Facile Friedel-Crafts alkylation of arenes under solvent-free conditions.

The Friedel-Crafts alkylation of arenes is an important part of electrophilic aromatic substitution reactions. However, the reactivity of arenes is weakened by electron-withdrawing substituents, leading to limited substrate scopes and applications. Herein, we developed an efficient HOTf-promoted Friedel-Crafts alkylation reaction of broad arenes with α-aryl-α-diazoesters under metal-free and solvent-free conditions.

B(9)-OH-o-Carboranes: Synthesis, Mechanism, and Property Exploration.

Herein, we present a chemically robust and efficient synthesis route for B(9)-OH-o-carboranes by the oxidation of o-carboranes with commercially available 68% HNO3 under the assistance of trifluoromethanesulfonic acid (HOTf) and hexafluoroisopropanol (HFIP). The reaction is highly efficient with a wide scope of carboranes, and the selectivity of B(9)/B(8) is up to 98:2. The success of this transformation relies on the strong electrophilicity and oxidizability of HNO3, promoted through hydrogen bonds of the Brønsted acid HOTf and the solvent HFIP. Mechanism studies reveal that the oxidation of o-carborane involves an initial electrophilic attack of HNO3 to the hydrogen atom at the most electronegative B(9) of o-carborane. In this transformation, the hydrogen atom of the B-H bond is the nucleophilic site, which is different from the electrophilic substitution reaction, where the boron atom is the nucleophilic site. Therefore, this is an oxidation-reduction reaction of o-carborane under mild conditions in which N(V) → N(III) and H(-I) → H(I). The derivatization of 9-OH-o-carborane was further examined, and the carboranyl group was successfully introduced to an amino acid, polyethylene glycol, biotin, deoxyuridine, and saccharide. Undoubtedly, this approach provides a selective way for the rapid incorporation of carborane moieties into small molecules for application in boron neutron capture therapy, which requires the targeted delivery of boron-rich groups.

Trifluoromethanesulfonic Acid Promoted Controllable Electrophilic Aromatic Nitration.

In this work, we developed a facile and controllable electrophilic aromatic nitration method with commercially available 68% HNO3 as the nitrating reagent and trifluoromethanesulfonic acid (HOTf) as the catalyst in hexafluoroisopropanol or under solvent-free conditions. The electrophilic nitration products of different arenes can be obtained in almost quantitative yields by tuning the loading of HOTf. The strong acidity and water absorbing property of HOTf allowed this transformation to reach completion in a short time at room temperature.

A Method for Highly Selective Halogenation of o-Carboranes and m-Carboranes.

A facile halogenation method for highly selective synthesis of 9-X-o-carboranes, 9,12-X2-o-carboranes, 9-X-12-X'-o-carboranes, 9-X-m-carboranes, 9,10-X2-m-carboranes, and 9-X-10-X'-m-carboranes (X, X' = Cl, Br, I) has been developed on the basis of our previous work. The success of this transformation relies on the usage of trifluoromethanesulfonic acid (HOTf), the easily available strong Brønsted acid. The addition of HOTf greatly increases the electrophilicity of N-haloamides through hydrogen bonding interaction, resulting in the low loading of N-haloamides, short reaction time, and mild reaction conditions. Additionally, the solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is also essential to further increase the acidity of HOTf.

Palladium-Catalyzed Regioselective B(9)-Amination of o-Carboranes and m-Carboranes in HFIP with Broad Nitrogen Sources.

Amination of carboranes has a good application prospect in organic and pharmaceutical synthesis. However, the current methods used for this transformation suffer from limitations. Herein, we report a practical method for a highly regioselective formation of a B-N bond by Pd(II)-catalyzed B(9)-H amination of o- and m-carboranes in hexafluoroisopropanol (HFIP) with different nitrogen sources under air atmosphere. The silver salt and HFIP solvent play critical roles in the present protocol. The mechanistic study reveals that the silver salt acts as a Lewis acid to promote the electrophilic palladation step by forming a heterobimetallic active catalyst PdAg(OAc)3; the strong hydrogen-bond-donating ability and low nucleophilicity of HFIP enhance the electrophilic ability of Pd(II). It is believed that these N-containing carboranes are potentially of great importance in the synthesis of new pharmaceuticals.

Synthesis of Six-Membered N-Heterocycle Frameworks Based on Intramolecular Metal-Free N-Centered Radical Chemistry.

The formation of intramolecular C-N bond represents a powerful strategy in organic transformation as the great importance of N-heterocycles in the fields of natural products and bioactive molecules. This personal account describes the synthesis of cyclic phosphinamidation, benzosultam, benzosulfoximine, phenanthridine and their halogenated compounds through transition-metal-free intramolecular oxidative C-N bond formation. Mechanism study reveals that N-X bond is initially formed under the effect of hypervalent halogen, which is very unstable and easily undergoes thermal or light homolytic cleavage to generate nitrogen radical. Then the nitrogen radical is trapped by the arene to give aryl radical. Rearomatization of aryl radical under the oxidant to provide corresponding N-heterocycle. Under suitable conditions, the N-heterocycles can be further transformed to halogenated N-heterocycles.

Practical Synthesis of B(9)-Halogenated Carboranes with N-Haloamides in Hexafluoroisopropanol.

The B(9)-H halogenation of o-carborane and m-carborane was achieved with excellent selectivities in hexafluoroisopropanol (HFIP) under simple reaction conditions: single reagent [trichloroisocyanuric acid (TCCA), tribromoisocyanuric acid (TBCA) or N-iodosuccinimide (NIS)], catalyst-free, air-/moisture-tolerant, and convenient work-up. With this method, a variety of 9-halogenated o-carboranes and m-carboranes were obtained in good to excellent yields with broad tolerance of functional groups.

Hydroboration Reaction and Mechanism of Carboxylic Acids using NaNH2(BH3)2, a Hydroboration Reagent with Reducing Capability between NaBH4 and LiAlH4.

Hydroboration reactions of carboxylic acids using sodium aminodiboranate (NaNH2[BH3]2, NaADBH) to form primary alcohols were systematically investigated, and the reduction mechanism was elucidated experimentally and computationally. The transfer of hydride ions from B atoms to C atoms, the key step in the mechanism, was theoretically illustrated and supported by experimental results. The intermediates of NH2B2H5, PhCH═CHCOOBH2NH2BH3-, PhCH═CHCH2OBO, and the byproducts of BH4-, NH2BH2, and NH2BH3- were identified and characterized by 11B and 1H NMR. The reducing capacity of NaADBH was found between that of NaBH4 and LiAlH4. We have thus found that NaADBH is a promising reducing agent for hydroboration because of its stability and easy handling. These reactions exhibit excellent yields and good selectivity, therefore providing alternative synthetic approaches for the conversion of carboxylic acids to primary alcohols with a wide range of functional group tolerance.

Syntheses of Bromo-N-heterocycles through Dibromohydantoin-Promoted Tandem C-H Amination/Bromination.

Herein, we report a metal-free radical tandem C-H amination and bromination reaction with dibromohydantoin (DBH) as both the amination and bromination reagents and water as the main solvent. The reaction involves in intramolecular C-H amination and electrophilic bromination using cheap commercially available DBH. The products represent heterocyclic building blocks, readily modifiable by classical cross-coupling reactions.

Synthesis of Phenanthridines through Iodine-Supported Intramolecular C-H Amination and Oxidation under Visible Light.

Herein, we report a metal-free and step-economic synthesis of phenanthridines from 2-biarylmethanamines under mild conditions. The reaction involves iodine-supported intramolecular C-H amination and oxidation of 5,6-dihydrophenanthridine under air and benign visible light. The mechanism study reveals that visible light plays a key role in both these steps.

One-Pot Synthesis of Iodo-Dibenzothiazines from 2-Biaryl Sulfides.

Herein, we report a metal-free and step-economic synthesis of iodo-dibenzothiazines from 2-biaryl sulfides under mild reaction conditions. The reaction involves sulfoximination of sulfides, intramolecular C-H amination, and iodization using cheap commercially available reagents. The products represent heterocyclic building blocks, readily modifiable by classical cross-coupling reactions.

New Approaches for Biaryl-Based Phosphine Ligand Synthesis via P═O Directed C-H Functionalizations.

Given the important influence of phosphine ligands in transition metal-catalyzed reactions, chemists have searched for straightforward and efficient methodologies for the synthesis of diverse phosphine ligands. Although significant progress has been made in this aspect over the past decades, the development of new phosphorus-containing ligands with properties superior to their predecessors remains a central task for chemists. Recently, researchers have demonstrated that biphenyl monophosphine ligands function as highly efficient ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. In 1998, Buchwald introduced a new class of air-stable phosphine ligands based on the dialkylbiaryl phosphine backbone. These ligands have been successfully used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen, and carbon-oxygen construction processes as well as serving as supporting ligands for a number of other reactions. At the same time, the use of the biphenyl monophosphine ligands often allows reactions to proceed with short reaction times and low catalyst loadings and under mild reaction conditions. However, the synthesis of chiral biphenyl monophosphine ligands, especially those the chirality of which is due to biaryl axial chirality, is very limited. In this Account, we summarize our methodologies for the synthesis of this kind of biphenyl monophosphine ligands including the P═O directed C-H functionalization, P═O directed diastereoselective C-H functionalization, P═O directed enantioselective C-H functionalization, and metal-free diastereoselective radical oxidative C-H amination under mild reaction conditions. With these methods, a series of biphenyl phosphine ligand precursors containing achiral or axially chiral centers and precursors possessing both axial chirality and a chirogenic phosphorus center with different electronic properties and steric effect have been obtained under different reaction conditions. For the preparation of chiral biphenyl monophosphine ligands, which not only possess axial chirality but in many cases also possess chirality at phosphorus, the primary means of introducing chirality is through the use of the menthyl phenylphosphinate. As a chiral auxiliary group, the menthyl phenylphosphinate has some unique features: (i) it is easy to prepare; (ii) the products contain both axial chirality and central chirality on the phosphorus atom; (iii) the menthyl group could easily be transformed into other functional groups, which is crucial for the diversity of the corresponding biphenyl ligands. In our reaction, the P═O group not only acts as the directing group but also facilitates the construction of the phosphine ligands. In addition, the application of these products in asymmetric catalysis has also been studied with good results obtained in some reactions. The further application of these ligands, especially the chiral biphenyl monophosphine ligands in catalysis reactions is underway in our laboratory, and we hope different kinds of reactions will be achieved with these ligands.

Tandem Oxidative C-H Amination and Iodization to Synthesize Difunctional Atropoisomeric P-Stereogenic Phosphinamides.

An efficient metal-free tandem intramolecular oxidative C-H amination and iodization of phosphinamide was performed and a series of new phosphorus heterocyclic compounds was obtained. This method provides a concise and highly valuable pathway for the synthesis of difunctional atropoisomeric P-stereogenic phosphinamides.

Asymmetric Synthesis of Chiral Atropisomeric Bis-Aryl Organophosphorus from Menthyl H-Phosphinate.

This review describes new methods for the synthesis of chiral monophosphine ligands with menthyl phenylphosphinate as a chiral auxiliary through asymmetric Suzuki-Miyaura cross-coupling reactions and asymmetric C-H functionalization. The chiral menthyl phenylphosphinate as a chiral auxiliary is easy to prepare and the menthyl group can easily be transformed into other functional groups, with the chiral center synchronously remaining. These methodologies provide highly efficient and practical strategies for the synthesis of novel axially chiral biaryl monophosphine oxides and their corresponding phosphines. Meanwhile, these reactions are easy to handle and exhibit wide scope for substrates with excellent diastereomeric ratios.

Asymmetric Suzuki-Miyaura cross-coupling for the synthesis of chiral biaryl compounds as potential monophosphine ligands.

Efficient asymmetric Suzuki-Miyaura coupling reactions have been employed for the first time to synthesize chiral biaryl compounds with phosphinate groups as chiral auxiliaries. A series of functionalized chiral biaryls are thereby synthesized in excellent yields and good diastereoselectivities (up to >95:5 d.r.) and axially chiral monophosphorus ligands are obtained through further functionalizations.

P(O)R2-directed Pd-catalyzed C-H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands.

Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C-H activation; the functionalized products are produced with good enantioselectivity.

9,9'-Bis-o-carboranes: synthesis and exploration of properties.

A highly efficient Pd-catalyzed B(9)-H/B(9)-H oxidative dehydrogenation coupling of carboranes to synthesize 9,9'-bis-o-carboranes has been developed. The properties and derivatization of 9,9'-bis-o-carborane were also examined, which provided diverse bis-o-carborane derivatives and bis-nido-carborane.

Unravelling the underlying mechanism of the reduction of aldehydes/ketones with metal borohydride in an aprotic solvent.

The reduction mechanism of aldehyde/ketones with M(BH4)n is not fully understood, even though the hydroboration mechanism of weak Lewis base borane complexes is known to involve a four-membered ring transition state. Herein, the reduction mechanism of M(BH4)n in aprotic solvents has been elucidated for a six-membered ring, in which hydride transfer to the C atom from the B atom, formation of an L·BH3 adduct, and disproportionation of (BH3(OR)-) borane are involved. The metal cations and solvents participate in and significantly influence the reaction procedure. We believe that this mechanistic study would provide a further reference for the application of M(BH4)n in organic reactions.

Triborane (B3H7)-mediated regioselective substitution reactions of pyridine derivatives.

There exists an interplay between borane and a Lewis base in their adducts. However, studies on these adducts so far have mainly focused on the different reactions of B-H bonds with limited attention given to the influence of borane on the chemistry of the Lewis base, except for BF3 and BAr3. Herein, we have synthesized novel borane adducts with pyridine derivatives, Py·B3H7, in which the coordination of B3H7 efficiently achieved the intra-molecular charge transfer. The strong B-N bond in these adducts resulted in the formation of stable dearomatic intermediates of pyridine derivatives, confirmed by 1H and 11B NMR spectroscopy, from which different reactions have transpired to realize C(sp3)-H and C(sp2)-H functionalization under mild conditions. The B3H7 pyridine derivatives are stable and do not dissociate or decompose during the reaction process. The high stability of the B-N bond makes this method a good option for boron-containing drugs with potential for use in boron neutron capture therapy (BNCT).

Nickel-catalyzed C-P cross-coupling of diphenylphosphine oxide with aryl chlorides.

A novel protocol for the preparation of various diarylphosphine oxide compounds via a Ni-catalyzed cross-coupling of aryl chlorides with R(2)P(O)H has been developed. Notably, this process exhibits the following very attractive features: (i) the process is simpler and operates under mild reaction conditions; (ii) the process is generally cheaper in part because the more accessible aryl chloride is used to form the C-P bond; (iii) the process avoids the need for simultaneous preparation and use of Ar(2)P(O)M.