Scope of the palladium-catalyzed aryl borylation utilizing bis-boronic acid

The Suzuki-Miyaura reaction has become one of the more useful tools for synthetic organic chemists. Until recently, there did not exist a direct way to make the most important component in the coupling reaction, namely the boronic acid. Current methods to make boronic acids often employ harsh or wasteful reagents to prepare boronic acid derivatives and require additional steps to afford the desired boronic acid. The scope of the previously reported palladium-catalyzed, direct boronic acid synthesis is unveiled, which includes a wide array of synthetically useful aryl electrophiles. It makes use of the newly available second generation Buchwald XPhos preformed palladium catalyst and bis-boronic acid. For ease of isolation and to preserve the often sensitive C-B bond, all boronic acids were readily converted to their more stable trifluoroborate counterparts.     

Palladium-catalyzed tandem reaction of yne-propargylic carbonates with boronic acids: a simple method for the synthesis of fused aromatic rings through allene-mediated electrocyclization

The palladium-catalyzed tandem reactions of yne-propargylic carbonates with aryl boronic acids, 2-furyl boronic acid, and 2-thiopheneboronic acid, followed by 6pi-electrocyclization to give fused ring aromatic products such as naphthalene, benzofuran, and benzothiophene derivatives are realized. Screening of the reaction conditions revealed that the combination of [Pd(PPh3)4] in THF gave the best results in terms of reactivity and product yields in the reaction of yne-propargylic carbonates with phenylboronic acid. The reaction is sensitive toward steric hindrance when substituted phenylboronic acids are employed. However, when we take 2-furyl boronic acid as the organometallic reagent, most substrates perform very well to give benzofuran derivatives. In addition, 2-thiopheneboronic acid is also a very effective coupling reagent to give bezothiophenes in high yields. A mechanism is proposed that involves the formation of an allenylpalladium complex from Pd0 and propargylic carbonate, followed by insertion of an intramolecular triple bond and the Suzuki coupling reaction, and then electrocyclization.     

Heck-type coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyl compounds: a systematic investigation

The competition between Heck-type coupling and conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls has been systematically investigated in a toluene-H(2)O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to alpha,beta-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems.     

Efforts directed toward the synthesis of colchicine: application of palladium-catalyzed siloxane cross-coupling methodology

[reaction: see text] Colchicine is an important and synthetically challenging natural product. The key synthetic step in this approach to the synthesis of colchicine involved a palladium-catalyzed cross-coupling reaction between 5-bromotropolone (4) and an aryl siloxane to form the aryl-tropolone bond. The coupling of a variety of highly functionalized aryl siloxane derivatives was investigated and optimized coupling conditions were developed. It was discovered that a palladium catalyst with a high degree of phosphine ligand coordination (5 equiv of phosphine/mol Pd) was necessary to efficiently couple aryl siloxanes with 5-bromotropolone (4). In addition, the coupling approach has provided a direct comparison between siloxane and boronic acid coupling technologies that demonstrated that aryl siloxanes and boronic acids produce similar yields of highly functionalized biaryl products.     

Rhodium‐Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile

An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium‐catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon‐bound cyanating reagent which undergoes cross‐coupling with the aryl boronic acid. The reaction expands the degree of functional‐group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.     

A direct copper-catalyzed route to pyrrolo-fused heterocycles from boronic acids

A convenient route to prepare azaindoles and related pyrrolo-fused heterocycles from boronic acids, DBAD (di-tert-butyl-diazodicarboxylate) and enolizable aldehydes and ketones is presented. The reaction proceeds via a one-pot four-step cascade sequence with key steps involving a copper-catalyzed boronic acid coupling to DBAD and a Fischer indolization providing access to a variety of pharmaceutically interesting heterocycles including pyrrolo-pyridines, -pyrimidines, -quinolines, and -isoquinolines from readily available aza–aryl boronic acid precursors.     

Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant

[reaction: see text]. In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)-mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates, and sodium tetraphenylborate furnishes beta-arylated and alkenylated products in good to excellent yields. The reactions with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.     

Heterogeneous Pd/C-catalyzed ligand-free, room-temperature Suzuki-Miyaura coupling reactions in aqueous media

A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis.     

CuI-catalyzed direct synthesis of diaryl thioethers from aryl boronic acids and arylsulfonyl chlorides

A CuI-catalyzed direct coupling of aryl boronic acids with arylsulfonyl chlorides for the preparation of diaryl thioethers was developed. The reaction is initiated by a PPh₃ reduction of the arylsulfonyl chloride, followed by a CuI-catalyzed C–S coupling with an aryl boronic acid. Various arylsulfonyl chlorides can directly serve as a sulfur source in this mild and efficient reaction giving the desired products in moderate to good yields. Moreover, this practical method has also been applied to the thioetherification of aryl iodides and acetylacetones.     

Copper(II)-mediated o-arylation of 3-hydroxy-2-oxindoles with boronic acids at room temperature

Synthesis of 3-aryloxy-2-oxindole derivatives from 3-hydroxy-2-oxindoles and aryl boronic acids through copper(II)-promoted reaction is achieved. This reaction provides an efficient protocol for the coupling between aryl boronic acid and tertiary aliphatic alcohol, opening a new avenue to format corresponding 3-phenyl-3-aryloxy-2-oxindole core, which has potentially value in the field of life-science.     

Decarboxylative Conjunctive Cross‐coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross‐coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross‐coupling cascade of vinyl boronic esters. Excellent functional‐group tolerance is displayed, and application of a range of carboxylic acids, including secondary α‐amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross‐coupling was also applied to the synthesis of sedum alkaloids.     

An Alternative Route to Complex Allenes or Cyclooctatrienes via a Suzuki Cyclocarbopalladation Cascade

The 4-exo-dig cyclocarbopalladation of vinyl bromides substituted with a triple or double bond resulted in impressive cascade reactions leading to different compounds under Suzuki cross-coupling conditions upon a slight modification of the starting material. When the starting compound carries a triple bond, a single cascade occurs providing a structure containing an allene, a tetrasubstituted cyclopropane, and a cyclobutene with complete stereoselectivity. When the related starting material possessing a double bond is reacted under the same conditions in the presence of various vinyl boronic esters or acids, an efficient 8π-electrocyclization provides tricyclic systems comprised of a cyclobutene unit, as well as a cyclooctatriene. Five carbons of the latter can be selectively decorated with different substituents depending on the choice of the starting material and the boronic coupling partner.     

Synthesis of high enantiopurity N-protected alpha-amino ketones by thiol ester-organostannane cross-coupling using pH-neutral conditions

An efficient synthesis of high enantiopurity N-protected alpha-amino ketones is described. Complementing other studies using boronic acids and thiol esters, this Cu(I) diphenylphosphinate (CuDPP)-mediated, palladium-catalyzed coupling of alpha-amino thiol esters with aryl, heteroaryl, allyl, and alkenyl organostannanes gives N-protected alpha-amino ketones in high yields with high enantiopurity (in almost all cases) under mild and pH-neutral reaction conditions. The viability of pi-deficient heteroarylstannanes is an advantage of this reaction compared to the related boronic acid system.     

Ketone synthesis under neutral conditions. Cu(I) diphenylphosphinate-mediated,palladium-catalyzed coupling of thiol esters and organostannanes

[reaction: see text] A versatile approach to ketone synthesis is described. The reaction relies on the palladium-catalyzed, copper diphenylphosphinate-mediated coupling of thiol esters with organostannanes under neutral reaction conditions. This reaction complements the previously described coupling of thiol esters with boronic acids that used dual thiophilic-borophilic activation methodology.     

Regioselective dicouplings: application to differentially substituted pyrroles

[reaction: see text] In an effort to develop a more concise route to differentially substituted pyrroles (such as that found in the lamellarins), a completely regioselective one-pot double Suzuki coupling has been discovered. The key feature is the use of a ligand-free palladium catalyst under optimized conditions, which results only in coupling of the C5 bromide. At this point, addition of a second boronic acid and a phosphine ligand enables coupling at the remaining C4 bromide.     

Chemoselective Suzuki–Miyaura Cross‐Coupling via Kinetic Transmetallation

Chemoselective Suzuki–Miyaura cross‐coupling generally requires a designed deactivation of one nucleophile towards transmetallation. Here we show that boronic acids can be chemoselectively reacted in the presence of ostensibly equivalently reactive boronic acid pinacol (BPin) esters by kinetic discrimination during transmetallation. Simultaneous electrophile control allows sequential chemoselective cross‐couplings in a single operation in the absence of protecting groups.     

Preparation, properties, and synthetic potentials of novel boronates in a fluorous version (fluorous boronates)

[reaction: see text] A series of boronic acids were attached to a fluorous tag by esterification. Functional transformations of these boronates together with the fluorous Suzuki coupling reaction illustrated their usefulness in fluorous-phase techniques.     

Transition-metal-free Suzuki-type coupling reactions: scope and limitations of the methodology

The scope and limitations of the transition-metal-free Suzuki-type coupling of aryl halides and arylboronic acids to form biaryls are presented. Confirmation that the reaction is indeed metal-free is presented. The effects of changing base, solvent, reaction temperature, phase-transfer catalyst, and substrate are shown and the implications of these results discussed in terms of their impact on the synthetic versatility of the methodology. The main findings are that the reaction works well for aryl bromides, water is necessary as a solvent for the reaction, the optimum temperature for the reaction is 150 degrees C, the reaction is best performed by using microwave promotion with the exception of an electron-poor aryl bromide example where conventional heating may be used, only limited boronic acids can be used as coupling partners, sodium carbonate is the best base for the reaction, tetrabutylammonium bromide proves to be the best phase-transfer catalyst for the reaction, the reaction is limited to couplings between aryl halides and aryl boronic acids with sp(2)-sp(3) couplings proving ineffective, and NaBPh(4) can be used in the place of phenylboronic acid as a phenylating agent.     

Highly effective activation of aryl chlorides for Suzuki coupling in aqueous media using a ferrocene-based Pd(II)–diimine catalyst

The Suzuki coupling of aryl chlorides with boronic acids using a ferrocene-containing Pd(II)–diimine complex as catalyst, in aqueous media, under microwave heating is reported. A small amount of the catalyst (0.1%) was found to be highly effective for coupling unactivated aryl chlorides with boronic acids to form sterically hindered ortho-substituted biaryls. The same catalyst also enabled the coupling of aryl bromides and iodides with various boronic acids in very high yields. The catalyst is air stable and the catalytic reaction can be completed in 15 min.     

Scyllo-inositol as a convenient protecting group for aryl boronic acids in Suzuki–Miyaura cross-coupling reactions

Herein, we report air- and water-stable borate complexes between scyllo-inositol and aryl boronic acids. The complexes were less reactive than free aryl boronic acids under Suzuki–Miyaura cross-coupling reaction conditions; thus, the borate complexes were used as protected boronic acids. Although protecting groups for organoboronic acids are useful in coupling reactions, especially those used to produce π-conjugated molecules, only a few reports describing the use of protecting groups for boronic acids have been published. The proposed unique structural borate complex provides a novel protective method for aryl boronic acids.