First-Row d-Block Element-Catalyzed Carbon-Boron Bond Formation and Related Processes.

Organoboron reagents represent a unique class of compounds because of their utility in modern synthetic organic chemistry, often affording unprecedented reactivity. The transformation of the carbon-boron bond into a carbon-X (X = C, N, and O) bond in a stereocontrolled fashion has become invaluable in medicinal chemistry, agrochemistry, and natural products chemistry as well as materials science. Over the past decade, first-row d-block transition metals have become increasingly widely used as catalysts for the formation of a carbon-boron bond, a transformation traditionally catalyzed by expensive precious metals. This recent focus on alternative transition metals has enabled growth in fundamental methods in organoboron chemistry. This review surveys the current state-of-the-art in the use of first-row d-block element-based catalysts for the formation of carbon-boron bonds.

The transition metal-catalysed hydroboration reaction.

The use of transition metals to catalyse the addition of hydridoboranes to unsaturated organic molecules was initially realised several decades ago. Although this area of chemistry received considerable attention at the time, interest in this reaction and its use in organic synthesis waned for several years. Like a phoenix rising from the ashes, this amazing catalytic reaction has grown to include the use of earth-abundant metal catalysts and a much wider range of organic substrates. Indeed, it is now commonly utilised as a diagnostic tool to assess the reactivity and catalytic ability of newly generated transition metal and main group complexes. As this field is progressing so rapidly, this review highlights some important advances up to the end of 2021 and into early 2022. Excluded from this review are 'hydroboration' reactions using diboron sources.

Selective, Transition Metal-free 1,2-Diboration of Alkyl Halides, Tosylates, and Alcohols.

Defunctionalization of readily available feedstocks to provide alkenes for the synthesis of multifunctional molecules represents an extremely useful process in organic synthesis. Herein, we describe a transition metal-free, simple and efficient strategy to access alkyl 1,2-bis(boronate esters) via regio- and diastereoselective diboration of secondary and tertiary alkyl halides (Br, Cl, I), tosylates, and alcohols. Control experiments demonstrated that the key to this high reactivity and selectivity is the addition of a combination of potassium iodide and N,N-dimethylacetamide (DMA). The practicality and industrial potential of this transformation are demonstrated by its operational simplicity, wide functional group tolerance, and the late-stage modification of complex molecules. From a drug discovery perspective, this synthetic method offers control of the position of diversification and diastereoselectivity in complex ring scaffolds, which would be especially useful in a lead optimization program.

Base-Mediated Radical Borylation of Alkyl Sulfones.

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal-free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2 neop2 ), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late-stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates.

Ni-Catalyzed Borylation of Aryl Sulfoxides.

A nickel/N-heterocyclic carbene (NHC) catalytic system has been developed for the borylation of aryl sulfoxides with B2 (neop)2 (neop=neopentyl glycolato). A wide range of aryl sulfoxides with different electronic and steric properties were converted into the corresponding arylboronic esters in good yields. The regioselective borylation of unsymmetric diaryl sulfoxides was also feasible leading to borylation of the sterically less encumbered aryl substituent. Competition experiments demonstrated that an electron-deficient aryl moiety reacts preferentially. The origin of the selectivity in the Ni-catalyzed borylation of electronically biased unsymmetrical diaryl sulfoxide lies in the oxidative addition step of the catalytic cycle, as oxidative addition of methoxyphenyl 4-(trifluoromethyl)phenyl sulfoxide to the Ni(0) complex occurs selectively to give the structurally characterized complex trans-[Ni(ICy)2 (4-CF3 -C6 H4 ){(SO)-4-MeO-C6 H4 }] 4. For complex 5, the isomer trans-[Ni(ICy)2 (C6 H5 )(OSC6 H5 )] 5-I was structurally characterized in which the phenyl sulfinyl ligand is bound via the oxygen atom to nickel. In solution, the complex trans-[Ni(ICy)2 (C6 H5 )(OSC6 H5 )] 5-I is in equilibrium with the S-bonded isomer trans-[Ni(ICy)2 (C6 H5 )(SOC6 H5 )] 5, as shown by NMR spectroscopy. DFT calculations reveal that these isomers are separated by a mere 0.3 kJ/mol (M06/def2-TZVP-level of theory) and connected via a transition state trans-[Ni(ICy)2 (C6 H5 )(η2 -{SO}-C6 H5 )], which lies only 10.8 kcal/mol above 5.

Transition Metal Catalyst-Free, Base-Promoted 1,2-Additions of Polyfluorophenylboronates to Aldehydes and Ketones.

A novel protocol for the transition metal-free 1,2-addition of polyfluoroaryl boronate esters to aldehydes and ketones is reported, which provides secondary alcohols, tertiary alcohols, and ketones. Control experiments and DFT calculations indicate that both the ortho-F substituents on the polyfluorophenyl boronates and the counterion K+ in the carbonate base are critical. The distinguishing features of this procedure include the employment of commercially available starting materials and the broad scope of the reaction with a wide variety of carbonyl compounds giving moderate to excellent yields. Intriguing structural features involving O-H⋅⋅⋅O and O-H⋅⋅⋅N hydrogen bonding, as well as arene-perfluoroarene interactions, in this series of racemic polyfluoroaryl carbinols have also been addressed.

Ni-Catalyzed Traceless, Directed C3-Selective C-H Borylation of Indoles.

A highly efficient and general protocol for traceless, directed C3-selective C-H borylation of indoles with [Ni(IMes)2] as the catalyst is reported. Activation and borylation of N-H bonds by [Ni(IMes)2] is essential to install a Bpin moiety at the N-position as a traceless directing group, which enables the C3-selective borylation of C-H bonds. The N-Bpin group which is formed is easily converted in situ back to an N-H group by the oxidative addition product of [Ni(IMes)2] and in situ-generated HBpin. The catalytic reactions are operationally simple, allowing borylation of a variety of substituted indoles with B2pin2 in excellent yields and with high selectivity. The C-H borylation can be followed by Suzuki-Miyaura cross-coupling of the C-borylated indoles in an overall two-step, one-pot process providing an efficient method for synthesizing C3-functionalized heteroarenes.

Copper-Catalyzed Oxidative Cross-Coupling of Electron-Deficient Polyfluorophenylboronate Esters with Terminal Alkynes.

We report herein a mild procedure for the copper-catalyzed oxidative cross-coupling of electron-deficient polyfluorophenylboronate esters with terminal alkynes. This method displays good functional group tolerance and broad substrate scope, generating cross-coupled alkynyl(fluoro)arene products in moderate to excellent yields. Thus, it represents a simple alternative to the conventional Sonogashira reaction.

Organocatalytic trans Phosphinoboration of Internal Alkynes.

We report the first trans phosphinoboration of internal alkynes. With an organophosphine catalyst, alkynoate esters and the phosphinoboronate Ph2 P-Bpin are efficiently converted into the corresponding trans-α-phosphino-ß-boryl acrylate products in moderate to good yield with high regio- and Z-selectivity. This reaction operates under mild conditions and demonstrates good atom economy, requiring only a modest excess of the phosphinoboronate. X-ray crystallography experiments allowed structural assignment of the unprecedented and densely functionalized (Z)-α-phosphino-ß-boryl acrylate products.

Phosphinoboration of Diazobenzene: Intramolecular FLP Synthon for PN2 B-Derived Heterocycles.

Phosphinoboration of diazobenzene with Ph2 PBR'2 cleanly affords products of the form Ph2 P(PhNNPh)BR'2 (2: R'2 =catechol, cat; 4: R'2 =phenanthrenediol, quin) and shows evidence of Ph2 P(PhNNPh)Bpin 7 (pin: pinacol). The mechanism of these reactions was probed computationally and shown to proceed via intermediates involving a diazobenzene-adduct of the boron center of the PB reagent. The resulting PNNB species 2 and 4 are shown to be frustrated Lewis pairs (FLPs). Despite the presence of weakly Lewis acidic boron centers, these species react with diazobenzene. Additionally, the FLP reactivity of 2 was further probed with 4-phenyl-1,2,4-triazole-3,5-dione, 1,10-phenanthroline-5,6-dione, and benzyl azide to give unique five-, six-, and eight-membered heterocyclic rings. Thus, phosphinoboration provides a new avenue to FLPs in which donor and acceptor sites are linked by nitrogen atoms.

Double Phosphinoboration of CO2 : A Facile Route to Diphospha-Ureas.

The reactions of CO2 with a series of phosphinoboranes, including R2 PBpin (R=Ph, tBu; pin=pinacol), R2 PBMes2 (R=Ph, tBu; Mes=2,4,6-Me3 -C6 H2 ), and R2 PBcat (R=Ph, tBu, Mes; cat=catechol) are described. Although R2 PBpin and R2 PBMes2 afford products of the form R2 PCO2 Bpin (R=Ph 1, tBu 4) and R2 PCO2 BMes2 (R=Ph 2, tBu 3), respectively, R2 PBcat lead to further reaction affording the diphospha-ureas, (R2 P)2 CO (R=Ph 5, tBu 6, Mes 7), together with O(Bcat)2 . Computational studies provide insight into the mechanism, revealing an intermediate derived from double phosphinoboration of CO2 .

Copper-boryl mediated organic synthesis.

Organoboron compounds are valuable synthetic intermediates that find application in a diverse variety of processes including both C-X and C-C bond-forming transformations. This has been achieved by using a variety of boron derivatives. Of these, boronate esters are probably the most versatile and, reflecting this, methods for the generation of boronate esters are of considerable current interest. Given the mild reaction conditions, good functional group tolerance, and low cost of the metal catalyst, the use of copper-boryl reagents is particularly attractive. In this review, methodologies in copper-boryl chemistry are discussed and the many different transformations possible are surveyed.

Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse.

Although known for over 90 years, only in the past two decades has the chemistry of diboron(4) compounds been extensively explored. Many interesting structural features and reaction patterns have emerged, and more importantly, these compounds now feature prominently in both metal-catalyzed and metal-free methodologies for the formation of B-C bonds and other processes.

The Phosphinoboration of N-Heterocycles.

The addition of phosphinoboronate ester Ph2 PBpin (pin=1,2-O2 C2 Me4 ) (1) to a number of different N-heterocycles has been investigated. Reaction of 1 with pyridine resulted in highly selective formation of the corresponding 1,4-addition product, with addition of the electron-deficient Bpin group to the pyridine nitrogen atom and the phosphido group to the para carbon atom. Conversely, reactions of para-substituted pyridine derivatives occurred predominately to afford 1,2-addition products while quinoline reacted to afford the 1,2-adduct which ultimately isomerized to afford the corresponding 1,4-addition product. Preliminary computational studies have been undertaken to explore possible pathways for these transformations including transfer of the PPh2- anion from [B(PPh2 )2 pin]- to the 4-position of a borenium/boronium activated pyridine and concerted pathways for 1,2-addition via intramolecular nucleophilic attack of PPh2 at C2 of a Ph2 PBpin-coordinated pyridine via a four-centered transition state and intramolecular transfer of PPh2 to the 2-position of a boron-activated pyridine in a phosphido-bridged dimer involving a six-centered transition state.

Thioboration of α,ß-unsaturated ketones and aldehydes toward the synthesis of ß-sulfido carbonyl compounds.

Herein a direct ß-sulfido carbonyl compound synthesis by the easy activation of RS-Bpin reagents with α,ß-unsaturated ketones and aldehydes is reported. This convenient methodology can be performed at room temperature with no other additives. The key point of this reactivity is based on the Lewis acidic properties of the boryl unit of the RS-Bpin reagent interacting with the C═O oxygen. Consequently, the SR unit becomes more nucleophilic and promotes the 1,4- versus the 1,2-addition, as a function of the involved substrate. The thioborated products can be further transformed into ß-sulfido carbonyl compounds by addition of MeOH.

The phosphinoboration reaction.

The synthesis of phosphinoboronate esters containing a single P-B bond is reported, together with preliminary reactivity studies towards a range of organic substrates. These compounds add readily to aldehydes, ketones, aldimines, and α,ß-unsaturated enones to give primarily the corresponding 1,2-addition products containing a new P-C bond. The first examples of transition-metal-catalyzed phosphinoborations of C-C multiple bonds in which P-C and B-C bonds are formed in a single step are also disclosed; allenes react by a highly regioselective 1,2-addition whereas terminal alkynes undergo a formal 1,1-addition.

Pyridinones are not antioxidants as shown by kinetics of free radical autoxidation, but they prevent radical oxidations catalyzed by toxic heavy metals.

Three 2-methyl-3-hydroxypyridinones, 1-methyl-, 1; 1-(4-methoxy)phenyl-, 2; and 1-(4-dimethylamino)phenyl-, 3, were discovered not to possess strong antioxidant properties contrary to literature reports. These pyridinones were not active chain-breaking antioxidants toward peroxyl radicals generated from styrene or methyl oleate initiated by azobis-2-methylpropylnitrile (AIBN) in solution compared to known phenolic antioxidants, 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC) or 2,6-di-tert-butyl-4-methoxyphenyl (DBHA). Pyridinone 2 exhibited weak antioxidant activity in cumene, kinh = 1.3 × 10(3) M(-1) s(-1), compared to 2,6-di-tert-butyl-4-methylphenol (BHT), kinh = 4.3 × 10(3) M(-1) s(-1). The pyridinones were not active antioxidants during lipid peroxidation initiated by azobis-2-amidinopropane·2HCl (ABAP) in aqueous-lipid dispersions of 0.50 M sodium dodecyl sulfate (SDS) micelles where 2 did not inhibit peroxidation of methyl oleate at pH 7.0 or 4.0, while BHT exhibited effective suppression of oxygen uptake. In addition, 2 did not exhibit any cooperative antioxidant effect in combination with Trolox during inhibited peroxidation of linoleic acid in micelles. Pyridinones were effective preventative antioxidants in aqueous-lipid dispersions against reactions initiated by heavy metal ions, notably copper; for example, 2 blocked peroxidation of linoleic acid initiated by Cu ions in SDS micelles. In particular, both 2 and 3 were active in preventing the rapid pro-oxidation effects, "spikes", of very rapid oxygen uptake when phenolic antioxidants PMHC or Trolox were added to peroxidations initiated by Cu(2+). A proposal is given to account for such pro-oxidant effects.

Metal-free borylative ring-opening of vinyl epoxides and aziridines.

A rational approach towards the borylative ring-opening of vinylepoxides and vinylaziridines, by the in situ formed MeO(-)→bis(pinacolato)diboron adduct, has been developed. The enhanced nucleophilic character of the Bpin (sp(2)) moiety from the reagent favours the SN2' conjugated B addition with the concomitant opening of the epoxide and aziridine rings. The reaction proceeds with total chemoselectivity towards the polyfunctionalised (-OH or -NHTs) allyl boronate. Theoretical calculations have determined the transition states that come from the reaction of the vinylic substrates with the activated MeO(-)→bis(pinacolato)diboron adduct, and a plausible mechanism for the organocatalytic borylative ring opening reaction has been suggested.

Arylspiroboronate esters: from lithium batteries to wood preservatives to catalysis.

The addition of catechol derivatives to boric acid affords a diverse family of compounds called arylspiroboronate esters. Due to boron's relatively low toxicity towards mammals, arylspiroboronate esters have several biological applications and are active for the treatment of wood against fungi and rot. These compounds are also finding increased use in organic synthesis and in catalysis. This critical review presents the synthesis, properties and applications of these remarkable compounds (149 references).

Cu-mediated vs. Cu-free selective borylation of aryl alkyl sulfones.

A Cu-catalysed borylation of aryl alkyl sulfones was developed for the high yield synthesis of versatile arylboronic esters using a readily prepared NHC-Cu catalyst. In addition, the selective cleavage of either alkyl(C)-sulfonyl or aryl(C)-sulfonyl bonds of a cyclic sulfone via Cu-free or Cu-mediated processes generates the corresponding sulfinate salts, which can be further derivatised to provide sulfonyl-containing boronate esters, such as sulfones and sulfonyl fluorides.