Cycloaddition Cu -catalyzed

The enantioselective Cu-catalyzed cycloaddition of the reactive enone 4 to the alkyne 5 proceeded efficiently, but with only modest enantiomeric excess. This was improved at a later point in the synthesis, by recrystallization of 2. 

The scope of the Cu-catalyzed cycloaddition between propargylamines and electron-deficient olefins in the presence of catalytic amounts of a copper salt was subsequently expanded to a one-pot, three-component coupling strategy involving phenols as third components [65]. In this case, reactive Michael acceptors such as ethyl 2-aryl- or alkylsulfonyl cinnamates 57 are involved in the process. This sequence leading to 3(4)-phenoxymethyl pyrrolidines 60 and their isomeric pyrrolidines 61 comprises of the relay process of... 

Tetrazoles Nitriles undergo Cu-catalyzed cycloaddition with Me3SiN3 and adducts are desilylated in situ to furnish five-substituted tetrazoles. 

Scheme 22 Cu-catalyzed cycloaddition of terminal alkynes and sulfonyl azides [79]...

Successful dimerization by intramolecular Cu -catalyzed cycloaddition yielded macrocycle 121 in 80% yield (Scheme 27) and was reported by Gin and co-workers [100]. 

Up to now, a variety of heterogeneous Cu-catalyzed cycloaddition reactions for the assembly of bioactive heterocycles have been reported. Most examples are the Huisgen-type 1,3-dipolar cycloadditions, but there are rare reports on the heterogeneous Cu-catalyzed synthesis of heterocycles through other types of cycloaddition reactions. 

It was shown that CNTs provide an excellent environment for Cu-catalyzed cycloaddition reactions [208]. The kinetics of reactions are accelerated and conversion rates improved in CNTs relative to catalysts deposited on the outer... 

Proposed mechanism for the Cu -catalyzed cycloaddition of an azide and a terminal alkyne (click reaction)... 

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

The chiral BOX-metal(II) complexes can also catalyze cycloaddition reactions of other ketonic substrates [45]. The reaction of ethyl ketomalonate 37 with 1,3-conju-gated dienes, e.g. 1,3-cyclohexadiene 5c can occur with chiral BOX-copper(II) and zinc(II) complexes, Ph-BOX-Cu(OTf)2 (l )-21a, and Ph-BOX-Zn(OTf)2 (l )-39, as the catalysts (Scheme 4.29). The reaction proceeds with good yield and ee using the latter complex as the catalyst. Compared to the copper(II)-derived catalyst, which affects a much faster reaction, the use of the zinc(II)-derived catalyst is more convenient because the reaction gives 94% yield and 94% ee of the cycloaddition product 38. The cycloaddition product 38 can be transformed into the optically active CO2-... 

M. Meldal and C. W. Tomqe, Cu-catalyzed azide-alkyne cycloaddition, Chem. Rev., 108 (2008) 2952-3015. 

It is of interest to mention that DFT study performed, prior to experimental observations, revealed for Cu(I)-catalyzed cycloaddition of nitrile oxides to 1-alkynes, a stepwise mechanism involving unprecedented metalacycle intermediates, which appear to be common for a variety of dipoles (382). 

As far as catalytic enantioselective cycloadditions to imines are concerned, the only non-Zr-catalyzed process is a Cu-catalyzed protocol reported by Jorgensen (Eq. 6.22) [112]. It should be noted, however, that high enantioselectivities are attained only with highly substituted versions of the Danishefsky diene. 

Two recent publications feature metal vinylidenes functioning as 1,3-dipole equivalents, as in the Cu-catalyzed Huisgen cyclization (Section 9.4.5). Fiirstner and coworkers described intramolecular Diels-Alder reactions of unactivated die-nynes catalyzed via a proposed [4+3]-diene/copper vinylidene cycloaddition [59]. 

Four donor acceptor [2]catenanes possessing cyclobis(paraquat-p-phenylene), as the 7i-electron acceptor, and 1,5-dioxynaphthalene-containing macrocyclic polyethers, as the 7i-electron donor moieties, have been constructed employing Cu+-catalyzed Huisgen 1,3-dipolar cycloaddition and Cu+2-mediated Eglinton coupling condition in the final step <07JA8236>. Desymmetrized [2]catenanes were synthesized by means of a template synthesis of pseudorotaxanes between 7i-rich crown ethers and a 7i-deficient pyromellitic subunit,... 

Thus the first electron transfer to Pb relates to the reaction (a) in Section 7.4.3.1.1, and the second involves the oxidation of the cyclobutyl radicals either by electron transfer/deprotonation with Cu" in equation (17) or by ligand transfer of chlorine with PlAci in equation (18). When the product of a generic reaction is itself a radical cation (such as in Sections 7.4.3.1.8 and 7.4.3.1.9), an electron-transfer chain or ETC process can ensue, as in the hole-catalyzed cycloadditions and autoxidations of dienes,The electron-transfer propagation sequence for the latter is simply given as in equations (19) and (20). 

An approach to inducing an ot-helical conformation in peptides that is more definitive than relying on salt-bridging interactions involves chemical ligation of side-chain residues using either ring-closing olefin metathesis or Cu-catalyzed azide cycloaddition to an alkyne (click chemistry) [147-153]. This approach,... 

Surprisingly, high enantioselectivities were observed when using BSA as the host harboring 32 (85-98% ee in favor of the endo-products 35) [122], In the case of 32/HSA (Fig. 15), the reaction of 33a with 34 led to an ee-value of only 85%. BSA or HSA alone did not catalyze the reaction. Since a good expression system for HSA has been reported [126,127], this system could be employed in a future study regarding the directed evolution of enantioselective hybrid catalysts. Iterative CASTing (Fig. 2) based on the model in Fig. 15 could then be used to increase the enantioselectivity of the present Diels-AIder cycloaddition or of other Cu"-catalyzed processes. However, a procedure for en masse purification of HSA mutants needs to be developed first. 

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