Catalytic copper

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

The asymmetric addition of different types of nucleophiles at the C-l position of 3,4-dihydroisoquinolines were highlighted in a number of publications. Schreiber et al. described an enantioselective addition of terminal alkynes 136 to 3,4-dihydroisoquinolinium bromide 137 in the presence of triethylamine, catalytic copper bromide, and QUINAP <06OL143>. The resulting 1-substituted tetrahydroquinolines 138 were isolated in high yield and high enantiomeric excess in most cases. 

Finally, Lipshutz and co-workers developed catalytic copper(i)-assisted polyfunctionalizations of zirconacyclopen-tenes of type 93 by trapping the intermediary zirconium enolates 94 with an aldehyde to form the corresponding 2,3-disubstituted cyclopentanones 95 (Scheme 40).146... 

Note Acrylamide may contain the following impurities acetamide, acrylic acid, acrylonitrile, copper, formaldehyde, hydroquinone, methylacrylamide, hydroquinone monomethyl ether, peroxide, propanamide, and sulfate. When acrylamide is produced using a copper catalyt, copper salts may be added to aqueous solutions at concentrations >2 ppm (NICNAS, 2002). Commercial solutions 30-50%) are usually inhibited with copper salts to prevent polymerization. In addition, solutions containing oxygen will prevent polymerization. 

Copper-catalyzed amidation has also been achieved, and an example is the amidation of 5-bromopyrimidine 130 with cyclohexanecarboxamide 142 which went in 86% yield in the presence of catalytic copper iodide and a diamine ligand <2001JA7727, 2002JA7421>. 

B-rings of their constituent dihydrochalcone monomers. A concise synthesis of verbenachal-cone (316) by catalytic copper-mediated coupling of phenol and aryl halides has been reported by Xing et al., who also prepared two further derivatives for preliminary structure-activity studies. One of the latter, the corresponding bichalcane (deoxo) derivative of verbenachalcone showed no activity in the neural outgrowth stimulation bioassay mentioned above. 

Ethyl acrylate reacts efficiently under the copper-catalyzed Grignard addition protocol, in which the combination of low temperatures (-20 - -50 C) and catalytic copper(I) chloride (2.6%) was necessary to afford moderate to excellent yields of 1,4-addition products, while elaboration of complex a,(3-unsatu-rated esters is not predictable.91 a In contrast, addition to the a,(3-unsaturated ester (116) affords the... 

The conjugate addition of organocopper reagents to polyalkenic carbonyl compounds presents an opportunity in which either 1,4-, 1,6- and sometimes 1,8-addition can occur. Much of the early woik in this area was conducted in the study of the reaction of a dienoate or dienone with an alkylcuprate or a catalytic copper/organomagnesium combination. The predominant mode of addition for the reaction of a dienoate and a copper-based organomagnesium reagent was found to be 1,6 not 1,4.72 If the opportunity of 1,8-addition was present, then this mode prevailed.73 However, a truly systematic study has not been carried out with the various reagents. 

The reaction of a conjugated dienone and a catalytic copper/organomagnesium reagent produced a mixture of 1,2-, 1,4-, and 1,6-addition products.1 74 In contrast, the stoichiometric cuprates showed a marked preference for 1,6- over 1,4-addition (equation 28).1 75 However, both reagents are sensitive to steric demands, and the selectivity is often affected (Scheme 11).1... 

Dicarboxylation reactions of alkenes can be carried out such that predominately 1,2-addition of the two ester functions occurs (equation 61). The reaction takes place under mild conditions (1-3 bar, 25 C) in alcohol. It is stoichiometric in palladium, since the palladium(II) catalyst is reduced to palladium(O) in the process, but by use of an oxidant (stoichiometric copper chloride or catalytic copper chloride plus oxygen equation 62 and 63) the reaction becomes catalytic in palladium. In the reoxidation process, water is generated and the build-up of water increases the water gas shift reaction at the expense of the carboxylation. Thus a water scavenger such as triethyl orthoformate is necessary for a smooth reaction. 

The Glaser Coupling (or Hay Coupling) is a synthesis of symmetric or cyclic bisacetylenes via a coupling reaction of terminal alkynes. Mechanistically, the reaction is similar to the Eglinton Reaction the difference being the use of catalytic copper(I), which is reoxidized in the catalytic cycle by oxygen in the reaction medium. 

Ring enlargement of chromone to benzoxepins has been reported (see also Section 7.07.5). The in situ generation of benzopyrylium triflate 335 by reaction of 334 with Me3SiOTf followed by addition of ethyldiazoacetate and catalytic copper(ll) triflate yielded cyclopropane 336 as a single diastereomer. Treatment of compound 336 with trifluoroacetic acid resulted in the formation of 2,3-benzoxepin 337 (Scheme 47). 

As click chemistry requires catalytic copper, which is toxic to cells, in vivo applications have so far been restricted. To overcome this limitation, Bertozzi and coworkers introduced a second generation of click chemistry that is based on a strain-promoted reaction between a cyclooctyne and an azide moiety [31]. This reaction has been further improved over the past years and is a hot topic in ligation chemistry [32, 33]. 

A ligandless and base-free Gu-catalyzed protocol for the coupling of arylboronic acids and potassium aryltrifluoro-borates with primary and secondary aliphatic amines and anilines was developed. The process utilized catalytic copper(n) acetate monohydrate or CuCl2 and 4 AMS in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen (Equation (232)).1019-1021... 

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