped at the first B-H/C-H cross-coupling step to give a series of α-carboranyl benzamides, suggesting the preferential occurrence of B-C cross-coupling over that of B-N. The carboxylic acid directing group plays a key role in the B-C cross-coupling step, which is then removed through in situ decarboxylation. The CV results combined with control experiments indicate that high-valent Ir(V)-species may be involved in the reaction pathways, which is crucial for such cascade dehydrogenative cross-coupling reactions. The isolation and structural identification of a key intermediate, its controlled transformations, and deuterium labeling experiments support a new Ir-nitrene-mediated amination for B-H/N-H dehydrocoupling.

Regioselective Nucleophilic Alkylation/Arylation of B-H Bonds in o-Carboranes: An Alternative Method for Selective Cage Boron Functionalization.

A new protocol for regioselective nucleophilic cage B-H substitution in o-carboranes has been proposed that is complementary to the strategies of transition metal catalysis and electrophilic substitution. Magnesium-mediated site-selective nucleophilic cage B(3,6)-H and B(9)-H substitution reactions of o-carboranes give a series of B(3,6)-dialkylated and B(9)-alkylated/arylated o-carboranes in high yields. Both steric and electronic factors of cage C substituents play crucial roles in controlling the site selectivity.

Borylene Insertion into Cage B-H Bond: A Route to Electron-Precise B-B Single Bond.

A new strategy to construct electron-precise B-B single bond via direct borylene insertion into B-H bond is described. Reduction of bromoborylene stabilized by carborane-fused silylenes with 2 equiv of sodium gives a new compound with a B-B single bond. Both experimental and density functional theory results suggest that such an electron-precise B-B single bond is formed via in situ generated borylene insertion into B-H bond.