anti-Markovnikov Hydroboration Research Articles

Hydroboration and hydrosilylation of alkenes catalyzed by an unsymmetrical magnesium methyl complex.

The hydroboration and hydrosilylation of alkenes catalyzed by the unsymmetrical β-diketiminate magnesium methyl complex [(DippXylNacnac)MgMe (THF)] (1) have been reported. When complex 1 was employed as a highly efficient catalyst in the hydroboration of various alkenes with HBpin, only the anti-Markovnikov hydroboration products were obtained in high yields and with high regioselectivities under mild reaction conditions (60 °C). To our surprise, it showed different regioselectivities in the hydrosilylation of a range of alkenes with PhSiH3. Aromatic alkene substrates afforded the corresponding branched Markovnikov hydrosilylation products in high yields and with high regioselectivities; conversely, aliphatic alkenes produced the linear anti-Markovnikov products in moderate yields. This is completely consistent with the corresponding density functional theory (DFT) calculations. In addition, the practical utility was demonstrated via scale-up reactions of boronate esters and a preliminary plausible mechanism of hydroboration and hydrosilylation have been investigated as well.

Selective Electroreductive Hydroboration of Olefins with B2pin2

Organoboron showed great potential in the synthesis of various high-value chemical compounds. Direct hydroboration of olefins has been witnessed over time as a mainstream method for the synthesis of organoboron compounds. In this work, an electroreductive anti-Markovnikov hydroboration approach of olefins with readily available B2pin2 to synthesize valuable organoboron compounds with high chemo- and regioselectivities under metal catalyst-free conditions was reported. This protocol exhibited broad substrate scope and good functional-group tolerance on styrenes and heteroaromatic olefins, providing synthetically useful alkylborons with high efficiency and even various deuterium borylation products with good D-incorporation when CD3CN was employed as solvent. Furthermore, gram-scale reactions and extensive functional derivatization further highlighted the potential of this method.

Selective hydroboration of terminal alkynes catalyzed by heterometallic clusters with uranium–metal triple bonds

Selective hydroboration of terminal alkynes catalyzed by heterometallic clusters with uranium–metal triple bonds

Hydroboration of Terminal Alkenes and trans-1,2-Diboration of Terminal Alkynes Catalyzed by a Manganese(I) Alkyl Complex.

A MnI-catalyzed hydroboration of terminal alkenes and a 1,2-diboration of terminal alkynes with pinacolborane (HBPin) is described. For alkenes, anti-Markovnikov hydroboration takes place; for alkynes the reaction proceeds with excellent trans-1,2-selectivity. The most active pre-catalyst is bench-stable alkyl bisphosphine MnI complex fac-[Mn(dippe)(CO)3(CH2CH2CH3)]. The catalytic process is initiated by migratory insertion of a CO ligand into the Mn-alkyl bond to yield an acyl intermediate, which undergoes B-H bond cleavage of HBPin (for alkenes) and rapid C-H bond cleavage (for alkynes), forming the active MnI boryl and acetylide catalysts [Mn(dippe)(CO)2(BPin)] and [Mn(dippe)(CO)2(C≡CR)], respectively. A broad variety of aromatic and aliphatic alkenes and alkynes was efficiently and selectively borylated. Mechanistic insights are provided based on experimental data and DFT calculations revealing that an acceptorless reaction is operating involving dihydrogen release.

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry.

This review discusses recent advances in the chemistry of saturated boronic acids, boronates, and trifluoroborates. Applications of the title compounds in the design of boron-containing drugs are surveyed, with special emphasis on α-amino boronic derivatives. A general overview of saturated boronic compounds as modern tools to construct C(sp3 )-C and C(sp3 )-heteroatom bonds is given, including recent developments in the Suzuki-Miyaura and Chan-Lam cross-couplings, single-electron-transfer processes including metallo- and organocatalytic photoredox reactions, and transformations of boron "ate" complexes. Finally, an attempt to summarize the current state of the art in the synthesis of saturated boronic acids, boronates, and trifluoroborates is made, with a brief mention of the "classical" methods (transmetallation of organolithium/magnesium reagents with boron species, anti-Markovnikov hydroboration of alkenes, and the modification of alkenyl boron compounds) and a special focus on recent methodologies (boronation of alkyl (pseudo)halides, derivatives of carboxylic acids, alcohols, and primary amines, boronative C-H activation, novel approaches to alkene hydroboration, and 1,2-metallate-type rearrangements).

Hydroboration of Alkenes Catalysed by a Nickel N-Heterocyclic Carbene Complex: Reaction and Mechanistic Aspects.

The pentamethylcyclopentadienyl N-heterocyclic carbene nickel complex [Ni(η5 -C5 Me5 )Cl(IMes)] (IMes=1,3-dimesitylimidazol-2-ylidene) efficiently catalyses the anti-Markovnikov hydroboration of alkenes with catecholborane in the presence of a catalytic amount of potassium tert-butoxide, and joins the very exclusive club of nickel catalysts for this important transformation. Interestingly, the regioselectivity can be reversed in some cases by using pinacolborane instead of catecholborane. Mechanistic investigations involving control experiments, 1 H and 11 B NMR spectroscopy, cyclic voltammetry, piezometric measurements and DFT calculations suggest an initial reduction of the NiII precursor to a NiI active species with the concomitant release of H2 . The crucial role of the alkoxo-catecholato-borohydride species resulting from the reaction of potassium tert-butoxide with catecholborane in the formation of an intermediate nickel-hydride species that would then be reduced to the NiI active species, is highlighted.

Coordination structure dominated performance of single-atomic Pt catalyst for anti-Markovnikov hydroboration of alkenes

The rational design of efficient single-atomic (SA) catalysts is essential and highly desirable but impeded by the lack of sufficient acknowledge between structure and property. To this end, it is critical to clarify the effect of the coordination structure of active metal centers on the catalytic activities for the design of such catalysts. Here, we report that different coordination structures of SA Pt catalysts can dramatically influence their activities for anti-Markovnikov hydroboration of alkenes. Compared with the other two coordination structures (Pt-N4 and Pt-O2), the SA Pt species coordinated with three O atoms (Pt-O3) display the highest turnover number value of 3288 for the hydroboration reaction to access the important alkylboronic esters. Density functional theory calculations reveal that a superior catalytic activity can be expected for alkene hydroboration over the three O coordinated Pt species due to the lowest reaction energy (Δ G ) limiting step from the reaction phase diagram.

Synthesis of the Oligosaccharides of Burkholderia pseudomallei and B. mallei Capsular Polysaccharide and Preliminary Immunological Studies of Their Protein Conjugates.

Efficient strategies were developed for the synthesis of 6-deoxy-d-manno-heptopyranose and its β-(1 → 3)-linked oligomers as fragments of the common and major capsular polysaccharide, type I O-PS, of Burkholderia pseudomallei and Burkholderia mallei. The unusual heptose was synthesized from mannose, highlighted by the facile Wittig reaction and anti-Markovnikov hydroboration of the resultant olefin. The difficult β-mannosidic linkage in the oligosaccharides was achieved in high stereoselectivity by H-bond-mediated aglycone delivery. All of the oligosaccharides were conjugated with the carrier protein CRM197. Preliminary immunological evaluations of the resultant glycoconjugates in mice verified their efficacy to elicit high titers of immunoglobulin G antibodies and robust T-cell-dependent immune responses. It was also found that the trisaccharide conjugates provoked the strongest immune responses, worthy of further in-depth study for vaccine development.

The directions of an external electric field control the catalysis of the hydroboration of C-O unsaturated compounds.

The orientation directions of an external electric field (EEF) in catalyzing chemical reactions are an important factor because they can significantly accelerate reaction activity. In this study, we explored a new anti-Markovnikov hydroboration reaction of C–O unsaturated compounds (e.g., benzaldehyde and benzophenone) with the aim of revealing the dominant direction of EEF in accelerating the reactions, and pinacolborane (HBpin) was selected as an efficient reductant. The calculation results showed that the EEF oriented along the direction of electron pair transform rather than that of the molecular dipole moment could reduce the barrier of the hydroboration of benzaldehyde by 20 kcal mol−1 when the EEF was up to 150 × 10−4 au. Moreover, the Markovnikov hydroboration of aldehyde and ketone was investigated for obtaining the mechanistic-switchover point. Unsatisfactorily, the EEF could just influence the respective barriers without a promising competition with the anti-Markovnikov hydroboration reactions.

AgSbF6-Catalyzed anti-Markovnikov hydroboration of terminal alkynes.

AgSbF6-Catalyzed anti-Markovnikov addition of pinacolborane (HBpin) to terminal alkynes to produce the E-vinylboronates is reported. This efficient methodology is scalable, compatible with sterically and electronically diverse alkynes, and works at room temperature under solvent-free condition. The utility of this method is demonstrated in the facile synthesis of the clinically important (E)-2,4,3',5'-tetramethoxystilbene.

Anti-Markovnikov Hydroboration of Unactivated 1,1-Disubstituted Olefins

Key words copper catalysis - enantioselective hydroboration - 1,1-disubstituted alkenes

η(4) -HBCC-σ,π-Borataallyl Complexes of Ruthenium Comprising an Agostic Interaction.

Thermolysis of [Cp*Ru(PPh2 (CH2 )PPh2 )BH2 (L2 )] 1 (Cp*=η(5) -C5 Me5 ; L=C7 H4 NS2 ), with terminal alkynes led to the formation of η(4) -σ,π-borataallyl complexes [Cp*Ru(μ-H)B{R-C=CH2 }(L)2 ] (2 a-c) and η(2) -vinylborane complexes [Cp*Ru(R-C=CH2 )BH(L)2 ] (3 a-c) (2 a, 3 a: R=Ph; 2 b, 3 b: R=COOCH3 ; 2 c, 3 c: R=p-CH3 -C6 H4 ; L=C7 H4 NS2 ) through hydroboration reaction. Ruthenium and the HBCC unit of the vinylborane moiety in 2 a-c are linked by a unique η(4) -interaction. Conversions of 1 into 3 a-c proceed through the formation of intermediates 2 a-c. Furthermore, in an attempt to expand the library of these novel complexes, chemistry of σ-borane complex [Cp*RuCO(μ-H)BH2 L] 4 (L=C7 H4 NS2 ) was investigated with both internal and terminal alkynes. Interestingly, under photolytic conditions, 4 reacts with methyl propiolate to generate the η(4) -σ,π-borataallyl complexes [Cp*Ru(μ-H)BH{R-C=CH2 }(L)] 5 and [Cp*Ru(μ-H)BH{HC=CH-R}(L)] 6 (R=COOCH3 ; L=C7 H4 NS2 ) by Markovnikov and anti-Markovnikov hydroboration. In an extension, photolysis of 4 in the presence of dimethyl acetylenedicarboxylate yielded η(4) -σ,π-borataallyl complex [Cp*Ru(μ-H)BH{R-C=CH-R}(L)] 7 (R=COOCH3 ; L=C7 H4 NS2 ). An agostic interaction was also found to be present in 2 a-c and 5-7, which is rare among the borataallyl complexes. All the new compounds have been characterized in solution by IR, (1) H, (11) B, (13) C NMR spectroscopy, mass spectrometry and the structural types were unequivocally established by crystallographic analysis of 2 b, 3 a-c and 5-7. DFT calculations were performed to evaluate possible bonding and electronic structures of the new compounds.

Why Does the Intramolecular Trimethylene-Bridged Frustrated Lewis Pair Mes2 PCH2 CH2 CH2 B(C6 F5 )2 Not Activate Dihydrogen?

The methyl labelled C3 -bridged frustrated phosphane borane Lewis pair (P/B FLP) 2 b was prepared by treatment of Mes2 PCl with a methallyl Grignard reagent followed by anti-Markovnikov hydroboration with Piers' borane [HB(C6 F5 )2 )]. The FLP 2 b is inactive toward dihydrogen under typical ambient conditions, in contrast to the C2 - and C4 -bridged FLP analogues. Dynamic NMR spectroscopy showed that this was not due to kinetically hindered P⋅⋅⋅B dissociation of 2 b. DFT calculations showed that the hydrogen-splitting reaction of the parent compound 2 a is markedly endergonic. The PH(+) /BH(-) H2 -splitting product of 2 b was indirectly synthesized by a sequence of H(+) /H(-) addition. It lost H2 at ambient conditions and confirmed the result of the DFT analysis.

FeCl2-catalyzed hydroboration of aryl alkenes with bis(pinacolato)diboron

Alkylboronates were synthesized by a ligand-free ferrous chloride catalyzed anti-Markovnikov hydroboration of un-activated aryl alkenes with bis(pinacolato)diboron.

Iminopyridine oxazoline iron catalyst for asymmetric hydroboration of 1,1-disubtituted aryl alkenes.

The highly regio- and enantioselective iron-catalyzed anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes is reported by using a novel chiral iminopyridine oxazoline (IPO) ligand, in which the iminopyridine group is proposed to stabilize the iron and chiral oxazoline group to control enantioselectivity. This distinct class of reactive IPO ligands will likely be of high value for a large variety of asymmetric transformations using first-row transition metals.

Asymmetric cobalt catalysts for hydroboration of 1,1-disubstituted alkenes

Chiral iminopyridine oxazoline (IPO) ligands were designed, synthesized and utilized for the first cobalt-catalyzed highly regio- and enantioselective anti-Markovnikov hydroboration of 1,1-disubstituted aryl alkenes. These novel IPO ligands will likely be of high value for asymmetric transformations with first-row transition metals.

Intramolecular frustrated N/B lewis pairs by enamine hydroboration

A series of enamines undergoes anti-Markovnikov hydroboration with Piers' borane HB(C6F5)2 to yield C2-bridged frustrated N/B Lewis pairs, featuring weak N⋯B interaction. Some examples show typical frustrated Lewis pair reactions with dihydrogen or with 1-alkynes. One such N/B FLP serves as an active catalyst for the hydrogenation of enamines. Many of the new compounds were characterized by X-ray diffraction.

Polar Addition to C=C Group: Why Is Anti-Markovnikov Hydroboration–Oxidation of Alkenes Not "Anti-"?

For 137 years Markovnikov's rule has been extensively used in organic chemical education and research to describe the regioselectivity in electrophilic addition reactions to alkenes and alkynes. When the structures of the final reaction products are used as reference, the rule requests that certain polar addition reactions be termed anti-Markovnikov. We use first principles thermodynamic calculations to analyze six polar addition reactions to alkenes, expected to be of either Markovnikov or anti-Markovnikov regioselectivity. Our results show no difference between the two reaction types: in each case the alkene atomic charges and the form of the intermediate completely determine the course of the overall reaction and the form of the predominant final product. We redefine this type of regioselectivity and propose that teaching of organic chemistry should be based more on robust and portable concepts such as energy difference and atomic charge than on historical labels.

Synthesis and Ceramic Conversion Reactions of Pinacolborane- and Diethylborazine-Modified Poly(vinylsiloxane)s. The Development of a Processable Single-Source Polymeric Precursor to Boron-Modified Silicon Carbide

The design, synthesis, and properties of two new types of poly(borosiloxane) preceramic polymers, diethylborazine- (PVS−DEB) and pinacolborane-modified (PVS−PIN) poly(vinylsiloxane)s, are reported. The polymers are synthesized in excellent yields by the RhH(CO)(PPh3)3-catalyzed reactions of poly(vinylsiloxane) (PVS) with either diethylborazine (DEB−H) or pinacolborane (PIN−H). The spectroscopic data for the polymers, along with results of the RhH(CO)(PPh3)3-catalyzed hydroboration reactions of diethylborazine and pinacolborane with the model compound vinyltris(trimethylsiloxy)silane, are consistent with predominately anti-Markovnikov hydroboration of the polymer vinyl groups by the boranes. The degree of polymer hydroboration is simply controlled by varying the reactant ratios with the compositions of the PVS−DEB polymer ranging from (MeSiO1.5)0.42(PhSiO1.5)0.37(ViMe2SiO0.5)0.17(DEB(CH2)2Me2SiO0.5)0.04 to (MeSiO1.5)0.42(PhSiO1.5)0.37(DEB(CH2)2Me2SiO0.5)0.21 and those of the PVS−PIN polymers from (MeSiO1.5)0.42(PhSiO1.5)0.37(ViMe2SiO0.5)0.18(PIN(CH2)2Me2SiO0.5)0.03 to (MeSiO1.5)0.42(PhSiO1.5)0.37(PIN(CH2)2Me2SiO0.5)0.21. The borane-modified polymers are soluble and stable in ethers, acetone, methylene chloride, benzene, and pentane. Molecular weight analyses using SEC with refractive index, viscometry, and light-scattering triple detection show significant differences in hydrodynamic volume, molecular weight, radius of gyration, and conformation, which indicate that the PVS−PIN and PVS−DEB polymers adopt a more branched and spherical structure compared to the unmodified PVS. Bulk pyrolysis of the modified resins produced SiOCB ceramic chars with boron contents ranging from 0.3 to 0.7% depending upon the percentage of polymer modification. XRD and TEM studies of the 1800 °C chars of PVS and PVS−PIN showed significant differences in the degree of grain growth and distribution with the boron-modified char showing both a smaller average crystallite size and a more narrow size range. The PVS−PIN polymers were found to be excellent melt-processable, single-source precursors to small-diameter SiOCB fibers.

Group 5 Metallocene Complexes as Models for Metal-Mediated Hydroboration: Synthesis of a Reactive Borane Adduct, endo-Cp*2Nb(H2BO2C6H4), via Hydroboration of Coordinated Olefins

The olefin complexes Cp*2M(CH2CH(R))(H) (R = H (1), CH3 (2); M = Nb (a), Ta (b)) react cleanly with catecholborane (HBCat) and HBO2C6H3-4-tBu (HBCat‘) to give Cp*2M(H2BCat) (M = Nb (5a), Ta (5b)) and Cp*2M(H2BCat‘) (M = Nb (6a), Ta (6b)) and the anti-Markovnikov hydroboration products CatBCH2CH2R and Cat‘BCH2CH2R. Compounds 2a and 2b react with DBCat‘ (DBO2C6H3-4-tBu) to afford the deuterated analogs Cp*2M(D2BCat‘) (M = Nb (6a), Ta (6b)) where the deuterium label is incorporated exclusively in the metal complex. The hydride resonances in 6a exhibit large perturbations in chemical shift when deuterium is incorporated. On the basis of this isotopic labeling experiment, a mechanism is proposed where HBCat reacts with the 16-electron alkyl intermediates, Cp*2MCH2CH2R (R = H (3), Me (4)), via σ-bond metathesis or oxidative-addition/reductive-elimination sequences, to generate the alkylboranes and an intermediate hydride, Cp*2MH, that is trapped by additional borane to give Cp*2M(H2BCat) (5a and 5b). The solid-state structures for Cp*2Nb(η2-H2BO2C6H3-3-tBu) (16) and Cp2*Nb(η2-BH4) (17) were determined by X-ray diffraction. The metal−boron distances in these two compounds are identical within experimental error. While related group 5 catecholateboryl compounds have pronounced boryl character, the structural parameters for the hydride and boryl ligands in 16 are consistent with formulation as either a borohydride complex or a borane adduct of “Cp*2NbH”. In contrast to other group 5 boryl complexes, 6a reacts readily with various two-electron ligands with elimination of HBCat‘. For example, H2 reacts reversibly to form Cp*2NbH3 and HBCat‘, while “BH3” and CO react irreversibly to yield Cp*Nb(BH4) and Cp*2Nb(H)(CO) with elimination of HBCat‘, respectively. Ethylene and propylene react at 40 °C to regenerate 1a and 2a, with elimination of HBCat‘. When excess olefin is present, the liberated borane is converted to CatBCH2CH2R. Solutions of 1a and 2a catalyze olefin hydroboration under mild conditions. Relationships between the reactivity of 1a and 2a and other early metal and lanthanide catalysts are discussed.