Alkenyl Boronic Research Articles

Copper-Catalyzed Enantioselective Borylative Allyl-Allyl Coupling of Allenes and Allylic gem-Dichlorides.

A catalytic asymmetric reaction between allenes, bis(pinacolato)diboron, and allylic gem-dichlorides is reported. The method involves the coupling of a catalytically generated allyl copper species with the allylic gem-dichloride and provides chiral internal 1,5-dienes featuring (Z)-configured alkenyl boronate and alkenyl chloride units with high levels of chemo-, regio-, enantio-, and diastereoselectivity. The synthetic utility of the products is demonstrated with the synthesis of a range of optically active compounds. DFT calculations reveal key noncovalent substrate-ligand interactions that account for the enantioselectivity outcome and the diastereoselective formation of the (Z)-alkenyl chloride.

Polymerization Chemistry of Vinylboronic Acid Derivatives: Boron-Based Monomer Design and Polymer Reaction through Side-Chain Replacement

In chain-growth polymerization, (co)polymerization abilities of monomers are heavily dependent on the element or functional group attaching to vinyl moiety, resulting in the limitation of accessible polymers. The replacement of the element on the polymer main chain could lead to access new class of polymers with overcoming the synthetic limitations. Herein, we describe the usability of alkenylboronic acid derivatives as the monomers for radical polymerization and post-polymerization transformation through carbon-boron bond-cleaving side-chain replacement. The key for radical polymerization ability of alkenyl boronate was vacant p-orbital of boron for moderate stabilization of chain growth radical. The alkenyl boronate monomers are usable for copolymerization with common monomers as well as for RAFT polymerization. The C-B bond transformation allows syntheses of conventionally inaccessible polymers, such as poly(α-methyl vinyl alcohol), poly(α-methyl vinyl amine), styrene-vinyl alcohol copolymer, and ethylene-acrylate copolymer. Boron on the polymer main chain was also used as the trigger for stimuli-responsive backbone degradation of methacrylate polymer through C-B bond homolysis and β-scission. Thus, alkenyl boronate monomers have an impact on not only breakthrough of the limitation in polymer synthesis but also development of novel polymer functions.

Ligand-modulated regiodivergent alkenylboration of allylarenes: Reaction development and mechanistic study

Chain-walking has emerged as a promising strategy in organic synthetic methodology, but achieving site-selectivity in reactions involving competition among multiple potential positions remains a challenge. In this study, we presented a novel approach to ligand-modulated, nickel-catalyzed regiodivergent alkenylboration of allylarenes. Our method allows for highly chemoselective preparation of two classes of structurally different alkenyl boronates from the same starting by simply switching the ligand. Mechanistic investigations involving experiments and calculations suggest that the ligand-modulating regiodivergence arises from either regioselective β-H elimination or oxidative addition with organic halides. Our findings offer valuable insight into addressing site-selective issues in chain-walking reactions with multiple thermodynamically stable factors.

Diastereoselective Alkylation of Activated Nitrogen Heterocycles with Alkenyl Boronate Complexes

AbstractAlkenyl boronate complexes react with acylated quinolines and isoquinolines via 1,2‐metalate rearrangement to give alkylated, dearomatized heterocycles in good yields, diastereoselectivities, and regioselectivities. This multi‐component coupling is highly modular and can be used to access a wide scope of heterocyclic scaffolds. Chiral boronic esters made through this methodology possess high synthetic potential and can be transformed into various functional groups in one step without racemization.

Diastereoselective Alkylation of Activated Nitrogen Heterocycles with Alkenyl Boronate Complexes.

Alkenyl boronate complexes react with acylated quinolines and isoquinolines via 1,2-metalate rearrangement to give alkylated, dearomatized heterocycles in good yields, diastereoselectivities, and regioselectivities. This multi-component coupling is highly modular and can be used to access a wide scope of heterocyclic scaffolds. Chiral boronic esters made through this methodology possess high synthetic potential and can be transformed into various functional groups in one step without racemization.

Enantioselective synthesis of α-aminoboronates by NiH-catalysed asymmetric hydroamidation of alkenyl boronates.

Chiral α-aminoboronic acids and their derivatives are generally useful as bioactive compounds and some have been approved as therapeutic agents. Here we report a NiH-catalysed asymmetric hydroamidation process that with a simple amino alcohol ligand can easily produce a wide range of highly enantioenriched α-aminoboronates from alkenyl boronates and dioxazolones under mild conditions. The reaction is proposed to proceed by an enantioselective hydrometallation followed by an inner-sphere nitrenoid transfer and C–N bond forming sequence. The synthetic utility of this transformation was demonstrated by the efficient synthesis of a current pharmaceutical agent, Vaborbactam.

Cover Feature: Synthesis of 3‐Borylated Pyrrolidines by 1,3‐Dipolar Cycloaddition of Alkenyl Boronates and Azomethine Ylide (Chem. Eur. J. 54/2022)

Cover Feature: Synthesis of 3‐Borylated Pyrrolidines by 1,3‐Dipolar Cycloaddition of Alkenyl Boronates and Azomethine Ylide (Chem. Eur. J. 54/2022)

Synthesis of 3-Borylated Pyrrolidines by 1,3-Dipolar Cycloaddition of Alkenyl Boronates and Azomethine Ylide.

A scalable and efficient process for the preparation of 3-borylated pyrrolidines by 1,3-dipolar cycloaddition of N-benzyl azomethine ylide generated in situ has been developed. The optimized method included the use of LiF in DMSO at 110 °C and was suitable for α-mono-, α,β-di-, and α,β,β-trialkyl-, β,β-(hetera)cycloalkylidene-, CO2 Et-, as well as most β-(het)aryl-substituted alkenyl boropinacolates. The 1,3-dipolar reaction proceeded on a multigram scale providing 3-borylated pyrrolidines with diverse substitution patterns (including fused and spirocyclic ones) in a diastereoselective manner. The Pd(OH)2 -mediated N-debenzylation of pyrrolidine hydrochlorides was successfully performed to give the corresponding bifunctional building blocks on an up to 130 g scale, thus providing a substantial expansion of the synthetic and medicinal chemist's toolbox. Other reactions included the preparation of trifluoroborates, Zweifel-Aggarwal sp3 -sp2 coupling, and oxidative deborylation as an example of C-heteroatom bond formation.

Mechanistic Basis for the Iridium-Catalyzed Enantioselective Allylation of Alkenyl Boronates.

Iridium(phosphoramidite) complexes catalyze an enantio- and diastereoselective three-component coupling reaction of alkenyl boronic esters, organolithium reagents, and secondary allylic carbonates. The reaction proceeds through an allylation-induced 1,2-metalate shift of the alkenyl boronate to form non-adjacent stereocenters. Mechanistic investigations outline the overall catalytic cycle and reveal trends in reactivity and selectivity. Analysis of relative stereochemistry in products derived from a variety of 1,1-disubtituted alkenyl boronates provides insight into the transition state of the addition and indicates a concerted pathway. Kinetic analysis of the reaction revealed the kinetic order dependence in boronate, the catalyst, and both the slow- and fast-reacting enantiomer of allylic carbonate as well as the turnover-limiting step of the reaction. Determination of nucleophile-specific parameters N and sN for alkenyl boronate complexes enabled comparison to other classes of nucleophiles. DFT calculations indicate the addition of the alkenyl boronate to the cationic Ir(π-allyl) intermediate and the 1,2-metalate shift occur in a concerted mechanism. The stereoselectivity is determined by ligand-substrate steric repulsions and dispersion interactions in the syn addition transition state. Hammett studies supported the computational results with regard to electronic trends observed with both aryl-derived alkenyl boronates and aryl carbonates.

Copper-Catalyzed Reactions of Alkenyl Boronic Esters via Chan-Evans-Lam Coupling/Annulation Cascades: Substrate Selective Synthesis of Dihydroquinazolin-4-ones and Polysubstituted Quinolines.

Copper-catalyzed cascade cyclization reactions between alkenyl boronic esters and N-H-based nucleophiles have been established, providing new approaches for one-pot assembly of azacycles. Following the Chan-Evans-Lam C-N couplings, the cyclization processes occur via divergent pathways based on the utilized substrates, affording hydroamination product dihydroquinazolin-4-ones or aromatization product quinolines. Via this one-pot C-N coupling/annulation cascade, the target substituted azacycles can be obtained in moderate to good yields in each case.

Synthesis of Tri‐ and Tetrasubstituted Alkenyl Boronates from Alkynes

AbstractThe synthesis of organoboron compounds have attracted the attention of the synthetic community. In particular, molecules with C(sp2)‐B bonds enable the transformation to new C−C or C‐heteroatom bonds by well‐established methodologies. Alkenyl boronates have the possibility for further conversion of the boron moiety or functionalization of the double bond. This review gives an overview on the recent methodologies for the selective preparation of the challenging highly substituted alkenyl boronates from alkynes.

Diastereodivergent Synthesis of Cyclopentyl Boronic Esters Bearing Contiguous Fully Substituted Stereocenters.

The synthesis of molecules bearing two or more contiguous, quaternary stereocenters is challenging, owing to the difficulty in controlling stereochemistry whilst simultaneously constructing a sterically congested motif. Herein, we report the electrophile‐induced ring contractive 1,2‐metallate rearrangement of 6‐membered cyclic alkenyl boronate complexes for the synthesis of cyclopentyl boronic esters bearing two contiguous, fully substituted stereocenters with high levels of stereocontrol. Remarkably, simple variation of the reaction solvent enabled their diastereodivergent construction with facile access to complementary diastereomeric pairs. The utility of our methodology is demonstrated in the asymmetric total synthesis of (+)‐herbertene‐1,14‐diol.

Diastereodivergent Synthesis of Cyclopentyl Boronic Esters Bearing Contiguous Fully Substituted Stereocenters

AbstractThe synthesis of molecules bearing two or more contiguous, quaternary stereocenters is challenging, owing to the difficulty in controlling stereochemistry whilst simultaneously constructing a sterically congested motif. Herein, we report the electrophile‐induced ring contractive 1,2‐metallate rearrangement of 6‐membered cyclic alkenyl boronate complexes for the synthesis of cyclopentyl boronic esters bearing two contiguous, fully substituted stereocenters with high levels of stereocontrol. Remarkably, simple variation of the reaction solvent enabled their diastereodivergent construction with facile access to complementary diastereomeric pairs. The utility of our methodology is demonstrated in the asymmetric total synthesis of (+)‐herbertene‐1,14‐diol.

Asymmetric Synthesis of Tertiary and Secondary Cyclopropyl Boronates via Cyclopropanation of Enantioenriched Alkenyl Boronic Esters.

The cyclopropanation of alkenyl boronates and subsequent derivatization of the boronate handle are a convenient strategy to quickly build molecular complexity and access diverse compounds with a high sp3 fraction. Herein, we describe the asymmetric cyclopropanation of enantioenriched hydrobenzoin-derived alkenyl boronic esters toward the synthesis of tertiary and secondary cyclopropyl boronates.

Orthogonal C-B Bond Transformation as an Approach for Versatile Synthesis of End-Functionalized Polymers.

Conventionally inaccessible end-functionalized vinyl polymers were synthesized via orthogonal side-chain replacement for terminal and repeating units of poly(alkenyl boronate)s. A terminal-defined polymer of isopropenyl boronic acid pinacol ester (IPBpin) was synthesized via RAFT polymerization, and subsequent cobalt (Co)-catalyzed end olefination afforded the polymer carrying the C(sp2)-B bond at the terminal and the C(sp3)-B bond in repeating units. Herein, the terminal C(sp2)-B bond was selectively transformable via palladium (Pd)-catalyzed Suzuki-Miyaura cross coupling, and subsequent transformation of the repeating C(sp3)-B unit gave the poly(α-methyl vinyl alcohol) [poly(MVA)] bearing various functional groups at the terminal. The boron-based stepwise polymer reaction thus overcame the synthetic difficulty of the end-functionalized poly(MVA), which is ascribed to the poor polymerization ability of the corresponding acetate monomer, i.e., isopropenyl acetate.

Enantioselective Cross-Coupling of Alkenyl Boronates and Carbamoyl Chlorides

Enantioselective Cross-Coupling of Alkenyl Boronates and Carbamoyl Chlorides

Enantioselective Synthesis of Tertiary β‐Boryl Amides by Conjunctive Cross‐Coupling of Alkenyl Boronates and Carbamoyl Chlorides

Synthesis of versatile β tert-boryl amides is accomplished by conjunctive cross-coupling of α-substituted alkenyl boron “ate” complexes and carbamoyl chloride electrophiles. This reaction can be accomplished in an enantioselective fashion using a palladium catalyst in combination with MandyPhos. The addition of water results in enhanced chemoselectivity for the conjunctive coupling product relative to the Suzuki–Miyaura cross-coupling product. Transformations of the reaction products were examined as well as application to the synthesis of (+)-adalinine.

Enantioselective Synthesis of Tertiary β-Boryl Amides by Conjunctive Cross-Coupling of Alkenyl Boronates and Carbamoyl Chlorides.

Synthesis of versatile β tert-boryl amides is accomplished by conjunctive cross-coupling of α-substituted alkenyl boron "ate" complexes and carbamoyl chloride electrophiles. This reaction can be accomplished in an enantioselective fashion using a palladium catalyst in combination with MandyPhos. The addition of water results in enhanced chemoselectivity for the conjunctive coupling product relative to the Suzuki-Miyaura cross-coupling product. Transformations of the reaction products were examined as well as application to the synthesis of (+)-adalinine.

Electrochemical Fluorination of Vinyl Boronates through Donor-Stabilized Vinyl Carbocation Intermediates.

The electrochemical generation of vinyl carbocations from alkenyl boronic esters and boronates is reported. Using easy-to-handle nucleophilic fluoride reagents, these intermediates are trapped to form fully substituted vinyl fluorides. Mechanistic studies support the formation of dicoordinated carbocations through sequential single-electron oxidation events. Notably, this electrochemical fluorination features fast reaction times and Lewis acid-free conditions. This transformation provides a complementary method to access vinyl fluorides with simple fluoride salts such as TBAF.

Electrochemical Fluorination of Vinyl Boronates through Donor‐Stabilized Vinyl Carbocation Intermediates**

AbstractThe electrochemical generation of vinyl carbocations from alkenyl boronic esters and boronates is reported. Using easy‐to‐handle nucleophilic fluoride reagents, these intermediates are trapped to form fully substituted vinyl fluorides. Mechanistic studies support the formation of dicoordinated carbocations through sequential single‐electron oxidation events. Notably, this electrochemical fluorination features fast reaction times and Lewis acid‐free conditions. This transformation provides a complementary method to access vinyl fluorides with simple fluoride salts such as TBAF.