Copper intermediate

Acetylene itself (R = H) undergoes the reaction with R2CuLi instead of the Normant reagent. The use of R containing functional groups has been reported. If the alkyl iodide is omitted, the vinylic copper intermediate 64 can be converted... 

It has been found that A-tosyl aziridines undergo oxidative addition to palladium complexes to form azapalladacyclobutanes <06JA15415>. Reaction of aziridine 95 with Pd2(dba)3 and 1,10-phenanthroline provides the palladacycle 96 in 45% isolated yield. This compound is an air stable solid. Treatment the palladacycle 96 with catalytic Cul is believed to open the palladacycle to form a copper intermediate, which cyclizes to cyclopentyl alkylpalladium intermediate 97. Loss of Cul then provides the product palladacycle 97 as an air stable solid. Several different aziridines were examined in this reaction. Only a limited set of olefin substituted aziridines provided the azapalladacyclobutanes (e.g. 96). 

With ethoxypropadiene, the vinylic copper intermediate formed via the allylzinc-cation reacts with another molecule of ethoxyallene leading to the formation of enol ether 112 as an E-Z mixture [55],... 

A smoother transmetalation procedure should be ensured by the more electronegative character of aluminium, as first demonstrated by Wipf and Ireland [35]. Thus, hydroalumination of 1-hexyne with DIBAL-H, followed by addition of the cuprate 59, bearing non-transferable alkynyl groups, provides the copper intermediate 60. This adds smoothly to 2-cyclohexenone to produce the Michael adduct 61, in 72% yield (Scheme 2.18) [36],... 

Scheme 2.62. Michael addition of an alkenylzirconium compound", by successive transmetalation into zinc and copper intermediates.

Scheme 7.16. Favored and disfavored copper intermediates as proposed by Corey et al. [68aj.

The lower stereoselectivity in the transmetalation of the 21/ -stanny epimer has been attributed to jr-propynyllithium and-copper intermediates, the formation of which would be unfavorable starting from the (A7)-21/j-epimer due to steric interference of the solvated metal groups with the angular methyl group of the steroid21. 

Takahashi et al. have also extended the method to oxazirconacyclopentenes (e.g., 42). Here, transmetallation with CuCl and treatment with ethyl propiolate provides 2,5-dihydrofuran 43 with 70% isolated yield (Equation (l)).40 Deuterium-labeling experiments indicate that Michael addition of the copper intermediate is followed by an intramolecular conjugate addition of the hydroxy group to the acrylate moiety introduced in the first step. 

As mentioned in Section 9.12.2.1.1, the boron-zinc exchange can be performed stereoselectively if diisopropyl-zinc instead of diethylzinc is used. For example, hydroboration of the chiral, racemic endocyclic olefin 134 with diethylzinc, followed by twofold transmetallation and electrophilic capture of the resulting copper intermediate with allyl bromide was used for the highly diastereoselective formation of the stereotriad in product 136 (Scheme 35).35,35a 103 QorreSp0nding enantioselective transformations were carried out with chiral boranes and catalytic amounts of copper salts (see Section 9.12.2.2.2).36... 

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

In the case of the allenyl copper intermediate 724, its alkylation with (iodomethyl)zinc iodide and carbonyl compounds afforded dienes 7251032 (Scheme 189). 

All the starting materials were very easily prepared in a single-pot operation by treatment of the alkoxy-allene 96 [70] with lithium organocuprate either in Et20 (for the formation of the Z- vinyl copper intermediate Z-97) or in THF (for the formation of the -vinyl copper intermediate -97) and trapping the resulting alkenyl copper E- and Z-97 with different unsaturated alkyl halides to give 98a-j (Scheme 35) [71]. 

Grignard and lithium reagents the copper intermediates do not react with Michler s ketone 40, 60, 69, 119) [Gilman Color Test I (123)]. 

Since then, experiments have been reported which indicate that (1) organocopper compounds will couple with aryl halides (2) arylcopper compounds can be oxidatively and thermally dimerized (3) arylcopper compounds are intermediates in the Ullmann reaction (4) organocopper compounds are intermediates in copper-catalyzed decarboxylations and (5) copper-promoted coupling reactions are not restricted to aromatic halides. The copper(I) oxide-promoted coupling reactions, however, have still to yield firm evidence of a copper intermediate. 

One cannot distinguish between the analogous copper intermediates involved in oxidative electron-transfer and ligand-transfer reactions. In each the ionization of the ligand to copper(II) has an important role in the formation of carbonium ion intermediates. A reaction analogous to the copper-catalyzed decomposition of peroxides is the copper-promoted decomposition of diazonium salts (178). The diazonium ion and copper(I) afford aryl radicals which can undergo ligand-transfer oxidation with copper(II) halides (Sandmeyer reaction) or add to olefins (Meerwein reaction). 

Figure 18 A schematic representation of the proposed copper intermediates in cyclo-propanation (R and R as in Equation 28).

The cyanaiion step would proceed throu the cyanide ion transfer within the coordination sphere of a n-allyl type copper intermediate ... 

The coupling of aryl halides with copper is called the Ullmann reaction The reaction is clearly related to 13-9, but involves aryl copper intermediates. The reaction is of broad scope and has been used to prepare many symmetrical and unsym-metrical biaryls." When a mixture of two different aryl hahdes is used, there are three possible products, but often only one is obtained. For example, picryl chloride and iodobenzene gave only 2,4,6-trinitrobiphenyl." The best leaving group is iodo, and the reaction is most often done on aryl iodides, but bromides, chlorides, and even thiocyanates have been used. 

The exact mechanistic pathway of the Ullmann coupling is not known. There are two main pathways possible 1) formation of aryl radicals or 2) the formation of aryl copper [ArCu, ArCu " and ArCu " ] intermediates. Currently the most widely accepted mechanism assumes the formation of aryl copper intermediates, since many of these species can be isolated and they can react with aryl halides to give biaryls. 

Cu(bpy) jCl] , and [Cu(bpy) 3]have been photoreduced by irradiation in MeOH amd H,0 solutions to give [CuCtpy),]" " and HCHO as products. An alkyl-copper intermediate produced on laser flash photolysis of Cu(11)-polyacryltc acid complexes is reported... 

The mechanism of the Ullmann reaction has not been fully clarified, however, it should proceed via aryl-copper intermediates [13]. This proposal was supported by an improvement of the method by Koten and Noltes, who reacted an aryl-copper compound with... 

Cyclopropanes. In the presence of cuprous r-butoxide complexed with tri-/i-butylphosphine, methyl a-chloropropionate and methacrylonitrile react to form the isomeric cyclopropanes (1) and (2) via organo-copper intermediates. No reaction occurs in the absence of the ligand. This reaction was carried out... 

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