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.     

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.     

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.     

The palladium-catalyzed cross-coupling reactions of trifluoroethyl iodide with aryl and heteroaryl boronic acid esters

The cross-coupling reactions of 1,1,1-trifluoro-2-iodoethane with aryl and heteroaryl boronic acid esters have been successfully achieved. The new protocol allows for a convenient introduction of trifluoroethyl groups into a variety of aryl and heteroaryl moieties under mild conditions.     

A general synthesis of diarylketones by means of a three-component cross-coupling of aryl and heteroaryl bromides, carbon monoxide, and boronic acids

Pd(OAc)2/di-1-adamantyl-n-butylphosphine (cataCXium A) is highly active in the three-component Suzuki carbonylation and represents the most general catalyst system reported up to now. A broad range of aryl/heteroaryl bromides and aryl boronic acids can be coupled to the corresponding diarylketones at low catalyst loadings.     

Negishi cross-coupling of secondary alkylzinc halides with aryl/heteroaryl halides using Pd-PEPPSI-IPent

Pd-PEPPSI-IPent has proven to be an excellent catalyst for the Negishi cross-coupling reaction of secondary alkylzinc reagents with a wide variety of aryl/heteroaryl halides. Importantly, β-hydride elimination/migratory insertion of the organometallic leading to the production of isomeric coupling products has been significantly reduced using the highly-hindered Ipent ligand.     

Cobalt-catalyzed direct electrochemical cross-coupling between aryl or heteroaryl halides and allylic acetates or carbonates

The electroreduction of a mixture of functionalized aromatic or heteroaromatic bromides or chlorides and allylic compounds such as acetates or carbonates in an electrochemical cell fitted with a sacrificial iron anode affords, in the presence of cobalt halide associated with pyridine as ligand in acetonitrile or DMF, the corresponding coupling product in good yields.     

A novel approach for the synthesis of aryl amides

A novel and highly efficient approach for the synthesis of aryl amides in high yields by the reaction of carboxylic acids and isocyanides in methanol at ambient temperature is reported.     

Ni(COD)2/PCy3 catalyzed cross-coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates in THF at room temperature

Reaction conditions for the Ni(COD)(2)/PCy(3) catalyzed cross-coupling of aryl neopentylglycolboronates with aryl mesylates were developed. By using optimized reaction conditions, Ni(COD)(2)/PCy(3) was shown to be a versatile catalyst for the cross-coupling of a diversity of aryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates containing both electron-donating and electron-withdrawing substituents in their para, ortho, and meta positions in THF at room temperature. This Ni-catalyzed cross-coupling of aryl neopentylglycolboronates is also effective for the synthesis of heterobiaryls and biaryls containing electrophilic functionalities sensitive to organolithium and organomagnesium derivatives. In combination with the recently developed Ni-catalyzed neopentylglycolborylation, all Ni-catalyzed routes to functional biaryls and heterobiaryls are now easily accessible.     

A general and mild two-step procedure for the synthesis of aryl and heteroaryl sulfonamides from the corresponding iodides

A mild two-step preparation of aryl and heteroaryl sulfonyl chlorides and sulfonamides from their corresponding iodides is developed. Acid labile functionalities are shown to be stable under both the copper-catalysed coupling and the subsequent oxidative chlorination.     

Regioselective zincation of indazoles using TMP2Zn and Negishi cross-coupling with aryl and heteroaryl iodides

The metalation of various SEM-protected functionalized indazoles with TMP(2)Zn provides 3-zincated indazoles which undergo palladium-catalyzed Negishi cross-couplings in good yields.     

One-pot reductive amination and Suzuki-Miyaura cross-coupling of formyl aryl and heteroaryl MIDA boronates in array format

Formyl-substituted aryl and heteroaryl MIDA boronates were prepared by a DMSO-free method and used in the first reported one-pot reductive amination-Suzuki-Miyaura cross-coupling sequence. This sequence was then carried out in parallel array format, using microwave-assisted in situ release cross-coupling of MIDA boronates to generate a library with diversity along two axes, affording rapid and convenient access to an array of druglike molecules.     

Stereospecific cross-coupling of alpha-(thiocarbamoyl)organostannanes with alkenyl, aryl, and heteroaryl iodides

Racemic and scalemic PTC-protected alpha-hydroxystannanes cross-couple with alkenyl/aryl/heteroaryl iodides in moderate to good yields using copper(I) thiophene-2-carboxylate (CuTC) in THF at or below room temperature. Simple aryl iodides and 1-iodocyclohexene, two classes of electrophiles that typically react sluggishly, are also good substrates. Cross-couplings proceed with retention of configuration at the alkenyl- and stannyl-substituted stereocenters.     

A novel approach for the synthesis of alkyl and aryl sulfonamides

A novel approach for the synthesis of alkyl and aryl sulfonamides by the reaction of sulfonic acids, isocyanides and water in dichloromethane is reported at ambient temperature in excellent yields within 20 min. To the best of our knowledge this is the first report on the synthesis of this biologically important family using easily available sulfonic acids and isocyanides.     

A novel and convenient synthesis of benzonitriles: electrophilic cyanation of aryl and heteroaryl bromides

N-Cyano-N-phenyl-p-methylbenzenesulfonamide has been used as a more benign electrophilic cyanation reagent for the synthesis of various benzonitriles from (hetero)aryl bromides via formation of Grignard reagents. Electronically different and sterically demanding aryl bromides including functionalized substrates and heteroaryl bromides are successfully cyanated in good to excellent yields. The efficiency of the present methodology is shown by the expeditious syntheses of interesting pharmaceutical intermediates. Notably, chemoselective monocyanation of dibromoarenes is also achieved.     

Application of aryl siloxane cross-coupling to the synthesis of allocolchicinoids

In this communication, we report a new approach to the allocolchicine carbocyclic skeleton based upon an aryl siloxane coupling reaction and a phenanthrol ring expansion. These key steps allow for the selective functionalization of every carbon within the carbocyclic framework. The siloxane coupling-phenanthrol sequence was applied to the synthesis of two allocolchicinoids, including the first fully synthetic approach to N-acetyl colchinol-O-methyl ether (NCME).