Enantioselective reactions copper-catalyzed

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

A copper-catalyzed reaction using a chiral diphosphine hgand, DuPHOS, with an added lanthanide salt, provides good levels of enantioselectivity (67-91% ee) in additions of the simple allylboronate 31 to both aromatic and aliphatic ketones that present a large difference of steric bulk on the two sides of the carbonyl group. One such example is shown in Eq. 81. On the basis of B NMR experiments and on the lack of diastereoselectivity in crotylation reactions, the... 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

Jonasson, C., Roenn, M., Baeckvall, J.-E. An Enantioselective Route to Paeonilactone A via Palladium- and Copper-Catalyzed Reactions. 

Since the bisphosphine as well as a monophosphine greatly accelerate the copper-catalyzed reaction [59], a survey of the known diphosphine was carried out to find that 0.5% of copper(II) triflate and 0.5% of phosphine are sufficient, though enantioselectivity was at most 44% [60]. Chiral phosphite ligand bearing tartrate moiety 28 accelerated the reaction [61], but the ee was not so satisfactory at 40% (Eq. (12.30)) [62]. Chiral thiazolidinone 29 was developed as a chiral ligand to afford the product in 63% ee [63]. 

Enantioselective C-H insertion is clearly the domain of chiral dinuclear rhodium catalysts (see Chap. 16.2). Only very few examples of enantioselective copper-catalyzed reactions of this type have been reported. As a possible approach to the mitomycine ring system, Sulikowski has studied the cyclization of diazo esters 28 quite extensively using various chiral transition metal catalysts... 

AUylic substitution catalyzed by copper is a transformation that is related to ally-lie substitutions catalyzed by other transition metals discussed previously in this chapter, but several features of copper-catalyzed allylations make them worth differentiating. First, copper-catalyzed allylic substitutions are conducted with different types of nucleophiles tiian most allylic substitutions catalyzed by other metals. Second, the regioselectivity of the copper-catalyzed reactions is typically different from that of reactions catalyzed by complexes of other metals, particularly of reactions catalyzed by complexes of palladium. Thus, this last section of tiie chapter describes studies on allylic substitution catalyzed by copper, witii an emphasis on enantioselective examples. 

In the last few years, the use of NHC-Cu complexes in catalysis has grown exponentially, particularly for the transfer of carbon and heteroatom-based nucleophiles to various electrophilic substrates. Copper-catalyzed boron and silicon transfers have recently been reported, thus expanding the scope of NHC-copper-catalyzed reactions. Notably, the design of new chiral NHC ligands has enabled the successful development of efficient C-C and C-H bond forming enantioselective reactions. 

The chiral BOX-copper(ll) complexes, (S)-21a and (l )-21b (X=OTf, SbFg), were found by Evans et al. to catalyze the enantioselective cycloaddition reactions of the a,/ -unsaturated acyl phosphonates 49 with ethyl vinyl ether 46a and the cyclic enol ethers 50 giving the cycloaddition products 51 and 52, respectively, in very high yields and ee as outlined in Scheme 4.33 [38b]. It is notable that the acyclic and cyclic enol ethers react highly stereoselectively and that the same enantiomer is formed using (S)-21a and (J )-21b as the catalyst. It is, furthermore, of practical importance that the cycloaddition reaction can proceed in the presence of only 0.2 mol% (J )-21a (X=SbF6) with minimal reduction in the yield of the cycloaddition product and no loss of enantioselectivity (93% ee). 

Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents... 

It may be concluded from die different examples sliown here tiiat die enantio-selective copper-catalyzed allylic substitution reaction needs ftirdier improvemetiL High enantioselectivities can be obtained if diirality is present in tiie leaving group of die substrate, but widi external diiral ligands, enantioselectivities in excess of 9096 ee have only been obtained in one system, limited to die introduction of die sterically hindered neopeatyl group. 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

Using the results of an earlier study concerning enantioselective copper-catalyzed intramolecular C—H insertion of metal carbenoids,109 an interesting system for optimizing the proper combination of ligand, transition metal, and solvent for the reaction of the diazo compound (75) was devised (see Scheme 19).110 The reaction parameters were varied systematically on a standard 96-well microtiter/filtration plate. A total of five different ligands, seven metal precursors, and four solvents were tested in an iterative optimization mode. Standard HPLC was used to monitor stereoselectivity following DDQ-induced oxidation. This type of catalyst search led to the... 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

Feringa, B. L. Naasz, R. Imbos, R. Arnold, L. A. Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents. In Modem Organocopper Chemistry Krause, N. Ed. Wiley-VCH GmbH Weinheim, 2002 Chapter 7, pp 224—258. 

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