Alkenyl Boronic Research Articles

Ligand-Free Iron-Catalyzed Carbonylation of Aryl Iodides with Alkenyl Boronic Acids: Access to α,β-Unsaturated Ketones.

The application of earth-abundant and low-toxicity iron catalysts as replacements for palladium in carbonylative coupling reactions remains challenging and largely unexplored. Reported here is a highly efficient iron-catalyzed carbonylation of aryl iodides with alkenyl boronic acids under ligand-free conditions, enabling the synthesis of α,β-unsaturated ketones even at atmospheric CO pressure. The broad applicability, including its effectiveness with α-branched enones and biologically active molecules, along with high yields and selectivity, underlines the general applicability of this catalytic system.

Merging Organocatalysis with 1,2-Boronate Rearrangement: A Lewis Base-Catalyzed Asymmetric Multicomponent Reaction.

Catalytic asymmetric multicomponent 1,2-boronate rearrangements provide a practical approach for synthesizing highly valuable enantioenriched boronic esters. When applied to alkenyl or heteroaryl boronates, these reactions have relied mainly on transition-metal catalysis. Herein, we present an organocatalytic, Lewis base-catalyzed asymmetric multicomponent 1,2-boronate rearrangement, involving indoles, boronic esters, and Morita-Baylis-Hillman carbonates, leading to enantioenriched, highly substituted indole and indoline derivatives. Using cinchona alkaloid-based catalysts, high selectivity has been achieved, enabling expansion of the chemical space around pharmaceutically relevant indole and indoline derivatives.

Chemoselective and Stereoselective Allylation of Bis(alkenyl)boronates

AbstractBis(alkenyl)boronates react with optically active Ir(π‐allyl) species in a process that involves allylation of the more substituted olefin and 1,2‐metalate shift of the less substituted olefin. The method constructs valuable enantioenriched tertiary allylic boronic esters with high chemoselectivity, enantioselectivity and diastereoselectivity. Allylic functionalization reactions transform the 1,3‐stereodiad to 1,5‐ and 1,6‐stereochemical relationships.

Chemoselective and Stereoselective Allylation of Bis(alkenyl)boronates.

Bis(alkenyl)boronates react with optically active Ir(π-allyl) species in a process that involves allylation of the more substituted olefin and 1,2-metalate shift of the less substituted olefin. The method constructs valuable enantioenriched tertiary allylic boronic esters with high chemoselectivity, enantioselectivity and diastereoselectivity. Allylic functionalization reactions transform the 1,3-stereodiad to 1,5- and 1,6-stereochemical relationships.

Tandem Diboration–Protoboration of Terminal Alkynes: A Practical Route to α-Substituted Alkenyl Boronates

AbstractA practical method is introduced for the catalytic conversion of terminal alkynes into α-substituted vinyl boronic esters. The process employs catalytic amounts of nanoparticle-supported gold catalysts and catalytic amounts of copper to effect the overall transformation.

Palladium-Catalyzed Atroposelective Suzuki-Miyaura Coupling to Construct Axially Chiral Tetra-Substituted α-Boryl Styrenes.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is a valuable method for forming C─C bonds, including those between aryl moieties. However, achieving atroposelective synthesis of axially chiral styrenes via SM coupling remains challenging. In this study, a palladium-catalyzed atroposelective Suzuki-Miyaura coupling between gem-diborylalkenes and aryl halides is presented. Using the monophosphine ligand Me-BI-DIME (L2), a range of axially chiral tetra-substituted acyclic styrenes with high yields and excellent enantioselectivities are successfully synthesized. Control experiments reveal that the gem-diboryl group significantly influences the product enantioselectivities and the coupling prefers to occur at sites with lower steric hindrance. Additionally, the alkenyl boronate group in the products proves versatile, allowing for various transformations while maintaining high optical purities.

Regio‐ and Stereo‐Selective Synthesis of (E)‐β‐Alkenyl Boronates by Phosphene‐Free CuI‐Catalyzed Hydroboration and Carboboration of Alkynes and Access to Allyl‐Vinyl Ethers

AbstractA convenient and operationally trivial protocol to access synthetically versatile vinylboronates through CuI catalyzed hydroboration and carboboration of alkynes utilizing bis(pinacolato)diboron (B2pin2) as the boron precursor in a 1, 10‐phenanthroline (phen) ligand environment is reported. This is a highly efficient and practical method for the synthesis of regio‐ and stereoselective (E)‐β‐vinylboronates from simple aromatic and aliphatic alkynes. These organoboron compounds have further been utilized for the synthesis of allyl‐vinyl ethers, which are potential starting materials for the Claisen rearrangement via an improved CuII mediated coupling of allyl alcohols and vinylboronates. The vinylboronates were also subjected to Suzuki‐Miyaura cross coupling reaction, allowing access to the corresponding tri‐ and tetra‐substituted alkenes with good isolated yields.

Regioselective Alkynylation and Alkenylation at the More Hindered C-B Bond of 1,2-Bis(Boronic) Esters.

Selective transformations at the more sterically hindered sites of organic molecules represent a frontier in the ability to precisely modify molecules. The lack of effective synthetic methods stands in stark contrast to the large number of encumbered sites encountered in molecules of interest. Here, we demonstrate that 1,2-bis(boronates) undergo selective alkynylation and alkenylation at the more sterically hindered C-B bond. Our preliminary mechanistic studies disclosed that this reaction can proceed through two convergent pathways involving direct coupling of sterically encumbered site versus 1,2-boron migratory coupling. Notably, this method facilitated convenient access to alkenyl and alkynyl boron products, which can be diversified by an array of transformations.

A palladium-catalyzed synthesis of cyclic alkenyl boronates from alkenyl chlorides.

A palladium-catalyzed borylation of cyclic alkenyl chlorides with B2pin2 is reported. This transformation allows for the conversion of diverse cyclic alkenyl chlorides into synthetically versatile alkenyl boronates with moderate to excellent yields. The utility of this reaction has been demonstrated with practical Suzuki-Miyaura coupling and aziridination reactions, which allow access to functionalized olefins and valuable boron-substituted aziridines.

Ligand-controlled regiodivergent Ni-catalyzed trans-hydroboration/carboboration of internal alkynes with B2pin2

With the aid of the directing group strategy, an approach for the synthesis of alkenyl and 1-naphthyl boronates with stereo- and regioselectivity via ligand-controlled Ni-catalyzed trans-hydroboration/carboboration of internal alkynes was developed.

Copper-catalyzed remote double functionalization of allenynes

A copper-catalyzed highly regioselective remote boryl- or silyl-cupration of allenynes, providing an efficient protocol for the synthesis of conjugated allene-substituted alkenyl boronates or silanes, has been developed.

The reactivity of alkenyl boron reagents in catalytic reactions: recent advances and perspectives

Recent advances focusing on novel reactivity of alkenyl boron reagents in polar or radical pathways within catalytic reactions by employing transition metal catalysis, organocatalysis have been summarized and discussed.

Stereoselective Copper‐Catalyzed Olefination of Imines

AbstractAlkenes are an important class of organic molecules found among synthetic intermediates and bioactive compounds. They are commonly synthesized through stoichiometric Wittig‐type olefination of carbonyls and imines, using ylides or their equivalents. Despite the importance of Wittig‐type olefination reactions, their catalytic variants remain underdeveloped. We explored the use of transition metal catalysis to form ylide equivalents from readily available starting materials. Our investigation led to a new copper‐catalyzed olefination of imines with alkenyl boronate esters as coupling partners. We identified a heterobimetallic complex, obtained by hydrocupration of the alkenyl boronate esters, as the key catalytic intermediate that serves as an ylide equivalent. The high E‐selectivity observed in the reaction is due to the stereoselective addition of this intermediate to an imine, followed by stereospecific anti‐elimination.

Stereoselective Copper-Catalyzed Olefination of Imines.

Alkenes are an important class of organic molecules found among synthetic intermediates and bioactive compounds. They are commonly synthesized through stoichiometric Wittig-type olefination of carbonyls and imines, using ylides or their equivalents. Despite the importance of Wittig-type olefination reactions, their catalytic variants remain underdeveloped. We explored the use of transition metal catalysis to form ylide equivalents from readily available starting materials. Our investigation led to a new copper-catalyzed olefination of imines with alkenyl boronate esters as coupling partners. We identified a heterobimetallic complex, obtained by hydrocupration of the alkenyl boronate esters, as the key catalytic intermediate that serves as an ylide equivalent. The high E-selectivity observed in the reaction is due to the stereoselective addition of this intermediate to an imine, followed by stereospecific anti-elimination.

Nickel-Catalyzed Ligand-Controlled Regioselective Allylic Alkenylation of Allylic Alcohols with Easily Accessible Alkenyl Boronates: Synthesis of 1,4-Dienes.

A nickel-catalyzed direct reaction of allylic alcohols with easily accessible alkenyl boronates has been developed, which provides valuable 1,4-dienes with high regio- and stereoselectivity in good to excellent yields, wide substrate scope, and functional group compatibility. The catalytic system simply consists of Ni(cod)2 as the catalyst and a ligand, without a need for a base and alcohol activator in most cases. The proper choice of ancillary ligands is highly important for this reaction. Depending on the substitution pattern of allylic alcohols and/or alkenyl boronates, different ligands were used for improving the reaction efficiency.

Copper‐Catalyzed Highly Stereoselective Hydrodifluoroallylation of Cyclopropenes and Alkenyl Boronates with 3,3‐Difluoroallyl Sulfonium Salts†

Comprehensive SummaryDespite the paramount applications of organofluorine compounds in life and materials sciences, efficient strategies for stereoselectively constructing the C(sp3)‐CF2R bond at the stereogenic center remain limited. Here, we report a copper‐catalyzed hydrodifluoroallylation of cyclopropenes and alkenyl boronates with 3,3‐difluoroallyl sulfonium salts (DFASs). The use of DFASs overcomes the previous challenge of suppressing the reduction of fluoroalkylating reagents with M‐H species. The reaction provides an array of gem‐difluoroallyl cyclopropanes and borylalkanes with high efficiency and stereoselectivity under mild reaction conditions. Using chiral phosphine ligand could provide gem‐difluoroallyl borylalkanes with high enantioselectivities, paving a new way for the catalytic asymmetric fluoroalkylation with ubiquitous alkenes. The advantages of this protocol are synthetic convenience, high functional group tolerance, and the synthetic versatility of the resulting gem‐difluoroallyl cyclopropanes and borylalkanes. The synthetic utility of this approach has also been demonstrated by the diversified transformations of the gem‐difluoroallylated products and the rapid synthesis of bioactive molecule analogs.

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids.

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem-stamp strategy for the construction of the key isoprene unit, which consists of two steps: one-carbon extension of aldehydes to the alkenyl boronates by the boron-Wittig reaction and the rhodium-catalyzed reaction of alkenyl boronates with 2,3-allenols to yield enals. This chem-stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, β-carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3-allenols, creation of new non-natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

A Modular Approach for the Synthesis of Natural and Artificial Terpenoids

AbstractMany terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem‐stamp strategy for the construction of the key isoprene unit, which consists of two steps: one‐carbon extension of aldehydes to the alkenyl boronates by the boron‐Wittig reaction and the rhodium‐catalyzed reaction of alkenyl boronates with 2,3‐allenols to yield enals. This chem‐stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, β‐carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3‐allenols, creation of new non‐natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups.

Photocatalyzed regioselective hydrosilylation for the divergent synthesis of geminal and vicinal borosilanes

Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.

Synthesis of Boronates with a Protoilludane Skeleton

AbstractNaturally occurring sesquiterpenes with a protoilludane skeleton are frequently oxygenated at carbon atoms C4 and C8. Boronic acid pinacol esters (BPin) are potential precursors for hydroxy groups at these positions and synthetic methods have now been developed for their preparation. Introduction of a boronate in position C4 was achieved by Cu-catalyzed hydroboration of a photochemically generated cyclobutene precursor, which displayed the complete C15-carbon skeleton of protoilludanes. Introduction of BPin at carbon atom C8 was possible by starting with an alkenyl boronate as precursor in a photochemical transformation. A two-photon reaction cascade allowed for creation of the complete protoilludane skeleton with BPin selectively positioned at C8. Subsequent reactions were studied and the oxidative transformation of the boronates into the respective alcohols was shown.