Boryl Group Research Articles

Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation

AbstractHerein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C−NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β‐scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol‐containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β‐scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

Unified Approach to Deamination and Deoxygenation Through Isonitrile Hydrodecyanation: A Combined Experimental and Computational Investigation.

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C-NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β-scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol-containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β-scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol.

Carbene-Stabilized Phosphagermylenylidene: A Heavier Analog of Isonitrile.

Phosphagermylenylidenes (R-P═Ge), as heavier analogs of isonitriles, whether in their free state or as complexes with a Lewis base, have not been previously identified as isolable entities. In this study, we report the synthesis of a stable monomeric phosphagermylenylidene within the coordination sphere of a Lewis base under ambient conditions. This species was synthesized by Lewis base-induced dedimerization of a cyclic phosphagermylenylidene dimer or via Me3SiCl elimination from a phosphinochlorogermylene framework. The deliberate integration of a bulky, electropositive N-heterocyclic boryl group at the phosphorus site, combined with coordination stabilization by a cyclic (alkyl)(amino)carbene at the low-valent germanium site, effectively mitigated its natural tendency toward oligomerization. Structural analyses and theoretical calculations have demonstrated that this unprecedented species features a P═Ge double bond, characterized by conventional electron-sharing π and σ bonds, complemented by lone pairs at both the phosphorus and germanium atoms. Preliminary reactivity studies show that this base-stabilized phosphagermylenylidene demonstrates facile release of ligands at the Ge atom, coordination to silver through the lone pair on P, and versatile reactivity including both (cyclo)addition and cleavage of the P═Ge double bond.

Boryl Radical as a Catalyst in Enabling Intra- and Intermolecular Cascade Radical Cyclization Reactions: Construction of Polycyclic Molecules.

Cascade radical cyclization constitutes an atom- and step-economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox-active metal catalysts has recently shown robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium-based N-heterocyclic carbene (NHC)-boryl radical is capable of catalyzing cascade cyclization reactions in both intra- and intermolecular pathways, assembling [5,5] fused bicyclic and [6,6,6] fused tricyclic molecules, respectively. The catalytic reactions start with the chemo- and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal [3+2] or an intermolecular [2+2+2] cycloaddition process to construct bicyclo[3.3.0]octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a β-elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control.

Boryl Radical as a Catalyst in Enabling Intra‐ and Intermolecular Cascade Radical Cyclization Reactions: Construction of Polycyclic Molecules

AbstractCascade radical cyclization constitutes an atom‐ and step‐economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox‐active metal catalysts has recently shown robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium‐based N‐heterocyclic carbene (NHC)‐boryl radical is capable of catalyzing cascade cyclization reactions in both intra‐ and intermolecular pathways, assembling [5,5] fused bicyclic and [6,6,6] fused tricyclic molecules, respectively. The catalytic reactions start with the chemo‐ and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal [3+2] or an intermolecular [2+2+2] cycloaddition process to construct bicyclo[3.3.0]octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a β‐elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control.

Complexes of Borane and 1,3,5‐Triazinane‐Derived Carbenes

AbstractComplexes of borane with six‐membered N‐heterocyclic carbenes derived from readily accessible 1,3,5‐triazinium salts are described. Similar to the widely used imidazolium‐type borane complex, the obtained complexes behave as agents for the hydrogen atom transfer in the Giese reaction and as sources of the boryl radicals in addition to imines. The amine nitrogen of these complexes does not undergo alkylation, but it can bind with another borane molecule.

Dinuclear gold-catalyzed divergent dechlorinative radical borylation of gem-dichloroalkanes

The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.

Remote Boryl and Alkenyl Radical Migration of Olefin-Bearing Aryl Bromides

Remote Boryl and Alkenyl Radical Migration of Olefin-Bearing Aryl Bromides

Stereoselective Synthesis of Unsymmetrical 1,1-Diborylalkenes

Abstract1,1-Diborylalkene, a class of important diboryl species, serves as the synthetic precursor of multisubstituted olefin, which is a prevalent building block in natural products, functional materials, and pharmaceuticals. Current methods mainly afford symmetrical 1,1-diborylalkenes, and late-stage differentiation of the two identical boryl groups is required to achieve selective difunctionalization. In comparison, stereoselective synthesis of unsymmetrical 1,1-diborylalkenes (UDBA) are less-explored. This Synpacts article provides a brief summary of the achievements in the synthesis of UDBAs. In particularly, we highlight our recent work on the unsymmetrical 1,1-diborylation of alkynes using a neutral sp2–sp3 diboron reagent to access UDBAs and their controllable stepwise derivatization.1 Introduction2 Background: Unsymmetrical 1,1-Diborylalkene Synthesis3 Stereoselective Unsymmetrical 1,1-Diborylation of Alkynes with a Neutral sp2–sp3 Diboron Reagent4 Summary and Outlook

Enantioselective α-Boryl Carbene Transformations.

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

Photoinduced Radical Borylation of Alkyl Chlorides

AbstractThe traditional method for the preparation of alkylboronic esters involves transition metal catalysis or transition metal‐free methods relying on single electron transfer. Each method relies on the suitable choice of catalyst or electron transfer mediator. In this study, we have developed a new method for the synthesis of alkylboronic esters from alkyl chlorides and diboron(4) compounds, without the need for additional metal or non‐metal catalysts. We discovered that under 400 nm visible light irradiation, alkyl chlorides can be activated in the presence of bis(neopentyl glycolato)diboron and an alkoxide base to form alkyl radical intermediates, which then react with diboron(4) compounds, resulting in high yields of alkylboronic esters. The reaction is applicable to both primary and secondary alkyl chlorides. The simplicity of operation and the broad substrate scope of this method make it practical for the synthesis of valuable alkylboronic ester intermediates.

Dianionic and Neutral Diboron-Centered Classical Diradicaloids.

Herein, we report the syntheses and electronic structures of crystalline dianionic as well as neutral diboron-centered classical diradicaloids as boron analogues of classical Thiele, Chichibabin, and Müller (this only for dianionic diradicaloids!) hydrocarbons. These are based on borane radical anion and NHC-stabilized boryl radical spin carriers, respectively. All these dianionic diboron-centered diradicaloids exhibit triplet population at room temperature regardless of the π-conjugated spacer: p-phenylene, p,p'-biphenylene, or p,p″-terphenylene. In the case of neutral diboron-centered diradicaloids, the employed π-conjugated spacer plays a crucial role for the triplet population at room temperature: EPR inactive for p-phenylene vs EPR active for p,p'-biphenylene. The findings emphasize the importance of the spin carriers for the resulting ground-state: borane radical anion vs NHC-stabilized boryl radical along with the pivotal role of the π-conjugated spacer as spin-coupler between two spins. Notably, 100 years (a century) after the first report by Krause of the triphenyl borane radical-anion, being isoelectronic to the triphenylmethyl radical, we convey borane radical anion-based diradicaloids. Furthermore, while donor-stabilized boryl radicals were introduced in the 1980s by Giles and Roberts, said concept is herewith being extended to NHC-stabilized boryl radical-based diradicaloids.

Visible Light-Induced 1,2-Diphenyldisulfane-Mediated Defluoroborylation of Polyfluoroarenes.

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

Sodium-Mediated Reductive C-C Bond Cleavage Assisted by Boryl Groups.

In contrast to the well-established oxidative C=C double bond cleavage to give the corresponding carbonyl compounds, little is known about reductive C=C double bond cleavage. Here we report that C-C single bond cleavage in 1,2-diaryl-1,2-diborylethanes proceeds by reduction with sodium metal to yield α-boryl benzylsodium species. In combination with our previous reductive diboration of stilbenes, the overall transformation represents reductive cleavage of the C=C double bonds of stilbene to yield α-boryl-α-sodiated toluenes. This reductive two-step C=C double bond cleavage is applicable to ring-opening or ring-expansion reactions of polycyclic aromatic hydrocarbons.

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.