Boryl Group Research Articles

Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates.

Even though metal-catalyzed enantioselective hydroborations of alkenes have attracted enormous attention, few preparatively useful reactions of α-alkyl acrylic acid derivatives are known, and most use rhodium catalysts. No examples of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are known. In our continuing efforts to search for new applications of earth-abundant cobalt catalysts for broadly applicable organic transformations, we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild reaction conditions for efficient and highly regio- and enantioselective hydroboration of α-alkyl- and α-aryl- acrylates, giving β-borylated propionates. Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and C-C bonds, these intermediates could serve as valuable chiral synthons, some from feedstock carbon sources, for the synthesis of propionate-bearing motifs including polyketides and related molecules. Two-step syntheses of "Roche" ester from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), which are potential intermediates for several medicinally important classes of compounds, illustrate the power of the new methods. Mechanistic studies confirm the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in these reactions and rule out the possibility of a [L]Co-H-initiated route, which has been well-established in related hydroborations of other classes of alkenes. A mechanism involving an oxidative migration of a boryl group to the β-carbon of an η4-coordinated acrylate-cobalt complex is proposed as a plausible route.

A Boron Scan of Ethyl Acetoacetate Leads to Versatile Building Blocks.

Discovered in the 19th century, ethyl acetoacetate has been central to the development of organic chemistry, including its pedagogy and applications. In this study, we present borylated derivatives of this venerable molecule. A boron handle has been installed at either - or -position of acetoacetate by homologation of acyl-MIDA (N-methyliminodiacetic acid) boronates with diazoacetates. Either alkyl or boryl groups were found to migrate with regiochemistry being a function of the steric bulk of the diazo species. Boryl -ketoesters can be further modified into borylated pyrazolones and oximes, thereby expanding the synthetic toolkit and offering opportunities for additional modifications.

A Boron Scan of Ethyl Acetoacetate Leads to Versatile Building Blocks

AbstractDiscovered in the 19th century, ethyl acetoacetate has been central to the development of organic chemistry, including its pedagogy and applications. In this study, we present borylated derivatives of this venerable molecule. A boron handle has been installed at either ‐ or ‐position of acetoacetate by homologation of acyl‐MIDA (N‐methyliminodiacetic acid) boronates with diazoacetates. Either alkyl or boryl groups were found to migrate with regiochemistry being a function of the steric bulk of the diazo species. Boryl ‐ketoesters can be further modified into borylated pyrazolones and oximes, thereby expanding the synthetic toolkit and offering opportunities for additional modifications.

Asymmetric Cyclizations Catalyzed by Chiral Boryl Radicals

Asymmetric Cyclizations Catalyzed by Chiral Boryl Radicals

Photoinduced Dual C-F Bond Activation of Hexafluorobenzene Mediated by Boron Atom.

The reaction of laser-ablated boron atoms with hexafluorobenzene (C6 F6 ) was investigated in neon and argon matrices, and the products are identified by matrix isolation infrared spectroscopy and quantum-chemical calculations. The reaction is triggered by a boron atom insertion into one C-F bond of hexafluorobenzene on annealing, forming a fluoropentafluorophenyl boryl radical (A). UV-Vis light irradiation of fluoropentafluorophenyl boryl radical causes generation of a 2-difluoroboryl-tetrafluorophenyl radical (B) via a second C-F bond activation. A perfluoroborepinyl radical (C) is also observed upon deposition and under UV-Vis light irradiation. This finding reveals the new example of a dual C-F bond activation of hexafluorobenzene mediated by a nonmetal and provides a possible route for synthesis of new perfluorinated organo-boron compounds.

Lewis Base‐Boryl Radicals Promoted Selective Mono‐ and Di‐ Hydrodechlorination of Trichloroacetamides and Acetates

AbstractMono and dichloro‐substituted organic molecules are shown to possess significant roles in various fields, especially in medicinal chemistry. One approach to synthesizing these compounds involves the selective dechlorination of easily prepared trichloromethyl compounds. Nevertheless, developing a practical approach that allows selective mono‐ and dihydrodechlorination is a challenging task. Herein, we introduced a method for selective mono‐ and dihydrodechlorination of trichloroacetamides and acetates which was promoted by two different Lewis base‐boryl radicals. Accordingly, 4‐dimethylaminopyridine (DMAP)‐borane enabled mono‐substitution of chlorine atom by hydrogen while dihydro‐substitution of chlorine atoms was promoted by N‐heterocyclic carbene (NHC)‐boryl radical. Using deuterated Lewis base‐borane as deuterium atom source, mono‐ and dideuterodechlorination were also successfully took place. This protocol features broad substrate scope and operates under mild reaction conditions.

Vinylidene rearrangements of internal borylalkynes via 1,2-boryl migration.

Vinylidene rearrangement of alkynes is a well-established and powerful method for alkyne transformations, while use of borylalkynes has remained largely unexplored. This paper describes vinylidene rearrangements of internal borylalkynes using a cationic ruthenium complex. This rearrangement is applicable to alkynes with both tri-(B(pin), B(dan)) and tetracoordinate (B(mida)) boryl groups, and the reaction rate is dramatically affected by the Lewis acidity of the boryl group. Mechanistic study revealed that the rearrangement proceeds via 1,2-boryl migration regardless of the coordination number of the boron center. The migration mode was elucidated by theoretical calculations to indicate that the migration of the tricoordinate boryl groups is an electrophilic process in contrast to the previous vinylidene rearrangements of internal alkynes with two carbon substituents.

Visible light-induced halogen-atom transfer by N-heterocyclic carbene-ligated boryl radicals for diastereoselective C(sp3)-C(sp2) bond formation.

Photoinduced halogen-atom transfer (XAT) has rapidly emerged as a programmable approach to generate carbon-centered radical intermediates, mainly relying on silyl and α-aminoalkyl radicals as halogen abstractors. More recently, ligated boryl radicals have also been proposed as effective halogen abstractors under visible-light irradiation. In this study, we describe the use of this approach to enable C(sp3)-C(sp2) bond formation via radical addition of carbon-centered radicals generated via XAT onto chloroalkynes. Our mechanistic investigation reveals a complex interplay of highly reactive radical intermediates which, under optimized conditions, delivered the targeted vinyl chlorides in excellent yields and Z : E ratios. Finally, we demonstrated the synthetic value of these products in transition metal-based cross-coupling reactions.

Radical hydroboration for the synthesis of organoboron compounds.

Organoboron compounds demonstrate diverse applications in the fields of organic synthesis, materials science, and medicinal chemistry. Compared to the conventional hydroboration reaction, radical hydroboration serves as an alternative approach for the synthesis of organoborons via different mechanisms. In radical hydroboration, a boryl radical is initially generated from homolytic cleavage of a B-H or a B-B bond, which is then added to an unsaturated double bond to deliver a carbon radical. Subsequent hydrogen atom transfer or reduction of the carbon radical to form a carbanion followed by protonation gave the final product. Over the past few years, numerous efforts have been made for efficient synthesis of boryl radicals and the expansion of substrate scope of the radical hydroboration reaction. Here, we discuss the recent advancement of radical hydroboration and its associated mechanisms. Numerous radical hydroboration strategies employing N-heterocyclic carbene borane, bis(pinacolato)diboron and pinacolborane as the boron source were illustrated. Thermochemical, photochemical and electrochemical strategies for the generation of boryl radicals were also discussed in detail.

Hydroalkylation of styrenes enabled by boryl radical mediated halogen atom transfer.

In this study, we present an inexpensive, stable, and easily available boryl radical source (BPh4Na) employed in a Halogen Atom Transfer (XAT) methodology. This mild and convenient strategy unlocks the use of not only alkyl iodides as radical precursors but also of the more challenging alkyl and aryl bromides to generate C-centered radicals. The generated radicals were further engaged in the anti-Markovnikov hydroalkylation of electronically diverse styrenes, therefore achieving the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. A series of experimental and computational studies revealed the prominent role of BPh4Na in the halogen abstraction step.

Recent progress in the catalytic enantioselective reactions of 1,1-diborylalkanes.

Organoboron compounds are environmentally benign, have low toxicity and are versatile reagents that are extensively employed in organic synthesis, especially in the realm of asymmetric synthesis. The last several decades have witnessed a tremendous outburst of asymmetric reactions based on various organoboron compounds. Among them, 1,1-diborylalkanes, which contain two boryl groups at the same sp3-carbon atom, are regarded as some of the most versatile and powerful reagents for their unique structure and unusual reaction mode in organic synthesis. Moreover, owing to the stabilizing effect of the empty p-orbital of the neighboring boron atoms and the inherent good steric-hindrance, 1,1-diborylalkanes often exhibit extraordinary reactivity and stereoselectivity compared to other kinds of organoboron compounds in asymmetric synthesis. Herein, the present highlight summarizes and discusses the recent progress achieved in the catalytic enantioselective reactions of 1,1-diborylalkanes during the past decade.

Access to C(sp3) borylated and silylated cyclic molecules: hydrogenation of corresponding arenes and heteroarenes.

This paper presents a simple and cost-effective hydrogenation method for synthesizing a myriad of cycloalkanes and saturated heterocycles bearing boryl or silyl substituents. The catalyst used are heterogeneous, readily available, bench stable, and recyclable. Also demonstrated is the application of the method to compounds that possess both boryl and silyl groups. When combined with Ir-catalyzed sp2 C-H borylation, such hydrogenations offer a two-step complementary alternative to direct sp3 C-H borylations that can suffer selectivity and reactivity issues. Of practical value to the community, complete stereochemical analyses of reported borylated compounds that were never fully characterized are reported herein.

Boryl radical-mediated halogen-atom transfer (XAT) enables the Sonogashira-like alkynylation of alkyl halides.

Alkynes are a crucial class of materials with application across the wide range of chemical disciplines. The alkynylation of alkyl halides presents an ideal strategy for assembling these materials. Current methods rely on the intrinsic electrophilic nature of alkyl halides to couple with nucleophilic acetylenic systems, but these methods faces limitations in terms of applicability and generality. Herein, we introduce a different approach to alkynylation of alkyl halides that proceeds via radical intermediates and uses alkynyl sulfones as coupling partners. This strategy exploits the ability of amine-ligated boryl radicals to activate alkyl iodides and bromides through halogen-atom transfer (XAT). The resulting radicals then undergo a cascade of α-addition and β-fragmentation with the sulfone reagent, leading to the construction of C(sp3)-C(sp) bonds. The generality of the methodology has been demonstrated by its successful application in the alkynylation of complex and high-value molecules.

Boryls, their compounds and reactivity: a structure and bonding perspective.

Boryls and their compounds are important due to their diverse range of applications in the fields of materials science and catalysis. They are an integral part of boron chemistry, which has attracted tremendous research interest over the past few decades. In this perspective, we provide an in-depth analysis of the reaction chemistry of boryl compounds from a structure and bonding perspective. We discuss the reactivity of boryls in various transition metal complexes and diborane(4) compounds towards different substrate molecules, with a focus on their nucleophilic and electrophilic properties in various reaction processes. Additionally, we briefly discuss the reactivity of boryl radicals. Our analysis sheds new light on the unique properties of boryls and their potential for catalytic applications.

Copper-Catalyzed Diastereoselective Borylative Allylation of Alkenyl Sulfones and Base-Controlled Synthesis of Skipped Dienes.

Divergent functionalization of α,β-unsaturated sulfones under copper catalysis is reported. Diastereoselective borylative allylation of alkenyl sulfones was achieved with a copper catalyst, allyl phosphate, bis(pinacolato)diboron, and LiOMe. In this method, the addition of a copper-boryl complex to alkenyl sulfone and subsequent allylic substitution rendered boroallylated products in good yield with excellent syn-diastereoselectivity. In contrast, a stronger base (KOt-Bu) promoted the reaction further toward the formation of (E)-skipped dienes, through elimination of the sulfonyl and boryl groups.

Boryl radical catalysis enables asymmetric radical cycloisomerization reactions.

The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal of synthetic chemistry. In this work, we report a family of chiral N-heterocyclic carbene (NHC)-ligated boryl radicals as catalysts that enable catalytic asymmetric radical cycloisomerization reactions. The radical catalysts can be generated from easily prepared NHC-borane complexes, and the broad availability of the chiral NHC component provides substantial benefits for stereochemical control. Mechanistic studies support a catalytic cycle comprising a sequence of boryl radical addition, hydrogen atom transfer, cyclization, and elimination of the boryl radical catalyst, wherein the chiral NHC subunit determines the enantioselectivity of the radical cyclization. This catalysis allows asymmetric construction of valuable chiral heterocyclic products from simple starting materials.

Photocatalytic Boryl Radicals Triggered Sequential B─N/C─N Bond Formation to Assemble Boron-Handled Pyrazoles.

Vinyldiazo compounds are one of the most important synthons in the construction of a cyclic ring. Most photochemical transformations of vinyldiazo compounds are mainly focusing on utilization of their C═C bond site, while reactions taking place at terminal nitrogen atom are largely unexplored. Herein, a photocatalytic cascade radical cyclization of LBRs with vinyldiazo reagents through sequential B─N/C─N bond formation is described. The reaction starts with the addition of LBRs (Lewis base-boryl radicals) at diazo site, followed by intramolecular radical cyclization to access a wide range of important boron-handled pyrazoles in good to excellent yields. Control experiments, together with detailed mechanism studies well explain the observed reactivity. Further studies demonstrate the utility of this approach for applications in pharmaceutical and agrochemical research.

Alkylation and Arylation at Boron in NHC-Stabilized Phosphaborenes.

Phosphaborenes, featuring a phosphorus-boron multiple bond, remain a relatively untapped area in chemical research due to the limited synthetic methods. Introducing leaving groups as substituents to the phosphorus or boron can pave the way for enhanced functionalization and modification. In this study, we present the synthesis of phosphaborenes featuring an N-heterocyclic boryl group on phosphorus and halogen substituent on boron, with stabilization provided by an N-heterocyclic carbene. Straightforward alkylation/arylation of these phosphaborenes is achieved by substituting the halogen with benzyl and aryl groups at the boron terminus. Our approach offers an efficient route to produce a diverse array of phosphaborene structures.

Formation of C-B, C-C, and C-X Bonds from Nonstabilized Aryl Radicals Generated from Diaryl Boryl Radicals.

With the development of organoboron chemistry, boron-centered radicals have become increasingly attractive. However, their synthetic applications remain limited in that they have been used only as substrates for addition reactions or as initiators for catalytic reactions. We have achieved a new reaction pathway in which tetraarylborate salts are used as precursors for aryl radicals via boron radicals, by introducing a simple activation reagent. In addition, we carried out a diverse array of transformations involving these aryl radical precursors, which allowed the construction of new C-B, C-C, and C-X bonds in the presence of visible light.

Visible-Light-Enabled Radical Alkynylborylation of Activated Alkenes

AbstractA photoredox-catalyzed protocol for performing radical difunctionalization of alkenes using N-heterocyclic carbene (NHC) boranes and alkynyl bromines is described. The alkynylborylation difunctionalization reaction involves photoredox generation of boryl radical, with subsequent radical addition to the double bond followed by the capture of alkynyl bromide to form a C–C bond. This method features mild reaction conditions, remarkable chemoselectivity, broad substrate scope and good to excellent yields (up to 89%). The modification of coumarin derivatives indicates that this approach can provide a useful route for the synthesis of complex alkynylborylated products.