Exploring the Reactivity of α‐Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]‐Wittig Rearrangement and the Mechanistic Proposal Revisited

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α‐lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]‐Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α‐lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups. The more favored rearrangements are found for substrates with electron‐poor aryl groups that favor the anionic pathway.     

Silylium‐Ion‐Promoted (5+1) Cycloaddition of Aryl‐Substituted Vinylcyclopropanes and Hydrosilanes Involving Aryl Migration

A transition‐metal‐free (5+1) cycloaddition of aryl‐substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self‐regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4‐ rather than 3‐aryl‐substituted silacyclohexane derivatives as major products. Various control experiments and quantum‐chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane‐to‐cyclopropane rearrangement.     

Stereoselective radical aryl migration from silicon to carbon

Highly diastereoselective radical 1,5 phenyl migration reactions from silicon in diarylsilyl ethers to various C-centered radicals to form the corresponding 3-phenylated alcohols are described. Functionalized aryl groups can also be transferred. The effect of the variation of the attacking radical on the aryl transfer reaction is discussed. Best results are obtained for the phenyl migration to nucleophilic secondary alkyl radicals, where high yields (up to 81%) and high selectivities (up to 95% ds) have been obtained. The mechanism of the process is discussed and a model to explain the stereochemical outcome of the reaction is presented. Finally, stereoselective 1,4 aryl migration reactions from Si to C, including a new method for the alpha-arylation of esters, are presented.     

Density functional studies on the thermal aryl migration in beta-dicarbonyl ylides and related compounds

The potential energy surfaces for the unimolecular rearrangement reactions of beta-dicarbonyl ylides and beta-carbonylimidoyl ylides have been studied using the density functional method. All of the stationary points were determined at the B3LYP/LANL2DZdp level of theory. Four kinds of beta-dicarbonyl ylide species containing fluorine, chlorine, bromine, and iodine have been chosen in this work as model reactants. Also, five beta-carbonylimidoyl ylide molecules bearing nitrogen, phosphorus, arsenic, stibium, and bismuth have been used in the present study. In the latter reactions, two different reaction pathways have been proposed: (1) a 1,2-aryl shift to the pnicogen element and (2) A 1,2-aryl shift to the oxygen atom. That is, path 1 is reactant-->TS-1-->Pro-1 and path 2 is reactant-->TS-2-->Pro-2. Our theoretical findings strongly suggest that all intramolecular aryl migration reactions proceed via a one-step (concerted) reaction path. For the beta-dicarbonyl ylide species, the smaller the atomic number of the halogen atom, the lower the barrier height, the larger the reaction enthalpy, and, in turn, the easier it is to undergo the intramolecular aryl migration under thermal conditions. Alternatively, the heavier the pnicogen element in the beta-carbonylimidoyl ylides, the smaller the barrier height, and the larger the migration reaction enthalpy, even under thermal conditions. The results obtained allow a number of predictions to be made.     

Silylium-Ion-Promoted (5+1) Cycloaddition of Aryl-Substituted Vinylcyclopropanes and Hydrosilanes Involving Aryl Migration

A transition-metal-free (5+1) cycloaddition of aryl-substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self-regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4- rather than 3-aryl-substituted silacyclohexane derivatives as major products. Various control experiments and quantum-chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane-to-cyclopropane rearrangement.     

Synthesis of biaryls by intramolecular radical aryl migration from silicon to carbon

A new method for the preparation of biaryls via intramolecular 1,5 aryl migration reaction from silicon in silyl ethers to aryl radicals is presented. Various readily available diphenylsilyl ethers can be used as substrates in this reaction. Functionalized aryl groups can also be transferred. The analogous 1,4 aryl migration reaction is less efficient.     

Atroposelective radical aryl migration reactions from sulfur to carbon

The paper describes stereoselective radical aryl migration reactions from sulfur in sulfonates to aryl radicals for the synthesis of axially chiral biaryls. A chirality center in secondary benzylic sulfonates is used to diastereoselectively (atroposelectively) install a stereogenic axis via a 1,5 aryl migration reaction. Atroposelectivity has not been investigated in stereoselective radical chemistry before. Good yields (53-82%) but low selectivities (up to 2 to 1) were obtained.     

Lithium Choreography: Intramolecular Arylations of Carbamate‐Stabilised Carbanions and Their Mechanisms Probed by In Situ IR Spectroscopy and DFT Calculations

Deprotonation of O‐allyl, O‐propargyl or O‐benzyl carbamates in the presence of a lithium counterion leads to carbamate‐stabilised organolithium compounds that may be quenched with electrophiles. We now report that when the allylic, propargylic or benzylic carbamate bears an N‐aryl substituent, an aryl migration takes place, leading to stereochemical inversion and C‐arylation of the carbamate α to oxygen. The aryl migration is an intramolecular S_NAr reaction, despite the lack of anion‐stabilising aryl substituents. Our in situ IR studies reveal a number of intermediates along the rearrangement pathway, including a “pre‐lithiation complex,” the deprotonated carbamate, the rearranged anion, and the final arylated carbamate. No evidence was obtained for a dearomatised intermediate during the aryl migration. DFT calculations predict that during the reaction the solvated Li cation moves from the carbanion centre, thus freeing its lone pair for nucleophilic attack on the remote phenyl ring. This charge separation leads to several alternative conformations. The one having Li⁺ bound to the carbamate oxygen gives rise to the lowest‐energy transition structure, and also leads to inversion of the configuration. In agreement with the IR studies, the DFT calculations fail to locate a dearomatised intermediate.     

Pyrrolyl substituted allenylidene complexes of ruthenium

Pyrrolyl and indolyl substituted allenylidene complexes of ruthenium have been prepared from the trapping of cationic trans-[Cl(dppm)(2)Ru=C=C=C=CH(2)](+) with various pyrroles or N-methylindole. The reaction is rationalized as involving regioselective attack of the organometallic electrophile on the electron-rich heterocycle followed by proton migration to the terminal =CH(2) entity of the intermediate butenynyl substituted sigma-complex. Pyrrolyl substituted allenylidene complexes have spectroscopic and electrochemical properties intermediate between those of amino and aryl substituted congeners and can thus be regarded as vinylogous aminoallenylidene complexes. We present spectroscopic evidence that the pyrrole pi-system is efficiently incorporated into the metallabutatriene chromophore including resonance Raman spectroscopy. According to our results, the respective frontier orbitals are delocalized across the entire ClRuC(3)(pyrrolyl) entity which defies any classification of the individual redox events as metal or ligand centered redox processes. This issue has been specifically addressed by spectroelectrochemistry. The structure of the 1-methylindole-3-yl complex has been determined by X-ray crystallography. Bond parameters along the ruthenium-allenylidene chain are intermediate between those of amino and aryl substituted congeners and support our conclusions drawn from the spectroscopic results. While still electron rich, pyrrolyl substituted allenylidene complexes are easily deprotonated to their conjugate bases, which are substituted butenynyl complexes. This has been exemplified with the tetrahydroindole derived complex 3f.     

A convenient room temperature ipso‐nitration of arylboronic acid catalysed by molecular iodine using zirconium oxynitrate as nitrating species: An experimental and theoretical investigation

A simple and convenient protocol has been developed for ipso‐nitration of arylboronic acid catalysed by molecular iodine at room temperature, using zirconium oxynitrate as the nitrating species. The protocol is applicable to electronically diverse aryl‐ and heteroarylboronic acid moieties under mild reaction conditions with good to excellent isolated yields. Furthermore, a theoretical investigation has been performed for the same reaction, and reaction profiles are modelled using modern density functional theory (DFT). DFT‐based results support the experimentally observed results.     

Benzylic C-H activation and C-O bond formation via aryl to benzylic 1,4-palladium migrations

A procedure for benzylic C-H activation has been developed using a palladium 1,4-aryl to benzylic migration as a key step. Carboxylates and phenoxides readily trap the resulting benzylic palladium intermediates obtained from palladium ‘through space’ migration. Aryl bromides and iodides have been successfully employed in this reaction, furnishing moderate to good yields. The mechanism of this reaction has been studied by deuterium-labeling experiments, which suggest that the migration of palladium from an aryl to a benzylic position occurs reversibly. The reaction conditions developed for the migration process also oxidize the neighboring benzylic alcohols to the corresponding aldehydes and ketones.     

Etude du mécanisme de la transformation photochimique d'alkylarènesulfonamido-2 cyclohexène-2 one en alkylamino-2 aryl-3 cyclohexène-2 one

When excited in their triplet excited state 2-arenesulfanamido-2-cyclohexenones lead to a very efficient desulfonation reaction and to migration of the aryl substituent. A wavelength effect was observed on the desulfonation product from direct irradiations. Furthermore, at 254 nm, a concentration effect and a quantum yield higher than unity indicate that a radical chain component was involved. The mechanism of this reaction is discussed taking into account the intramolecular character of the aryl migration.     

Beta-aryl eliminations from Rh(I) iminyl complexes

beta-Aryl eliminations from a series of iminyl complexes to form rhodium aryl complexes and free nitriles are reported. Iminyl complexes [Rh(PEt3)3(N=CArAr')] were prepared from [Rh(COE)Cl]2, PEt3, LiN(SiMe3)2, and the imines HN=CArAr'. One example of these complexes was characterized by X-ray diffraction. Heating of these complexes in cyclohexane generated the rhodium aryl complexes and free nitriles in high yields; heating in benzene formed the same products in slightly lower yields. Complexes with varied aryl groups on the imine were studied to assess the migratory aptitudes of the aryl groups. Migration of the o-anisyl group occurred much faster than migration of a phenyl group; migration of a phenyl group occurred slightly faster than migration of the more electron-rich p-anisyl group; and migration of a phenyl group occurred slightly faster than migration of the more hindered o-tolyl group. Kinetic studies showed that the reaction was inverse first-order in the concentration of added phosphine and zero-order in added nitrile. These results show that the beta-aryl elimination most likely occurs by dissociation of phosphine from the starting complex and carbon-carbon bond cleavage of the resulting 14-electron intermediate.     

Copper‐Catalyzed One‐Pot Trifluoromethylation/Aryl Migration/Carbonyl Formation with Homopropargylic Alcohols

A novel copper‐catalyzed one‐pot functionalization of homopropargylic alcohols that involves trifluoromethylation, aryl migration, and formation of a carbonyl moiety has been developed. This reaction constitutes the first direct conversion of homopropargylic alcohols into CF₃‐containing 3‐butenal or 3‐buten‐1‐one derivatives in a regioselective manner. Mechanistic studies indicate that the 1,4‐aryl migration proceeds through a radical pathway.     

Heck arylations of pent-4-enoates or allylmalonate using a palladium/tetraphosphine catalyst

The Heck reaction of aryl halides with functionalised alk-1-enes should be a powerful method for the synthesis of functionalised (E)-1-arylalk-1-ene derivatives. The major problem of this reaction is the palladium-catalysed migration of the carbon-carbon double bond along the alkyl chain when there are no substituents on the C3 carbon of the alk-1-enes. We observed that for the arylation of ethyl pent-4-enoate, ethyl 2-methylpent-4-enoate or dimethyl allylmalonate this migration could be partially or completely controlled using appropriate reaction conditions. The ramification on the alkyl chain and the substituents on the aryl halide have also an important influence on this migration. Moreover, the cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/1/2[PdCl(C₃H₅)]₂ system catalyses this reaction with a wide range of aryl bromides using very high ratio substrate/catalyst in good yields.     

Mild and efficient copper-catalyzed cyanation of aryl iodides and bromides

An efficient copper-catalyzed cyanation of aryl iodides and bromides is reported. Our system combines catalytic amounts of both copper salts and chelating ligands. The latter, which have potential nitrogen- and/or oxygen-binding sites, have never previously been used in this type of reaction. A protocol has been developed that enables the cyanation of aryl bromides through the copper-catalyzed in situ production of the corresponding aryl iodides using catalytic amounts of potassium iodide. Aryl nitriles are obtained in good yields and excellent selectivities in relatively mild conditions (110 degrees C) compared with the Rosenmund-von Braun cyanation reaction. Furthermore, the reaction is compatible with a wide range of functional groups including nitro and amino substituents. The protocol reported herein involves two main innovations: the use of catalytic amounts of ligands and the use of acetone cyanohydrin as the cyanating agent in copper-mediated cyanation reactions.     

Copper-mediated fluorination of aryl iodides

The synthesis of aryl fluorides has been studied intensively because of the importance of aryl fluorides in pharmaceuticals, agrochemicals, and materials. The stability, reactivity, and biological properties of aryl fluorides can be distinct from those of the corresponding arenes. Methods for the synthesis of aryl fluorides, however, are limited. We report the conversion of a diverse set of aryl iodides to the corresponding aryl fluorides. This reaction occurs with a cationic copper reagent and silver fluoride. Preliminary results suggest this reaction is enabled by a facile reductive elimination from a cationic arylcopper(III) fluoride.     

Synthesis of substituted carbazoles, indoles, and dibenzofurans by vinylic to aryl palladium migration

Substituted carbazoles, indoles, and dibenzofurans are readily prepared in moderate to excellent yields by the palladium-catalyzed cross-coupling of alkynes and appropriately substituted aryl iodides. This process proceeds by carbopalladation of the alkyne, heteroatom-directed vinylic to aryl palladium migration, and ring closure via intramolecular arylation or a Mizoroki-Heck reaction. Results from the deuterium labeling experiments are consistent with the proposed mechanism.     

Palladium-Catalyzed Synthesis of Benzophenanthrosilines by C−H/C−H Coupling through 1,4-Palladium Migration/Alkene Stereoisomerization

A new and efficient synthesis of 8H-benzo[e]phenanthro[1,10-bc]silines from 2-((2-(arylethynyl)aryl)silyl)aryl triflates under palladium catalysis has been developed. The reaction mechanism was experimentally investigated and a catalytic cycle involving C−H/C−H coupling through a new mode of 1,4-palladium migration with concomitant alkene stereoisomerization is proposed.     

Application of the Pictet-Spengler reaction to aryl amine substrates linked to deactivated aromatic heterosystems

Three new substrates with an aryl amine moiety attached to quinoxalines, triazoles and tetrazoles either via C or N have been used for the Pictet-Spengler reaction. The substrates have been designed by applying the concept of ‘aryl amine attached to a deactivated heteroaromatic ring’ in a manner to facilitate endo cyclization. This is in contrast to the substrates used traditionally and reported earlier by us that are based on either aliphatic or aryl amine, respectively, attached to an activated heterocyclic ring. The Pictet-Spengler condensation of the three substrates with aldehydes led to the synthesis of novel N-rich polyheterocyclic system hitherto not reported. Our modified strategy opens up possibilities to design novel substrates with aryl amines linked via C or N to either deactivated or activated heterocyclic privileged structure, which in turn can be used for the synthesis of novel fused polyheterocyclic skeletons.