Palladium-catalyzed carbene insertion into benzyl bromides

Palladium can catalyze the insertion of ethyl diazoacetate into benzyl bromides. The key step in the catalytic cycle is the migratory insertion of a carbene, derived from ethyl diazoacetate, into a Pd-C bond.     

Convenient one-pot synthesis of (E)-beta-aryl vinyl halides from benzyl bromides and dihalomethanes

(E)-beta-aryl vinyl iodides are synthesized in high yield with excellent stereoselectivity from benzyl bromides by a one-pot homologation/stereoselective elimination procedure. Convenient conditions involving the anion of diiodomethane and an excess of base provide complete consumption of the benzyl bromide and elimination from a diiodoalkane intermediate. Similar conditions provide (E)-beta-aryl vinyl chlorides and bromides by employing the anions of ICH(2)Cl or CH(2)Br(2). The functional group tolerance and facile purification allows rapid access to a wide range of functionalized vinyl halides.     

Mechanistic role of benzylic bromides in the catalytic autoxidation of methylarenes

Different pathways for benzylic bromide transformations were examined under conditions of cobalt-bromide catalysis in acetic acid. It has been shown that benzylic bromides participate in the catalytic cycle through their catalyzed and noncatalyzed oxidation, through their reaction with Co(III), and through cobalt(II)-catalyzed solvolysis. The rates of the direct reduction of Co(III) by several benzylic bromides were measured under an argon atmosphere; the reaction occurs by a mechanism involving two forms of Co(III). The same reaction under an oxygen atmosphere initiates the cobalt-bromide-catalyzed oxidation of benzyl bromide, thus leading to the regeneration of inorganic bromide and the fast reduction of Co(III). Solvolysis of benzylic bromides plays only a minor role in the regeneration of inorganic bromide in glacial acetic acid.     

Palladium catalyzed-dehalogenation of aryl chlorides and bromides using phosphite ligands

The catalytic system based on Pd-phosphite for the dehalogenation reactions of aryl chlorides and bromides is described. The Pd-phosphite catalyst effectively promoted the dehalogenation of aryl halides to give dehalogenated products in moderate to excellent yields. The aryl chlorides required strong bases such as NaO^tBu for this transformation, whereas the aryl bromides were dehalogenated in the presence of weak bases such as Cs₂CO₃. This catalytic system exhibited tolerance to functional groups such as methoxy, amine, hydroxyl, ether, amide, benzyl and ketone groups. It also demonstrated chemoselectivity in that bromochlorobenzene was converted only to chlorobenzene.     

Palladium-catalyzed coupling reactions of (ArCH2)Ti(O-i-Pr)3 with aromatic or heteroaromatic bromides

Three benzyltitanium compounds of (ArCH₂)Ti(O-i-Pr)₃ (Ar = Ph (1a), 4-MeOC₆H₄ (1b), 4-FC₆H₄ (1c)) were prepared and used as benzyl nucleophiles for coupling reactions with aromatic or heteroaromatic bromides. The simple catalytic system of 1 mol % Pd(OAc)₂ and 2 mol % PCy₃ worked efficiently for a wide variety of aromatic bromides, producing diarylmethanes in good to excellent yields of up to 96%. Coupling reactions of hindered aromatic bromides or aromatic bromides containing electron-withdrawing substituents were slower over longer reaction times of 3–6 h. Reactions of heteroaromatic bromides of bromopyridines, bromofurans, or bromothiophenes with benzyl reagents of 1a or 1b required either longer reaction times of 12–24 h or a higher reaction temperature of 80 °C, producing pyridyl-, furyl-, and thienyl-arylmethanes in moderate yields.     

Kinetics and mechanism of the reaction of substituted benzyl bromides with copper in dimethylformamide

The reaction of copper metal with various substituted benzyl bromides in dimethylformamide has been studied and the kinetic and thermodynamic parameters of the reaction have been obtained. Hammett plots of log(k/k°) vs the substituent constant σ gave good correlations (ρ = 0.24, S_ρ = 0.03, r = 0.951). The structure of the organic group has little effect on the rate of reaction of substituted benzyl bromides with copper. In the absence of atmospheric oxygen, oxidative dissolution of copper occurred by the mechanism of single‐electron transfer with the formation of 1,2‐diphenylethanes and copper(I) complexes. The stereochemistry and intermediate compound were also studied and the reaction mechanism is discussed. Copyright © 2005 John Wiley & Sons, Ltd.     

Cu-mediated chemoselective trifluoromethylation of benzyl bromides using shelf-stable electrophilic trifluoromethylating reagents

Copper-mediated chemoselective trifluoromethylation at the benzylic position by the use of shelf-stable electrophilic trifluoromethylating reagents 3 in good to high yields under mild conditions is described for the first time. The generality of this trifluoromethylation for a wide variety of benzyl bromides facilitates the rapid creation of structural diversity of medicinal candidates in drug discovery.     

Initial investigation into the Suzuki-Miyaura vinylation of hindered aryl bromides utilizing potassium vinyltrifluoroborate

An initial study of the Suzuki-Miyaura cross-coupling of potassium vinyltrifluoroborate (2) and hindered aryl bromides is presented. Coupling of benzyl 3,5-bis(benzyloxy)-4-bromobenzoate (1) leads to a mixture of the desired styrene derivative, and the reduced product.     

A convenient one-pot preparation of glycosyl bromides as well as glycosyl acetates from benzyl glycosides using N-bromosuccinimide.

Some conversions of benzyl glycoside using NBS were examined and one-pot preparation of glycosyl acetates and bromides were developed. An efficient O-debenzylation at non-anomeric position was also observed.     

Enantioselective nickel-catalyzed cross-coupling reactions of trialkynylindium reagents with racemic secondary benzyl bromides

The first enantioselective sp-sp3 cross-coupling reaction between alkynyl organometals and racemic benzyl bromides is reported. The coupling is performed at room temperature by using NiBr2diglyme and (S)-(iPr)-Pybox as the catalytic system and trialkynylindium reagents as nucleophiles. The reaction is stereoconvergent, both enantiomers of the racemic benzyl bromide are converted into one enantiomer of the product, and stereospecific. The reaction takes place efficiently in good yields and with high atom economy, as the triorganoindium reagents transfer the three organic groups attached to indium (only 40 mol % of R3In is used).     

Synthesis of benzyl bromides with hexabromoacetone: an alternative path to drug intermediates

A series of benzyl bromides were efficiently prepared from the corresponding alcohols with Br₃CCOCBr₃/PPh₃ at low temperatures and under neutral conditions. The present protocol was applied to the heterocyclic analogues and to the successful synthesis of the precursor of the antiulcer drug omeprazole, thus furnishing an alternate, mild method for the preparation of these drug intermediates. A significant steric factor was observed throughout both series supporting a S_N2 mechanism.     

NaIO4-mediated selective oxidation of alkylarenes and benzylic bromides/alcohols to carbonyl derivatives using water as solvent

A new transition-metal-free, sodium metaperiodate (NaIO4)-mediated direct oxidation of methylarenes and benzylic bromides to the corresponding aromatic carboxylic acids is described. Under the same reaction conditions, benzylic alcohols are selectively oxidized to afford the corresponding aldehydes in good yields without undergoing overoxidation. Unprecedentedly, oxidation of benzyl bromide, toluene, or benzyl alcohol with NaIO4 underwent nuclear bromination followed by oxidation to give 4-bromobenzoic acid in 60-79% yields.     

An efficient synthesis of benzyl bromides from aromatic aldehydes using polymethylhydrosiloxane and (bromodimethyl)sulfonium bromide or N-bromosuccinimide

Polymethylhydrosiloxane (PMHS) in combination with (bromodimethyl)sulfonium bromide or NBS has been utilized for the first time for reductive bromination of aromatic aldehydes at room temperature to afford the corresponding benzyl bromides in excellent yields.     

Radical additions to allyl bromides. A synthetically useful, ‘Tin-Free’ method for carbon-carbon bond formation

The scope and limitations of a novel free radical chain process involving the addition of benzyl radicals to substituted allyl bromides were examined and extended to explore the effect of α-substitution on the allyl bromide (R′), and the use of pyrrolidine amides and oxazolidinone as activating substituents (Z) as the first steps toward the development of a stereoselective, radical-based C-C bond-forming reaction which is environmentally benign.     

Use of tetrahydropyrimidinium salts for highly efficient palladium-catalyzed cross-coupling reactions of aryl bromides and chlorides

New, sterically demanding 1,3-dialkyl-3,4,5,6-tetrahydropyrimidinium salts (2) as NHC precursors have been synthesized and characterized. These salts, in combination with palladium acetate, provided active catalysts for the cross-coupling of aryl chlorides and bromides under mild conditions. The catalytic system was applied to the Heck, Suzuki and benzaldehyde (Kumada) coupling reactions. Catalyst activity was found to be influenced by the presence of a methoxy group on the ring of the p-position of benzyl substituent of the ligand precursor.     

Copper(I)-catalyzed addition of trifluoromethylated benzyl radicals derived from aryltrifluoroethyl bromides to terminal olefins

Relatively unreactive aryltrifluoroethyl bromides were reacted with 1-octene in the presence of CuCl and 2,2′-bipyridyl at high temperatures. Trifluoromethylated benzyl radical was generated, and a diastereomer mixture of radical adducts was obtained with a (60-70):(40-30) diastereomer ratio. Ph₃SnH reduction of the adducts gave the corresponding hydrocarbons with an isolated trifluoromethyl group. The reactions with styrene or aromatic and aliphatic silyl enol ethers led to the formation of trifluorodiphenylbutene and β-trifluoromethylated ketones, respectively.     

Studies on Solubilization. (Part I). Note on the synthesis of some quaternary N-(ω-aryloxyalkyl) piperidinium,pyridinium, benzyl-dimethyl-ammonium,and trimethyl-ammonium bromides

A series of new N-(ω-aryloxyalkyl) piperidinium, pyridinium, benzyl dimethyl ammonium, and trimethyl ammonium bromides is described.     

Efficient and selective Stille cross-coupling of benzylic and allylic bromides using bromobis(triphenylphosphine)(N-succinimide)palladium(II)

Allylic and benzylic bromides are cross-coupled with organostannanes efficiently using the precatalyst [Pd(NCOC₂H₄CO)(PPh₃)₂Br] 1. Significantly, these reactions do not require the use of hexamethylphosphoramide (HMPA) as the solvent, or additional ligands, such as trifurylphosphine or triphenylarsine. Selectivity for benzyl bromide over bromobenzene is observed for precatalyst 1, against the precatalysts, bromobis(triphenylphosphine)(benzyl)palladium(II) and bis(triphenylphosphine)palladium(II) bromide.     

Biphasic Suzuki coupling reactions of aryl or benzyl bromides employing cobalt-containing phosphine ligand coordinated palladium complex

Biphasic Suzuki-coupling reactions of aryl and benzyl bromides employing a cobalt-containing phosphine ligand chelated palladium complex 2 were carried out in various reaction conditions. Comparisons of the catalytic efficiencies in the presence/absence of a phase-transfer agent, TBAB, were presented. In addition, the effects of altering solvents, temperatures, catalysts, and substrates on the reactions were monitored and reported. Better yields were commonly observed while a phase-transfer agent TBAB was participated in the reactions. The factor of reaction time is more crucial than that of temperature in short reaction hour experiments. Obviously, an induction period for the reduction of Pd(II) to Pd(0) active species is needed for this type of reaction.     

Photodissociation of alkyl bromides

The branching ratios for the production of Br(4²P_{$\text{1}\text{2}$}) following the broadband flash photolysis of the alkyl bromides, CH₃Br and C₂H₅Br, and the perfluorinated molecules, CF₃Br, C₂F₅ Br and n-C₃F₇ Br, have been determined using time-resolved atomic absorption spectroscopy. The production of electronically excited bromine atoms is shown to be inefficient in the case of the alkyl bromides while the perfluorinated molecules yield decreasing amounts of Br(4²P_{$\text{1}\text{2}$}) as the molecular complexity increases, i.e., CF₃Br > C₂F₅Br > C₃F₅Br > C₃F₇. It is also shown that the hydrogenated bromides deactive electronically excited atoms almost two orders of magnitude faster than do the perfluorinated bromides.