Stoichiometric in Copper

Cu(OAc)2 (2equiv), ArB(OH)2 (2equiv), EtjN (2equiv) and pyridine (2equiv), CH2CI2, 48h 

Moderate to good yields, good substrate scope 

1 selective between arylbismuthates and aryl boronic adds (1.25 equiv) DCM, 4A MS,rt, O2, 7 days  

Yields 42-81%, good substrate scope of purine and boronic add 

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In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

It has been speculated that the mechanism of copper-mediated (stoichiometric in copper) arylations of phenols involves the following elemental steps (i) transmetal-lation of Cu(II) with the arylboronic acid (ii) coordination of the phenol nucleophile to copper(II) and (iii) reductive elimination, slowly via the Cu(II) species or via air oxidation to the Cu(III) species which can be expected to undergo reductive eUmination more rapidly, thereby regenerating a potentially catalyticaUy active copper(I) species (Scheme 4.2). A plausible catalytic mechanism (not illustrating the potential role of substrates as copper ligands) is also shown. 

Castro introduced a stoichiometric-in-copper synthesis of the benzothiophene 90 framework via the formal [3 + 2] cycloaddition route, involving the coupling-cydi-zation cascade of stable copper] I) acetylides 88 and ortho-bromothiophenol 87 (Scheme 9.32) [139]. Later, the same researchers suggested that this reaction proceeded through the formation of a reactive ortho-alkynylthiophenol intermediate 89, which, upon the concomitant cyclization, accomplished the assembly of the... 

A formal [3 + 2] cydoaddition route leading to the preparation of di- and tri-substituted indoles 264 from ortho-haloanilines 261 and copper(I) acetylides 262 was introduced by Castro (Scheme 9.92) [75, 76, 111], simultaneously with the mentioned earlier coupling-cyclization reaction en route to benzofurans 57 (Scheme 9.21). It is believed that this stoichiometric in copper cascade reaction proceeded with the generation of an intermediary ortho-alkynylaniline 263 [77]. Attempts to turn this reaction into a more practical catalytic process, using basic conditions to generate Cu(I)-acetylide from a terminal alkyne in the presence of Cul, provided poor yields of the respective indoles 264. 

Trifluoromethylation reactions by cross-coupling in the presence of NHC-Cu species have also been reported. Although most of these methods remain stoichiometric in copper with the use of a pre-formed or in situ generated [(NHC)CuCF3] species, they represent a real breakthrough in the field of trifluoromethylation chemistry. Recently, Lalic also described the [(IPr)CuOTf]-catalyzed fluorination of alkyl triflates using KF as a fluoride source. This method is an elegant way to efficiently incorporate a fluorine atom on an aliphatic chain. It could be performed with radiolabeled F and therefore find some applications for PET probes. 

As described above, when CuCl is regenerated in the reaction, the process can be catalytic in copper. In other cases, a stoichiometric amount (2 equiv.) of CuCl is used. Although CuCN shows similar reactivity, CuBr and Cul are not so effective as compared to CuCl. Allylation benzene, naphthalene, and anthracene formation, as well as acylation are representative examples, which are described below. 

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. 

Discovery and Development of a New O—H Bond Arylation Reaction From Stoichiometric to Catalytic in Copper... 

It should be mentioned that galvanostatic diffusion measurements may also be carried out as has been done by Pastorek and Rapp [39] and by Osterwald and Schwartzlose [40] for oxygen in copper. Recently, Rickert and coworkers have determined the chemical or effective diffusion coefficient in non-stoichiometric compounds. This involves, for example, replacing the gold sink in cell XII by a non-stoichiometric compound which conducts electronically. The cell used by Chu, Rickert and Weppner [32,33]... 

Copper-mediated arylation of various nucleophilic groups, including phenols, anilines and thiophenols, with boronic acids has been reported by several groups (Scheme 2.178) As an organometallic species is used as the aryl donor, the copper(II) acts as a net oxidant, and must be used stoichiometrically. Inclusion of an oxidant, such as molecular oxygen as in the Wacker reaction (Section 6.1) can allow a system that is catalytic in copper. Aryl trifluoroborates have also been used as the aryl donor. ... 

Our current mechanistic imderstanding of copper(l)-catalysed 1,4-ACA is derived from the cumulative experimental data obtained from the studies carried out with the stoichiometric (uncatalysed) addition of lithium organocuprates [104, 105]. This approach is based on the assumption that each catalytic event in copper(l)-catalysed reactions can be considered as a single addition reactimi of an... 

Vinylboronic acids can be used in place of the vinyl halides in copper-promoted syntheses of vinyl ethers (Schane 2.77) [107]. In contrast to the catalytic amount of copper that was needed for the cross-coupling reactions described previously, this chemistry needed a stoichiometric amount of the copper. A significant advantage to the system was the observation that it could be carried out at room temperature and was successful under air. While only a single substrate was presented, this demonstrated that the approach had potential for the selective synthesis of vinyl ethers. 

Alternatively, Arsenyan employed trimethoxyvinylsilane as vinyl source in copper-promoted V-vinylation of amides, but the use of stoichiometric amounts of Cu(OAc)2 are required [124]. 

Significant improvement in copper-catalyzed iV-arylation is realized after the introduction of arylboronic acids as the aryl donors independently by Lam et al. [69,70], Chan et al. [71], and Evans et al. [72] utilizing stoichiometric amount of Cu(OAc)2. 

In 1928, this copper metal-silieide alloy system was patented by Michael Corson [1]. It was subsequently known as Corson bronze. In tMs alloy, the silicide could be nickel, chromium or cobalt based. In copper, a small addition of silicon and nickel or eobalt in a stoichiometric ratio of 1 2 results in the formation of an X2Si silicide that has a significant strengthening effect on the copper while keeping thermal and electrical conductivity nearer that of pure copper. Likewise, chromium will form a Cr2Si3 silicide. However, with a Brinell hardness of only 135 (75 HRB), the simple silicide system found limited use. 

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