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.

Reaction of 4-Bpin-o-Carborane with Ketones: Sequential Carbon Vertex Alkylation and B-B Bond Activation.

Diboron compounds are important reagents in a series of transition metal catalyzed or metal-free borylation reactions. We describe herein a unique reactivity of 4-Bpin-o-carborane with ketones under basic conditions, leading to sequential cage carbon alkylation, B-B bond activation and unexpected O-migration. The reaction was compatible with a good substrate scope including dialkyl or alkyl aryl ketones. The reaction mechanism is also proposed, involving cage CH deprotonation, nucleophilic attack of ketone, and O-migration along with B-B bond cleavage.

Iridium-catalyzed regioselective B(3,6)-dialkenylation or B(4)-alkenylation of o-carboranes via B-H activation and 1,2-carbon migration of alkynes.

An efficient Ir-catalyzed cage boron alkenylation of 1-(2'-picolyl)-o-carboranes with diarylacetylenes has been developed, leading to a wide variety of B-H geminal addition products via 1,2-carbon migration of alkynes. The steric effect of cage carbon substituents has a great impact on the regioselectivity of such alkenylation reactions.

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.

Ir-catalyzed enantioselective B-H alkenylation for asymmetric synthesis of chiral-at-cage o­carboranes.

The asymmetric synthesis of chiral-at-cage o-carboranes, whose chirality is associated with the substitution patterns on the polyhedron, is of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. Herein we report an intermolecular Ir-catalyzed enantioselective B-H alkenylation for efficient and facile synthesis of chiral-at-cage o-carboranes with new skeletons under mild reaction conditions. Generally very good to excellent yields with up to 99% ee can be achieved in this Ir-catalyzed B-H alkenylation. The enantiocontrol model is proposed based on Density Functional Theory calculations in which the use of chiral phosphoramidite ligand is essential for such asymmetric o-carborane B-H alkenylation.

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.

Pd-catalyzed selective tetrafunctionalization of diiodo-o-carboranes.

A palladium-catalyzed highly selective tetrafunctionalization of 3,6-I2-o-carborane and 4,7-I2-o-carborane has been developed, leading to the preparation of 3,6-dialkenyl-4,11-R2-o-carboranes and 4,7-dialkenyl-5,11-R2-o-carboranes (R = alkyl, allyl and aryl) in moderate to excellent yields. This represents a new strategy for selective synthesis of polyfunctionalized o-carborane derivatives via a one-pot process.

Pd-Catalyzed sequential B(3)-I/B(4)-H bond activation for the synthesis of 3,4-benzo-o-carboranes.

A palladium-catalyzed sequential B(3)-I and B(4)-H bond activation has been achieved for the synthesis of 3,4-benzo-o-carboranes via a formal [2 + 2 + 2] cycloaddition of 3-I-o-carborane with 2 equiv. of arylalkynes. This represents a new protocol to construct o-carborane-fused cyclics in one process, in which the Pd fragment migrates formally from the B(3) to B(4) position of the cage.

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.

Palladium-catalyzed intramolecular dehydrogenative coupling of BH and OH: synthesis of carborane-fused benzoxaboroles.

A Pd-catalyzed intramolecular dehydrogenative coupling of BH and OH for the construction of cage B-O bonds has been developed, leading to a new class of 1,3- and 1,4-o-carboranobenzoxaborole derivatives. This represents a new route to C,B-carborane-fused heterocycles.

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.

Jasmonate-mediated wound signalling promotes plant regeneration.

Wounding is the first event triggering regeneration1-4. However, the molecular basis of wound signalling pathways in plant regeneration is largely unclear. We previously established a method to study de novo root regeneration (DNRR) in Arabidopsis thaliana5,6, which provides a platform for analysing wounding. During DNRR, auxin is biosynthesized after leaf detachment and promotes cell fate transition to form the root primordium5-7. Here, we show that jasmonates (JAs) serve as a wound signal during DNRR. Within 2 h of leaf detachment, JA is produced in leaf explants and activates ETHYLENE RESPONSE FACTOR109 (ERF109). ERF109 upregulates ANTHRANILATE SYNTHASE α1 (ASA1)-a tryptophan biosynthesis gene in the auxin production pathway8-10-dependent on the pre-deposition of SET DOMAIN GROUP8 (SDG8)-mediated histone H3 lysine 36 trimethylation (H3K36me3)11 on the ASA1 locus. After 2 h, ERF109 activity is inhibited by direct interaction with JASMONATE-ZIM-DOMAIN (JAZ) proteins to prevent hypersensitivity to wounding. Our results suggest that a dynamic JA wave cooperates with histone methylation to upregulate a pulse of auxin production and promote DNRR in response to wounding.

Enantioselective Synthesis of Chiral-at-Cage o-Carboranes via Pd-Catalyzed Asymmetric B-H Substitution.

Carborane cage chirality is an outstanding issue of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. The synthesis of optically active carborane derivatives, whose chirality is associated with the substitution patterns on the polyhedron, will open new avenues to carborane chemistry. We report herein an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantioselectivities by a strategy of palladium-catalyzed asymmetric intramolecular B-H arylation and cyclization. This represents the first example of the enantioselective reaction on carboranes, providing an efficient way for the construction of chiral-at-cage compounds with new skeletons.

Synthesis of carborane-fused carbo- and heterocycles via zirconacyclopentane intermediates.

A variety of carborane-fused carbo- and heterocycles were prepared in good to high isolated yields via the reaction of carborane-fused zirconacyclopentane with a series of substrates such as S8, Se, Te, CO, XylNC, MeOOC-CH[double bond, length as m-dash]N2, PhPCl2, nBu2SnCl2 and Me2GeCl2. However, it was found that the Zr-C bond in the zirconacyclopentane did not show any reactivity towards PhBCl2, PhCN and PhCH[double bond, length as m-dash]NPh. This approach represents a promising route to functionalized carboranes that are difficult to access by conventional methods.

Transition-Metal-Catalyzed Selective Cage B-H Functionalization of o-Carboranes.

Carboranes are a class of carbon-boron molecular clusters with unusual thermal and chemical stabilities. They have been proved as very useful building blocks in supramolecular design, optoelectronics, nanomaterials, boron neutron capture therapy agents and organometallic/coordination chemistry. Thus, the functionalization of o-carboranes has received growing interests. Over the past decades, most of the works in this area have been focused on cage carbon functionalization as the weakly acidic cage C-H proton can be readily deprotonated by strong bases. In sharp contrast, selective cage B-H activation/functionalization among chemically very similar ten B-H vertices is very challenging. Considering the differences in electron density of ten cage B-H bonds in o-carborane and the nature of transition metal complexes, we have tackled this selectivity issue by means of organometallic chemistry. Our strategy is as follows: using electron-rich transition metal catalysts for the functionalization of the most electron-deficient B(3,6)-H vertices (bonded to both cage CH vertices); using electron-deficient transition-metal catalysts for the functionalization of relatively electron-rich B(8,9,10,12)-H vertices (with no bonding to both cage CH vertices); and using the combination of directing groups and electrophilic transition metal catalysts for the functionalization of B(4,5,7,11)-H vertices (bonded to only one cage CH vertex). Successful applications of such a strategy result in the preparation of a large variety of cage B-functionalized carboranes in a regioselective and catalytic manner, which are inaccessible by other means. It is believed that as this field progresses, other cage B-functionalized carboranes are expected to be synthesized, and the results detailed in this concept article will further these efforts.

Iridium-catalysed regioselective borylation of carboranes via direct B-H activation.

Carboranes are carbon-boron molecular clusters, which can be viewed as three-dimensional analogues to benzene. They are finding many applications in medicine, materials and organometallic chemistry. On the other hand, their exceptional thermal and chemical stabilities, as well as 3D structures, make them very difficult to be functionalized, in particular the regioselective functionalization of BH vertex among ten similar B-H bonds. Here we report a very efficient iridium-catalysed borylation of cage B(3,6)-H bonds of o-carboranes with excellent yields and regioselectivity using bis(pinacolato)diboron (B2pin2) as a reagent. Selective cage B(4)-H borylation has also been achieved by introducing a bulky TBDMS (tert-butyldimethylsilyl) group to one cage carbon vertex. The resultant 3,6-(Bpin)2-o-carboranes are useful synthons for the synthesis of a wide variety of B(3,6)-difunctionalized o-carboranes bearing cage B-X (X=O, N, C, I and Br) bonds.

Photoarylation of Iodocarboranes with Unactivated (Hetero)Arenes: Facile Synthesis of 1,2-[(Hetero)Aryl]n -o-Carboranes (n=1,2) and o-Carborane-Fused Cyclics.

Photoarylation of iodocarboranes with unactivated arenes/heteroarenes at room temperature has been achieved, for the first time, thus leading to the facile synthesis of a large variety of cage carbon mono(hetero)arylated and di(hetero)arylated o-carboranes. This work represents a clean, efficient, transition-metal-free, and cheap synthesis of functionalized carboranes, which has significant advantages over the known methods.

Facile Synthesis of N-Carboranyl Amines through an ortho-Carboryne Intermediate.

The efficient o-carboryne precursor 1-Li-2-OTf-o-C2 B10 H10 reacts with lithium amides at room temperature to give a series of N-carboranyl amines in moderate to high isolated yields. This reaction is compatible with a broad substrate scope from primary to secondary, alkyl to aryl amines. The reaction mechanism is also proposed on the basis of experimental results and DFT calculations. This represents the first general and efficient method for the synthesis of 1-NR(1) R(2) -o-carboranes.

Transition-metal-mediated three-component cascade cyclization: selective cage B-C(sp2) coupling of carborane with aromatics and synthesis of carborane-fused tricyclics.

Zirconium/nickel comediated one-pot three-component cascade cyclization of carboryne, alkene, and 2-bromophenyltrimethylsilylacetylene has been achieved, leading to the formation of a series of C,C,B-substituted carborane-fused tricyclics. On the basis of experimental results, a plausible mechanism is proposed including [2 + 2 + 1] cross-cyclotrimerization followed by intramolecular direct selective cage B-C(sp(2)) coupling. This represents the first example of direct cage B-C(phenyl) coupling via cage B-H activation.