Mechanistic Insight into Hydroboration of Imines from Combined Computational and Experimental Studies

Boron Lewis acid-catalyzed and catalyst-free hydroboration reactions of imines are attractive due to the mild reaction conditions. In this work, the mechanistic details of the hydroboration reactions of two different kinds of imines with pinacolborane (HBpin) are investigated by combining density functional theory calculations and some experimental studies. For the hydroboration reaction of N-(α-methylbenzylidene)aniline catalyzed by tris[3,5-bis(trifluoromethyl)phenyl]borane (BAr^F₃), our calculations show that the reaction proceeds through a boron Lewis acid-promoted hydride transfer mechanism rather than the classical Lewis acid activation mechanism. For the catalyst- and solvent-free hydroboration reaction of imine, N-benzylideneaniline, our calculations and experimental studies indicate that this reaction is difficult to occur under the reaction conditions reported previously. With a combination of computational and experimental studies, we have established that the commercially available BH₃ ⋅ SMe₂ can serve as an efficient catalyst for the hydroboration reactions of N-benzylideneaniline and similar imines. The hydroboration reactions catalyzed by BH₃ ⋅ SMe₂ are most likely to proceed through a hydroboration/B−H/B−N σ-bond metathesis pathway, which is very different from that of the reaction catalyzed by BAr^F₃.     

Cyclic Amine/Borane Lewis Pairs by the Reaction of N,N‐Diallylaniline with Lancaster′s H2B‐C6F5 Reagent

Twofold hydroboration of N,N‐diallylaniline with the C₆F₅BH₂?SMe₂ reagent gave the respective hetero‐bicyclo[3.3.0]octane and hetero‐methylbicyclo[3.2.0]heptane compounds 4 and 5 as the major products, both showing strong internal N‐B amine Lewis base/borane Lewis acid adduct formation. A DFT analysis indicated their formation (and that of a small amount of several isomeric five‐membered heterocyclic products) under thermodynamic control. Compound 5 underwent fragmentation with propene liberation to form compound 7 with a formal N=B bond at 100 °C. This product was also obtained from the isomer 4 at much higher temperature (300 °C).     

Regio- and enantiocontrol in the room-temperature hydroboration of vinyl arenes with pinacol borane

The catalyzed hydroboration of vinyl arenes was carried out using pinacol borane instead of catechol borane, as the former reagent and the product boronates are significantly easier to handle. By careful choice of catalyst, either the branched or the linear product can be obtained in greater than 96% selectivity. Interestingly, common ligands such as BINAP and Josiphos give opposite asymmetric induction with pinacol borane as compared with catechol borane, while P,N-ligands such as Quinap gave the same sense of induction. The hydroboration of 6-methoxynaphthalene proceeded with the greatest regio- (95:5) and enantioselectivity (94:6) of all vinyl arenes examined. The hydroboration product was then employed in a concise synthesis of the nonsteroidal antiinflammatory agent, Naproxen.     

Cationic Zinc Hydride Catalyzed Carbon Dioxide Reduction to Formate: Deciphering Elementary Reactions,Isolation of Intermediates,and Computational Investigations

Zinc has been an element of choice for carbon dioxide reduction in recent years. Zinc compounds have been showcased as catalysts for carbon dioxide hydrosilylation and hydroboration. The extent of carbon dioxide reduction can depend on various factors, including electrophilicity at the zinc center and the denticity of the ancillary ligands. In a few cases, the addition of Lewis acids to zinc hydride catalysts markedly influences carbon dioxide reduction. These factors have been investigated by exploring elementary reactions of carbon dioxide hydrosilylation and hydroboration by using cationic zinc hydrides bearing tetradentate tris[2-(dimethylamino)ethyl]amine and tridentate N,N,N′,N′′,N′′-pentamethyldiethylenetriamine in the presence of triphenylborane and tris(pentafluorophenyl)borane.     

Boron Lewis Acid‐Catalyzed Hydroboration of Alkenes with Pinacolborane: BArF3 Does What B(C6F5)3 Cannot Do!

The transition‐metal‐free hydroboration of various alkenes with pinacolborane (HBpin) initiated by tris[3,5‐bis(trifluoromethyl)phenyl]borane (BAr^F₃) is reported. The choice of the boron Lewis acid is crucial as the more prominent boron Lewis acid tris(pentafluorophenyl)borane (B(C₆F₅)₃) is reluctant to react. Unlike B(C₆F₅)₃, BAr^F₃ is found to engage in substituent redistribution with HBpin, resulting in the formation of Ar^FBpin and the electron‐deficient diboranes [H₂BAr^F]₂ and [(Ar^F)(H)B(μ‐H)₂BAr^F₂]. These in situ‐generated hydroboranes undergo regioselective hydroboration of styrene derivatives as well as aliphatic alkenes with cis diastereoselectivity. Another ligand metathesis of these adducts with HBpin subsequently affords the corresponding HBpin‐derived anti‐Markovnikov adducts. The reactive hydroboranes are regenerated in this step, thereby closing the catalytic cycle.     

Formylborane Formation with Frustrated Lewis Pair Templates

Boranes R₂BH react with carbon monoxide by forming the respective borane carbonyl compounds R₂BH(CO). The formation of (C₆F₅)₂BH(CO) derived from the Piers borane, HB(C₆F₅)₂, is a typical example. Subsequent CO‐hydroboration does not take place, since the formation of the formylborane is usually endothermic. However, an “η²‐formylborane” was formed by CO‐hydroboration with the Piers borane at vicinal phosphane/borane frustrated Lewis pair (FLP) templates. Subsequent treatment with pyridine liberated the intact formylborane from the FLP framework, and (pyridine)(C₆F₅)₂B? CHO was then isolated as a stable compound. This product underwent typical reactions of carbonyl compounds, such as Wittig olefination.     

Poly(propylene sulfide)–borane: convenient and versatile reagent for organic synthesis

Poly(trimethylene sulfide)–borane adduct has been used as an efficient borane reagent in hydroboration reactions to produce various organoboranes, which have then been used without isolation in further reactions that involve single, double and triple migrations of alkyl groups. The presence of the polymer causes no problems, but there are practical advantages associated with its use, including lack of odour and easy recoverability.     

A Frustrated and Confused Lewis Pair

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates ^iPr2ArNCO (^iPr2Ar=2,6‐iPr₂C₆H₃) and ^Ph2tBuArNCO (^Ph2tBuAr=2,6‐Ph₂‐4‐tBuC₆H₂) with Piers’ borane (HB(C₆F₅)₂). While hydroboration of smaller isocyanates such as ^iPr2ArNCO leads to isocyanate—N/B FLP adducts, hydroboration of the bulkier ^Ph2tBuArNCO allows isolation of the substrate‐free aminoborane with a short, covalent N?B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a “normal” FLP along the reaction pathway, supported by high‐level DFT studies and variable‐temperature NMR spectroscopy. These results underscore the possibility of FLP behavior in systems that possess no obvious frustrated Lewis acid–base interaction.     

Organoboranes for synthesis. 4 : Oxidation of organoboranes with pyridinium chlorochromate. A direct synthesis of aldehydes from terminal alkenes via hydroboration

The oxidation of trialkylboranes containing primary a1kyl groups with pyridinium chlorochromate (PCC) in methylene chloride provides the corresponding aldehydes in good yields. The stoichiometry for the oxidation of alcohols, borate esters and trialkylboranes with PCC has been examined. In view of the poor regioselectivity (only 94% primary alkyl groups) and functional group tolerance observed in the hydroboration with borane (BH₃.THF or BH₃.SMe₂), a more selective hydroborating agent, bis(3-methyl-2-butyl)borane (disiamylborane), was utilized for the preparation of aldehydes from terminal alkenes. However, the formation of 3-methyl-2-butanone as a by-product, and the requirement of six moles of PCC per mole of aldehyde are major disadvantages in this method. This difficulty was circumvented by employing monochloroborane-dimethyl sulfide for hydroboration. This reagent exhibits high regioselectivity (⪢ 99% primary alkyl groups) in the hydroboration of terminal alkenes. Oxidation of the resulting dialkylchloroborane following hydrolysis affords the desired aldehydes in satisfactory yields. Consequently, the hydroboration of terminal alkenes, followed by PCC oxidation, represents a direct convenient method for the transformation of alkenes into the corresponding aldehydes.     

Synthetic, spectroscopic and structural studies of two novel phosphanyl(organyl)borane compounds

The titanium (II) complex, Cp₂Ti(HBcat)₂, catalyzes the hydroboration of diphenylvinylphosphine by catecholborane and pinacolborane to afford exclusive anti-Markovnikov phosphanyl(organyl)boranes cleanly, rapidly and in good yields. Spectroscopic and X-ray studies of the phosphanyl(organyl)borane products show no evidence of boron-phosphorus interaction, indicating that the compounds preclude formation of Lewis pairs.     

Microwave-Mediated Modification of Selected Limonoids with DMAB Reagent and Antibacterial Studies

N,N-Dimethylaniline.borane (DMAB) is a stable, multifaceted electrophilic boron agent that displays hydroboration of C = C as well as selective reduction of functional groups under reflux, microwave, and ultrasound conditions. Natural products contain a plethora of functional groups that govern the specific bioactivity. It will be interesting to correlate the change in a functional group with the concern for change in bioactivity. Current research emphasizes the influence of microwave irradiation on moderately reactive DMAB reagent towards the functional group modification of selected limonoid-phytochemicals of Meliaceae family viz. cedrelone, azadirone, nimbin, and azadiradione. DMAB conveniently reduces the ketone, epoxide group into alcohol, and does a hydroboration reaction on the C = C bond. It does not show interest to reduce the ester group irrespective of 30 min of MW irradiation. Except for these reducing properties, the reagent DMAB unveils chemo-selective nature in respect of different functional groups and utilizes in an asymmetric synthesis. The coalescence of amine.borane with microwave irradiation brings forth a commodious and prompt method for the selective reduction of functional groups. The bioactive efficacy of modified phytochemicals is further taken for the antimicrobial studies.     

Semihydrogenation of Alkynes Catalyzed by a Pyridone Borane Complex: Frustrated Lewis Pair Reactivity and Boron–Ligand Cooperation in Concert

The metal-free cis selective hydrogenation of alkynes catalyzed by a boroxypyridine is reported. A variety of internal alkynes are hydrogenated at 80 °C under 5 bar H₂ with good yields and stereoselectivity. Furthermore, the catalyst described herein enables the first metal-free semihydrogenation of terminal alkynes. Mechanistic investigations, substantiated by DFT computations, reveal that the mode of action by which the boroxypyridine activates H₂ is reminiscent of the reactivity of an intramolecular frustrated Lewis pair. However, it is the change in the coordination mode of the boroxypyridine upon H₂ activation that allows the dissociation of the formed pyridone borane complex and subsequent hydroboration of an alkyne. This change in the coordination mode upon bond activation is described by the term boron-ligand cooperation.     

Why Does the Intramolecular Trimethylene‐Bridged Frustrated Lewis Pair Mes2PCH2CH2CH2B(C6F5)2 Not Activate Dihydrogen?

The methyl labelled C₃‐bridged frustrated phosphane borane Lewis pair (P/B FLP) 2 b was prepared by treatment of Mes₂PCl with a methallyl Grignard reagent followed by anti‐Markovnikov hydroboration with Piers’ borane [HB(C₆F₅)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.     

Structure and dynamic features of an intramolecular frustrated Lewis pair

Di(mesityl)cyclohexenylphosphine undergoes hydroboration with Piers' borane [HB(C₆F₅)₂] to yield the cyclohexylene‐anellated frustrated Lewis pair 5 . This P/B pair splits H₂ with the formation of the product 4 and adds to the C?O double bond of phenyl isocyanate to yield 6 . In the crystal, compound 5 features a puckered four‐membered heterocyclic core structure with a long P? B bond (av. 2.197(5) Å). The activation energy of the P? B cleavage of the frustrated Lewis pair 5 was determined by dynamic ¹⁹F NMR spectroscopy at ΔG^≠(298 K)=12.1±0.3 kcal mol^?1.     

Chiral induction from solvents—lactic acid esters in the asymmetric hydroboration of ketones

The hydroboration of acetophenone in the chiral solvent (S)-methyl lactate exhibits moderate enantioselectivities. A six-membered transition state involving the ketone, the borane, and the lactate as the only chiral source is proposed. Molecular modeling explains the experimentally observed enantioselectivities. Calculated ee-values are in accordance with those experimentally observed. Improved ee-values (up to 60%) can be obtained in the presence of stoichiometric amounts of Lewis acid at lower reaction temperatures.     

Hydroboration of Arynes with N‐Heterocyclic Carbene Boranes

Arynes were generated in situ from ortho‐silyl aryl triflates and fluoride ions in the presence of stable N‐heterocyclic carbene boranes (NHC? BH₃). Spontaneous hydroboration ensued to provide stable B‐aryl‐substituted NHC‐boranes (NHC? BH₂Ar). The reaction shows good scope in terms of both the NHC‐borane and aryne components and provides direct access to mono‐ and disubstituted NHC‐boranes. The formation of unusual ortho regioisomers in the hydroboration of arynes with an electron‐withdrawing group supports a hydroboration process with hydride‐transfer character.     

Kinetics and mechanism of hydroboration of oct-1-and-4-ene by dimeric dialkylboranes

The kinetics and mechanism of hydroboration of oct-1-and-4-ene with a series of dimeric dialkylboranes was investigated. The kinetic results showed that the hydroboration of terminal olefins proceeds via a three-halves-order mechanism, first-order with respect to the olefin and one-half-order with respect to the dimer. Using dicyclohexylborane, diisopinocamphenylborane, and 3,6-dimethylborepane the observed rate constants for the hydroboration of oct-4-ene were approximately 6 times smaller than those for oct-1-ene. Supporting computations showed that both steric and electronic effects influence the rate of hydroboration of both internal and terminal olefins. A model computational study of the isomerization of oct-4-ene with di(prop-2-yl)borane showed that formation of the terminal hydroborated complex is thermodynamically favored over the internal complex.     

The asymmetric hydroboration of simple alkenylsilanes: chiral α-silylalkyl- boranes and alcohols

The detailed study of the asymmetric hydroboration of various vinyl-silanes with monoisopinocampheylborane ( IPCBH₂) is presented. In all cases, β-substitution on the vinylsilane gives monomeric dialkylborane adducts with the boryl group α to the silicon. These studies show that the larger the groups on silicon are, the more positive the influence on the enantioselectivity of the process. Moderate asymmetric induction (24–40%) is observed only for vinyl-silanes which contain a substituent trans to the silicon. A model for the asymmetric hydroboration of alkenes with this reagent is proposed. The complete characterization of the borane intermediates was achieved employing NMR ( ¹¹B, ¹³C, ¹H, ²⁹Si).     

Ring cleavage rearrangement of cyclobutylmethylboranes

Boranes derived from hydroboration of methylenecyclobutane with borane/THF, 9-borabicyclo[3.3.1]nonane, and borane-methyl sulfide rearranged on heating in situ at 100–160°C to open chain structures. Products after oxidation were the unrearranged cyclobutylmethanol, and 4-penten-1-ol, 1,4-pentanediol and 1,5-pentanediol. The unsaturated alcohol was the major product in reactions with a stoichiometric ratio of alkene to BH bonds, and the diols were formed with excess borane. With borane-methyl sulfide as hydroborating reagent, the rate of rearrangement at 100°C in triglyme was not significantly dependent upon the initial alkene/borane ratio $\text{3}\text{1}$ or $\text{1.15}\text{1}$ or the presence of excess methyl sulfide. However, an equivalent amount of pyridine prevented rearrangement. Rearrangement in THF using borane/THF also occurred at comparable rates in the presence and absence of excess borane. Little or no isomerization of the boron function into the cyclobutane ring was observed. Results are interpreted on the basis of a concerted four-center mechanism which requires a vacant boron orbital.     

Selective Metal‐free HB(C6F5)2 Catalyzed Allene Cyclotrimerization: Formation of 1,3,5‐Trimethylenecyclohexane and Its Tris‐hydroboration Product

Allene is cyclotrimerized under metal‐free conditions with the borane HB(C₆F₅)₂ catalyst to selectively give 1,3,5‐trimethylenecyclohexane ( 3 a ). Three‐fold hydroboration of the 1,3,5‐cyclotrimer with Piers’ borane gives the all‐cis 1,3,5‐CH₂B(C₆F₅)₂ substituted cyclohexane product 14 .