Stereospecific 1,2-Migrations of Boronate Complexes Induced by Electrophiles

The stereospecific 1,2-migration of boronate complexes is one of the most representative reactions in boron chemistry. This process has been used extensively to develop powerful methods for asymmetric synthesis, with applications spanning from pharmaceuticals to natural products. Typically, 1,2-migration of boronate complexes is driven by displacement of an α-leaving group, oxidation of an α-boryl radical, or electrophilic activation of an alkenyl boronate complex. The aim of this article is to summarize the recent advances in the rapidly expanding field of electrophile-induced stereospecific 1,2-migration of groups from boron to sp² and sp³ carbon centers. It will be shown that three different conceptual approaches can be utilized to enable the 1,2-migration of boronate complexes: stereospecific Zweifel-type reactions, catalytic conjunctive coupling reactions, and transition metal-free sp²–sp³ couplings. A discussion of the reaction scope, mechanistic insights, and synthetic applications of the work described is also presented.     

Stereoselective Direct Chlorination of Alkenyl MIDA Boronates: Divergent Synthesis of E and Z α‐Chloroalkenyl Boronates

The individual molecules of α‐chloroalkenyl boronates include both an electrophilic C−Cl bond and a nucleophilic C−B bond, which makes them intriguing organic synthons. Reported herein is a stereodivergent synthesis of both E and Z α‐chloroalkenyl N ‐methyliminodiacetyl (MIDA) boronates through the direct chlorination of alkenyl MIDA boronates using t BuOCl and PhSeCl reagents, respectively. Both reaction processes are stereospecific and the use of sp³‐B MIDA boronate is the key contributor to the reactivity. The synthetic value of the boronate products was also demonstrated.     

Synthesis of α‐Chiral Ketones and Chiral Alkanes Using Radical Polar Crossover Reactions of Vinyl Boron Ate Complexes

Vinyl boron ate complexes of enantioenriched secondary alkyl pinacolboronic esters undergo stereospecific radical‐induced 1,2‐migration in radical polar crossover reactions. In this three‐component process various commercially available alkyl iodides act as radical precursors and light is used for chain initiation. Subsequent oxidation and protodeborylation leads to valuable α‐chiral ketones and chiral alkanes, respectively, with excellent enantiopurity.     

Selective Boryl‐Anion Migration in a Vinyl sp2−sp3 Diborane Induced by Soft Borane Lewis Acids

An intramolecular 1,2‐boryl‐anion migration from boron to carbon has been achieved by selective activation of the π system in [(vinyl)B₂Pin₂)]^? using “soft” BR₃ electrophiles (BR₃=BPh₃ or 9‐aryl‐BBN). The soft character is key to ensure 1,2‐migration proceeds instead of oxygen coordination/B?O activation. The BR₃‐induced 1,2‐boryl‐anion migration represents a triple borylation of a vinyl Grignard reagent using only B₂Pin₂ and BR₃ and forms differentially protected 1,1,2‐triborylated alkanes. Notably, by increasing the steric bulk at the β position of the vinyl Grignard reagent used to activate B₂Pin₂, 1,2‐boryl‐anion migration can be suppressed in favor of intermolecular {BPin}^? transfer to BPh₃, thus enabling simple access to unsymmetrical sp²?sp³ diboranes.     

Formation of C(sp2)Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²)? boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

Formation of C(sp2)?Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

BCl₃ is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp²) boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2‐carboboration of alkynes is also achieved using BCl₃ to generate trisubstituted vinyl boronate esters.     

C(sp3)H Activation without a Directing Group: Regioselective Synthesis of N‐Ylide or N‐Heterocyclic Carbene Complexes Controlled by the Choice of Metal and Ligand

N‐Ylide complexes of Ir have been generated by C(sp³)?H activation of α‐pyridinium or α‐imidazolium esters in reactions with [Cp*IrCl₂]₂ and NaOAc. These reactions are rare examples of C(sp³)?H activation without a covalent directing group, which—even more unusually—occur α to a carbonyl group. For the reaction of the α‐imidazolium ester [ 3 H]Cl, the site selectivity of C?H activation could be controlled by the choice of metal and ligand: with [Cp*IrCl₂]₂ and NaOAc, C(sp³)?H activation gave the N‐ylide complex 4 ; in contrast, with Ag₂O followed by [Cp*IrCl₂]₂, C(sp²)?H activation gave the N‐heterocyclic carbene complex 5 . DFT calculations revealed that the N‐ylide complex 4 was the kinetic product of an ambiphilic C?H activation. Examination of the computed transition state for the reaction to give 4 indicated that unlike in related reactions, the acetate ligand appears to play the dominant role in C?H bond cleavage.     

An Olefinic 1,2‐Boryl‐Migration Enabled by Radical Addition: Construction of gem‐Bis(boryl)alkanes

A series of in situ formed alkenyl diboronate complexes from alkenyl Grignard reagents (commercially available or prepared from alkenyl bromides and Mg) with B₂Pin₂ (bis(pinacolato)diboron) react with diverse alkyl halides by a Ru photocatalyst to give various gem‐bis(boryl)alkanes. Alkyl radicals add efficiently to the alkenyl diboronate complexes, and the adduct radical anions undergo radical‐polar crossover, specifically, a 1,2‐boryl‐anion shift from boron to the α‐carbon sp² center. This transformation shows good functional‐group compatibility and can serve as a powerful synthetic tool for late‐stage functionalization in complex compounds. Measurements of the quantum yield reveal that a radical‐chain mechanism is operative in which the alkenyl diboronates acts as reductive quencher for the excited state of the photocatalyst.     

Diboryldiborenes: π‐Conjugated B4 Chains Isoelectronic to the Butadiene Dication

B(sp²)–B(sp³) diborane species based on bis(catecholato)diboron and N‐heterocyclic carbenes (NHCs) underwent catechol/bromide exchange selectively at the sp³‐hybridized boron atom. The reduction of the resulting 1,1‐dibromodiborane adducts led to reductive coupling and isolation of doubly NHC‐stabilized 1,2‐diboryldiborenes. These compounds are the first examples of molecules exhibiting π‐electron delocalization over an all‐boron chain.     

Formation of Olefins by Eliminative Dimerization and Eliminative Cross‐Coupling of Carbenoids: A Stereochemical Exercise

Two carbenoids combine to generate an olefin by a mechanism involving formation of an ate complex, 1,2‐metalate rearrangement, and β‐elimination. As each stage of this eliminative coupling is stereospecific, the overall stereochemical outcome can be understood and, in principle fully controlled, providing that the absolute stereochemical configurations of the reacting carbenoid species are defined. In contrast to traditional alkene syntheses, the eliminative cross‐coupling of carbenoids offers a connective approach to olefins capable of precisely targeting a given isomer regardless of the nature of the features distinguishing the isomers. The formation of olefins by the eliminative dimerization and eliminative cross‐coupling of carbenoids is reviewed with a range of illustrative examples, including the reactions of α‐lithiated haloalkanes, epoxides, and carbamates. An emphasis is placed on stereochemical analysis and methods to generate sp³‐hybridized carbenoids in stereodefined form are surveyed.     

Silver‐Mediated Intermolecular 1,2‐Alkylarylation of Styrenes with α‐Carbonyl Alkyl Bromides and Indoles

A new iron‐facilitated silver‐mediated radical 1,2‐alkylarylation of styrenes with α‐carbonyl alkyl bromides and indoles is described, and two new C?C bonds were generated in a single step through a sequence of intermolecular C(sp³)?Br functionalization and C(sp²)?H functionalization across the alkenes. This method provides an efficient access to alkylated indoles with broad substrate scope and excellent selectivity.     

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

The one‐pot sequential coupling of benzylamines, boronic esters, and aryl iodides has been investigated. In the presence of an N‐activator, the boronate complex formed from an ortho‐lithiated benzylamine and a boronic ester undergoes stereospecific 1,2‐metalate rearrangement/anti‐S_N2′ elimination to form a dearomatized tertiary boronic ester. Treatment with an aryl iodide under palladium catalysis leads to rearomatizing γ‐selective allylic Suzuki–Miyaura cross‐coupling to generate 1,1‐diarylalkanes. When enantioenriched α‐substituted benzylamines are employed, the corresponding 1,1‐diarylalkanes are formed with high stereospecificity.     

Synthesis,Structures and Properties of C(sp2)‐Centered Homo‐ and Hetero‐Nuclear Gold Complexes

C(sp²)‐centered homo‐ and hetero‐nuclear gold complexes have attracted widespread interests in recent decades. Studies of this type of complexes may deepen the understandings of the intermediates in Au‐catalyzed organic reactions and explore new applications in catalytic and material science. The focuses of this review include the synthesis, structural characteristics, properties and applications of C(sp²)‐centered homo‐ and hetero‐nuclear gold complexes according to different structural classifications.     

Synthesis and Reactivity of Paramagnetic Nickel Polypyridyl Complexes Relevant to C(sp2)–C(sp3)Coupling Reactions

A number of new transition metal catalyzed methods for the formation of C(sp²)–C(sp³) bonds have recently been described. These reactions often utilize bidentate polypyridyl‐ligated Ni catalysts, and paramagnetic Ni^I halide or aryl species are proposed in the catalytic cycles. However, there is little knowledge about complexes of this type. Here, we report the synthesis of paramagnetic bidentate polypyridyl‐ligated Ni halide and aryl complexes through elementary reactions proposed in catalytic cycles for C(sp²)–C(sp³) bond formation. We investigate the ability of these complexes to undergo organometallic reactions that are relevant to C(sp²)–C(sp³) coupling through stoichiometric studies and also explore their catalytic activity.     

Steric Effect of Carboxylate Ligands on Pd‐Catalyzed Intramolecular C(sp2)–H and C(sp3)–H Arylation Reactions

A bulky carboxylic acid bearing three cyclohexylmethyl substituents at the α‐position, namely, tri(cyclohexylmethyl)acetic acid, is demonstrated to act as an efficient ligand source in Pd‐catalyzed intramolecular C(sp²)?H and C(sp³)?H arylation reactions. The reactions proceed smoothly under mild reaction conditions, even at room temperature due to the steric bulk of the carboxylate ligands, which accelerates the rate‐determining C?H bond activation step in the catalytic cycle.     

Transition-Metal-Free Synthesis of Heterobiaryls through 1,2-Migration of Boronate Complex

The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp²–sp² cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl–heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive ¹¹B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.     

Reactions of stabilized criegee intermediates from the gas‐phase reactions of O3 with selected alkenes

The gas‐phase reactions of O₃ with 1‐octene, trans‐7‐tetradecene, 1,2‐dimethyl‐1‐cyclohexene, and α‐pinene have been studied in the presence of an OH radical scavenger, primarily using in situ atmospheric pressure ionization tandem mass spectrometry (API‐MS), to investigate the products formed from the reactions of the thermalized Criegee intermediates in the presence of water vapor and 2‐butanol (1‐octene and trans‐7‐tetradecene forming the same Criegee intermediate). With H₃O⁺(H₂O)_n as the reagent ions, ion peaks at 149 u ([M + H]⁺) were observed in the API‐MS analyses of the 1‐octene and trans‐7‐tetradecene reactions, which show a neutral loss of 34 u (H₂O₂) and are attributed to the α‐hydroxyhydroperoxide CH₃(CH₂)₅CH(OH)OOH, which must therefore have a lifetime with respect to decomposition of tens of minutes or more. No evidence for the presence of α‐hydroxyhydroperoxides was obtained in the 1,2‐dimethyl‐1‐cyclohexene or α‐pinene reactions, although the smaller yields of thermalized Criegee intermediates in these reactions makes observation of α‐hydroxyhydroperoxides from these reactions less likely than from the 1‐octene and trans‐7‐tetradecene reactions. Quantifications of 2,7‐octanedione from the 1,2‐dimethyl‐1‐cyclohexene reactions and of pinonaldehyde from the α‐pinene reactions were made by gas chromatographic analyses during reactions with cyclohexane and with 2‐butanol as the OH radical scavenger. The measured yields of 2,7‐octanedione from 1,2‐dimethyl‐1‐cyclohexene and of pinonaldehyde from α‐pinene were 0.110 ± 0.020 and 0.164 ± 0.029, respectively, and were independent of the OH radical scavenger used. Reaction mechanisms are presented and discussed. © 2001 Wiley Periodicals, Inc. Int J Chem Kinet 34: 73–85, 2002     

Alternating Radical Stabilities: A Convergent Route to Terminal and Internal Boronates

Pinacolato boronates (Bpin) with an empty p‐orbital on boron stabilize an adjacent carbon radical, in contrast to diethanolamino boronates [B(DEA)] where the boron is sp³‐hybridized. By alternately placing a pinacol or diethanolamine moiety on the boron atom, thus stabilizing or not stabilizing the corresponding adjacent radical, it is possible to control the behavior of α‐boronyl xanthates and construct a large variety of terminal or internal boronates in a modular fashion. The remarkable tolerance of polar groups and the ability to introduce quaternary centers are particularly noteworthy features of this process.     

Synthesis of α‐Aryl Esters and Nitriles: Deaminative Coupling of α‐Aminoesters and α‐Aminoacetonitriles with Arylboronic Acids

Transition‐metal‐free synthesis of α‐aryl esters and nitriles using arylboronic acids with α‐aminoesters and α‐aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp³)? N bonds into C(sp³)? C(sp²) bonds. The reaction conditions are mild, demonstrate good functional‐group tolerance, and can be scaled up.     

Modular Stereoselective Synthesis of (1→2)‐C‐Glycosides based on the sp2–sp3 Suzuki–Miyaura Reaction

This work reports a modular and rapid approach to the stereoselective synthesis of a variety of α‐ and β‐(1→2)‐linked C‐disaccharides. The key step is a Ni‐catalyzed cross‐coupling reaction of D ‐glucal pinacol boronate with alkyl halide glycoside easily prepared from commercially available D ‐glucal. The products of this sp²–sp³ cross‐coupling reaction can be converted to glucopyranosyl, mannopyranosyl, or 2‐deoxy‐glucopyranosyl C‐mannopyranosides by one‐ or two‐step stereoselective oxidative–reductive transformations. To the best of our knowledge, we demonstrated the first synthetic application of a challenging sp²–sp³ Suzuki‐Miyaura cross‐coupling reaction in carbohydrate chemistry.