Suzuki-Miyaura cross-coupling of alkenyl tosylates with alkenyl MIDA boronates

A practical procedure for the palladium-catalysed Suzuki-Miyaura coupling of various alkenyl tosylates with alkenyl MIDA boronates has been developed. Commercially available trans-bromo[N-succinimidyl-bis(triphenylphosphine)]palladium(II) [Pd(PPh₃)₂NBS] is an effective catalyst under the slow release conditions of MIDA boronates; with less activated alkenyl tosylates addition of the cheap, air-stable tricyclohexylphosphine tetrafluoroborate enhances reactivity.     

Suzuki-Miyaura cross-coupling reactions of potassium vinyltrifluoroborate with aryl and heteroaryl electrophiles

We have previously reported that the palladium-catalyzed cross-coupling reaction of potassium vinyltrifluoroborate with aryl electrophiles proceeds with good yields. Herein, we describe recent progress in optimizing the reaction, as well as outlining the scope and limitations of the reaction. The cross-coupling reaction can generally be effected using 2 mol % of PdCl2 and 6 mol % of PPh3 as a catalyst system in THF/H2O with Cs2CO3 as a base. Moderate to good yields are obtained in the presence of a variety of functional groups.     

Synthesis of sulfur-containing aryl and heteroaryl vinyls via Suzuki-Miyaura cross-coupling for the preparation of SERS-active polymers

The preparation of sulfur-containing aryl and heteroaryl vinyl co-monomers via Suzuki-Miyaura cross-coupling between the corresponding mercaptomethyl arylboronates and in situ-generated vinyl bromides is described. Surface-enhanced Raman scattering (SERS) studies of the target compounds on gold nanoparticles confirmed their potential as spectroscopic tags in the fabrication of SERS-encoded polymers for combinatorial screening and biomedical diagnostics.     

Regioselective synthesis and slow-release Suzuki-Miyaura cross-coupling of MIDA boronate-functionalized isoxazoles and triazoles

The efficient preparation of heterocycles with a range of substitutions ortho to heteroatoms remains as a challenge in organic synthesis, particularly relevant to the construction of druglike molecules due to the ubiquitous presence of such moieties in that chemical space. Modular installation of heterocyclic building blocks using Suzuki-Miyaura cross-coupling is a conceptually useful strategy to address this challenge, though this has historically been met with technical difficulty due to issues of inaccessibility and instability of the requisite heterocyclic boronates. Herein we report a mild and highly regioselective cycloaddition approach which affords convenient access to stable MIDA boronate-functionalized isoxazoles and triazoles and their subsequent efficient Suzuki-Miyaura cross-coupling. This methodology is then further applied to a set of druglike compounds in an efficient one-pot telescoped sequence in line with green chemistry principles.     

Suzuki-Miyaura cross-coupling of heteroaryl halides and arylboronic acids in continuous flow

General continuous-flow conditions for the Suzuki-Miyaura cross-coupling of heteroaryl halides and (hetero)arylboronic acids have been developed. A wide range of heterobiaryl products is obtained in excellent yields (20 examples) employing low catalyst loadings (0.05-1.5 mol % Pd).     

Suzuki-Miyaura cross-coupling of 3-pyridyl triflates with 1-alkenyl-2-pinacol boronates

Palladium-catalyzed Suzuki-type couplings of 3-pyridyl triflates with alkenyl pinacol boronates proceed in good to excellent yield. Optimized conditions use Pd(PPh(3))(4) (10 mol %) as catalyst with K(3)PO(4) (3 equiv) as base in dioxane.     

Palladium-catalyzed amination of aryl and heteroaryl tosylates at room temperature

Mild palladium-catalyzed aminations of aryl tosylates and the first aminations of heteroaryl tosylates are described. In the presence of the combination of L2Pd(0) (L = P(o-tol)3) and the hindered Josiphos ligand CyPF-t-Bu, a variety of primary alkylamines and arylamines react with both aryl and heteroaryl tosylates at room temperature to form the corresponding secondary arylamines in high yields with complete selectivity for the monoarylamine. These reactions at room temperature occur in many cases with catalyst loadings of 0.1 mol % and 0.01 mol % in one case, constituting the most efficient aminations of aryl tosylates by nearly 2 orders of magnitude. This catalyst is made practical by the development of a convenient method to synthesize the L2Pd(0) precursor. This complex is stable to air as a solid. In contrast to conventional relative rates for reactions of aryl sulfonates, the reactions of aryl tosylates are faster than parallel reactions of aryl triflates, and the reactions of aryl tosylates are faster than parallel or competitive reactions of aryl chlorides.     

An efficient silane-promoted nickel-catalyzed amination of aryl and heteroaryl chlorides

A new silane-promoted nickel-catalyzed amination of aryl chlorides with 0.5 mol % of Ni(acac)2, 1 mol % of 3,5,6,8-tetrabromo-1,10-phenanthroline, and polymethylhydrosiloxane was developed. A broad range of aryl and heteroaryl chlorides can be coupled with secondary amines and anilines to give the desired (het)arylamines in good to excellent yields. The reaction is sensitive to the nature and amount of the silane promoter.     

Palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with aryl and heteroaryl chlorides

An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields.     

Direct guanidinylation of aryl and heteroaryl halides via copper-catalyzed cross-coupling reaction

A modified Ullmann reaction using p-methoxybenzyl (PMB) guanidine as guanidinylation agent yielded various aryl and heteroaryl guanidines in good yields.     

One-pot primary aminomethylation of aryl and heteroaryl halides with sodium phthalimidomethyltrifluoroborate

A one-pot primary aminomethylation of aryl halides, triflates, mesylates, and tosylates via Suzuki-Miyaura cross-coupling reactions with sodium phthalimidomethyltrifluoroborate followed by deamidation with ethylenediamine is reported.     

Triazole-based monophosphines for Suzuki-Miyaura coupling and amination reactions of aryl chlorides

[reaction: see text] A new class of triazole-based monophosphine 1 (ClickPhos) has been prepared via efficient 1,3-dipolar cycloadditions of readily available azides and acetylenes. Palladium complexes derived from these ligands provide highly active catalysts for Suzuki-Miyaura coupling and amination reactions of aryl chlorides.     

Suzuki-Miyaura cross-coupling reactions of aryl tellurides with potassium aryltrifluoroborate salts

[reaction: see text] Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected by the presence of electron-withdrawing or electron-donating substituents in both the potassium aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction was monitored by electrospray ionization mass spectrometry where some reaction intermediates were detected and analyzed.     

New ligands for a general palladium-catalyzed amination of aryl and heteroaryl chlorides

The synthesis and application of monodentate N-substituted heteroarylphosphines is described. In general, the ligands are conveniently prepared by selective metallation at the 2-position of the respective N-substituted heterocycle (pyrrole, indole) by using n-butyllithium/tetramethylethylenediamine (TMEDA) followed by quenching with dialkyl- or diarylchlorophosphines. Of the different ligands prepared, the new dialkyl-2-(N-arylindolyl)phosphines (cataCXium P) perform excellently in the palladium-catalyzed amination of aryl and heteroaryl chlorides. Coupling of both activated and deactivated chloroarenes proceeds under mild conditions (room temperature to 60 degrees C). By using optimized conditions remarkable catalyst productivity (total turnover number, TON, up to 8000) and activity (turnover frequency, TOF=14000 h(-1) at 75% conversion) are observed.     

Revisiting the Hirao cross-coupling: improved synthesis of aryl and heteroaryl phosphonates

The palladium-catalyzed cross-coupling of dialkylphosphite with aromatic electrophiles (Hirao coupling) was re-investigated. Some limitations in terms of palladium loadings and substrate reactivity are alleviated with the use of Pd(OAc)₂ complexed to 1,1′-bis(diphenylphosphino)ferrocene (dppf) as a ligand. Various aryl and heteroaryl halides are employed to deliver both known and novel substituted phosphonates. The first examples of aryl chloride couplings are also reported.     

Suzuki-Miyaura cross-coupling of aryl carbamates and sulfamates: experimental and computational studies

The first Suzuki-Miyaura cross-coupling reactions of the synthetically versatile aryl O-carbamate and O-sulfamate groups are described. The transformations utilize the inexpensive, bench-stable catalyst NiCl(2)(PCy(3))(2) to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups are tolerated, in addition to those that possess ortho substituents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative addition with carbamates or sulfamates occurs via a five-centered transition state, resulting in the exclusive cleavage of the aryl C-O bond. Water is found to stabilize the Ni-carbamate catalyst resting state, which thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest.     

An active ferrocenyl triarylphosphine for palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl halides

Pd-catalyzed Suzuki-Miyaura reaction of aryl chlorides was accomplished through the use of an active ferrocene-based triarylphosphine ligand. This air- and moisture-stable ligand was found to be effective for the cross-coupling of aryl halides at room temperature to 115 degrees C.     

Comparison of arylboron-based nucleophiles in Ni-catalyzed Suzuki-Miyaura cross-coupling with aryl mesylates and sulfamates

The efficiency of arylboron-based nucleophiles, boronic acid, potassium trifluoroborate, neopentylglycolboronate, and pinacol boronate in nickel-catalyzed Suzuki-Miyaura cross-coupling reactions with the two C-O electrophiles, mesylates, and sulfamates was compared. Arylboronic acid is the most reactive and most atom-economic of the four boron species studied. Arylpotassium trifluoroborate cross-couples efficiently only in the presence of water. In the absence of water, aryl neopentylglycolboronate is more efficient, less expensive, and more atom-economic than aryl pinacolboronate.