Synthesis of Highly Functionalizable Symmetrically and Unsymmetrically Substituted Triarylboranes from Bench-Stable Boron Precursors

A novel and convenient methodology for the one-pot synthesis of sterically congested triarylboranes by using bench-stable aryltrifluoroborates as the boron source is reported. This procedure gives systematic access to symmetrically and unsymmetrically substituted triarylboranes of the types BAr₂Ar’ and BArAr'Ar’’, respectively. Three unsymmetrically substituted triarylboranes as well as their iridium-catalyzed C−H borylation products are reported. These borylated triarylboranes contain one to three positions that can subsequently be orthogonally functionalized in follow-up reactions, such as Suzuki-Miyaura cross-couplings or Sonogashira couplings.     

Large‐Scale and Facile Preparation of Pure Ammonia Borane through Displacement Reactions

Ammonia borane (AB) is the most widely studied hydride for hydrogen storage in addition to being a useful reducing agent. Attempts to synthesize pure AB through simple displacement reactions date back to the 1960s; but have been thwarted by the formation of the diammoniate of diborane (DADB), an ionic byproduct. Based on our recent characterization of the formation mechanism of DADB, we have developed a large‐scale synthesis of pure AB by both increasing the basicity of the Lewis base of the borane carrier and using a nonpolar solvent to limit the formation of an intermediate, the ammonia diborane (AaDB). Conditions were optimized for the preparation of pure AB by two displacement reactions, either ammonia with dimethylsulfide borane or ammonia with dimethylaniline borane in toluene at room temperature. These procedures are also suitable for preparation of other amine boranes which had the same problem of forming ionic byproducts during displacement reactions.     

Synthetic Approaches to Trifluoromethoxy‐Substituted Compounds

Because of the unique properties of the trifluoromethoxy group, molecules bearing this moiety will find applications in various fields, particularly in the life sciences. However, despite the great interest in this functional group, only a small number of trifluoromethoxylated molecules are currently synthetically accessible. Over the last few years, several innovative and promising strategies for the synthesis of trifluoromethoxylated compounds have been described. This Minireview discusses these existing methods with a particular focus on more recent advances.     

Pd-catalyzed borylative polycyclization of enediynes to alkylboronates

Pd-catalyzed bicyclization of 1-ene-6,11-diynes with bis(pinacolato)diboron smoothly affords synthetically useful homoallylic alkylboronates under mild conditions, avoiding the use of highly nucleophilic or basic reagents. One C-B bond and two new C-C bonds are created, and two new stereogenic centers are stereospecifically formed in a single tandem operation. The obtained products suggest a cascade reaction in which the last step is the transmetalation of bis(pinacolato)diboron, this being faster than a possible β-hydride elimination process. The reaction is general and has been applied to enediynes with different substituents on the alkene unit, the bridging groups, and the alkyne moiety. The bicyclized alkylboronates thus obtained can be functionalized by oxidation to alcohols, formation of trifluoroborate salts, or by Suzuki coupling reactions.     

Synthetic Approaches to Star‐Shaped Molecules with 1,3,5‐Trisubstituted Aromatic Cores

Herein, we summarize the synthetic approaches that have been developed for the synthesis of star‐shaped molecules. Typically, to design such highly functionalized molecules, simple building blocks are first assembled through trimerization reactions, starting from commercially available starting materials. Then, these building blocks are synthetically manipulated to generate extended star‐shaped molecules. We also discuss the syntheses of star‐shaped molecules that contain 2,4,6‐trisubstituted 1,3,5‐triazine or 1,3,5‐trisubstituted benzene rings as a central core and diverse substituted styrene, phenyl, and fluorene derivatives at their periphery, which endows these molecules with extended conjugation. A variety of metal‐catalyzed reactions, such as Suzuki, Buchwald–Hartwig, Sonogashira, Heck, and Negishi cross‐coupling reactions, as well as metathesis, have been employed to functionalize a range of star‐shaped molecules. The methods described herein will be helpful for designing a wide range of intricate compounds that are highly valuable in the fields of supramolecular chemistry and materials science. Owing to space limitations, we will not cover all of the publications on this topic. Instead, we will focus on examples that were reported by our research group and other relevant recent literature. Apart from the trimerization sequence, this Minireview has been structured based on the key reactions that were used to prepare the star‐shaped molecules and other higher analogues. Finally, some examples that do not fit into this classification are discussed.     

Bowls,Hoops, and Saddles: Synthetic Approaches to Curved Aromatic Molecules

This review summarizes recent advances in the chemistry of curved aromatic molecules. By focusing on the key accomplishments of the last decade, we provide a general overview of synthetic methods capable of efficient induction of internal strain in π‐conjugated frameworks. The review is structured according to the topology change involved in the strain‐inducing reaction step (cyclizations, eliminations, ring expansions and contractions), and highlights the striking diversity of structures achievable with modern synthetic methodology.     

Chiral Organoborane Lewis Pairs Derived from Pyridylferrocene

In an effort to develop a new class of redox‐active chiral Lewis pairs, pyridine and borane moieties with different steric and electronic properties were introduced onto a planar chiral 1,2‐disubstituted ferrocene framework. Metathesis of lithiated, stannylated, or mercuriated pyridylferrocenes with boron halides afforded (pR)‐2‐[bis(pentafluorophenyl)boryl]‐1‐(3,5‐dimethylpyrid‐2‐yl)ferrocene ( 4‐Pf ), (pR)‐2‐[dimesitylboryl]‐1‐(3,5‐dimethylpyrid‐2‐yl)ferrocene ( 4‐Mes ), (pS)‐2‐(bis(pentafluorophenyl)boryl)‐1‐(2‐trimethylsilylpyrid‐6‐yl)ferrocene ( 5‐Pf ), or (pS)‐2‐[dimesitylboryl]‐1‐(2‐trimethylsilylpyrid‐6‐yl)ferrocene ( 5‐Mes ). The borylated products were analyzed by multinuclear NMR spectroscopy, HRMS, and single‐crystal X‐ray diffraction. Chiral HPLC and optical‐rotation measurements were employed to assess the stereoselectivity of the borylation process and to establish the correct stereochemical assignments. The strength of the B–N interactions were investigated in solution and in the solid state. Compounds 4‐Pf and 4‐Mes formed robust ‘closed’ B?N heterocyclic systems that proved to be perfectly stable to air and moisture, whereas 5‐Pf established a dynamic equilibrium, in which the B?N heterocycle was observed exclusively at room temperature, but opened up at high temperature according to ¹⁹F NMR exchange spectroscopy data. As a consequence, 5‐Pf reacted readily with a molecule of water to generate a ring‐opened pyridinium borate. The combination of bulky borane and bulky pyridyl groups in 5‐Mes led to a completely ‘open’ frustrated Lewis pair system with uncomplexed pyridine and borane groups, even at room temperature. Electrochemical studies were performed and the effect of preparative ferrocene oxidation on the structural features was also explored.     

Synthesis of Cyclic Amine Boranes through Triazole‐Gold(I)‐Catalyzed Alkyne Hydroboration

The first catalytic alkyne hydroboration of propargyl amine boranecarbonitriles is accomplished with triazole‐Au^I complexes. While the typical [L‐Au]⁺ species decomposes within minutes upon addition of amine boranecarbonitriles, the triazole‐modified gold catalysts (TA‐Au) remained active, and allowed the synthesis of 1,2‐BN‐cyclopentenes in one step with good to excellent yields. With good substrate tolerability and mild reaction conditions (open‐flask), this new method provides an alternative route to reach the interesting cyclic amine borane with high efficiency.     

氮杂环丙烷衍生物的合成方法研究进展

氮杂环丙烷衍生物是重要的有机中间体,广泛应用于某些药物和具有生物活性化合物的合成,同时它还是许多天然产物的重要构件砌块。长期以来它的合成方法研究一直受到人们的广泛关注,文章对此进行了比较详细的综述。     

In Situ Generation of Silylzinc by Si−B Bond Activation Enabling Silylzincation and Silaboration of Terminal Alkynes

A new protocol has been designed for the in situ generation of unstable Si?Zn species through the reaction of dialkylzinc, phosphine, and silylborane (Si?B). Successive reactions with various terminal alkynes using this protocol enabled highly controllable regio‐/stereo‐/chemoselective silylzincation and silaboration on demand without the need for a transition‐metal catalyst.     

Hydroboration of Graphene Oxide: Towards Stoichiometric Graphol and Hydroxygraphane

Covalently functionalized graphene materials with well‐defined stoichiometric composition are of a very high importance in the research of 2D carbon material family due to their well‐defined properties. Unfortunately, most of the contemporary graphene‐functionalized materials do not have this kind of defined composition and, usually, the amount of heteroatoms bonded to graphene framework is in the range of 1–10 at. %. Herein, we show that by a well‐established hydroboration reaction chain, which introduces ?BH₂ groups into the graphene oxide structure, followed by H₂O₂ or CF₃COOH treatment as source of ?OH or ?H, we can obtain highly hydroxylated compounds of precisely defined composition with a general formula (C₁O_0.78H_0.75)_n, which we named graphol and highly hydroxylated graphane (C₁(OH)_0.51H_0.14)_n, respectively. These highly functionalized materials with an accurately defined composition are highly important for the field of graphene derivatives. The enhanced electrochemical performance towards important biomarkers as well as hydrogen evolution reaction is demonstrated.     

Carbopyronine荧光染料中间体的有效合成方法

在非质子路易斯酸的辅助下高收率的合成了Carbopyronine荧光染料中间体2,7-双二甲氨基-9,10-二氢-9,9-二甲基蒽环。反应关键步骤是路易斯酸辅助下的环化反应,考查了几种路易斯酸的效果。确立了环化反应的最佳条件为： 2.5mol的路易斯酸与1mol的叔醇2在0 ˚C反应6 h,再于室温下反应10 h。     

A Highly Effective Ruthenium System for the Catalyzed Dehydrogenative Cyclization of Amine–Boranes to Cyclic Boranes under Mild Conditions

We recently disclosed a new ruthenium‐catalyzed dehydrogenative cyclization process (CDC) of diamine–monoboranes leading to cyclic diaminoboranes. In the present study, the CDC reaction has been successfully extended to a larger number of diamine–monoboranes ( 4 – 7 ) and to one amine–borane alcohol precursor ( 8 ). The corresponding NB(H)N‐ and NB(H)O‐containing cyclic diaminoboranes ( 12 – 15 ) and oxazaborolidine ( 16 ) were obtained in good to high yields. Multiple substitution patterns on the starting amine–borane substrates were evaluated and the reaction was also performed with chiral substrates. Efforts have been spent to understand the mechanism of the ruthenium CDC process. In addition to a computational approach, a strategy enabling the kinetic discrimination on successive events of the catalytic process leading to the formation of the NB(H)N linkage was performed on the six‐carbon chain diamine–monoborane 21 and completed with a ¹⁵N NMR study. The long‐life bis‐σ‐borane ruthenium intermediate 23 possessing a reactive NHMe ending was characterized in situ and proved to catalyze the dehydrogenative cyclization of 1 , ascertaining that bis σ‐borane ruthenium complexes are key intermediates in the CDC process.     

A Synthetic Route to Human Insulin Using Isoacyl Peptides

The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the A chain and the complicated topology of this 51‐mer peptide hormone consisting of two chains and three disulfide bonds. Reported herein is a new synthetic route utilizing the isoacyl peptide approach to address the hydrophobicity problems. The incorporation of isoacyl dipeptide segments into both A and B chains greatly improved their preparation and purification, and the RP‐HPLC recovery of the chain ligation intermediates. The new route affords human insulin with a yield of 68 % based on the starting purified A chain and an overall yield of 24 % based on the substitution of the resin used for the preparation of A chain. To the best of our knowledge, this represents the most efficient route of human insulin chemical synthesis reported to date.