Borinic Esters Research Articles

Exploring Border Conditions for Spontaneous Emergence of Chirality in Allylboration of 1,2,3-Triazolic Aldehydes.

A case of spontaneous chirality generation was observed during a synthetic project studying the allylboration of 1,2,3-triazolic aldehydes. Here, we present computational studies supported by experimental findings targeting the elucidation of border conditions required for the observation of spontaneous chirality generation in the reaction of 1-Ar-1H-1,2,3-triazole-4-carbaldehydes 1a,b with triallylborane. Three possible sources of symmetry breaking were found computationally. Thus, dimerization of the initial reaction products, alcoholates 4a,b, gives dimers 5a,b (homochiral) and 6a,b (heterochiral). The latter were computed to be more stable thermodynamically, which can lead to amplification of the initial stochastic imbalance of the enantiomers of 4a,b via the reservoir mechanism. Furthermore, enantiomeric excess can be increased during the transfer of the second allylic group in the reaction of optically active boronates 4a,b with 1a,b, which was computed to be enantioselective due to the strong activating and stereoregulating properties of the 1,2,3-triazole group. In addition, reactions of borinic esters 8a,b, products of the previous reaction with triallylborane, recovered in each case two molecules of 4a,b of the same handedness, which can lead to additional chirality amplification. Experimentally, reactions of optically active alcohols (+)-R-2a,b with triallylborane provided chiral alcoholates 4a,b, which were reacted with equivalent amounts of corresponding aldehydes 1a,b. Unexpectedly, in two series of 10 experiments each, preferential formation of both enantiomers of the newly formed product was observed: seven times S and three times R in the case of 1a and six times S and four times R in the case of 1b.

Boronyl Borinic Esters: Preparation as B2 pin2 /sec BuLi/TFAA Adducts, Structural Insights and Reactivity in Pd-catalyzed Allylic Borylation.

Novel boronyl borinic ester I was generated by quenching the B2 pin2 /sec BuLi-ate complex with trifluoroacetic acid anhydride (TFAA) via ring-opening in the 1,3,2-dioxaborolane moiety on ate-boron. Detailed NMR studies of the B2 pin2 /sec BuLi-ate complex in solution and in solid state allowed us to assume its oligomeric nature in solids with only ate-boron involved in the oligomerization process. The O-trifluoroacetyl pinacolate residue on borinic ester I initially formed on quenching with TFAA undergoes an unusual intramolecular transesterification with the carbonyl group of trifluoroacetyl forming othroester moiety in a few hours at r. t. to give boronyl borinic ester II. A solution of these reagents I/II was proved to be efficient for borylation of (2-fluoroallyl)pyridinium salts that are highly base sensitive.

Oxygenated Boron Species Generated In Situ by Protonolysis Enables Precision Synthesis of Alternating Polyesters

Recently, Lewis pairs composed of organobases and organoboranes have shown high catalytic activity for the synthesis of polyethers by ring-opening polymerization of epoxides. Surprisingly, copolymerization of cyclic anhydride and a large excess of epoxide we conducted at elevated temperatures were free of polyether formation when catalyzed by a phosphazene base and triethylborane (Et3B), even after complete anhydride consumption. As a result, polyesters with (near) perfect alternating sequence distribution, controlled and narrowly distributed molar mass were readily obtained. Experimental and calculational results attributed the unexpected chemoselectivity to the protonolysis of Et3B and the newly formed oxygenated boron species. Most importantly, the reversible interchange of acyloxyborane and borinic ester at the propagating chain ends suppressed the reaction between hydroxy species and epoxide (formation of ethers) while maintaining the catalytic activity for the reaction between carboxy species and epoxide (formation of esters). The polyesters containing catalyst residues exhibited good cytocompatibility despite these changes. The in situ structure and activity evolvement of boron species revealed here will pave new pathways for rational design of metal-free catalysts.

A novel borinate ester copolymer for Poly(Frustrated Lewis pair) gels

The versatile chemistry of boronic acid and boronate ester containing polymers has led to key applications in drug delivery, chemical sensing, and dynamic materials. However, their use in polymeric Frustrated Lewis pairs (FLP) remains unreported. In this paper we report the synthesis of a novel fluorinated borinate ester copolymer which, when combined with a suitable Lewis basic copolymer, generates polymeric FLP networks capable of responsive gelation. The borinate ester moiety, bis(pentafluorophenyl)borinic acid tetrafluorophenyl ester, was affixed to a polystyrene copolymer by a two-step post-polymerisation modification, which can be easily upscaled and purified. The Gutmann-Beckett method suggests these fluorinated borinate ester moieties are amongst the most Lewis acidic boron-containing polymers reported to date. Upon mixing with a Lewis basic copolymer poly(styrene-co-p-diphenylphosphino styrene), gelation cannot be achieved due to steric hindrance around the Lewis centres. However, network formation can be triggered by addition of small molecules such as diethylazodicarboxylate (DEAD) and cyclic ethers. The physical parameters and nature of the crosslinks of the gels prepared from different crosslinkers were probed by rheology. All networks demonstrated strong elastic behaviour, corresponding to covalently crosslinked materials. DEAD crosslinked gels displayed different behaviour to those triggered by cyclic ethers, indicating that mechanism of small molecule activation also plays an important role in the mechanical properties of poly(FLP) gels.

Annulative coupling of vinylboronic esters: aryne-triggered 1,2-metallate rearrangement.

A stereoselective annulative coupling of a vinylboronic ester ate-complex with arynes producing cyclic borinic esters has been developed. An annulation reaction that proceeded through the formation of two C–C bonds and a C–B bond was realized by exploiting a 1,2-metallate rearrangement of boronate triggered by the addition of a vinyl group to the strained triple bond of an aryne. The generated aryl anion would then cyclize to a boron atom to complete the annulation cascade. The annulated borinic ester could be converted to boronic acids and their derivatives by oxidation, halogenation, and cross-coupling. Particularly, halogenation and Suzuki–Miyaura coupling proceeded in a site-selective fashion and produced highly substituted alkylboronic acid derivatives.

Highly Diastereoselective Strain-Increase Allylborations: Rapid Access to Alkylidenecyclopropanes and Alkylidenecyclobutanes.

Allylboration of carbonyl compounds is one of the most widely used methods in the stereoselective synthesis of natural products. However, these powerful transformations are so far limited to allyl- or crotylboron reagents; ring-strained substituents in the α-position have not been investigated. Such substrates would lead to an increase in strain energy upon allylboration and as such cause a significant increase in the activation barrier of the reaction. Indeed, no reaction was observed between an α-cyclopropyl allylboronic ester and an aldehyde. However, by converting the boronic ester into the much more reactive borinic ester, the allylboration proceeded well giving alkylidenecyclopropanes in high yield. This process was highly diastereoselective and gives rapid access to versatile alkylidenecyclopropanes and alkylidenecyclobutanes. The chemistry shows a broad substrate scope in terms of both the range of vinylcycloalkyl boronic esters and aldehydes that can be employed. The intermediate boronate complexes were also found to be potent nucleophiles, reacting with a range of non-carbonyl-based electrophiles and radicals, leading to an even broader range of alkylidenecyclopropanes and alkylidenecyclobutanes. Using 11B NMR experiments, we were able to track the intermediates involved, and DFT calculations supported the experimental findings.

(2-Fluoroallyl)boration of Ketones with (2-Fluoroallyl)boronates.

Efficient routes toward activation of gem-chlorofluorocyclopropane-derived (2-fluoroallyl)boronates for allylboration of various ketones including functionalized and low-reactive ones were developed. Increasing the boron electrophilicity by the transformation of a boronate moiety into a borinic ester with nBuLi/trifluoroacetic anhydride (TFAA) makes (2-fluoroallyl)boration of acetyl arenes/hetarenes and aliphatic ketones possible with high diastereoselectivity. For low-reactive or sterically hindered ketones (e.g., benzophenone, adamantanone), "CuF"-based catalysts were developed: (NHC)CuF·HF and (NHC)CuOTf in the presence of an excess of KHF2 (NHC = IPr, SIPr, IPrCl).

Site-Selective and Stereoselective C-H Alkylations of Carbohydrates via Combined Diarylborinic Acid and Photoredox Catalysis.

Diphenylborinic acid serves as a cocatalyst for site- and stereoselective C-H alkylation reactions of carbohydrates under photoredox conditions using quinuclidine as the hydrogen atom transfer mediator. Products arising from selective abstraction of the equatorial hydrogens of cis-1,2-diol moieties, followed by C-C bond formation with net retention of configuration, are obtained. Computational modeling supports a mechanism involving formation of a tetracoordinate borinic ester, which accelerates hydrogen atom transfer with the quinuclidine-derived radical cation through polarity-matching and/or ion-pairing effects.

Stereospecific β-l-Rhamnopyranosylation through an SN i-Type Mechanism by Using Organoboron Reagents.

Stereospecific β-l-rhamnopyranosylations were conducted using a 1,2-anhydro-l-rhamnopyranose donor and mono-ol or diol acceptors in the presence of a glycosyl-acceptor-derived borinic or boronic ester. Reactions proceeded smoothly to provide the corresponding β-l-rhamnopyranosides (β-l-Rhap) with complete stereoselectivity in moderate to high yields without any further additives under mild conditions. Mechanistic studies of the borinic ester mediated glycosylation using 13 C kinetic isotope effect (KIE) measurements and DFT calculations were consistent with a concerted SN i mechanism with an exploded transition state. In addition, the present glycosylation method was applied successfully to the synthesis of a trisaccharide, α-l-Rhap-(1,2)-β-l-Rhap-(1,4)-Glcp, derived from Streptococcus pneumoniae serotypes 7B, 7C, and 7D.

Stereospecific β‐l‐Rhamnopyranosylation through an SNi‐Type Mechanism by Using Organoboron Reagents

AbstractStereospecific β‐l‐rhamnopyranosylations were conducted using a 1,2‐anhydro‐l‐rhamnopyranose donor and mono‐ol or diol acceptors in the presence of a glycosyl‐acceptor‐derived borinic or boronic ester. Reactions proceeded smoothly to provide the corresponding β‐l‐rhamnopyranosides (β‐l‐Rhap) with complete stereoselectivity in moderate to high yields without any further additives under mild conditions. Mechanistic studies of the borinic ester mediated glycosylation using 13C kinetic isotope effect (KIE) measurements and DFT calculations were consistent with a concerted SNi mechanism with an exploded transition state. In addition, the present glycosylation method was applied successfully to the synthesis of a trisaccharide, α‐l‐Rhap‐(1,2)‐β‐l‐Rhap‐(1,4)‐Glcp, derived from Streptococcus pneumoniae serotypes 7B, 7C, and 7D.

Borinic Acid/Halide Co-catalyzed Semipinacol Rearrangements of 2,3-Epoxy Alcohols.

A new mode of catalysis of the semipinacol rearrangement of 2,3-epoxy alcohols is described. In combination with a halide salt additive, diarylborinic acids promote a Type II rearrangement that occurs with net retention of configuration. This unusual stereochemical outcome is consistent with a mechanism involving regioselective ring opening of the epoxy alcohol by halide, followed by rearrangement of the resulting halohydrin-derived borinic ester. The protocol is applicable to a range of substrates, enabling ring contractions and expansions as well as stereospecific syntheses of acyclic β-hydroxycarbonyl compounds.

Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides.

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having multifarious bioactivities. Although chemical O-glycosylation is a commonly beneficial strategy to synthesize disaccharide nucleosides, the preparation of substrates such as glycosyl donors and acceptors requirestedious protectinggroup manipulations and a purification at each synthetic step. Meanwhile, several research groups have reported that boronic and borinic esters serve as a protecting or activating group of carbohydrate derivatives to achieve the regio- and/or stereoselective acylation, alkylation, silylation, and glycosylation. In this article, we demonstrate the procedure for the regioselective O-glycosylation of unprotected ribonucleosides utilizing boronic acid. The esterification of 2',3'-diol of ribonucleosides with boronic acid makes the temporary protection of diol, and, following O-glycosylation with a glycosyl donor in the presence of p-toluenesulfenyl chloride and silver triflate, permits the regioselective reaction of the 5'-hydroxyl group to afford the disaccharide nucleosides. This method could be applied to various nucleosides, such as guanosine, adenosine, cytidine, uridine, 5-metyluridine, and 5-fluorouridine. This article and the accompanying video representuseful (visual) information for the O-glycosylation of unprotected nucleosides and their analogs for the synthesis of not only disaccharide nucleosides, but also a variety of biologically relevant derivatives.

A Protocol for Direct Stereospecific Amination of Primary, Secondary, and Tertiary Alkylboronic Esters.

The direct, stereospecific amination of alkylboronic and borinic esters can be conducted by treatment of the organoboron compound with methoxyamine and potassium tert-butoxide. In addition to being stereospecific, this process also enables the direct amination of tertiary boronic esters in an efficient fashion.

Synthesis and boron interaction of new amino acid containing phthalocyanines and the precursor

A new phthalonitrile precursor with tyrosine substituent and the zinc phthalocyanine derived from it were synthesized and their interaction with diphenylborinic acid was studied. The new compounds were characterized by using elemental analysis, IR, 1H and 11B-NMR and UV-VIS spectral data. 11B-NMR data demonstrated that boron atom attached to the phthalonitrile precursor is in a bulky tetra-coordinated state with the formation of a coordinative N-B bond while completely planar phthalocyanine moieties with high aggregation tendencies at the concentrations used in NMR measurements lead the borinic ester side of the molecule into a planar tri-coordinated form. Moreover, the consequences of the presence of diphenylborinic ester groups on the spectral, photophysical and photochemical properties of the new zinc phthalocyanine are investigated in detail.

Effect of boron doping level on the photocatalytic activity of graphene aerogels

Heteroatom-doped three-dimensional (3D) graphene-based macroscopic assemblies (GMAs) are receiving considerable attention for application as heterogeneous photocatalysts. However, the relationship between the concentration and the bonding state of heteroatoms at the atomic scale and the resulting photoelectronic and photocatalytic properties of 3D GMAs remain unexplored. Herein, we describe a simple, environmentally benign, one-pot hydrothermal reduction-induced self-assembly process to prepare boron-doped graphene aerogels by using graphene oxide and boric acid as carbon (C) and boron (B) sources, respectively. By rationally adjusting the dopant elemental precursor, the B content was modulated from ∼0.14 to ∼3.37 at%. The as-synthesized B-doped bulk graphene monoliths with well-defined interconnected 3D porous networks can effectively degrade acridine orange (AO), a well-known recalcitrant and biologically toxic pollutant, under visible light irradiation. Particularly, the aerogel with a moderate B loading of ∼2.15 at% displayed a superior photodegradation efficiency of ∼98%, which is 2.13 times higher than the undoped material. The generation of oxygenated B derivatives, such as borinic esters and boronic acids, on the edge sites and defect regions of the 2D graphene building blocks was primarily responsible for the exceptional photocatalytic activity. Besides, these macroscale photocatalysts are highly stable and easily recyclable for practical applications.

Novel 1,2-cis-stereoselective glycosylations utilizing organoboron reagents and their application to natural products and complex oligosaccharide synthesis

In this mini-review article, 1,2-cis-stereoselective glycosylation methods utilizing organoboron reagents and 1,2-anhydroglycosyl donors that were developed in our laboratory, including regio- and 1,2-cis-stereoselective glycosylations using glycosyl-acceptor-derived boronic ester catalysts and 1,2-cis-stereoselective glycosylations using glycosyl-acceptor-derived borinic ester catalysts, are recounted. Representative applications of these methods to the synthesis of biologically active natural products and a complex oligosaccharide are also described.

Mechanism of an Organoboron-Catalyzed Domino Reaction: Kinetic and Computational Studies of Borinic Acid-Catalyzed Regioselective Chloroacylation of 2,3-Epoxy Alcohols.

A mechanistic study of the borinic acid-catalyzed chloroacylation of 2,3-epoxy alcohols is presented. In this unusual mode of catalysis, the borinic acid activates the substrate toward sequential reactions with a nucleophile (epoxide ring-opening by chloride) and an electrophile (O-acylation of the resulting alkoxide). Reaction progress kinetic analysis of data obtained through in situ FTIR spectroscopy is consistent with a mechanism involving turnover-limiting acylation of a chlorohydrin-derived borinic ester. This proposal is further supported by investigations of the effects of aroyl chloride substitution on reaction rate. The kinetics experiments also shed light on the effects of chloride concentration on reaction rate and indicate that the catalyst is subject to inhibition by the product of the chloroacylation reaction. Computational modeling is employed to gain insight into the effects of the organoboron catalyst on the regioselectivities of the epoxide ring-opening and acylation steps. The density functional theory calculations provide a plausible pathway for selective chlorinolysis at C-3 and benzoylation at O-1, as is observed experimentally.

1,2-cis-α-Stereoselective Glycosylation Utilizing a Glycosyl-Acceptor-Derived Borinic Ester and Its Application to the Total Synthesis of Natural Glycosphingolipids.

1,2-cis-α-Stereoselective glycosylations were conducted using a 1,2-anhydroglucose donor and mono-ol acceptors in the presence of a glycosyl-acceptor-derived borinic ester. Reactions proceeded smoothly under mild conditions to provide the corresponding α-glycosides with high stereoselectivity in moderate to high yields. In addition, the present method was applied successfully to the direct glycosylation of a protected ceramide acceptor and the total synthesis of natural glycosphingolipids (GSLs).

ChemInform Abstract: Glycosyl‐Acceptor‐Derived Borinic Ester‐Promoted Direct and β‐Stereoselective Mannosylation with a 1,2‐Anhydromannose Donor.

AbstractThe first direct and highly β‐stereoselective mannosylation of 1,2‐anhydromannose and mono‐ol acceptors is developed utilizing a glycosyl‐acceptor‐derived borinic ester under mild conditions is reported.

Glycosyl-Acceptor-Derived Borinic Ester-Promoted Direct and β-Stereoselective Mannosylation with a 1,2-Anhydromannose Donor.

β-Stereoselective mannosylations were conducted using a 1,2-anhydromannose donor and mono-ol acceptors in the presence of a glycosyl-acceptor-derived borinic ester. Reactions proceeded smoothly under mild conditions to provide the corresponding β-mannosides with high stereoselectivity in moderate to high yields. In addition, the present glycosylation method was applied successfully to the total synthesis of acremomannolipin A.