Potassium Aryl Research Articles

Preparation of arylboronic and diarylborinic acids from potassium aryl(fluoro)borates

Preparation of arylboronic and diarylborinic acids from potassium aryl(fluoro)borates

Combining two relatively weak bases (Zn(TMP)2 and KOtBu) for the regioselective metalation of non-activated arenes and heteroarenes.

Co-operation between two relatively weak Brønsted bases, Zn(TMP)2 and KOtBu, produces a bimetallic base strong enough to regioselectively zincate non-activated arenes such as naphthalene, biphenylene and anthracene under mild conditions. This co-operativity is also effective with a range of more sensitive five-membered ring heterocyclic substrates including benzoxazole and caffeine. Metalation products have been intercepted with iodine, affording the relevant iodo-(hetero)arenes in good to excellent yields with finely tuned regioselective control. Combining NMR spectroscopic and X-ray crystallographic studies has uncovered that depending on the solvent, a complicated ligand distribution process of mixed aryl/alkoxy higher order zincate intermediates, (THF) n K2Zn(Ar)2(OtBu)2, that can liberate lower order zincates of the form [(THF)2KZn(Ar)(OtBu)2]2 and eliminate potassium aryl species. While this ligand redistribution process seems to operate for non-substituted (hetero)arene metalation products, for non-activated alkylarenes such as mesitylene or m-xylene the higher-order zincates resulting from their lateral metalation are stable in solution and the solid state, which is attributed to the greater π-stabilisation that these systems can provide to the K cations. Adding another layer of complexity to this heterobimetallic system, over time the Zn(TMP)2/2KOtBu combination reacts with the THF solvent of these reactions, to afford an unusual decomposition product which contains an s-trans-1,3-butadienyl (C4H5 -) fragment coordinated to Zn within a potassium zincate structure. The formation of the latter is attributed to the initial synergistic α-zincation of THF, followed by subsequent ring opening and oxygen extrusion.

Phenoxythiazoline (FTz)‐Cobalt(II) Precatalysts Enable C(sp2)–C(sp3) Bond‐Formation for Key Intermediates in the Synthesis of Toll‐like Receptor 7/8 Antagonists**

AbstractEvaluation of the relative rates of the cobalt‐catalyzed C(sp2)–C(sp3) Suzuki–Miyaura cross‐coupling between the neopentylglycol ester of 4‐fluorophenylboronic acid and N‐Boc‐4‐bromopiperidine established that smaller N‐alkyl substituents on the phenoxyimine (FI) supporting ligand accelerated the overall rate of the reaction. This trend inspired the design of optimal cobalt catalysts with phenoxyoxazoline (FOx) and phenoxythiazoline (FTz) ligands. An air‐stable cobalt(II) precatalyst, (FTz)CoBr(py)3 was synthesized and applied to the cross‐coupling of an indole‐5‐boronic ester nucleophile with a piperidine‐4‐bromide electrophile that is relevant to the synthesis of reported toll‐like receptor (TLR) 7/8 antagonist molecules including afimetoran. Addition of excess KOMe⋅B(OiPr)3 improved catalyst lifetime due to attenuation of alkoxide basicity that otherwise resulted in demetallation of the FI chelate. A first‐order dependence on the cobalt precatalyst and a saturation regime in nucleophile were observed, supporting turnover‐limiting transmetalation and the origin of the observed trends in N‐imine substitution.

Introducing Trifluoromethoxyarenes as Halide Surrogates in Mechanochemical Realizations of Ni‐catalyzed Cross‐coupling Reactions

AbstractSince the introduction of the TM‐catalyzed cross‐couplings their scope of starting materials has been growing systematically, allowing for more flexible design of synthetic routes with the coupling as a key step, particularly late‐stage modifications. Herein we present the use of trifluoromethoxyarenes as halide surrogates in Ni‐catalyzed couplings with arylboronic acids, potassium aryl trifluoroborates and aryl trialkoxysilanes, under mechanochemical conditions. In total, 22 biphenyl structures were obtained in good yields. Successful gram scale experiments confirm the usefulness of our protocol. The developed transformations’ mechanism was discussed in relation to the experimental and literature data and DFT calculations. The unusual reactivity of potassium benzoyltrifluoroborates was uncovered. 6 examples of resulting benzophenones were obtained in very good yields and the protocol was extended to gram scale. The described methods present a powerful tool when combined with the recent advances in organofluorine chemistry.

Iron-Catalyzed C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling Using an Alkoxide Base

The synthesis and characterization of phenoxy(imine) iron(II) alkyl precatalysts for C(sp2)–C(sp3) Suzuki–Miyaura cross-coupling of aryl boronic esters and alkyl bromides is described. Addition of phenoxyimines (FI) to (py)2Fe(CH2SiMe3)2 (py = pyridine) afforded the high-spin iron(II) alkyl derivatives, (FI)Fe(CH2SiMe3)(py) with varying N-imine substituents. With both neopentyl glycol-protected (BNeo) and pinacol-protected boronic ester (BPin) aryl nucleophiles, an iron-catalyzed cross-coupling method was realized that utilizes mild alkoxide bases. Optimal performance was observed in nonpolar solvents with anisole and fluorobenzene identified as more benign alternatives to benzene. The scope of this transformation includes high efficiency C(sp2)–C(sp3) bond formation with both primary and secondary alkyl bromides with electron-deficient aryl and heteroaryl nucleophiles. Substrates with base-sensitive functionality including ester and nitrile groups were tolerated, highlighting the broader compatibility with an alkoxide base. Radical clock experiments support the formation of electrophile-derived radicals during catalysis, and experiments with preformed potassium aryl boronates demonstrate the role of boronate intermediates in transmetalation.

Catalytic Synthesis of Atropisomeric o-Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction.

Herein, we report a modular and convergent strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.

Transition-Metal-Free C-C, C-O, and C-N Cross-Couplings Enabled by Light.

Transition-metal-catalyzed cross-couplings to construct C-C, C-O, and C-N bonds have revolutionized chemical science. Despite great achievements, these metal catalysts also raise certain issues including their high cost, requirement of specialized ligands, sensitivity to air and moisture, and so-called "transition-metal-residue issue". Complementary strategy, which does not rely on the well-established oxidative addition, transmetalation, and reductive elimination mechanistic paradigm, would potentially eliminate all of these metal-related issues. Herein, we show that aryl triflates can be coupled with potassium aryl trifluoroborates, aliphatic alcohols, and nitriles without the assistance of metal catalysts empowered by photoenergy. Control experiments reveal that among all common aryl electrophiles only aryl triflates are competent in these couplings whereas aryl iodides and bromides cannot serve as the coupling partners. DFT calculation reveals that once converted to the aryl radical cation, aryl triflate would be more favorable to ipso substitution. Fluorescence spectroscopy and cyclic voltammetry investigations suggest that the interaction between excited acetone and aryl triflate is essential to these couplings. The results in this report are anticipated to provide new opportunities to perform cross-couplings.

ChemInform Abstract: Copper‐Mediated Oxidative Trifluoromethylthiolation of Potassium Aryltrifluoroborates with Elemental Sulfur and Ruppert—Prakash Reagent.

A facile procedure for the copper-mediated oxidative trifluoromethylthiolation of potassium aryl- and heteroaryltrifluoroborates with Ruppert–Prakash reagent and elemental sulfur is presented. Aryl trifluoromethyl thioethers can be prepared in good to moderate yield under mild reaction conditions.

ChemInform Abstract: Diastereo‐Divergent Synthesis of Saturated Azaheterocycles Enabled by tBuOK‐Mediated Hydroamination of Alkenyl Hydrazones.

Abstract2,5‐Cis pyrrolidines are synthesized by reaction of γ,δ‐unsaturated N‐benzyl hydrazones.

Copper-Mediated Oxidative Trifluoromethylthiolation of Potassium Aryltrifluoroborates with Elemental Sulfur and Ruppert–Prakash Reagent

A facile procedure for the copper-mediated oxidative trifluoromethylthiolation of potassium aryl- and heteroaryltrifluoroborates with Ruppert–Prakash reagent and elemental sulfur is presented. Aryl trifluoromethyl thioethers can be prepared in good to moderate yield under mild reaction conditions.

Nano-Pd/Al(OH)3-Catalyzed Suzuki–Miyaura Coupling Reaction of Potassium Aryl- and Heteroaryltrifluoroborates with Electrophiles in Alcohols

Highly active aluminium hydroxide supported nanopalladium-catalyzed Suzuki–Miyaura coupling reactions of potassium aryl- and heteroaryltrifluoroborates with aryldiazonium salts or aromatic, heteroaromatic halides have been achieved, respectively. Most substrates were shown to cross-couple with ease to aryl compounds as well as to a variety of heteroaromatic bromides in good to excellent yields.

Palladium-catalyzed direct C-H arylation of pyridine N-oxides with potassium aryl- and heteroaryltrifluoroborates.

An efficient ligand-free Pd(OAc)2-catalyzed selective arylation of pyridine N-oxides using potassium (hetero)aryltrifluoroborates as coupling partners via C-H bond activation was achieved in the presence of TBAI. This approach has a broad substrate scope and shows moderate to high yields.

Synthesis and characterization of potassium aryl- and alkyl-substituted silylchalcogenolate ligands.

Treatment of either triphenyl(chloro)silane or tert-butyldiphenyl(chloro)silane with potassium metal in THF, followed by addition of 18-crown-6, affords [K(18-crown-6)][SiPh3] () and [K(18-crown-6)][SiPh2(t)Bu] (), respectively, as the reaction products in high yield. Compounds and were fully characterized including by multi-nuclear NMR, UV/vis and IR spectroscopies. Addition of elemental chalcogen to either or , results in facile chalcogen insertion into the potassium-silicon bond to afford the silylchalcogenolates, [K(18-crown-6)][E-SiPh2R] (E = S, R = Ph (); E = Se, R = Ph (); E = Te, R = Ph (); E = S, R = (t)Bu (); E = Se, R = (t)Bu (); E = Te, R = (t)Bu ()), in moderate to good yield. The silylchalcogenolates reported herein were characterized by multi-nuclear NMR, UV/vis and IR spectroscopies, and their solid-state molecular structures were determined by single-crystal X-ray crystallography. Importantly, the reported compounds crystallize as discrete monomers in the solid-state, a structural feature not previously observed in silylchalcogenolates, providing well-defined access routes into systematic metal complexation studies.

ChemInform Abstract: Accessing 2‐(Hetero)arylmethyl‐, ‐allyl‐, and ‐propargyl‐2,1‐borazaronaphthalenes: Palladium‐Catalyzed Cross‐Couplings of 2‐(Chloromethyl)‐2,1‐borazaronaphthalenes.

AbstractThe cross‐coupling reactions of 2‐(chloromethyl)‐2,1‐borazaronaphthalene with potassium (hetero)aryl‐ and alkenyltrifluoroborates as well as terminal alkynes provides access to a variety of novel azaborines, allowing a library of pseudobenzylic substituted azaborines to be prepared from a common starting material.

ChemInform Abstract: Silver‐Mediated Fluorination of Potassium Aryltrifluoroborates with Selectfluor®.

AbstractThis modified, robust and simple protocol for the fluorination of potassium aryl trifluoroborates furnishes aryl fluorides for a broad substrate scope in good yields.

ChemInform Abstract: Biscarboxy‐Functionalized Imidazole and Palladium as Highly Active Catalytic System in Protic Solvents: Methanol and Water.

Abstract1,3‐Bis(carboxymethyl)imidazole BCI is used as ligand in the Pd‐catalyzed cross‐coupling between aryl bromides and arylboronic acids, potassium aryl trifluoroboronates or cinnamylboronic acid

Novel SF5-Anilines and SF5-Aryl Ethers from SF5-Substituted Potassium Aryl Trifluoroborates

The copper-catalyzed coupling of SF 5 -substituted potassium aryl trifluoroborates with amines and alcohols is reported. This method provides a simple access to novel 3-pentafluorosulfanyl-substituted anilines and aryl ethers, which are potential important building blocks for drug discovery and agrochemicals.

Synthesis of Biphenyl Tyrosine Via Cross-Coupling Suzuki-Miyaura Reaction Using Aryltrifluoroborate Salts

We reported a fast and easy method for obtaining biarylic units from tyrosine derivatives via Suzuki-Miyaura cross-coupling using a variety of substituted and unsubstituted potassium aryl- and heteroaryltrifluoroborate salts. The scope of the methodology was also extended to the formation of bis-tyrosine linked dipeptide bonds, leading to biologically interesting compounds. Some biarylic units were obtained as free amino acids through the one step cleavage reaction in good yields.

Accessing 2-(hetero)arylmethyl-, -allyl-, and -propargyl-2,1-borazaronaphthalenes: palladium-catalyzed cross-couplings of 2-(chloromethyl)-2,1-borazaronaphthalenes.

The synthesis of 2-(chloromethyl)-2,1-borazaronaphthalene has provided an opportunity to expand dramatically the functionalization of the azaborines. This azaborinyl building block can serve as the electrophile in palladium-catalyzed cross-coupling reactions to form sp3–sp and sp3–sp2 bonds. The cross-coupling reactions of 2-(chloromethyl)-2,1-borazaronaphthalene with potassium (hetero)aryl- and alkenyltrifluoroborates as well as terminal alkynes provides access to a variety of novel azaborines, allowing a library of pseudobenzylic substituted azaborines to be prepared from one common starting material.

A General Suzuki–Miyaura Coupling of Aryl Chlorides with Potassium Aryltrifluoroborates­ in Water Catalyzed by an Efficient CPCy Phendole-phos–Palladium Complex

General examples of the palladium-catalyzed Suzuki–Miyaura cross-coupling of aryl or heteroaryl chlorides with potassium aryl- or heteroaryltrifluoroborates in water are presented. The palladium complex comprising of palladium(II) acetate and ‘CPCy Phendole-phos’ is found to be a highly effective catalyst system for this coupling reaction with low catalyst loading (down to 0.005 mol% Pd).