Cp*RhIII-Catalyzed Sterically Controlled C(sp3)−H Selective Mono- and Diarylation of 8-Methylquinolines with Organoborons**

Herein, the Rh^III-catalyzed selective monoarylation and diarylation (symmetrical and unsymmetrical) of 8-methylquinolines with organoboron reagents are disclosed. The selective monoarylation of primary C(sp³)−H bonds is achieved by using 7-substituted 8-methylquinolines or by changing the quantity of the aryl boronic acids. The method is also applicable for the arylation of 2-ethylpyridines, and the heteroarylation with thiophene-2-ylboronic acids. Symmetrical and unsymmetrical diarylation of 8-methylquinolines have been carried out in one-pot and sequential manner, respectively. Late-stage monoarylation of oxime derivatives and gram-scale synthesis of monoarylated products has also been carried out. A mechanistic study revealed that the current reaction is first order with respect to both reactants and a five-membered rhodacycle intermediate may be involved in the catalytic cycle.     

The amination of difluoro(diethoxyphosphoryl)acetyl chloride: Facile synthetic route to novel amides containing difluoromethylenephosphonate moiety

A convenient route for the synthesis of novel amides containing at least one β-keto-α,α-difluoromethylenephosphonate group has been elaborated. The procedure requires simple stirring of an amine and difluoro(diethoxyphosphoryl)acetyl chloride in THF in the presence of a catalytic amount of DMAP. A wide range of amines has been accepted, including aliphatic and aromatic diamines, diaminobenzidine or amine derivatives, such as Ciprofloxacin.     

Rate and Computational Studies for Pd-NHC-Catalyzed Amination with Primary Alkylamines and Secondary Anilines: Rationalizing Selectivity for Monoarylation versus Diarylation with NHC Ligands

The relative rates of arylation of primary alkylamines with different Pd-NHC catalysts have been measured, as have the relative rates of arylation of the secondary aniline product in an attempt to understand the key ligand design features necessary to have high selectivity for the monoarylated amine product. As the substituents on the N-aryl ring of the NHC increase in size, selectivity for monoarylation increases and this is further enhanced by chlorinating the back of the NHC ring. Computations have been performed on the catalytic cycle of this transformation in order to understand the selectivity obtained with the different catalysts.     

Palladium-mediated N-arylation of heterocyclic diamines: insights into the origin of an unusual chemoselectivity

The chemoselectivity of the palladium-mediated reaction of bromobenzene with various heterocyclic diamines was studied. Whatever the ligand used, 3-aminopyrrolidine underwent arylation of the secondary amine function (>82%), whereas the more flexible 3-aminoazepinine was arylated on its primary function (>70%). The ratio "arylation of primary amine versus arylation of secondary amine" of 3-aminopiperidine with bromobenzene varied from 90:10 (BINAP, electron-enriched and hindered biphenyls L2 or L3) to 32:68 with the Josiphos-type ligand L10. The same trend was observed when 4-aminopiperidine was used (82:18 with L2 and 17:83 with L10). This selectivity can be tuned by the choice of aryl halide partners having different steric and electronic properties. A cooperative effect of both nitrogens of diamines during the reaction was deduced from competitive experiments. Finally, 13C and 31P NMR experiments, carried out with 3-aminopyrrolidine at room temperature, support a fast coordination of the primary amine to the metal. Indeed, a palladium complex resulting from the unusual displacement of one phosphane group of the intermediate ArPdX(BINAP) by the primary amino group was characterized.     

Highly regioselective synthesis of chiral diamines via a Buchwald–Hartwig amination from camphoric acid and their application in the Henry reaction

In this work the synthesis of new asymmetric diamine ligands from camphoric acid is described. The new diamines can be directly prepared in a regioselective arylation of the less hindered primary amine group of (+)‐cis‐1,2,2‐trimethylcyclopentane‐1,3‐diamine via a Buchwald–Hartwig amination in high yields. The resulting diamines incorporate a secondary and primary amine group and were successfully applied as ligands in a copper‐catalyzed Henry reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Palladium-Catalyzed Arylation of Sulfones

A procedure was developed for monoarylation of sulfones with aryl halides in the presence of palladium complexes. Optimal reaction conditions were found, and the scope of application of the proposed procedure was determined. The arylation occurs only with those sulfones which are relatively strong CH acids; the corresponding monoarylated sulfones are formed in moderate to high yields. The arylation of carbanions derived from the sulfones and some other CH acids requires the presence of an additional equivalent of base. The presence of the latter is also necessary in stoichiometric reactions of carbanions with the palladium complex CF3C6H4Pd(PPh3)2Br; no reaction occurs in the absence of a base. A new mechanism of arylation was proposed, where the key stage is deprotonation of palladium intermediate ArPdL2CHXY which activates the reductive elimination stage.     

Chemospecific and ligand free CuI catalysed heterogeneous N-arylation of amines with diheteroaryl halides at room temperature

A ligand free, copper-catalyzed N-arylation reaction of amines with diheteroaryl halides in heterogeneous medium at room temperature has been developed. The protocol is very effective for low boiling amines and useful for amines available in aqueous solution. The reaction gives chemospecific arylation of amines with diheteroaryl halides in the mixture monoheteroaryl halides, diheteroaryl halides and carbocyclic aryl halides. The reaction is also chemospecific with respect to arylation of aliphatic amines. Monoarylated piperazines were also synthesized at room temperature following this protocol.     

Microwave-mediated one step synthesis of tri- and tetracyclic heterocyclic molecules

Abstract

Tricyclic and tetracyclic compounds related to vasicine and batracyclin, respectively, have been synthesized via condensation of dicarboxylic acids (aliphatic acid, homophthalic acid, and aromatic acid) with diamines (aliphatic, aminobenzyl amine, and aromatic amine) under solvent-free condition.     

Synthesis of polyamideamines from 5-oxazolones

Polyamideamines with a sequence of two amide and one amine linkage in a main chain were synthesized from the polyaddition of 2-isopropylidene-4-alkyl-3-oxazolin-5-ones and primary diamines. The polyaddition reaction proceeded through 1,4-conjugate addition of an amine group to 3-oxazolin-5-one and subsequent ring opening of the intermediate addition product with another amine. Although aliphatic diamines gave oily polymers, xylylenediamines afforded amorphous solid polymers. The reduced viscosities and polymer melt temperature of the polymers were 0.05–0.12 and 90–130°C., respectively.     

Mild palladium-catalyzed selective monoarylation of nitriles

Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using alpha-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with alpha-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.     

Preparation of polymer-bound 1,2 - and 1,3 - diamines

Two modified copolymers were used for the preparation of polymer bound symmetrical aliphatic diamines using phase transfer catalysis (P.T.C.). These compounds are potential ligands for transition metal ions.     

Control of product selectivity by a styrene additive in ruthenium-catalyzed C-H arylation

A unique effect of styrene additive on product selectivity was observed for RuH(2)(CO)(PPh(3))(3)-catalyzed C-H arylation of acetophenone derivatives bearing two ortho C-H bonds. Without styrene, the C-H arylation with arylboronates gives diarylation products as the major products throughout the reaction, but the use of styrene as an additive switches the product selectivity and leads to selective formation of monoarylation products.     

The Dual Role of Benzophenone in Visible‐Light/Nickel Photoredox‐Catalyzed C−H Arylations: Hydrogen‐Atom Transfer and Energy Transfer

A dual catalytic protocol for the direct arylation of non‐activated C(sp³)?H bonds has been developed. Upon photochemical excitation, the excited triplet state of a diaryl ketone photosensitizer abstracts a hydrogen atom from an aliphatic C?H bond. This inherent reactivity was exploited for the generation of benzylic radicals which subsequently enter a nickel catalytic cycle, accomplishing the benzylic arylation.     

Rhodium‐Catalyzed Enantioposition‐Selective Hydroarylation of Divinylphosphine Oxides with Aryl Boroxines

The rhodium‐catalyzed hydroarylation of divinylphosphine oxides (RP(O)(CH=CH₂)₂) with aryl boroxines ((ArBO)₃) gives the corresponding monoarylation products (RP(O)(CH=CHAr)CH₂CH₃) in high yields. One of the two vinyl groups in the phosphine oxide undergoes oxidative arylation while the other one is reduced to an ethyl moiety. These reactions proceed with high selectivity in terms of the enantiotopic vinyl groups in the presence of (R)‐DTBM‐segphos/Rh to give the P‐stereogenic monoarylation products with high enantioselectivity.     

Monoacylation of unprotected symmetrical diamines with resin-bound benzoic acids

A protocol for monoacylation of unprotected symmetrical diamines with a resin-bound benzoic acid is described. The nature of the resin (gel-based polystyrene vs highly crosslinked macroporous polystyrene) was found to play a minor role in acylation selectivity. Rather, the concentration of the diamine dictates the ratio of mono- and diacylated products. Thus, by employing a high concentration of symmetrical diamine (e.g., 1 M, 20 equiv), monoacylation can be selectively achieved for a variety of unprotected symmetrical alkyl and aryl diamines.     

Direct arylation of simple azoles catalyzed by 1,10-phenanthroline containing palladium complexes: an investigation of C4 arylation of azoles and the synthesis of triarylated azoles by sequential arylation

Direct triarylation and sequential triarylation reactions of simple azoles catalyzed by [Pd(phen)(2)]PF(6) are described. Simple azoles, such as N-methylimidazole, thiazole, and oxazole, were observed to undergo triaryaltion reactions even at their C4 positions when treated with aryl iodides in the presence of [Pd(phen)(2)]PF(6) as a catalyst and a stoichiometric amount of Cs(2)CO(3) in DMA at 150 °C. Using excess amounts of azoles, selective C5 monoarylation was achieved by using the same catalytic system. Subsequent efforts demonstrated that C5 arylated azoles undergo exclusive C2 arylation using [Pd(phen)(2)]PF(6) as the catalyst with galvinoxyl as an additive. Finally, unprecedented C4 arylation reactions of 2,5-diaryl-azoles occur by using the new catalytic system to give the corresponding triarylated products in good to excellent yields. The results of mechanistic studies suggest that the C2 arylation process takes place by way of an electrophilic aromatic substitution (S(E)Ar) palladation pathway, while arylation reactions at the C4 position occur via a S(E)Ar palladation and/or radical mechanism. Finally, a concise, three-step synthesis of the Tie-2 Tyrosine Kinase Inhibitor has been executed starting with commercially available N-methylimidazole by a route that employs the new sequential arylation process.     

Native amine-directed site-selective C(sp3)-H arylation of primary aliphatic amines with aryl iodides

Direct C(sp³)-H functionalization of N-unprotected aliphatic amines represents one of the most efficient and straightforward strategies for amine synthesis. Despite some recent progress in this field, the NH₂-directed γ-C(sp³)-H arylation of primary aliphatic amines except α-amino esters remained an unmet challenge. In this report, we established a simple and efficient method for site-selective C(sp³)-H arylation of primary aliphatic amines by aryl iodides. In the presence of only 5 mol% Pd(OAc)₂, a wide range of aliphatic amines including O-benzyl and O-silyl amino alcohols were arylated at γ- or δ-positions by aryl iodides containing a broad scope of functional groups. The synthetic application of this method had also been demonstrated by large-scale synthesis, the synthesis of a fingolimod analogue, and the conjugation with natural d-menthol and fluorescent 1,8-naphthalimide.     

Dramatic Mechanistic Change in Acid‐Catalyzed Arylation of Azafulleroids Depending on their Ambident N/C Basicity: Formation of Cyclopentene Centered Pentakisadduct

Azafulleroid, amino‐bridged [5,6]‐open fullerene, has the ambident N/C basicity of the incorporated enamine moiety. Acid‐catalyzed arylation of N‐substituted azafulleroids proceeded via two types of initial N/C protonation to perform monoarylation or 1,4‐bisarylation for the N‐alkyl substituents and shuttlecock‐type pentakisarylation for the N‐phenyl substituent. The dramatic product change was explained by considering the possible mechanism as well as the DFT computational results.     

Direct synthesis of polyamides via catalytic dehydrogenation of diols and diamines

We report a direct synthesis of polyamides via catalytic dehydrogenation of diols and diamines. A PNN pincer ruthenium complex, the Milstein catalyst, was used for this reaction and polyamides with number average molecular weight from ～10 to 30 kDa could be obtained from a wide variety of diols and diamines bearing aliphatic or aromatic, linear or cyclic spacers. Because of the high catalytic selectivity of primary amine over secondary amine, polyamines could be conveniently incorporated into linear polyamides without tedious protection/deprotection steps. Compared with conventional condensation method, this catalytic system avoids the requirement of stoichiometric preactivation or in situ activation reagents and provides a much cleaner process with high atomic economy.     

General but discriminating fluorescent chemosensor for aliphatic amines

Aliphatic amines are sensitively and discriminatively detected through binding with demethylated naphthol AS-BI (7-bromo-3-hydroxy-2-naphth-o-hydroxyanilide, 2) and fluorescence of the resulting complex. Recognition of the amine by the chemosensor 2 occurs via proton transfer of the naphtholic proton to the amine and is facilitated by the presence of the phenol group. Amine basicity is the primary controller of detection. Poorly basic aromatic and conjugated amines such as pyridine and aniline are not detected. Hydrogen bonding within the complex allows further differentiation of aliphatic amines. Doubly primary, conformationally flexible diamines are the most sensitive to detection, followed by secondary amines.