Hydroboration Of Ketones Research Articles

Efficient Hydroboration of Ketones and Imines Using Amidophosphine‐Borane Under Catalyst‐Free Conditions

AbstractWe report here the use of amidophosphine borane {(BH₃)₂(PPh)₂N(CH₂)C₆H₅} as a competent reducing agent for the hydroboration of ketones and imines under mild and catalyst‐free reaction conditions yielding the corresponding secondary alcohols and secondary amines after aqueous work. Solid amidophosphine boranes, which are easy to synthesize, and easy to handle demonstrated excellent reactivity and functional group tolerance toward a wide variety of ketones and imines, including aromatic, heteroaromatic, and aliphatic derivatives with electron‐withdrawing and electron‐donating substitutions, thus showing excellent chemoselectivity.

Phosphine‐substituted N‐coordinated Stannylene: Efficient Catalyst in Ketone Hydroboration

AbstractP‐substituted stannylene (Ph2PCH2)(L)Sn containing N,C,N‐pincer ligand (L=[2,6‐(Me2NCH2)2C6H3]) was prepared. The complex was further oxidised to prepare P‐substituted organotin (IV) compounds (Ph2PCH2)(L)SnX2. Finally, P(S)‐substituted N‐coordinated stannylene [(Ph2P(S)CH2](L)Sn containing P atom in the oxidation state +V was also prepared. All these P‐substituted organotins were tested as catalysts for the hydroboration of ketones to see the effect of oxidation numbers of Sn/P atoms. Stannylene (Ph2PCH2)(L)Sn showed remarkable conversions with TOF about 1800 h−1 and is suitable for the reduction of several ketones. The mechanistic studies are also discussed.

Air-Stable Iron(III) Salen Complexes for Selective Hydroboration of Ketones and Unactivated Imines without Base Activation.

Herein, we designed and synthesized a series of air-stable, cost-effective, and readily synthesizable iron(III) salen complexes (Fe-1 and Fe-2) for facilitating the selective hydroboration of ketones and unactivated imines with pinacolborane in the absence of any additive. These catalyst systems exhibited good yields, chemoselectivity, high atom economy, and a broad substrate scope under mild reaction conditions with a minimal catalyst loading of 0.2 mol %. The catalytic efficiency of Fe-1 has been demonstrated through the hydroboration of diverse aromatic, aliphatic, and heterocyclic ketones and imines with a turnover number of up to 1000, highlighting its broad substrate scope. Ketones are chemoselectively hydroborated over other functional groups such as imines, alkenes, esters, nitriles, acids, and alcohols. Besides, the synthetic utility of this strategy has also been showcased by the construction of a natural chiral monoterpenoid carveol. This protocol can be readily scaled up for gram-scale synthesis of alcohols, which underscores the potential industrial applicability of our catalyst system in the synthesis of secondary alcohols on a larger scale.

Aldehyde and Ketone Hydroboration Mediated by a Heterogeneous Single‐Site Molybdenum‐Dioxo Catalyst: Scope and Mechanistic Implications

AbstractEfficient hydroboration of aldehydes and ketones is demonstrated using a single‐site MoO2 catalyst supported on activated carbon. Under mild conditions with low catalytic loadings, the reaction exhibits chemoselectivity towards carbonyl reduction over halides, alkene, alkyne, nitrile, and ester groups, affording high yields of desired products. Furthermore, competition studies between aldehyde and ketone reduction using HBpin and HBcat indicate that HBpin preferably functionalizes aldehydes, while HBcat can functionalize either substrate under specific conditions. Mechanistic studies suggest that the reaction proceeds via the initial formation of a molybdenum‐hydride species upon B−H activation and subsequent molybdenum‐alkoxide species upon carbonyl activation by the Mo center. The experimental activation energy of 14.3 kcal/mol alignssatisfactorily with the DFT computed ΔH≠ of 18.7 kcal/mol, further supporting the proposed mechanism. Combined experimental/computational analyses reveal that excess HBpin can possibly deactivate the catalyst. The presence of excess benzaldehyde efficiently mitigates deactivation by HBpin, providing significantly higher catalyst recyclability. Overall, this non‐toxic, air‐ and moisture‐stable, active, and selective catalyst demonstrates significant potential for green processes.

Pt(PPh3)4 and Pt(PPh3)4@IL catalyzed hydroboration of ketones

An efficient method for the reduction of various ketones via [Pt(PPh3)4]-catalyzed hydroboration with HBpin has been successfully developed for the first time. The protocol is suitable for symmetrical and unsymmetrical derivatives possessing electron donating or withdrawing functional groups. O-borylated products were easily converted to 2° alcohols via hydrolysis with high isolated yields. According to the low-temperature NMR spectroscopy, a reaction mechanism was proposed. Additionally, effective immobilization of the catalyst in the ionic liquid [BMIM][NTf2] was applied to increase the productivity of the process by carrying out reactions under the repetitive batch mode, obtaining higher TON values and limiting the amount of expensive Pt used. The catalyst stability and almost neglectable leaching were confirmed by ICP-MS analysis of the extracted mixture. A simple separation method via extraction with n-heptane, efficient catalyst immobilization, and the commercial availability of the Pt complex, make this protocol an attractive method for the hydroboration of ketones

Mechanistic study of homoleptic trisamidolanthanide-catalyzed aldehyde and ketone hydroboration. Chemically non-innocent ligand participation.

Carbonyl bond hydroboration is a valuable synthetic route to functionalized alcohols but relies on sometimes unselective and sluggish reagents. While rapid and selective aldehyde and ketone hydroboration mediated by trisamidolanthanide catalysts is known, the origin of the selectivity is not well-understood and is the subject of this contribution. Here the aldehyde and ketone HBpin hydroboration reaction mechanisms catalyzed by La[N(SiMe3)2]3 are investigated both experimentally and theoretically. The results support initial carbonyl oxygen coordination to the acidic La center, followed by intramolecular ligand-assisted hydroboration of the carbonyl moiety by bound HBpin. Interestingly, ketone hydroboration has a higher energetic barrier than that of aldehydes due to the increased steric encumbrance and decreased electrophilicity. Utilizing NMR spectroscopy and X-ray diffraction, a bidentate acylamino lanthanide complex associated with the aldehyde hydroboration is isolated and characterized, consistent with the relative reaction rates. Furthermore, an aminomonoboronate-lanthanide complex produced when the La catalyst is exposed to excess HBpin is isolated and characterized by X-ray diffraction, illuminating unusual aminomonoboronate coordination. These results shed new light on the origin of the catalytic activity patterns, reveal a unique ligand-assisted hydroboration pathway, and uncover previously unknown catalyst deactivation pathways.

Metal-Organic Frameworks Based on a Janus-Head Biquinoline Ligand as Catalysts in the Transformation of Carbonyl Compounds into Cyanohydrins and Alcohols.

A new family of metal-organic frameworks (MOFs) named GR-MOFs with the chemical formula {[M x (BCA) y ](H2O) z (DMF) w } (x,y,z,w: 1,1,2,0; 1,1.5,0,1; 1,2,2,1; and 1,1,0,2 for GR-MOF-11 to 14, respectively) based on s-block [M: Sr (GR-MOF-11), Ba (GR-MOF-14)] and d-block [M: Y (GR-MOF-12) and Cd (GR-MOF-13)] metals together with the biquinoline ligand 2,2'-bicinchoninic acid (H2BCA) has been synthetized by a solvothermal route and fully characterized by elemental and thermogravimetric analysis, Fourier transform infrared spectroscopy, photoluminescence, particle size distribution through optical microscopy, electrophoretic mobility, and finally, X-ray single-crystal and powder diffraction. The structural characterization reveals that these 2D and 3D MOFs possess a rich variety of coordination modes that maintained the Janus-head topology on the ligand in most of the cases. The new MOFs were studied in the catalyzed cyanosilylation and hydroboration of an extensive group of aldehydes and ketones, wherein the s-block metal-based MOFs GR-MOF-11 and GR-MOF-14 provided the highest efficiency ever reported in the MOF-catalyzed cyanosilylation of carbonyl compounds by using only 0.5 mol % of catalyst loading, room temperature, and solvent-free conditions. Furthermore, the hydroboration of ketones has been reported for the first time with this type of s-block metal catalysts obtaining from moderate to good conversions.

Germanium Hydride Catalyzed Selective Hydroboration and Cyanosilylation of Ketones

AbstractTwo new examples of β‐diketiminate or NacNac analogues, i. e., conjugated bis‐guanidinate (CBG) stabilized low valent germanium chloride (1) and germanium hydride (2) complexes, are reported. Deprotonation of LH upon treatment with n‐BuLi and an in situ generated LLi further treated with GeCl2⋅dioxane afforded LGeCl in 79 % yield. Compound 1 reacted with hydride source NaHBEt3 in toluene, afforded Ge (II) hydride (2) in 76 % yield. Both compounds 1 and 2 were characterized by NMR and mass spectroscopic methods. Further, germanium hydride catalyzed hydroboration and cyanosilylation of a wide range of ketones have been investigated. Control reactions suggest hydroboration reactions occurred via insertion and Ge−O/B−H bond metathesis pathways. It is worthy of mentioning that, in the case of hydroboration of ketones, reducible groups such as alkene, alkyne, halide, ester, nitro, and heterocycles were untouched. Furthermore, compound 2 was employed for the reduction of carbonate, formate, and anhydride substrates via the hydroboration technique.

Asymmetric Hydroboration of Ketones by Cooperative Lewis Acid–Onium Salt Catalysis: A Quantum Chemical and Microkinetic Study to Combine Theory and Experiment

We apply microkinetic modeling in homogeneous catalysis and show how it can be used to reveal important details of a complex mechanism and how this can lead to a direct comparison between theory and experiment. While regularly used in heterogeneous catalysis, its applications to organic chemistry or homogeneous catalysis are still comparatively scarce. This approach is exemplarily applied to the mechanism of the asymmetric hydroboration of acetophenone with a highly active cooperative Lewis acid–ammonium salt catalyst. In combination with density functional theory, it is a gateway to shed light into important mechanistic details. In our study, it reveals that the counterion of the ammonium salt of the catalyst facilitates the hydride transfer step of the cycle. Chloride replacing iodide speeds up the main reaction but simultaneously has the same effect on a side reaction that consumes the product. This observation is confirmed by experimental measurements of both the main catalytic cycle and the side reaction. A sensitivity analysis showed that the transition from the product complex to the hydride transfer is rate-limiting and that it determines the enantioselectivity. Based on this insight, an enantioselective kinetic model was applied, from which the difference of the Gibbs free energy barriers of the two pathways forming the two enantiomers can be extracted. The barriers are in fairly good agreement with the ones calculated by DFT, which reveal that the asymmetric backbone interacts with the reactant sterically to favor asymmetric product formation.

Iron(0) tricarbonyl η4-1-azadiene complexes and their catalytic performance in the hydroboration of ketones, aldehydes and aldiminesviaa non-iron hydride pathway

Six iron(0) tricarbonyl complexes (1a-f) with a η4-1-azadiene moiety were prepared and their performance in the hydroboration of unsaturated organic compounds was investigated. All the complexes exhibit catalytic activity towards hydroboration of ketones, aldehydes and aldimines with pinacolborane (HBpin) as a hydride source to lead to secondary alcohols, primary alcohols, and secondary amines, respectively, after hydrolysis of the hydroboration products. Of the iron(0) tricarbonyl complexes, complex 1e is the most robust one and was employed throughout the catalytic investigation. Its preference towards the three types of substrates is as follows: aldimines > aldehydes ≫ ketones. In total, 24 substrates were examined for the catalytic hydroboration reactivity and generally, isolation yields ranging from 40% to 95% were achieved. Mechanistic investigation suggests that the catalytic hydroboration of the substrates proceeds via intramolecular hydride transfer without going through an Fe-H intermediate. As indicated by 1H NMR spectroscopic monitoring, the substrates and the borane agent bind to the iron centre and the imine N atom, respectively, which facilitates the hydride transfer by activating the B-H bond and polarizing the double bond of the substrates.

Diplumbane-catalysed solvent- and additive-free hydroboration of ketones and aldehydes.

A new diplumbane, namely [Pb(CH2SiMe3)3]2, was synthesized and structurally characterized. This group 14 element compound was found to catalyse the hydroboration of ketones and aldehydes under mild conditions without the use of additives and solvents, leading to the synthesis of a range of alcohols in high yields after hydrolysis.

Carbodiphosphorane-Catalyzed Hydroboration of Ketones and Imines

We report the use of a cyclic carbodiphosphorane catalyst for ketone and imine hydroboration reactions. Ketone hydroboration reactions are particularly rapid, typically reaching completion within 15 min using a 1 mol % catalyst loading at 25 °C. To our knowledge, this represents the first use of a carbodiphosphorane as an organocatalyst. The carbodiphosphorane exhibited superior catalytic activity in comparison to other neutral carbon nucleophiles tested, including an N-heterocyclic carbene, an N-heterocyclic olefin, and phosphorus ylides.

Synthesis and Structure of a Dimeric Yttrium Complex [LSi(BH3)(C5Me4)Y(CH2SiMe3)2]2 (L = PhC(NtBu)2) and Its Catalytic Application for Hydroboration of Ketones and Aldehydes

Synthesis and Structure of a Dimeric Yttrium Complex [LSi(BH₃)(C₅Me₄)Y(CH₂SiMe₃)₂]₂ (L = PhC(N<i>t</i>Bu)₂) and Its Catalytic Application for Hydroboration of Ketones and Aldehydes

Cover Feature: [(Me6TREN)MgOCHPh2][B(C6F5)4]: A Model Complex to Explore the Catalytic Activity of Magnesium Alkoxides in Ketone Hydroboration (Eur. J. Inorg. Chem. 45/2021)

The Cover Feature shows a concerted carbonyl hydroboration mechanism involving Mg−O, B−H, and C=O bonds. Homoleptic magnesium alkoxides catalyze ketone hydroboration with a turn-over frequency (TOF) reaching up to 59,400 h−1 and exhibit exceptional functional group tolerance. This TOF is so far the best observed in a main group catalyst without the involvement of a metal hydride intermediate. The newly proposed mechanism finds general applicability in magnesium alkoxides and stimulates interest in exploring other metal alkoxides in reduction chemistry. More information can be found in the Full Paper by L. Maron, A. Venugopal and co-workers.

(Me6TREN)MgOCHPh2][B(C6F5)4]: A Model Complex to Explore the Catalytic Activity of Magnesium Alkoxides in Ketone Hydroboration

AbstractThe sterically hindered monomeric alkoxomagnesium compound [(Me6TREN)MgOCHPh2][B(C6F5)4] (1) has been used to explore the role of magnesium alkoxides in ketone hydroboration. Experiments and DFT calculations are suggestive of a concerted reaction pathway traversing through a six‐membered transition state involving Mg−OCHPh2, B−H, and C=O bonds. Prompted by this hypothesis, we investigated the activity of [Mg(OCHPh2)2] (3), which exhibits turn‐over frequency reaching up to 59,400 h−1 under solvent‐free conditions and stability towards C=C, −OH, −NH2 and −NO2. Due to the non‐existence of a metal hydride intermediate, such catalytic reactions will not get hindered in the presence of additional reactive functional groups.

Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth-Metal Complexes Supported with Phenoxy-Functionalized TsDPEN Ligands

Six novel chiral rare-earth-metal complexes bearing the phenoxy-functionalized TsDPEN ligand H3L1 (H3L1 = N-((1R,2R)-2-((3,5-di-tert-butyl-2-hydroxybenzyl)amino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide) were synthesized successfully and well characterized. The solid-state structures of four tetranuclear rare-earth-metal complexes [RE2L13]2 (RE = Nd (1), Sm (2), Eu (3), Gd (4)) and the dual-core yttrium complex Y2L13 (5) were determined by X-ray diffraction, respectively. The structure of lanthanum complex 6 was speculated by the 1H DOSY spectroscopy in THF-d8 together with DFT calculations. Complexes 1–5 were employed to catalyze the enantioselective hydroboration of ketones and α,β-unsaturated ketones using pinacolborane (HBpin) as a reductant, and complex 1 gave better outcomes in comparison to the others. The corresponding secondary alcohols were obtained in excellent yields and moderate ee values. The same results were also achieved using the combined catalyst system of the neodymium amide Nd[N(SiMe3)2]3 with the phenoxy-functionalized TsDPEN ligand H3L1 in a 1:1.5 molar ratio.

Recent Advances in Metal‐Catalyzed Asymmetric Hydroboration of Ketones

AbstractMetal‐catalyzed asymmetric reduction of unsaturated functions is a highly useful and fundamental transformation to give diverse chiral synthons. In particular, the enantioselective reduction of prochiral ketones is of great synthetic interest, since it can provide optically active chiral alcohols which have wide applications in organic synthesis, materials science, and pharmaceutical chemistry. Numerous and diverse metal catalytic systems for asymmetric hydrogenation and hydrosilylation of ketones extensively evolved in terms of activity, selectivity, and practicality, while only limited varieties of metal catalysts for the asymmetrichydroborationhad been documented until 2010.Diverseandnewmetal complexes with a range of multi‐dentate chiral ligands have recently emerged as catalysts for the enantioselective ketone hydroboration, which are highly differentiated from the precedence in several aspects. This Minireview summarizes recent examples of the metal catalyst systems for the asymmetric hydroboration of ketones published from 2015 to 2020. Diverse catalytic working modes involved in a process of enantiodifferentiating hydride transfer, are discussed with a strong emphasis on the steric and electronic effects of chiral ligands.

Enantiopure Calcium Iminophosphonamide Complexes: Synthesis, Photoluminescence, and Catalysis

The synthesis of calcium complexes ligated by three different chiral iminophosphonamide ligands, L‐H (L=[Ph2P{N(R)CH(CH3)Ph}2]), L′‐H (L′=[Ph2P{NDipp}{N(R)CH(CH3)Ph}]), (Dipp=2,6‐iPr2C6H3), and L′′‐H (L′′=[Ph2P{N(R)CH(CH3)naph}2]), (naph=naphthyl) is presented. The resulting structures [L 2Ca], [L′ 2Ca], and [L′′ 2Ca] represent the first examples of enantiopure homoleptic calcium complexes based on this type of ligands. The calcium complexes show blue–green photoluminescence (PL) in the solid state, which is especially bright at low temperatures. Whereas the emission of [L′′ 2Ca] is assigned to the fluorescence of naphthyl groups, the PL of [L 2Ca] and [L′ 2Ca] is contributed by long‐lived phosphorescence and thermally activated delayed fluorescence (TADF), with a strong variation of the PL lifetimes over the temperature range of 5–295 K. Furthermore, an excellent catalytic activity was found for these complexes in hydroboration of ketones at room temperature, although no enantioselectivity was achieved.

A Boron–Oxygen Transborylation Strategy for a Catalytic Midland Reduction

The enantioselective hydroboration of ketones is a textbook reaction requiring stoichiometric amounts of an enantioenriched borane, with the Midland reduction being a seminal example. Here, a turno...

Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones

AbstractEnantiopure secondary alcohols are fundamental high‐value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working.