Regioselective Hydroboration Research Articles

A simple synthesis of surfactant-free polycrystalline CuO nanoparticles supported on carbon nanofibers for regioselective hydroboration of alkynes.

Copper oxide nanoparticles (CuO NPs) with a clean surface supported on carbon nanofibers (CNFs) in one-pot were prepared by simple solid-state grinding and aging followed by thermal treatment, yielding CuO nanoparticles with high (23.8 wt%) and uniform CuO loading in the absence of surfactants and solvent. The CuO NPs on CNFs (CuO/CNF) showed excellent catalytic activity in transforming a wide variety of alkynes into alkenyl boronates using B2Pin2 as a boron source in the absence of ligand and additives with high regioselectivity under mild conditions. Moreover, the present CuO/CNF catalyst was recyclable and possesses excellent chemoselectivity. The developed green synthetic approach is expected to offer exciting opportunities for designing monometallic or bimetallic nanoparticle catalysts on different supports applied in heterogeneous catalysis.

Visible-light-induced 1,2-diphenyldisulfane-catalyzed regioselective hydroboration of electron-deficient alkenes

A photoinduced PhSSPh-catalyzed regioselective borylation of electron-deficient alkenes has been developed for the synthesis of borylated carbonyl, nitrile, sulfone, phosphonate, trifluoromethyl, andgem-diboron compounds.

Nickel-catalyzed Markovnikov 1,2-Hydroboration of In Situ Generated 1,3-Dienes Using a Secondary Homoallylic Carbonate as the 1,3-Diene and Hydride Source

Transition metal-catalyzed regioselective hydroboration of 1,3-dienes has received continuous interest in the field of organic synthesis. Herein, we describe the nickel-catalyzed Markovnikov 1,2-hydroboration of in situ generated 1,3-dienes with bis(pinacolato)diboron using a secondary homoallyic carbonate as the 1,3-diene and hydride source. The catalytic hydroboration of in situ generated 1,3-dienes proceeded in the presence of Ni(cod)2/P(p-MeOC6H4)3 as the catalyst to give the corresponding secondary allylic boronates in 42–77% yields with high regioselectivity (12 examples).

Regioselective Markovnikov Cobalt-Catalyzed Hydroboration of Alkynes

Regioselective Markovnikov Cobalt-Catalyzed Hydroboration of Alkynes

Multifaceted Substrate–Ligand Interactions Promote the Copper-Catalyzed Hydroboration of Benzylidenecyclobutanes and Related Compounds

A unified synthetic strategy to access tertiary four-membered carbo/heterocyclic boronic esters is reported. Use of a Cu(I) catalyst in combination with a modified dppbz ligand enables regioselective hydroboration of various trisubstituted benzylidenecyclobutanes and carbo/heterocyclic analogs. The reaction conditions are mild, and the method tolerates a wide range of medicinally relevant heteroarenes. The protocol can be conveniently conducted on gram-scale, and the tertiary boronic ester products undergo facile diversification into valuable targets. Reaction kinetics and computational studies indicate that the migratory insertion step is turnover-limiting and accelerated by electron-withdrawing groups on the dppbz ligand. Energy decomposition analysis (EDA) calculations reveal that electron-deficient P-aryl groups on the dppbz ligand enhance the T-shaped π/π interactions with the substrate and stabilize the migratory insertion transition state.

Reaction Pathways and Redox States in α‐Selective Cobalt‐Catalyzed Hydroborations of Alkynes

AbstractCobalt(II) alkyl complexes supported by a monoanionic NNN pincer ligand are pre‐catalysts for the regioselective hydroboration of terminal alkynes, yielding the Markovnikov products with α:β‐(E) ratios of up to 97:3. A cobalt(II) hydride and a cobalt(II) vinyl complex appear to determine the main reaction pathway. In a background reaction the highly reactive hydrido species specifically converts to a coordinatively unsaturated cobalt(I) complex which was found to re‐enter the main catalytic cycle.

Reaction Pathways and Redox States in α-Selective Cobalt-Catalyzed Hydroborations of Alkynes.

Cobalt(II) alkyl complexes supported by a monoanionic NNN pincer ligand are pre‐catalysts for the regioselective hydroboration of terminal alkynes, yielding the Markovnikov products with α:β‐(E) ratios of up to 97:3. A cobalt(II) hydride and a cobalt(II) vinyl complex appear to determine the main reaction pathway. In a background reaction the highly reactive hydrido species specifically converts to a coordinatively unsaturated cobalt(I) complex which was found to re‐enter the main catalytic cycle.

Multigram Synthesis of Heterabicyclo[n.1.0]alkan‐1‐yl Trifluoroborates

An approach to the synthesis of oxa‐ and azabicyclo[n.1.0]alkan‐1‐yl trifluoroborates on a multigram scale was developed. Two synthetic strategies were evaluated: the first based on the lithiation–borylation of the corresponding 2‐bromoallyl derivatives, and the other relying on regioselective hydroboration of the appropriate hetera‐substituted enynes. The second method appeared to be more efficient in terms of scalability and substrate scope. Further steps included ring closing‐metathesis, mild palladium‐catalyzed cyclopropanation with diazomethane, and reaction with KHF2 and furnished the title compounds in up to 50 g scale in a single run (10–41 % overall yield, 4–5 steps).

Regioselective Hydroboration and Hydrosilylation of N-Heteroarenes Catalyzed by a Zinc Alkyl Complex.

Readily available zinc alkyl complexes showed good activity and regioselectivity in catalyzing hydroboration and hydrosilylation of N-heteroarenes. Hydroboration of benzo-fused N-heterocycles gave exclusive 1,2-addition products in 80-97% yields. Reactions of pyridines afforded a mixture of 1,2-, 1,4-, and 1,6-products in yields of 55-95%, with 1,2-dihydropyridine as the main product. Bis-hydrosilylation was observed for quinoline derivatives, generating bis-1,2-hydrosilylation products in 76-96% yields. Kinetic studies and control experiments were conducted to gain some insights into the reaction mechanism.

Radical-Hydroboration-Involved One-Pot Synthesis of Boron-Handled Glycol Derivatives

A one-pot two-step protocol for the direct synthesis of boron-handled glycol derivatives is reported. The procedure starts by an NHC–boryl-radical-promoted regioselective hydroboration of glycol-protected cinnamaldehydes. After that, the reaction mixture is treated with pinacol in the presence of HCl, leading to the direct formation of pinacol boronate handled glycol monoalkyl ethers. In this acid-triggered conversion, a reductive ring-opening of glycol-derived acetal moiety takes place, during which an NHC–borane unit serves as the hydride source.

Origin of the ligand effect in the cobalt catalyzed regioselective hydroboration of 1,3-diene.

Hydroboration of 1,3-dienes can provide useful intermediates with multiple functionalities. However, achieving high regioselectivity is still a challenge. Recent experimental research studies indicate that this challenge could be overcome by the ligand effect. We made DFT calculations to elucidate the origin of ligand controlled regioselectivity in cobalt catalyzed hydroboration of 2-substituted 1,3-diene. The following conclusions have been reached: when using PHOX ((2-oxazolinyl)-phenyldiphenylphosphine) as the ligand, the favorable 1,4-selective oxidative hydrogen migration pathway was suggested to start with the rate-determining step of 1,4-selective oxidative hydrogen migration followed by reductive boryl migration. The unique 1,4-selectivity is proposed to be a result of the less steric hindrance between the substrate and the ligand PHOX. When dppp (1,3-bis-(diphenylphosphino)propane) is used as the ligand, the favorable pathway is proposed to be a 1,2-selective oxidative boryl migration pathway which involves 1,2-selective oxidative boryl migration and reductive hydrogen migration. Interestingly, another smaller-bite angle bisphosphine ligand dppe (1,2-bis(diphenylphosphino)ethane) favors the 1,4-selective oxidative boryl migration pathway. DFT calculations revealed that the preferred oxidative boryl migration pathway with both dppp and dppe is attributed to their electron-rich properties which accelerate the oxidative boryl migration step. The larger bite angle of dppp than that of dppe leads to bulkier steric hindrance and promotes 1,2-selective reductive hydrogen migration. On the other hand, for dppe with a smaller bite angle, the steric effect in the reductive hydrogen migration step is not dominant and 1,4-selective reductive hydrogen migration is favored. It is expected that the analysis of the ligand effect on the regioselectivity would enable further catalyst design.

Ligand-free, catalytic and regioselective hydroboration of selenoalkynes

The copper-catalyzed hydroboration of selenoalkynes in a regio- and stereoselective fashion is reported, delivering selenium-containing vinylboronate products in good yields.

Hydroboration of Alkenes and Alkynes Employing Earth‐Abundant Metal Catalysts

AbstractIron complexes [BIAN]Fe(I)(η6‐toluene) (M1) and [BIAN]FeCl2 (M2) (BIAN=bis(2,6‐diisopropylaniline)acenaphthene) were found to be viable catalysts for the regioselective hydroboration of alkynes and alkenes. The hydroboration of alkynes and alkenes in the presence of HBpin and an activator at 70 °C afforded linear vinyl and alkyl boronic esters, respectively. Selectivity up to 98% was observed for alkyl boronic esters and exclusive formation of trans product was observed for vinyl boronic esters.

A Versatile NHC-Parent Silyliumylidene Cation for Catalytic Chemo- and Regioselective Hydroboration.

This study describes the first use of a silicon(II) complex, NHC-parent silyliumylidene cation complex [(IMe)2SiH]I (1, IMe = :C{N(Me)C(Me)}2) as a versatile catalyst in organic synthesis. Complex 1 (loading: 10 mol %) was shown to act as an efficient catalyst (reaction time: 0.08 h, yield: 94%, TOF = 113.2 h-1; reaction time: 0.17 h, yield: 98%, TOF = 58.7 h-1) for the selective reduction of CO2 with pinacolborane (HBpin) to form the primarily reduced formoxyborane [pinBOC(═O)H]. The activity is better than the currently available base-metal catalysts used for this reaction. It also catalyzed the chemo- and regioselective hydroboration of carbonyl compounds and pyridine derivatives to form borate esters and N-boryl-1,4-dihydropyridine derivatives with quantitative conversions, respectively. Mechanistic studies show that the silicon(II) center in complex 1 activated the substrates and then mediated the catalytic hydroboration. In addition, complex 1 was slightly converted into the NHC-borylsilyliumylidene complex [(IMe)2SiBpin]I (3) in the catalysis, which was also able to mediate the catalytic hydroboration.

Zinc-Catalysed Hydroboration of Terminal and Internal Alkynes.

A regioselective hydroboration of alkynes has been developed by using commercially available zinc triflate as a catalyst, in the presence of catalytic amount of NaBHEt3 . The reaction tolerates a wide range of terminal alkynes having several synthetically useful functional groups and proceeds regioselectively to furnish hydroborated products in moderate to excellent yields. This system shows moderate chemoselectivity towards terminal C≡C bond over terminal and internal C=C bond and internal C≡C bond.

Iridium‐Catalyzed Distal Hydroboration of Aliphatic Internal Alkenes

The regioselective hydroboration of aliphatic internal alkenes remains a great challenge. Reported herein is an iridium-catalyzed hydroboration of aliphatic internal alkenes, providing distal-borylated products in good to excellent yields with high regioselectivity (up to 99:1). We also demonstrate that the C-B bond of the distal-borylated product can be readily converted into other functional groups. DFT calculations indicate that the reaction proceeds through an unexpected IrIII /IrV cycle.

Iridium‐Catalyzed Distal Hydroboration of Aliphatic Internal Alkenes

AbstractThe regioselective hydroboration of aliphatic internal alkenes remains a great challenge. Reported herein is an iridium‐catalyzed hydroboration of aliphatic internal alkenes, providing distal‐borylated products in good to excellent yields with high regioselectivity (up to 99:1). We also demonstrate that the C−B bond of the distal‐borylated product can be readily converted into other functional groups. DFT calculations indicate that the reaction proceeds through an unexpected IrIII/IrV cycle.

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors.

Galectins are carbohydrate recognition proteins that bind carbohydrates containing galactose and are involved in cell signaling and cellular interactions, involving them in several diseases. We present the synthesis of (aryltriazolyl)methyl galactopyranoside galectin inhibitors using a highly diastereoselective hydroboration of C1-exo-methylene pyranosides giving inhibitors with fourfold or better selectivity for galectin-1 over galectin-3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N and dissociation constants down to 170 µM.

Polyoxometalate-loaded Nanocellulose Sponge as a Novel Catalyst for the Regioselective Hydroboration of Phenylacetylene

Polyoxometalate-loaded Nanocellulose Sponge as a Novel Catalyst for the Regioselective Hydroboration of Phenylacetylene

Synthesis of the Deacetoxytubuvaline Fragment of Pretubulysin and its Lipophilic Analogues for Enhanced Permeability in Cancer Cell Lines

In the last two decades, tubulysins have emerged as alternatives to microtubule depolymerizing agents such as colchicine and vinblastine, which are well-established anticancer agents. However, the complex structure of tubulysins has always posed a challenge for synthetic chemists to scale up the production of these compounds. We report a new strategy for the practical gram-scale synthesis of a (4R)-4-[(tert-butoxycarbonyl)amino]-5-methylhexanoic acid through regioselective cleavage of a chiral aziridine ring with a vinyl Grignard reagent to afford tert-butyl [(1R)-1-isopropylbut-3-en-1-yl]carbamate, which was subjected to regioselective hydroboration–oxidation with 9-BBN. The resulting (4R)-4-[(tert-butoxycarbonyl)amino]-5-methylhexanoic acid was successfully transformed into the deacetoxytubuvaline fragment of pretubulysin or its highly lipophilic methyl-substituted thiazole and oxazole analogues for incorporation into pretubulysins. Increasing the lipophilicity of tubulysin or pretubulysin molecules should enhance their cell permeability and cytotoxicity in cancer cell lines.