Highly regioselective catalytic oxidative coupling reactions: synthetic and mechanistic investigations

A highly efficient and regioselective Pd-catalyzed method for the oxidative coupling of arylpyridine derivatives is reported. Remarkably, the reactions proceed at room temperature and are compatible with diverse functionalities, including aryl halides and thiophenes. Mechanistic studies suggest that these transformations proceed via a previously unprecedented mechanism involving two different pyridine-directed C-H activation reactions-one at a PdII center and one at PdIV.     

Applications of surfactant-modified clays to synthetic organic chemistry

Two triphase catalysts (SLL) have been developed for organic phase-aqueous phase reactions catalyzed by suitable modified clay (solid phase). These triphase catalysts have been applied to nucleophilic displacement on activated (benzylic) as well as unactivated organic halides and provide a convenient and effective method of preparation of the corresponding products. Other useful transformations to, which these triphase catalysts have been successfully applied are the synthesis of 9,9-dichloro bicyclo[6.1.0]nonane, O-alkylation and C-alkylation of β-naphthol.     

Carbon-carbon bond formations at the benzylic positions of N-benzylxanthone imines and N-benzyldi-1-naphthyl ketone imine

Two N-benzyl imines are designed to allow for carbon-carbon bond formations at the aminated benzylic positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhydrylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields. Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.     

Nickel or Palladium‐Catalyzed Decarbonylative Transformations of Carboxylic Acid Derivatives

Carboxylic acid derivatives containing acyl halides, anhydrides, esters, amides and acyl nitriles are highly appealing electrophiles in transition‐metal‐catalyzed carbon‐carbon bond‐forming reactions due to their ready availability and low cost, which can provide divergent transformations of carboxylic acids into other value‐added products. In this Minireview, we focus on the recent advances of decarbonylative transformations of carboxylic acid derivatives in carbon‐carbon bond formations using Ni or Pd catalysts. A series of reaction types, product classifications and reaction pathways are presented herein, which show the advantageous features of carboxylic acid derivatives as alternative to aryl or alkyl halides in terms of reactivity and compatibility. The well‐accepted mechanism of nickel‐ or palladium‐catalyzed decarbonylative transformations involves initial oxidative addition of carboxylic acid derivatives, followed by decarbonylation or transmetalation (or insertion), and reductive elimination to generate the products, thereby regenerating the catalysts.     

Intra‐ and Intermolecular Nickel‐Catalyzed Reductive Cross‐Electrophile Coupling Reactions of Benzylic Esters with Aryl Halides

Nickel‐catalyzed cross‐electrophile coupling reactions of benzylic esters and aryl halides have been developed. Both inter‐ and intramolecular variants proceed under mild reaction conditions. A range of heterocycles and functional groups are tolerated under the reaction conditions. Additionally, the first example of a stereospecific cross‐electrophile coupling of a secondary benzylic ester is described.     

A theoretical study of substituent effects on allylic ion and ion pair SN2 reactions

An ab initio study of ionic and ion pair displacement reactions involving allylic systems has been carried out at the RHF/6-31+G* level. The geometries and natural charges show the absence of conjugative stabilization in the ionic transition states, thus differing from traditional explanations. The high reactivity of allyl halides is explained by electrostatic polarization of the double bond. Substituent effects were also studied; in general, electron-withdrawing groups lower the barriers of the ionic S(N)2 reactions but increase the barriers of the ion pair reactions. The allylic reactions are compared with related benzylic systems. Hammett correlations give rho of opposite sign for the ionic and ion pair displacement reactions, in agreement with some experimental results.     

Benzylic manganese halides, sulfonates, and phosphates: preparation, coupling reactions, and applications in organic synthesis

The use of highly active manganese, prepared by the Rieke method, for the direct preparation of benzylic manganese reagents was investigated. The oxidative addition of the highly active manganese (Mn) to benzylic halides was easily completed under mild conditions. More importantly, benzylic manganese sulfonates and phosphates were prepared by direct oxidative addition of Mn to the carbon-oxygen bonds of benzylic sulfonates and phosphates. The resulting benzylic manganese reagents were found to undergo cross-coupling reactions with a variety of electrophiles. The majority of these reactions were carried out in the absence of any transition metal catalyst under mild conditions. This approach also provided a facile synthetic route to the preparation of resorcinolic lipids.     

Silver-catalyzed benzylation and allylation reactions of tertiary and secondary alkyl halides with grignard reagents

Treatment of alkyl halides, including tertiary alkyl bromides, with benzylic or allylic Grignard reagent in the presence of a catalytic amount of silver nitrate in ether yielded the corresponding cross-coupling products in high yields. The coupling reactions of tertiary alkyl halides provide efficient access to quaternary carbon centers.     

Metal-catalyzed reactions of diborons for synthesis of organoboron compounds

Metal-catalyzed borylation of alkenes, alkynes, arenes, and organic halides with B-B or H-B compounds has been developed for the synthesis of organoboron compounds from simple organic substrates. The platinum(0)-catalyzed addition of bis(pinacolato)diboron to alkenes and alkynes provided a method for the stereoselective synthesis of cis-bis(boryl)alkanes or cis-bis(boryl)alkenes. The addition of diboron to 1,3-dienes with platinum(0) complexes provided a new access to cis-1,4-bis(boryl)-2-butene derivatives, which are versatile reagents for diastereoselective allylboration of carbonyl compounds. The first one-step procedure for the syntheses of aryl-, vinyl-, and allylboronates was achieved via crosscoupling reactions of diborons with aryl and 1-alkenyl halides or triflates and allyl acetates. Direct C-H borylation of arenes catalyzed by a transition metal complex was studied as an economical protocol for the synthesis of a variety of arylboron derivatives. Ir-catalyzed C-H borylation of arenes, heteroarenes, and benzylic positions of alkylarenes by bis(pinacolato)diboron or pinacolborane furnished aryl-, heteroaryl-, and benzylboron compounds. This article discusses the mechanisms of these reactions and their synthetic applications.     

Metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into aromatic amides with molecular iodine in aq ammonia, and hydrogen peroxide

Various primary alcohols, particularly benzylic alcohols, could be converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq. NH₃, followed by reaction with ∼30% aq H₂O₂. Similarly, various benzylic halides could be also converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq NH₃, followed by reaction with ∼30% aq H₂O₂. The present reactions involve the metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into the corresponding aromatic amides, respectively.     

Enantioselective thiourea-catalyzed additions to oxocarbenium ions

Asymmetric, catalytic reactions of oxocarbenium ions are reported. Simple, chiral urea and thiourea derivatives are shown to catalyze the enantioselective substitution of silyl ketene acetals onto 1-chloroisochromans. A mechanism involving anion binding by the chiral catalyst to generate a reactive oxocarbenium ion is invoked. Catalysts bearing tertiary benzylic amide groups afforded highest enantioselectivities, with the optimal structure being derived from enantioenriched 2-arylpyrrolidine derivatives.     

A direct synthesis of functionalized styrenes and terminal 1,3-dienes via aqueous Wittig chemistry with formalin

A direct synthesis of functionalized styrenes including synthetically valuable styryl halides and terminal 1,3-dienes is reported directly from benzylic and allylic alcohols and aqueous formalin involving microwave assisted phosphonium salt formation and Wittig olefination under mildly basic conditions.     

Efficient asymmetric synthesis of α-alkylated benzylic methyl sulfonates

The first highly efficient auxiliary-controlled synthesis of various α-substituted sulfonic acid derivatives is described. Alkyl or aryl halides were reacted with lithiated benzylic sulfonic esters bearing 1,2:5,6-di-O-isopropylidene-α-d-allofuranose as a removable enantiopure alcohol auxiliary to give the alkylated products in excellent diastereomeric excesses. The racemization-free cleavage conditions provided highly enantioenriched sulfonic acid derivatives (ee≥98%).     

Repairing the Thiol‐Ene Coupling Reaction

Thiol‐ene coupling (TEC) reactions emerged as one of the most useful processes for coupling different molecular units under reaction mild conditions. However, TEC reactions involving weak C? H bonds (allylic and benzylic fragments) are difficult to run and often low yielding. Mechanistic studies demonstrate that hydrogen‐atom transfer processes at allylic and benzylic positions are responsible for the lack of efficiency of the radical‐chain process. These competing reactions cannot be prevented, but reported herein is a method to repair the chain process by running the reaction in the presence of triethylborane and catechol. Under these reaction conditions, a unique repair mechanism leads to an efficient chain reaction, which is demonstrated with a broad range of anomeric O‐allyl sugar derivatives including mono‐, di‐, and tetrasaccharides bearing various functionalities and protecting groups.     

The synthesis and reactions of 4-(2- and 3-thienyl)-tetrahydroisoquinolines

Tetrahydroisoquinoline derivatives substituted in the 4-position by either a 2- or 3-substituted thiophene ring have been synthesised. Simple electrophilic substitution reactions of these systems take place as expected in the α-position of the thiophene ring. Metalation reactions are more complex and take place at the benzylic 4-position of the tetrahydroisoquinoline nucleus in the case of the 2-substituted thiophene derivatives or at either the thiophene α-positions or the benzylic 4-position depending on the nature of the attacking electrophile in the case of the 3-substituted thiophene system.     

A rapid,efficient and green procedure for transformation of alkyl halides/ tosylates to organochalcogens in water

A one-pot and efficient synthesis of dialkyl dichalcogenides (S, Se) in aqueous media under catalyst-free conditions using benzylic, allylic and primary halides with elemental sulfur and selenium has been developed. Also, this procedure was extended to preparation of trisulfides and triselenides from secondary and tertiary halides in same condition. In all cases, products can be obtained in good to excellent yield in short reactions time.     

Intermolecular Friedel-Crafts reaction catalyzed by InCl3

Our recent discovery that In(III) salts were able to activate halides catalytically under mild conditions for the intermolecular Friedel-Crafts cyclization prompted us to explore this highly efficient activation in intermolecular Friedel-Crafts reactions. The alkylation of p-xylene with allylic and benzylic halides was demonstrated under catalytic and mild condition to afford in some cases quantitative yields of the monoalkylated products without the need to employ large excesses of reactants.     

N-Boc-Amides in Cross-Coupling Reactions

Since 2015, the use of amides as electrophilic partners in cross-coupling reactions has experienced exponential growth. Diverse amide derivatives have been studied and among them N-Boc-amides have shown good activities towards various cross-coupling reactions and presents, in our view, an important synthetic usefulness. This review describes the recent developments of these chemical transformations involving N-Boc-amides.     

Reactions of hypervalent iodine reagents with palladium: mechanisms and applications in organic synthesis

The unique reactivity of hypervalent iodine reagents with Pd0 and PdII complexes has been exploited for a variety of synthetically useful organic transformations. For example, IIII reagents have been used in place of aryl halides for diverse Pd-catalyzed C-C and C-heteroatom bond-forming cross-coupling reactions. In addition, these reagents have found application in Pd-catalyzed oxidation reactions, including the oxidative functionalization of C-H bonds and the 1,2-aminooxygenation of olefinic substrates. This review discusses both the synthetic utility and the interesting mechanistic features of these transformations.     

"On water" sp3-sp2 cross-couplings between benzylic and alkenyl halides

Organic-solvent-free cross-couplings between benzylic and alkenyl halides have been developed. Various alkenyl halides can be efficiently benzylated by combining the precursor halides in the presence of Zn dust and a Pd catalyst at room temperature, in water as the only medium.