Boron Enolates Research Articles

Generation of Bis(pentafluorophenyl)boron Enolates from Alkynes and Their Catalyst‐Free Alkyne Coupling

Carbon‐carbon bond forming reactions are powerful synthetic tools for constructing organic molecular frameworks. In this study, strongly Lewis acidic bis(pentafluorophenyl)boron enolates were generated from alkynes through oxygen transfer from 2,6‐dibromopyridine N‐oxide using tris(pentafluorophenyl)borane [B(C6F5)3]. Boron enolates were highly reactive owing to the strong acidity of the boron centers, and thus immediately coupled with alkynes. N‐Ethynylphthalimide reacted as an alkyne with 2,6‐dibromopyridine N‐oxide and B(C6F5)3 to form a semi‐stable bis(pentafluorophenyl)boron enolate through the coordination of the carbonyl group to the boron center. This enolate underwent coupling with another alkyne.

Generation of Bis(pentafluorophenyl)boron Enolates from Alkynes and TheirCatalyst-Free Alkyne Coupling.

Carbon-carbon bond forming reactions are powerful synthetic tools for constructing organic molecular frameworks. In this study, strongly Lewis acidic bis(pentafluorophenyl)boron enolates were generated from alkynes through oxygen transfer from 2,6-dibromopyridine N-oxide using tris(pentafluorophenyl)borane [B(C6F5)3]. Boron enolates were highly reactive owing to the strong acidity of the boron centers, and thus immediately coupled with alkynes. N-Ethynylphthalimide reacted as an alkyne with 2,6-dibromopyridine N-oxide and B(C6F5)3 to form a semi-stable bis(pentafluorophenyl)boron enolate through the coordination of the carbonyl group to the boron center. This enolate underwent coupling with another alkyne.

Boron-Catalyzed Michael Reaction of Donor-Acceptor Carboxylic Acid Pairs Enabling Direct Synthesis of 1,5-Dicarboxylic Acids.

A boron-catalyzed Michael reaction using pairs of carboxylic acids was developed. The reaction occurs through dual activation of the two substrates by a boron catalyst, which facilitates boron enolate formation from the donor carboxylic acid with simultaneous activation of the α,β-unsaturated carboxylic acid as the acceptor. α-Aryl and α-alkenyl carboxylic acids were applicable as donors. The versatility and utility of this reaction were demonstrated by the direct use of pharmaceuticals as donor carboxylic acids.

Group transfer polymerization of polar conjugated monomers using pinacolborane and thiourea anions

AbstractGroup transfer polymerization (GTP) plays a crucial role in polymerizing (methyl) acrylate. The utilization of cheap and easily synthesized thiourea anion (TUA) combined with pinacolborane (HBpin) undergoes controlled GTPs of methyl methacrylate (MMA), methacrylate (MA), and α‐methylenebutyrolactone (MBL) at ambient temperature. The mechanistic study reveals that the TUA′‐1 having ‐NEt2 moiety works out as a cocatalyst to assist HBpin undergoes the 1,4‐hydroboration reaction with α, β‐unsaturated acrylates to in situ generate a boron enolate (boryl ketene acetal [BKA]). Different from typical GTP, in which silyl ketene acetal (SKA) is used as an initiator, this work shows that BKA could act as an initiator with the assistance of the cocatalyst TUA′‐1 to generate the polymer. The chain end groups of the obtained polymer are characterized by MALDI‐TOF‐MS, indicating one of the chain ends features a hydride from the HBpin and another chain end has a linear or back‐biting cyclic structure. Moreover, the polymerization process is strongly supported by density functional theory (DFT) calculations. The application of BKA expands the research area of GTP reactions. The tunable and structural properties of TUA/hydroboranes significantly broaden the types of initiators in the GTP and pave a new methodology to achieve functional polymers.

Approaching Dianionic Tetraoxadiborecine Macrocycles: 10-Membered Bora-Crown Ethers Incorporating Borafluorenate Units.

The addition of non-benzenoid quinones, acenapthenequinone or aceanthrenequinone, to the 9-carbene-9-borafluorene monoanion (1) affords the first examples of dianionic 10-membered bora-crown ethers (2-5), which are characterized by multi-nuclear NMR spectroscopy (1 H, 13 C, 11 B), X-ray crystallography, elemental analysis, and UV/Vis spectroscopy. These tetraoxadiborecines have distinct absorption profiles based on the positioning of the alkali metal cations. When compound 4, which has a vacant C4 B2 O4 cavity, is reacted with sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, a color change from purple to orange serves as a visual indicator of metal binding to the central ring, whereby the Na+ ion coordinates to four oxygen atoms. A detailed theoretical analysis of the calculated reaction energetics is provided to gain insight into the reaction mechanism for the formation of 2-5. These data, and the electronic structures of proposed intermediates, indicate that the reaction proceeds via a boron enolate intermediate.

Approaching Dianionic Tetraoxadiborecine Macrocycles: 10‐Membered Bora‐Crown Ethers Incorporating Borafluorenate Units

AbstractThe addition of non‐benzenoid quinones, acenapthenequinone or aceanthrenequinone, to the 9‐carbene‐9‐borafluorene monoanion (1) affords the first examples of dianionic 10‐membered bora‐crown ethers (2–5), which are characterized by multi‐nuclear NMR spectroscopy (1H, 13C, 11B), X‐ray crystallography, elemental analysis, and UV/Vis spectroscopy. These tetraoxadiborecines have distinct absorption profiles based on the positioning of the alkali metal cations. When compound 4, which has a vacant C4B2O4 cavity, is reacted with sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate, a color change from purple to orange serves as a visual indicator of metal binding to the central ring, whereby the Na+ ion coordinates to four oxygen atoms. A detailed theoretical analysis of the calculated reaction energetics is provided to gain insight into the reaction mechanism for the formation of 2–5. These data, and the electronic structures of proposed intermediates, indicate that the reaction proceeds via a boron enolate intermediate.

Diastereoselective, Catalytic Access to Cross-Aldol Products Directly from Esters and Lactones.

High oxidation-state carbonyl coupling partners including esters and lactones were reacted with enones to give aldol-type products directly using two-fold organoborane catalysis. This new retrosynthetic disconnection to aldol-type products is compatible with enolisable coupling partners, without self-condensation, and couples the high reactivity of secondary dialkylboranes with the stability of pinacolboronic esters. Excellent chemoselectivity, substrate scope (including those containing reducible functionalities and free alcohols) and diastereocontrol were achieved to access both the syn- and anti-aldol-type products. Mechanistic studies confirmed the two-fold catalytic role of the single secondary borane catalyst for boron enolate formation and formation of an aldehyde surrogate from the ester or lactone coupling partner.

Diastereoselective, Catalytic Access to Cross‐Aldol Products Directly from Esters and Lactones

Diastereoselective, Catalytic Access to Cross‐Aldol Products Directly from Esters and Lactones

Oxidative Cross-coupling of Boron and Silicon Enolates

Oxidative Cross-coupling of Boron and Silicon Enolates

Unprecedented Rearrangement of β-Difluoroboryloxy Ethers: A Route to C-2 Alkyl-chromenones

AbstractThe addition of boron trifluoride etherate (BF3·OEt2) to allenic ketones has led to the isolation of the isolated boron difluoride enolates. The single-crystal structure of boron enolate has been solved. The unprecedented C1–C10 migration of (Z)-β-difluoroboryloxy ether derivatives is observed to deliver rearranged phenol derivatives which are functionalized to C-2 alkyl-chromenones. Interestingly the isolated boron enolates have exhibited significant anticancer properties.

Convergent Synthesis of the C1-C29 Framework of Amphidinolide F.

The complete carbon framework of the macrocyclic marine natural product amphidinolide F has been prepared by a convergent synthetic route in which three fragments of similar size and complexity have been coupled. Key features of the syntheses of the fragments include the stereoselective construction of the tetrahydrofuran in the C1–C9 fragment by oxonium ylide (free or metal-bound) formation and rearrangement triggered by the direct generation of a rhodium carbenoid from 1-sulfonyl-1,2,3-triazole, the highly diastereoselective aldol reaction between a boron enolate and an aldehyde with 1,4-control to prepare the C10–C17 fragment, and the formation of the tetrahydrofuran in the C18–C29 fragment by intramolecular nucleophilic ring opening of an epoxide with a hydroxyl group under acidic conditions.

Transformations of Main-Group Organometallics Induced by Transition Metals

AbstractThe oxidative dehydrometallation of silyl or boron enolates is induced by palladium(II) catalyst to result in the versatile introduction of α,β-unsaturated carbon–carbon double bonds via palladium enolates. Selective oxidative cross- and homo-coupling reactions of silyl or boron enolates induced by vanadium(V) oxidant provide a selective synthetic method for accessing 1,4-dicarbonyl compounds in a nucleo­phile-nucleophile coupling mode. The ligand coupling reaction of main-group organometallic compounds induced by vanadium(V) oxi­dant provides a unique method for intramolecular carbon–carbon bond formation of nucleophiles. The last two reactions are a complementary strategy for the nucleophile-electrophile coupling reaction. The dehydrometallation and coupling reactions probably proceed through two- and one-electron oxidation processes, respectively.1 Introduction2 Palladium-Catalyzed Dehydrometallation3 Homo- and Cross-Coupling of Main-Group Organometallic Compounds4 Oxidative Ligand Coupling of Main-Group Organometallic Compounds5 Conclusion

Copper-Catalyzed Reductive Ireland-Claisen Rearrangements of Propargylic Acrylates and Allylic Allenoates.

The copper-catalyzed reductive Ireland-Claisen rearrangement of propargylic acrylates led to 3,4-allenoic acids. The use of silanes or pinacolborane as stoichiometric reducing agents and triethylphosphite as a ligand facilitated the divergent and complementary selectivity for the synthesis of diastereomeric anti- and syn-rearranged products, respectively. Copper-catalyzed reductive Ireland-Claisen rearrangement of allylic 2,3-allenoates proceeded effectively only when pinacolborane was used as a reductant to generate various 1,5-dienes in excellent yields and with good diastereoselectivities in some cases. Mechanistic studies showed that the silyl and boron enolates, rather than the copper enolate, underwent a stereospecific rearrangement via a chairlike transition state to afford the corresponding Claisen rearrangement products.

Mechanistic Insight into the 1,3,2-Diazaphospholene-Catalyzed Reductant (HBpin/NH3BH3)-Controlled Reaction of Allyl 2-Phenylacrylate: Claisen Rearrangement or Hydrogenation?

Mechanistic study on the 1,3,2-diazaphospholene (1)-catalyzed reduction reaction of allyl 2-phenylacrylate 4 with HBpin or ammonia borane (AB) was systematically performed by the density functional theory (DFT) method. When HBpin is employed as the reductant, the reductive Ireland-Claisen (IC) rearrangement reaction occurs. First, the active species P-hydrido-1,3,2-diazaphospholene 3 is generated through the metathesis reaction of 1 with HBpin. Next, the terminal C═C double bond of 4 is inserted into the P-H bond of 3 to produce 6a through the 1,2-addition (Markovnikov) step, which is followed by the pinB-H bond activation to afford key boron enolate 8. Then, 8 undergoes the [3,3] rearrangement that is followed by the alcoholysis reaction with methanol leading to the final product γ,δ-unsaturated carboxylic acid. The [3,3] rearrangement step is the rate-determining step with the Gibbs energy barrier (ΔG≠) and Gibbs reaction energy (ΔG) of 23.9 and -27.5 kcal/mol, respectively. When AB is employed as the reductant, the transfer hydrogenation reaction occurs through two comparable pathways, 1,2- and 1,4-transfer hydrogenation pathways. The former pathway directly leads to the hydrogenation product with the ΔG≠ and ΔG values of 22.4 and -27.7 kcal/mol, respectively. The latter pathway produces an enolate intermediate (rate-determining step, ΔG≠/ΔG = 24.1/-0.3 kcal/mol) first, which then prefers to undergo the enol-keto tautomerism instead of the [3,3] rearrangement to afford the hydrogenation product. Obviously, the generation of the boron enolate plays a crucial role in the reductive IC rearrangement reaction because it prevents the enol-keto tautomerism.

C−Boron Enolates Enable Palladium Catalyzed Carboboration of Internal 1,3‐Enynes

AbstractA new family of carbon‐bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These C−boron enolates are demonstrated to activate 1,3‐enyne substrates in the presence of a Pd0/Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate‐equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site‐, regio‐, and diastereoselectivity by the described catalytic cis‐carboboration reaction.

C-Boron Enolates Enable Palladium Catalyzed Carboboration of Internal 1,3-Enynes.

A new family of carbon-bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These C-boron enolates are demonstrated to activate 1,3-enyne substrates in the presence of a Pd0 /Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate-equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site-, regio-, and diastereoselectivity by the described catalytic cis-carboboration reaction.

Rhodium-Catalyzed Deoxygenation and Borylation of Ketones: A Combined Experimental and Theoretical Investigation.

The rhodium-catalyzed deoxygenation and borylation of ketones with B2pin2 have been developed, leading to efficient formation of alkenes, vinylboronates, and vinyldiboronates. These reactions feature mild reaction conditions, a broad substrate scope, and excellent functional-group compatibility. Mechanistic studies support that the ketones initially undergo a Rh-catalyzed deoxygenation to give alkenes via boron enolate intermediates, and the subsequent Rh-catalyzed dehydrogenative borylation of alkenes leads to the formation of vinylboronates and diboration products, which is also supported by density functional theory calculations.

Formation of Boron Enolates by Nucleophilic Substitution

Enolates have proven to be one of the key building blocks available to the synthetic chemist. Here we summarize a novel strategy for their preparation, involving the addition of α-borylated nucleophiles to esters to yield boron enolates. The enolates prepared by the addition of lithiated geminal bis(boron) compounds to esters can be trapped with two equivalents of halogen and alkyl electrophiles to yield α,α-difunctionalized compounds.1 Introduction2 Ketone Difunctionalization3 Boron Enolates by Coupling4 Towards Sequential Trapping5 Summary and Outlook

Oxovanadium(v)-catalyzed oxidative cross-coupling of enolates using O2 as a terminal oxidant.

The oxovanadium(v)-catalyzed oxidative cross-coupling of enolates using O2 as a terminal oxidant is reported, where a boron enolate and a silyl enol ether were employed as enolates. The redox behavior of V(v/iv) in this reaction under O2 was investigated by ESR and 51V NMR experiments.

Deoxygenative α-alkylation and α-arylation of 1,2-dicarbonyls.

Construction of C–C bonds at the α-carbon is a challenging but synthetically indispensable approach to α-branched carbonyl motifs that are widely represented among drugs, natural products, and synthetic intermediates. Here, we describe a simple approach to generation of boron enolates in the absence of strong bases that allows for introduction of both α-alkyl and α-aryl groups in a reaction of readily accessible 1,2-dicarbonyls and organoboranes. Obviation of unselective, strongly basic and nucleophilic reagents permits carrying out the reaction in the presence of electrophiles that intercept the intermediate boron enolates, resulting in two new α-C–C bonds in a tricomponent process.