Copper catalysts imines

Benzophenone Process. Benzophenone, (CgH5 )2C=0, reacts with ammonia to form diphenylmethanimine, (CgHg )2C=NH. In the presence of copper catalysts, this is oxidized with oxygen to benzophenone azine, (CgHg )2C=N—N=C(CgHg The formation of the imine and its... 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

Allenylimines 186 are not easily accessible, and the most elegant approach is the reaction of alkynylimines 185 with triethylamine to generate 186 in situ the copper ) catalyst which is also present then catalyzes the cycloisomerization to the pyrrole 187 (Scheme 15.59) [120]. The method also is applicable to the imine substructure in 2-alkynylpyridines and related substrates, thus opening up a very elegant access to condensed aromatic nitrogen heterocydes. 

Other Systems In contrast to the highly successful alkynylation of imines, copper catalysts failed in the asymmetric alkynylation of aldehydes. On the other hand, the combination of various Uewis acids and chiral amines were studied extensively to... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

Although in some cases, copper catalysis has little effect on the stereochemistry, some asymmetric induction by chiral copper catalysts such as copper(i) complexes of aminotropone iminates (8) [79] or the chiral arylthiocopper compound (9) [80] has been achieved. Chiral zinc(n) complexes (8) also promote enantioselective conjugate addition [81]. 

Activated aromatic compounds add to A-carbamoyl imines in the presence of copper catalysts, and with good enantioselectivity when a chiral catalyst is used. A combination of AuCls/AgOTf facilitates the addition of arenes to A-tosyl... 

The reaction is somewhat selective for the cis-diastereomer. The use of chiral additives in this reaction leads to aziridines enantioselectively. " Imines can be formed by the reaction of an aldehyde and an amine, and subsequent treatment with Me3SiI and butyllithium gives an aziridine. " A-Tosyl imines react with diazoalkenes to form A-tosyl aziridines, with good cis-selectivity " and modest enantioselectivity in the presence of a chiral copper catalyst, " but excellent enantioselectivity with a chiral rhodium catalyst. . It is noted that A-tosyl aziridines are formed by the... 

However, at this stage relatively little progress has been made in research on asymmetric catalytic carbene transfer to imines. In 1995, Jacobsen and Jorgensen reported independently that reaction of ethyl diazoacetate with selected imines can be catalyzed by copper salts [27,28]. In the former case [27], moderate levels of enantioselection were found to be imparted by bisoxazoline ligands associated with the copper catalyst (Scheme 11). The observation of racemic pyrrolidine byproducts in the reaction was taken to support a mechanism of catalysis involving initial formation of a copper-bound azomethine yhde intermediate (Scheme 12 ). Collapse of this intermediate to the optically active aziridine apparently competes with dissociation of the copper to a free azomethine ylide. The latter can react with fumarate formed by diazoester decomposition in a dipolar cycloaddition to afford racemic pyrrolidine. 

More recently, the asymmetric hydrosilylation of aryl ketones and aryl imines has been developed using copper catalysts. " In this case, axially chiral biaryl bisphos-phine ligands boimd to copper generate remarkably active catalysts for tihe hydrosilylation of ketones. These reactions occur with high selectivity using the hydrosilane polymer... 

Asymmetric Aziridination of Alkenes. The copper-catalyzed aziridination reaction can be rendered enantioselective by the addition of chiral ligands. The first example of an enantioselective aziridination of an alkene employed the bis(oxazoline) ligand (4) (R = f-Bu) and copper(I) trifluoromethanesulfonate as the metal catalyst (eq 14). This catalyst system affords the aziridine in 97% yield and 61% ee. Other reports have appeared subsequently regarding the extended scope of this reaction. " Important contributions to this area include the copper/bis-(oxazoline)-catalyzed aziridination of aryl acrylate esters (eq 15) and the copper/bis(imine)-catalyzed aziridination of cyclic cis-alkenes with the bis(imine) ligand (5) (eqs 16 and 17). ... 

In 2004, Cristau et al. [114] found that chelating di-imine Chxn-Py-Al (Figure 8.8) generates a remarkable general copper catalyst for a-arylation in diethyl malonate and diethyl methylmalonate... 

Chiral Cu(I) salts have been utihzed in allylations of ketones [60] and imines (61), as well as in alkenylation and phenylation (62) of aldehydes. However, the role of these copper catalysts is not that of a Lewis acid. In these protocols the catalytically active allyl copper, alkenyl copper, and aryl copper species are... 

The copper-catalyzed addition of propioloylpyrazoles to azomethine imines has been achieved through the use of copper catalysts (Scheme 3.142) [151]. These enantioselective additions were carried out at subzero temperature and afforded the pyrazolines in good to outstanding yield. The enantioselectivity was also remarkably high and was fairly insensitive to the functional groups on the substrates. 

Chiba et al. developed an efficient copper -catalyzed synthesis of phenanthridine derivatives from biaryl-2-carbonitriles and Grignard reagents under an O2 atmosphere (Scheme 8.101). This Cu(OAc)2-catalyzed C-N bond formation involves an aromatic C-H bond activation process. This reaction proceeds via N-H imine formation by the nucleophiUc addition of a Grignard reagent to biaryl-2-carbonitrile and intramolecular aryl C(sp )-H functionaUzation with copper catalyst [174]. 

A series of tetradentate pyridyl-imine terminated Schiff-bases, bis(pyridyl-imine) terminated siloxane and other related polymers, can be used as ligands to host copper(II) ions. These CuBr2/polyL/TEMPO catalytic systems (polyL stands for polydimethylsiloxane derived pyridyl-imine terminated ligand) are effective for aerobic oxidations of primary and secondary alcohols under aqueous conditions. Chiral N,0-Hgands, e.g., inexpensive L-proline, can also be used to prepare copper catalysts that are particularly effective for the oxidation of sterically hindered, allylic or heterocyclic alcohols such as l-(3-pyridyl)ethanol, l-(2-furfuryl)ethanol. 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Scott et al. [45] prepared diimine derivatives of 2,2 -diamino-6,6 -dimethyl-biphenyl (as structure 37 in Scheme 19) as copper chelates for the catalyzed cyclopropanation reaction. All catalysts were active in this reaction but enan-tioselectivities varied importantly according to the substitution pattern of the imine aryl group only ortho-substituted ligands (by chloride or methyl groups) led to products with measurable enantioselectivity for the model test reaction (up to 57% ee with 37). 

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

In addition, the same group has used copper complexes of these ligands as efficient catalysts for enantioselective Cu-catalysed aza-Diels-Alder reactions of A-sulfonyl imines with Danishefsky s dienes, providing the corresponding six-membered heterocycles with enantioselectivities of up to 80% ee. ... 

Enantioselective Cyclopropanation. Enantioselective versions of both copper and rhodium cyclopropanation catalysts are available. The copper-imine class of catalysts is enantioselective when chiral imines are used. Some of the chiral ligands that have been utilized in conjunction with copper salts are shown in Scheme 10.10. 

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