Copper-catalyzed secondary amines

Iminium ions, generated in aqueous solution from secondary amines and formaldehyde, undergo a Barbier-type allylation mediated by tin, aluminum, and zinc. The reaction is catalyzed by copper and produces tertiary homoallylamines in up to 85% yield.67 The imines generated in situ from 2-pyridinecarboxaldehyde/2-quinolinecarboxaldehyde and aryl amines undergo indium-mediated Barbier allylation in aqueous media to provide homoallylic amines.68 Crotyl and cinnamyl bromides... 

Insertion of a carbene unit into the N—H bond of primary or secondary amines by copper salt catalyzed decomposition of diazo compounds has been known for a number of years14). The copper chelate promoted reaction of diazodiphenyl-methane 291) or 2-diazo-1,2-diphenyl-1-ethanone 292) with primary benzylamines or... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

Kinetic studies on catalytic amine carbonylation reactions are scarce, although Brackman (13) has reported kinetics on a copper(I)-copper(II) catalyzed production of ureas from cyclic secondary amines using carbon monoxide-oxygen mixtures at ambient conditions. Saegusa and coworkers (14) used cuprous salts and other group IB and IIB metal compounds to car bony late piperidine to N-formylpiperidine under more severe conditions. We have published (15) a brief report involving some of the studies described in this paper. 

The results show that a number of ruthenium carbonyl complexes are effective for the catalytic carbonylation of secondary cyclic amines at mild conditions. Exclusive formation of N-formylamines occurs, and no isocyanates or coupling products such as ureas or oxamides have been detected. Noncyclic secondary and primary amines and pyridine (a tertiary amine) are not effectively carbonylated. There appears to be a general increase in the reactivity of the amines with increasing basicity (20) pyrrolidine (pKa at 25°C = 11.27 > piperidine (11.12) > hexa-methyleneimine (11.07) > morpholine (8.39). Brackman (13) has stressed the importance of high basicity and the stereochemistry of the amines showing high reactivity in copper-catalyzed systems. The latter factor manifests itself in the reluctance of the amines to occupy more than two coordination sites on the cupric ion. In some of the hydridocar-bonyl systems, low activity must also result in part from the low catalyst solubility (Table I). 

Scheme 12.1. Copper-catalyzed reaction of aldehydes with alkynes and secondary amines.

In the presence of copper acetylide complexes, the reaction of aldehydes with acetylene and secondary amines (eq. (2)) leads to propargylamines [6]. In contrast to the synthesis of butynediol, this reaction is catalyzed homogeneously. 

Amide enolates mirror ester enolates in their amination reactions. Secondary amides can be used by employing two equivalents of the base, but yields in the only example found in the literature are low to fair.212 Ketene aminals react with azodicarboxylic esters at room temperature, but yields are low (Eq. 125).251 Eq. 126 shows the application of the copper-catalyzed enantioselective addition of mixed ketene acetal/aminals to azodicarboxylic esters previously described for silyl enol ethers in Eq. 94.252 Increasing bulk of the R substituent in the substrate causes partial or complete amination on the pyrrole, as evidenced by the yields of products 60 and 61 as R is varied. 

Hydrolysis of primary amides catalyzed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

Table 9.2 Copper/ligand catalyzed coupling between aryl halides and aliphatic secondary amines.

Copper(l) oxide nanoparticles catalyzed multicomponent coupling/ cycloisomerization reactions between various 2-hydroxybenzaldehydes, secondary amines, and nonactivated alkynes to give 2,3-disubstituted benzo [It] furans in good-to-excellent yields with high atom economy and high catalytic efficiency (14S2489). 

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