Cross-coupling Of Boronic Acids Research Articles

Stereodivergent Palladium-Catalyzed C-F Bond Functionalization of gem-Difluoroalkenes.

We herein describe a stereodivergent C-F bond functionalization of gem-difluoroalkenes. Using trisubstituted β,β-difluoroacrylates, both E and Z monofluoroalkene products can be obtained with excellent diastereoselectivities. The design of two different reaction manifolds, i.e., Pd(II)- versus Pd(0)-catalyzed cross-coupling of boronic acids, is the key to stereocontrol.

Regioselective Aldehyde Decarbonylation through Palladium-Catalyzed Nitrile Boronic Acid Cross-Coupling

AbstractAldehyde decarbonylation is a vital chemical transformation in the synthesis of natural products. Nature accomplishes this process through a family of decarbonylase enzymes, while in the laboratory, harsh transition metals and elevated temperatures are required. Herein, we report a mild aldehyde decarbonylation reaction that exhibits exclusive selectivity for ortho-aldehydes during a tandem nitrile boronic acid cross-coupling reaction. A wide substrate scope is displayed that includes regioselective removal of the ortho-aldehyde from phenyl boronic acids in the presence of meta- or para-aldehydes. A mechanistic investigation of the observed regioselectivity for ortho-aldehydes by density functional theory (DFT) calculations shows that the CO ligand extrusion is energetically more favorable for the ortho position as compared to the para position.

Catalytic Synthesis of Potassium Acyltrifluoroborates (KATs) from Boronic Acids and the Thioimidate KAT Transfer Reagent.

We report the synthesis of potassium acyltrifluoroborates (KATs) by a palladium-catalyzed cross-coupling of boronic acids and the thioimidate KAT transfer reagent. The combination of widely available aryl- and vinylboronic acids with commercially available thioimidate 1 using catalytic PdII and a CuII additive enables the preparation of KATs in high yields and with good functional group tolerance. This formal insertion of CO into organoboronic acids can also be applied to boronic acid pinacol esters and potassium organotrifluoroborates using a slightly modified procedure. The cross-coupling can be telescoped into the one-pot synthesis of amides and α-aminotrifluoroborates by exploiting the unique chemistry of KATs and their trifluoroborate iminium (TIM) derivatives.

Nickel-Mediated Cross-Coupling of Boronic Acids and Phthalimides for the Synthesis of Ortho-Substituted Benzamides.

The decarbonylative coupling of phthalimides with aryl boronic acids provides ready access to a broad range of ortho-substituted benzamides. This nickel-mediated methodology extends reactivity from previously described air-sensitive diorganozinc reagents of limited availability to easily handled and widely commercially available boronic acids. The decarbonylative coupling is tolerant of a broad range of functional groups and demonstrates little sensitivity to steric factors on either of the coupling partners.

Cobalt Catalyzed C-P Bond Formation by Cross-Coupling of Boronic Acids with P(O)H Compounds in Presence of Zinc.

In our current work, we have reported the first cobalt-catalyzed cross-coupling of arylboronic acid with alkyl/aryl phosphites under mild conditions. The reaction was carried out in the presence of zinc powder as an additive and ter-pyridine as a ligand. The use of non-precious cobalt salt makes the protocol advantageous, as it is inexpensive and more abundant than the previously used methods where precious metal salts (Pd and Pt) were used. The reaction has a wide substrate scope and the products were obtained in good yields.

Base-free Ni-catalyzed Suzuki-type cross-coupling reactions of epoxides with boronic acids.

A Ni-catalyzed Suzuki-type cross-coupling of boronic acids with epoxides without an exogenous base and with broad substrate scope has been developed. The product selectivity of styrenyl epoxides is different from that of previous work. This methodology uses readily available starting materials to access a range of substituted alcohols, which are valuable feedstock chemicals.

Highly enantioselective rhodium-catalyzed cross-coupling of boronic acids and racemic allyl halides

Although Csp2-Csp2 Suzuki-Miyaura couplings (SMCs) are widely used in small-molecule synthesis, related methods that allow the incorporation of Csp3-hybridized coupling partners, particularly in an asymmetric manner, are less developed. This protocol describes catalytic asymmetric SMC reactions that provide access to enantiomerically enriched cyclic allylic products. The method couples racemic allyl halide starting materials with sp2-hybridized boronic acid derivatives and is compatible with heterocyclic coupling partners. These reactions are catalyzed by a rhodium-ligand complex and typically display very high levels of enantioselectivity (>95% enantiomeric excess (ee)). In this protocol, we detail a procedure using a dihydropyridine-derived allyl chloride for the synthesis of (-)-(S)-tert-butyl-3-(4-bromophenyl)-3,6-dihydropyridine-1(2H)-carboxylate, an intermediate in the synthesis of the anticancer drug niraparib. This procedure affords 1.17 g (86% yield) of the coupling product with 96% ee. The initial experimental setup of the reaction takes 45-50 min, and the reaction is complete within 4-5 h.

One-Pot Homologation of Boronic Acids: A Platform for Diversity-Oriented Synthesis.

Formal homologation of sp(2)-hybridized boronic acids is achieved via cross-coupling of boronic acids with conjunctive haloaryl BMIDA components in the presence of a suitably balanced basic phase. The utility of this approach to provide a platform for diversity-oriented synthesis in discovery medicinal chemistry is demonstrated in the context of the synthesis of a series of analogues of a BET bromodomain inhibitor.

Copper-Catalyzed Oxidative Cross-Coupling of Boronic Acids and Masked Sulfides

Copper-Catalyzed Oxidative Cross-Coupling of Boronic Acids and Masked Sulfides

Enantiospecific sp(2)-sp(3) coupling of secondary and tertiary boronic esters.

The cross-coupling of boronic acids and related derivatives with sp(2) electrophiles (the Suzuki-Miyaura reaction) is one of the most powerful C-C bond formation reactions in synthesis, with applications that span pharmaceuticals, agrochemicals and high-tech materials. Despite the breadth of its utility, the scope of this Nobel prize-winning reaction is rather limited when applied to aliphatic boronic esters. Primary organoboron reagents work well, but secondary and tertiary boronic esters do not (apart from a few specific and isolated examples). Through an alternative strategy, which does not involve using transition metals, we have discovered that enantioenriched secondary and tertiary boronic esters can be coupled to electron-rich aromatics with essentially complete enantiospecificity. As the enantioenriched boronic esters are easily accessible, this reaction should find considerable application, particularly in the pharmaceutical industry where there is growing awareness of the importance of, and greater clinical success in, creating biomolecules with three-dimensional architectures.

Base and ligand free copper-catalyzed N-arylation of 2-amino-N-heterocycles with boronic acids in air

A wide range of N-arylated 2-amino-N-heterocycles were synthesized by a copper-catalyzed boronic acid cross coupling reaction at ambient temperature in air. This ligand and base free methodology is general and could provide rapid access to a diverse array of potential bioactive heterocyclic compounds.

Ligand-Free Cross-Coupling of Boronic Acids with Cu(NO3)2 Complexes of Amines in Aqueous Media

The efficient conversion of boronic acids, both arylboronic acids and alkylboronic acids, to the corresponding amines in water was accomplished in moderate to good yields using Cu(NO3)2 complexes of amines as the nitrogen source. The coupling reactions were performed in water at 30 °C for 2 hours.

ChemInform Abstract: Suzuki Cross‐Coupling/Reductive Debenzyloxycarbonylation Sequence for the Syntheses of [c]Annulated Isoquinolines: Application for the Syntheses of Pancratistatin‐Like Isoquinolines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Suzuki Cross-Coupling/Reductive Debenzyloxycarbonylation Sequence for the Syntheses of [c]Annulated Isoquinolines: Application for the Syntheses of Pancratistatin-like Isoquinolines

A two-step strategy involving Suzuki cross-coupling of boronic acids with a diverse array of alpha-iodoenones followed by hydrogenation is developed for the construction of [c]annulated isoquinolines. This mild and efficient procedure is also applied to the synthesis of highly oxygenated isoquinolines.

Ambient Temperature Synthesis of High Enantiopurity N-Protected Peptidyl Ketones by Peptidyl Thiol Ester−Boronic Acid Cross-Coupling

alpha-Amino acid thiol esters derived from N-protected mono-, di-, and tripeptides couple with aryl, pi-electron-rich heteroaryl, or alkenyl boronic acids in the presence of stoichiometric Cu(I) thiophene-2-carboxylate and catalytic Pd(2)(dba)(3)/triethylphosphite to generate the corresponding N-protected peptidyl ketones in good-to-excellent yields and in high enantiopurity. Triethylphosphite plays a key role as a supporting ligand by mitigating an undesired palladium-catalyzed decarbonylation-beta-elimination of the alpha-amino thiol esters. The peptidyl ketone synthesis proceeds at room temperature under nonbasic conditions and demonstrates a high tolerance to functionality.

2,3,2′,3′-Tetramethylbiphenyl

The title compound, C16H18, was synthesized by a palladium-catalyzed boronic acid cross-coupling reaction. A crystallographic twofold axis passes through the mid-point of the C—C bond connecting the two rings. In the crystal structure, two fairly close C—H...π(arene) contacts appear to be the only significant intermolecular interactions.

2,3,3′,4′-Tetramethylbiphenyl

2,3,3′,4′-Tetra­methyl­biphen­yl, C16H18, was synthesized in a palladium-catalysed boronic acid cross-coupling reaction. In the solid state, these weakly inter­acting unsymmetrical mol­ecules show an apparent dimerization of the ortho-dimethyl­phen­yl groups, a packing motif that is seen in a significant number of other ortho-dimethyl­phen­yl-containing compounds.

Tunable carbon-carbon and carbon-sulfur cross-coupling of boronic acids with 3,4-dihydropyrimidine-2-thiones.

Direct microwave-assisted Pd(0)-catalyzed/Cu(I)-mediated carbon-carbon cross-coupling of 3,4-dihydropyrimidine-2-thiones and boronic acids under Liebeskind-Srogl conditions leads to 2-aryl-1,4-dihydropyrimidines in moderate to high yield. In contrast, Cu(II)-mediated reaction of the same substrates leads to carbon-sulfur cross-coupling. [reaction: see text]

Substituted alkyne synthesis under nonbasic conditions: copper carboxylate-mediated, palladium-catalyzed thioalkyne-boronic acid cross-coupling.

[figure: see text] A new methodology for the synthesis of substituted alkynes is described. In the presence of copper(I) thiophene-2-carboxylate (CuTC) or copper (I) 3-methylsalicylate (CuMeSal), the palladium-catalyzed cross-coupling of thioalkyne derivatives with boronic acids affords functionalized alkynes in yields ranging from 39 to 91%. This coupling occurs efficiently under mild, nonbasic conditions with a wide variety of thioalkynes and boronic acids, providing a reaction complementary to the Sonogashira protocol.

Thiol ester-boronic acid cross-coupling. Catalysis using alkylative activation of the palladium thiolate intermediate.

Thiol esters and boronic acids do not participate in cross-coupling in the presence of palladium catalysts. However, efficient palladium-catalyzed thiol ester-boronic acid cross-coupling is observed when simple alkylating agents are present. Alkylative conversion of the very stable palladium-thiolate bond to a labile palladium-thioether bond is presumed to be crucial to the catalysis. Of the systems studied, 4-halo-n-butyl thiol esters were most effective in this cross-coupling.