Despite the rapid progress in the field of asymmetric catalysis, the search for new, efficient, and practical asymmetric catalytic transformations to facilitate the green synthesis of chiral natural products and drugs will continue to be a major ongoing effort in organic chemistry. Chiral phosphorus ligands have played a significant role in recent advances in transition-metal-catalyzed asymmetric transformations. However, there remain numerous challenging issues of reactivity and selectivity in catalysis. The development of new and efficient chiral phosphorus ligands with new structural motifs remains highly desirable. P-Chiral phosphorus ligands have been overlooked and are underdeveloped, except for the early success of DIPAMP, introduced first by Knowles in the early 1970s. It was not until the late 1990s that the development of P-chiral phosphorus ligands regained attention with the advent of bisP*, TangPhos, etc. Nonetheless, most P-chiral phosphorus ligands were either difficult to prepare or operationally inconvenient. The development of efficient, practical, and operationally convenient P-chiral phosphorus ligands with new structural motifs remains an important subject of research. This Account introduces the design and development of a series of practical and efficient P-chiral bis- and monophosphorus ligands based on a 2,3-dihydrobenzo[ d][1,3]oxaphosphole motif. Their unique structural and physical properties include conformational unambiguousness, high tunability of electronic and steric properties, and operational simplicity as air-stable solids, which make them practical and exceptional ligands for asymmetric catalysis. Chiral bisphosphorus ligands such as MeO-BIBOP (L3), WingPhos (L4), and iPr-BABIBOP (L7) have demonstrated excellent enantioselectivities and unprecedented turnover numbers (TONs) in various asymmetric hydrogenations and other transformations, providing practical and efficient solutions leading to chiral amines, alcohols, carboxylic acids, and α- and β-amino acids. Chiral biaryl monophosphorus ligands, including BI-DIME (L9), AntPhos (L15), iPr-BI-DIME (L11), etc., have proven to be a class of versatile and powerful ligands for a number of catalytic asymmetric transformations, including asymmetric Suzuki-Miyaura coupling, asymmetric palladium-catalyzed dearomative cyclization, asymmetric hydroboration/diboration, asymmetric nickel-catalyzed reductive coupling, asymmetric palladium-catalyzed intramolecular arylation, asymmetric alkene aryloxyarylation, asymmetric α-arylation, asymmetric Heck reaction, and asymmetric nucleophilic addition, providing efficient solutions leading to various synthetically challenging chiral structures such as chiral biaryls, chiral tertiary alcohols, chiral α-amino tertiary boronic esters, and chiral all-carbon quaternary stereocenters. The high enantioselectivities and TONs obtained with these ligands have resulted in the syntheses of several chiral natural products and therapeutic agents in concise and highly efficient manners. While our efforts on the development of P-chiral phosphorus ligands are ongoing, it should be emphasized that the development of ligands and catalysts with new structural motifs should continue in the search for new reactivity and selectivity to tackle current synthetic challenges. Such effort is destined to promote the advances of asymmetric catalysis as well as synthetic organic chemistry.

P-Chiral Phosphorus Ligands Based on a 2,3-Dihydrobenzo[d][1,3]oxaphosphole Motif for Asymmetric Catalysis

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.

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

The aggregation-induced electrochemiluminescence (AIECL) of carboranyl carbazoles in aqueous media was investigated for the first time. Quantum yields, morphologies, and particle sizes were observed to determine the electrochemiluminescence (ECL) performance of these aggregated organic dots (ODs). All compounds exhibit much higher ECL stability and intensity than the carborane-free compound, demonstrating the essential role of the carboranyl motif. Moreover, the results of cyclic voltammetry (CV) suggest that oxidation/reduction reactions take place at the carboranyl motif. The excited states of ODs were proposed to be generated by the mechanism of surface state transitions. More importantly, these compounds show a reductive-oxidative mechanism in contrast to other organic materials that show oxidative-reductive mechanisms. Our experiments and data have established the relation between AIE organic structures and ECL properties that has a strong potential for biological and diagnostic applications.

Aggregation-Induced Electrochemiluminescence of Carboranyl Carbazoles in Aqueous Media

Transition metal catalyzed regioselective amination of the cage B(4)–H bond in o-carboranes has been achieved for the first time using O-benzoyl hydroxylamines or organic azides as the amination reagents, leading to the preparation of a series of tertiary and secondary carboranyl amines. Both amination reactions proceeded under mild conditions without the addition of any external oxidants. Hydrogenolysis of the resultant product 4-N(CH2Ph)2-o-carborane afforded the primary carboranyl amine, 4-amino-o-carborane, in quantitative yield.

Transition Metal Catalyzed Direct Amination of the Cage B(4)-H Bond in o-Carboranes: Synthesis of Tertiary, Secondary, and Primary o-Carboranyl Amines.

The first example of a transition metal (BB)-carboryne complex containing two boron atoms of the icosahedral cage connected to a single exohedral metal center (POBBOP)Ru(CO)2 (POBBOP = 1,7-OP(i-Pr)2-2,6-dehydro-m-carborane) was synthesized by double B–H activation within the strained m-carboranyl pincer framework. Theoretical calculations revealed that the unique three-membered (BB)>Ru metalacycle is formed by two bent B–Ru σ-bonds with the concomitant increase of the bond order between the two metalated boron atoms. The reactivity of the highly strained electron-rich (BB)-carboryne fragment with small molecules was probed by reactions with electrophiles. The carboryne–carboranyl transformations reported herein represent a new mode of cooperative metal–ligand reactivity of boron-based complexes.

https://pubs.acs.org/doi/pdf/10.1021/jacs.6b05172

(BB)-Carboryne Complex of Ruthenium: Synthesis by Double B-H Activation at a Single Metal Center.

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.

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

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 Regioselective Cage B(8)–H Arylation of o-Carboranes via “Cage-Walking” Strategy

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.

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

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.

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

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...

Jie Zhang

Papers

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

Catalytic Regioselective Cage B(8)–H Arylation of o-Carboranes via “Cage-Walking” Strategy

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

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

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