Hydroboration-oxidation Research Articles

Enantioselective Synthesis of the Active Sex Pheromone Components of the Female Lichen Moth, Lyclene dharma dharma, and Their Enantiomers

The Lichen moth, Lyclene dharma dharma (Arctiidae, Lithosiinae), plays a significant role in forest ecosystem dynamics. A concise and novel method to synthesize the active sex pheromone components, (S)-14-methyloctadecan-2-one ((S)-1), (S)-6-methyloctadecan-2-one ((S)-2), and their enantiomers has been developed. Key steps in the synthesis include the use of Evans’ chiral auxiliaries, Grignard cross-coupling reactions, hydroboration–oxidation, and Wacker oxidation. The synthesized sex pheromone components hold potential value for studies on communication mechanisms, species identification, and ecological management.

Production of Long Chain Alcohols from Waste Polyethylene Pyrolysis Oil Using a One-Pot Hydroboration–Oxidation Process

Production of Long Chain Alcohols from Waste Polyethylene Pyrolysis Oil Using a One-Pot Hydroboration–Oxidation Process

SiO2 nanosphere coated tough catheter with superhydrophobic surface for improving the antibacteria and hemocompatibility.

Catheter infection is the most common complication after vascular catheter placement, which seriously threatens the survival of critically ill patients. Although catheters with antibacterial drug coatings have been used, catheter infections have not been effectively resolved. In this research, a SiO2 nanosphere-coated PTFE catheter (PTFE-SiO2) with enhanced antibacterial and excellent mechanical properties was prepared via dopamine as a graft bridge. The microscopic morphology results show that the nanospheres are uniformly dispersed on the surface of the catheter. The physicochemical characterization confirmed that PTFE-SiO2 had reliable bending resistance properties, superhydrophobicity, and cytocompatibility and could inhibit thrombosis. Antibacterial results revealed that PTFE-SiO2 could hinder the reproduction of E. coli and S. aureus. This research demonstrates the hydroxyl-rich materials obtained by hydroboration oxidation have the advantages of better dispersion of functional coatings, indicating their potential for helpful modification of catheters.

Total Synthesis of Stemarene and Betaerene Diterpenoids: Divergent Ring-Formation Strategy and Late-Stage C–H Functionalization

A unified protecting group-free approach to two stemarene and two betaerene diterpenoids through a bioinspired two-phase strategy has been developed, and three of them were obtained for the first t...

Host-guest molecular encapsulation of cucurbit[7]uril with dillapiole congeners using docking simulation and density functional theory approaches

Binding affinity and intermolecular interactions are essential characteristics that could be used to comprehend molecular recognition between molecules in supramolecular host-guest systems. This work presented a molecular docking simulation and density functional theory (DFT) calculation at the B3LYP-631g(d) level of theory on dillapiole and its derivatives (guest compounds) complexation with cucurbit[7]uril (host compound). The supramolecular host-guest inclusion complex binding energies, − 4.46 to − 5.47 kcal mol−1 and − 0.53 to − 15.38 kcal mol−1 for docking and DFT calculation, respectively, were calculated, and the intermolecular interactions such as the hydrogen bonding, electrostatic, dispersion, and pi-alkyl formation involved were observed. The negative binding energies of D1-CB [7], D2-CB [7], D3-CB [7], D4-CB [7], D5-CB [7], D6-CB [7], and D-CB [7], computed from both the theoretical approaches, suggested the possible inclusion of the guests inside the cucurbit[7]uril cavity, enabling the formation of stable inclusion compounds. However, the significant difference in the binding energy values from the DFT calculation demonstrated a clustered preference in terms of the complex stabilisation, with D2-CB [7], D3-CB [7], D5-CB [7], and D6-CB [7] dominantly favourable, while D1-CB [7], D4-CB [7], and D were inclusion complexes with the least favourable. Encapsulation of the guests’ structural frame as a whole or a part and steric constraint associated with the guests’ substituents positioning in addition to the intermolecular interactions were also noted to induce stabilisation in the binding energy, thus reflecting a preferable inclusion complex. Besides, the theoretical calculations on the rationalisation of the selected guests’ energy barrier were found to correlate well with experimental works of hydroboration oxidation synthesis to produce alcohol derivatives of dillapiole.

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration-oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles.

Isoxazolidines represent a very important class of N/O-containing heterocycles used as the key intermediates in the synthesis of more complex cyclic and acyclic compounds, including various biologically active molecules. Here, we present a fast and highly stereoselective approach towards both C-3/4-cis and C-3/4-trans isomers of 3-substituted isoxazolidin-4-ols. The strategy relies on a highly regio- and trans-stereoselective hydroboration–oxidation reaction of the 4,5-unsubstituted 2,3-dihydroisoxazoles with basic hydrogen peroxide. The consecutive oxidation/reduction route, sequentially employing Dess–Martin periodinane and ʟ-selectride, is used for the inversion of the C-3/4-trans relative configuration of the isoxazolidine ring. The significance of the method lies in its variability and applicability to a concise synthesis of various 4-hydroxyisoxazolidines, starting from the readily available C-alkyl/aryl-nitrones. The resemblance to 3-hydroxypyrrolidines certainly makes the 4-hydroxyisoxazolidines important and valuable structural fragments in drug discovery.

HYDROBORATION-OXIDATION OF GLYCIRRETHIC ACID’S DERIVATIVES

The hydroboration-oxidation reaction is widely used in the chemistry of terpenoids both for proving the structure of new compounds isolated from natural raw materials and for the directed synthesis of low molecular weight bioregulators. Moreover, most of the known examples affect mono- and sesquiterpenes, a much smaller number - for di- and triterpenoids: most are represented by hydroboration-oxidation of localized double bonds, examples for conjugated dienes are limited only by hydroboration-oxidation of cis-eudesma-6,11-diene, abietic acid and its methyl ester.
 We found that the reduction of the pentacyclic triterpenoid – glycyrrhetate methyl ester – diisobutylaluminium hydride in methylene chloride at -78 ° С and subsequent hydrolysis in the presence of ammonium chloride proceeds with the formation of 3β,30-dihydroxy-18βH-olean-9(11),12(13)-diene with a yield of 90%. It was shown that the hydroboration of the 1,3-diene system in it with a 3.3 molar excess of diborane in tetrahydrofuran is accompanied by the restoration of the carboxyl function, and after oxidation with the hydrogen peroxide-sodium acetate system of the organoboranes formed, three alcohols are mixed (2 : 1 : 1): 3β,11,30-trihydroxy-18βH-olean-12(13)-ene, 3β,12,30-trihydroxy-18βH-olean-9(11)-ene and 3β,9,30-trihydroxy-18βH-olean-12 (13)-ene, respectively. A similar mixture of triols was also obtained by hydroboration-oxidation of 3β-hydroxy-18βH-olean-9(11),12(13)-diene-30-oic acid. The hydroboration-oxidation reactions of 3β,30-dihydroxy-18βH-olean-9(11),12(13)-diene or the corresponding 30th acid proceed as monoprocesses predominantly at 9(11) double bonds.

Hydroboration–Oxidation of Terpenoids in Targeted Syntheses of Low-Molecular-Mass Bioregulators

Examples of hydroboration–oxidation of natural mono-, sesqui-, di-, and triterpenoids are reviewed. Diborane, BH3·THF, BH3·Me2S, disiamylborane, thexylborane, dicyclohexylborane, 9-borabicyclo[3,3,1]nonane (9-BBN), and diisopinocampheylborane are used as the hydroboration reagents; H2O2 mixed with KOH, NaOH, and NaOAc, as the oxidants. Most of the examples address mono- and sesquiterpenoids with far fewer describing di- and triterpenoids.

Trans-Hydroboration-oxidation products in Δ5-steroids via a hydroboration-retro-hydroboration mechanism.

Herein, we report for the first time a “trans-hydroboration–oxidation product” isolated and characterized under traditional hydroboration–oxidation conditions using cholesterol and diosgenin as substrates. These substrates are excellent starting materials because of the rigidity and different structural environments around the double bond. Further investigations based on experimental evidence, in conjunction with theoretical studies, indicate that the formation of this trans-species occurs via a retro-hydroboration of the major product to generate the corresponding Δ6-structure and the subsequent hydroboration by the β-face. Besides, the corresponding Markovnikov type products have been isolated in synthetically useful yields. The behavior of the reaction under a range of temperatures is also investigated.

Toward the Synthesis of SB-203207: Construction of Four Contiguous Nitrogen-Containing Stereogenic Centers.

SB-203207 is an altemicidin-type alkaloid that potently inhibits isoleucyl tRNA synthetase activity. Its main structural feature is a hexahydro-6-azaindene framework containing a unique β-hydroxy α,α-disubstituted α-amino acid moiety on the cyclopentane portion. Herein we have established a method for constructing the four contiguous nitrogen-containing stereogenic centers of SB-203207 by using as key steps the stereoselective alkylation of bowl-shaped tricyclic lactone to construct a quaternary carbon at C1, the stereoselective hydroboration-oxidation reaction to install the C2 hydroxy group, and the Curtius rearrangement to introduce a nitrogen atom onto the C1 quaternary carbon.

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene.

New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration–oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.

Toward the Synthesis of Yuzurimine-Type Alkaloids: Stereoselective Construction of the Heterocyclic Portions of Deoxyyuzurimine and Macrodaphnine.

The heterocyclic portions of yuzurimine-type alkaloids, such as deoxyyuzurimine and macrodaphnine, were synthesized by using a stereoselective hydroboration-oxidation reaction to install the C20 methyl group, the intramolecular Mitsunobu reaction to construct the E-ring portion, and the intramolecular SN2 reaction to construct the F-ring portion as key steps.

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.

Mild Ring‐Opening 1,3‐Hydroborations of Non‐Activated Cyclopropanes

AbstractThe Brown hydroboration reaction, first reported in 1957, is the addition of B−H across an olefin in an anti‐Markovnikov fashion. Here, we solved a long‐standing problem on mild 1,3‐hydroborations of non‐activated cyclopropanes. A three‐component system including cyclopropanes, boron halides, and hydrosilanes has been developed for borylative ring‐opening of cyclopropanes following the anti‐Markovnikov rule, under mild reaction conditions. Density functional theory (M06‐2X) calculations show that the preferred pathway involves a cationic boron intermediate which is quenched by hydride transfer from the silane.

Mild Ring-Opening 1,3-Hydroborations of Non-Activated Cyclopropanes.

The Brown hydroboration reaction, first reported in 1957, is the addition of B-H across an olefin in an anti-Markovnikov fashion. Here, we solved a long-standing problem on mild 1,3-hydroborations of non-activated cyclopropanes. A three-component system including cyclopropanes, boron halides, and hydrosilanes has been developed for borylative ring-opening of cyclopropanes following the anti-Markovnikov rule, under mild reaction conditions. Density functional theory (M06-2X) calculations show that the preferred pathway involves a cationic boron intermediate which is quenched by hydride transfer from the silane.

Total synthesis of akuammiline alkaloid (+)-strictamine

An asymmetric total synthesis of the akuammiline alkaloid (+)-strictamine is described. The key steps of the synthetic route involve an improved Johnson-Claisen rearrangement to facilitate the formation of the challenging C15–C20 linkage and the (E)-alkene side chain, intramolecular nucleophilic substitution cyclization to establish the E ring and diastereoselective Brown hydroboration of the terminal alkene to introduce the C16 stereocenter.

Diversity-Oriented Synthesis of cis-3,4-Dihydroxylated Piperidine and Its Higher Saturated and Unsaturated Homologues from d-Ribose and Their Glycosidase-Inhibition Study

The synthesis of six-, seven-, and eight-membered cis-dihydroxy azacycles has been accomplished from d -ribose using Vasella reductive amination as a key step and utilization of hydroboration–oxidation, Mitsunobu reaction, and ring-closing metathesis (RCM) reactions in a facile manner. These homologous dihydroxylated heterocyclic scaffolds were subjected to the glycosidase inhibition assays. However, only a moderate inhibitory activity for three out of five compounds was observed against α-glucosidases with a high degree of selectivity.

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

The synthesis of β-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether–alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration–oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks.

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

The synthesis of β-carba-xylo and arabino pyranosides of cholestanol is described. The synthetic strategy, which is analogous to the Postema approach to C-glycosides, centers on the ring closing metathesis of an enol ether–alkene precursor to give a cyclic enol ether that is elaborated to a carba-pyranoside via hydroboration–oxidation on the olefin. The method, which is attractive for its modularity and stereoselectivity, may find wider applications to carba-hexopyranosides and other complex cycloalkyl ether frameworks.

A Stereoselective Synthesis of a 3,4,5-Substituted Piperidine of Interest as a Selective Muscarinic (M1) Receptor Agonist

Syntheses of (1RS,2SR,6SR)-2-alkoxymethyl-, 2-hetaryl-, and 2-(hetarylmethyl)-7-arylmethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones, of interest as potential muscarinic M1 receptor agonists, are described. A key step in the synthesis of (1RS,2SR,6SR)-7-benzyl-6-cyclobutyl-2-methoxymethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-one, was the addition of isopropenylmagnesium bromide to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal. This gave the 4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-isopropenyloxazolidinone with the 5-isopropenyl and 4-tert-butyldimethylsilyloxymethyl groups cis-disposed about the five-membered ring by chelation controlled addition and in situ cyclisation. This reaction was useful for a range of organometallic reagents. The hydroboration–oxidation of (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-(1-methoxyprop-2-en-2-yl)-1,3-oxazolidin-2-one gave (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-[(SR)-1-hydroxy-3-methoxyprop-2-yl]-1,3-oxazolidin-2-one stereoselectively. 4,7-Diaza-9-oxabicyclo[4.3.0]nonan-8-ones with substituents at C2 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituent. The bicyclic system with a 2-furyl substituent at C2 was therefore identified as an important target. The addition of 1-lithio-1-(2-furyl)ethene to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal gave (4SR,5RS)-4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-[1-(2-furyl)ethenyl]-1,3-oxazolidinone after chelation controlled addition and in situ cyclisation. Following oxazolidinone N-benzylation, hydroboration at 35 °C, since hydroboration at 0 °C was unexpectedly selective for the undesired isomer, followed by oxidation gave a mixture of side-chain epimeric alcohols that were separated after SEM-protection and selective desilylation. Conversion of the neopentylic alcohols into the corresponding primary amines by reductive amination, was followed by N-nosylation, removal of the SEM-groups and cyclisation using a Mitsunobu reaction. Denosylation then gave the 2-furyloxazolidinonyl-fused piperidines, the (1RS,2SR,6SR)-epimer showing an allosteric agonistic effect on M1 receptors. Further studies resulted in the synthesis of other 2-substituted 4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones and an analogous tetrahydropyran