Enamines copper catalysts

CuBr/QUINAP System The CuBr/QUlNAP system was initially used in the enan-tioselective synthesis of proparyl amines via the reaction of alkynes and enamines (Scheme 5.5). It was rationalized that the enamines reacted with protons in terminal alkynes in the presence of copper catalyst to form zwitterionic intermediates in which both the generated iminiums and alkyne anions coordinate to the copper metal center. After an intermolecular transfer of the alkyne moiety to the iminium ion, the desired products were released and the catalyst was regenerated. The combination of CuBr as catalyst and the chiral ligand QUEMAP is crucial for the good reactivities and enantioselectivities seen in the reaction. Another potential... 

Instead of PdCOAc), other catalysts such as PdCl, PdCl 2 PhCN and [(ri -CjHjlPdCl] can be used without significant loss of activity . Comparison of the PdfOAcIj/CHjNj reagent with the CuCl/CH N system reveals some complementary behavior Cyclopropanation of carbonyl-substituted alkenes works well with palladium, but fails with the copper catalyst. The same was true for cyclopropanation of a P-arylenamine , although other enamines and 1,2-enediamines underwent the expected reaction with CuCl/CH N. In intramolecular competition... 

Alternatively, aliphatic alcohols may be converted directly to the respective dimethyl alkylamines by catalytic amination in the presence of dimethylamine and low-pressure hydrogen over copper catalyst. The mechanism is believed to involve catalytic dehydrogenation of the alcohol to an aldehyde, addition of DMA with concomitant water elimination to form the enamine, and then subsequent reduction to the alkyldimethylamine. This route is particularly favored with longer-chain alcohols, which are derived through hydrogenation of tallow, or palm fatty acids, or methyl esters... 

Azabicyclo[3.1.0] hex-2-enes and 4-carbonylpyrroles could be obtained respectively via copper-mediated/catalyzed reactions of Af-allyl/propargyl enamine carboxylates under an O2 atmosphere with different copper catalysts. Intramolecular cyclopropanation and carbooxygenation were involved during this reaction (Scheme 8.4). Three C(sp )-H bonds and one C(sp )-H bond were active for this transformation [14]. 

Copper complexes are particularly effective catalysts for the oxidative cleavage of enamines (equation 284)613-615 and 3-substituted indoles (equation 285)6 6,617 under extremely mild conditions ( 0°C). 

MacMillan has reported examples of synergistic catalysis in which copper salts are used. Although these results were driven by ad hoc hypotheses, most of these transformations are related to a Cu(i)/Cu(m) catalytic cycle. In any case, the superior performances offered by copper(i) salts, compared to strong Lewis acids tested in the processes, is an indication that the Lewis acidity of the metal salt is not playing a decisive role in these transformations. The complexation of the enamine 7i-system with Cu(iii)-R is expected to lead to rjl-iminium organocopper species that, upon reductive elimination, will form a carbon-carbon bond and liberate the active Cu(i) catalyst. Hydrolysis of the resulting iminium will also release the imidazolidinone catalyst to complete the organocatalytic cycle as shown in Scheme 18.7. 

MacMillan et al. studied the reactivity of transient enamines formed with organocatalysts with hypervalent iodine reagents in the presence of metal catalysts (Scheme 26.5a). They found that Cu(l) salts can be used in combination with chiral imidazolidinones to perform a-electrophilic trifluoromethylation [47], arylation [48], and vinylation [49] of aldehydes. As suggested by the authors, the most likely mechanism involves a copper-mediated I-O bond cleavage furnishing a highly... 

Iminium-based organocatalysis is somewhat less explored than enamine-based organocatalysis and has been mostly used in the activation of a,/S-conjugated aldehydes and ketones. Therefore, this type of catalysis has unsurprisingly been the subject of a limited number of studies under the umbrella of the metal-organic cooperative catalysis concept. In 2011, the Cdrdova group [55] reported the first enantioselective and chemoselective /3-silyl addition to a./S-unsaturated aldehydes using copper salts and chiral pyrrolidine derivatives as catalysts. As proposed, the chiral secondary amine forms an iminium salt with... 

The conditions reported by the Qin group for the intermolecular cyclopropanation of 3-substituted hexahydropyrroloindole provided unsuccessful results (Table 4.3, entry 3) [65, 69]. Furthermore, no conversion was observed using Cu(OTf)2, CuOTf, IMF copper(l) 27 or IMes gold(I) 15 complexes as catalysts (Table 4.3, entries 3-7) [116, 117]. Only starting material was recovered under the optimized conditions. This is probably due to the higher steric hindrance of the indole III-35, in comparison with methyl l//-indole-l-carboxylate, preventing the nucleophilic attack of the enamine moiety. 

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