Copper bromide-dioxane

Another phenoxide activating approach published by Buchwald et al. [18] is based on the reaction of cesium phenoxides with aryl bromides or iodides in the presence of catalytic amounts of copper(I) triflate and ethyl acetate in refluxing toluene (Scheme 3b). In certain cases equimolar amounts of 1-naphthoic acid have been added in order to increase the reactivity of the phenoxide. The authors assume the formation of a cuprate-like intermediate of the structure [(ArO)2Cu] Cs+ as the reactive species. In addition, diaryl ether formation between phenols and aryl halides has been achieved using a phosphazene base forming naked phenoxide in the presence of copper bromide in refluxing toluene or 1,4-dioxane [19]. 

Terminal allenes.1 Terminal acetylenes can be converted by a one-step reaction into terminal allenes by treatment with formaldehyde, diisopropylaminc, and copper(l) bromide in refluxing THF or dioxane. The Mannich base is an intermediate, but, surprisingly, preparation of the quaternary base is not necessary. The source of the introduced hydrogen is not clear. The highest yields are obtained with 2-propynylic alcohols, ethers, and esters. 

Only perfluoro-tert-butyl copper has been prepared by this method. The compound was isolated in 72% yield from the reaction of m-(tri-fluoromethyl)phenylcopper with perfluoro-fert-butyl bromide in ether-dioxane at 0°C(34). Exchange and cross-coupling reactions occur simultaneously in many reactions between organocopper reagents and various organic halides (69, 97, 174, 217, 220, 266, 297). However, the method is only of limited use as the new reagent [R Cu in Eq. (16)] and its precursor are capable of reacting with both species of halide, RX and R X, present in the mixture. 

A mixture of 6-bromo-4-(tri luoromethanesulfonyloxy)-5,8-dimethoxy-quinoline (1.35 g, 3.25 mmol), trimethyl[2-[(l,l-dimethylethoxycarbonyl)-amino]phenyl]tin (1.68 g, 4.70 mmol), lithium chloride (330 mg, 7.80 mmol), copper(I) bromide (25 mg, 0.17 mmol), and tetrakis(triphenylphosphine)palla-dium (0) (180 mg, 0.16 mmol) in dioxane (60 cm ) was heated at 90 °C for 60 h. After being cooled to rt, the mixture was partitioned between EtOAc and a 5 % aqueous ethylenediamine solution to remove any copper species, completely. After the usual work up, the residue was chromatographed (1.5 1 hexanes -EtOAc) to yield the title compound as a white solid (952 mg, 64%, several other fractions contained the title compound contaminated with 6-bromo-5,8-di-methoxy-4-methylquinoline) mp 166-168 °C. 

Homologation of acetylenes to allenes. A one-pot homologation of acetylenes to allenes involves reaction of an acetylenic compound with formaldehyde (1.6 equiv.), diisopropyl amine (1.2 equiv.), and copper(l) bromide at reflux in dioxane or THF (equation I). Other amines and metal salts can be employed, but diisopropylamine and copper(I) bromide give the most satisfactory results (26-97% yields). The reaction is general only for terminal acetylenes and is successful with propargylic alcohols, ethers, and acetates. Racemization is not observed with optically active... 

The aryl chlorides and aryl bromides are easily prepared by treatment of the arylthallium(III) bis(trifluoroacetates) with the corresponding copper(I) or copper(II) halides. The best yields were obtained with the copper(II) halides in dioxane under reflux. 2 These reactions have been successfully applied by Somei et al to the synthesis of indole derivatives by reaction of the arylthallium compounds with copper(II) salts in DMF. 127,133,134... 

Acetoxy-2,4-dimethyl-m-dioxane Alkyl dimethyl ethylbenzyl ammonium chloride Alkyl trimethyl ammonium bromide Betaine hydrochloride Bishydroxyethyl dihydroxypropyl stearaminium chloride Calcium hypochlorite N-Chlorosuccinimide Cocamine acetate Cocoalkonium chloride Cocopropylenediamine Cocotrimonium chloride Copper acetoarsenite Copper gluconate (ic) Dehydroacetic acid Dialkyl dimethyl ammonium chloride... 

Crabbe has described what appears to be a simple, general one-pot procedure for the homologation of substituted acetylenes to the corresponding allenes (80). The acetylenic compound is heated with formaldehyde, di-isopropylamine, and copper(l) bromide under reflux in dioxan or THF for several hours. Yields range from fair to excellent. The reaction has been shown to tolerate a wide range of functionality such as alcohols, esters, and ethers. Indeed, the best yields are obtained when an oxygen function is vicinal to the acetylene. 1,3-Dilithioalk-l-ynes have been shown to act as precursors to allene-l,3-dicarboxylic acids (81) on... 

During the course of the author s efforts directed toward the development of useful transformations of allenic compounds [66-77], the author found that the reaction of A -tosylated 2-ethynylaniline 1 with paraformaldehyde 2 and diisopropylamine 3 in dioxane in the presence of copper(l) bromide (Crabbe conditions) [78] afforded a 2-(aminomethyl)indole derivative 7 in 92% yield (Scheme 2) without forming the expected [2-(A -tosylamino)phenyl]allene. This reaction can be rationalized by Mannich-type MCR followed by indole formation through intramolecular hydroamination toward the activated alkyne moiety of a plausible intermediate 6. This is the first example of three-component indole formation without producing stoichiometric amount of salts as byproducts. 

Related Reagents. Bromine-r-Butylamine Bromine Chloride Bromine-l,4-Diazabicyclo[2.2.2]octane Bromine-1,4-Dioxane Bromine-Silver(I) Oxide Bromine-Triphenyl Phosphite iV-Bromosuccinimide A7-Bromosiiccinimide-Dimethylformamide 7V-Bromosuccinimide-Dimethyl Sulfide Al-Bromosuccinimide-Sodium Azide Copper(II) Bromide Hy-drobromic Acid Mercury(II) Oxide-Bromine Phosphoms(III) Bromide Pyridinium Hydrobromide Perbromide Sodium Bromide Thallium(III) Acetate-Bromine. 

---