Chiral copper catalyst

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Figure 3.54. Structures of some chiral phosphine ligands (left) and a chiral copper catalyst (right).

Chiral copper catalyst Cyclopropanation Cilastatin Pharmaceutical 92... 

Scheme 10.10. Chiral Copper Catalysts Used in Enantioselective Cyclopropanation...

The first asymmetric procedure consists of the addition of R2Zn to a mixture of aldehyde and enone in the presence of the chiral copper catalyst (Scheme 7.14) [38, 52]. For instance, the tandem addition of Me2Zn and propanal to 2-cyclohexenone in the presence of 1.2 mol% chiral catalyst (S, R, R)-1S gave, after oxidation of the alcohol 51, the diketone 52 in 81% yield and with an ee of 97%. The formation of erythro and threo isomers is due to poor stereocontrol in the aldol step. A variety of trans-2,3-disubstituted cyclohexanones are obtained in this regioselective and enantioselective three-component organozinc reagent coupling. 

In contrast, much more effective asymmetric reactions have been obtained by using chiral copper catalysts. Since the pioneering work of Nozaki and coworkers61 with a chiral salicylamide catalyst (30), a wide variety of other chiral complexes has been developed, the most significant of which are (31M34). Another useful catalyst is the cobalt complex (35). 

Enantiocontrol with 21-23 is lower than that achieved with chiral copper catalysts for reactions of diazoacetates with styrene and a few other alkenes examined thus far [68], but the carboxamidates display far greater stereocontrol than do the dirhodium(II) carboxylates for the same reactions [69]. However, Hashimoto has reported the use of chiral piperidinonate 24 and found exceptional enantiocontrol in the cyclopropanation of styrene and both mono- and... 

Finally, allylic substitution reactions with chiral copper catalysts have been reviewed.13 Little mechanistic detail of these reactions is known. 

The capabilities of 5-8 for enantioselective cyclopropanation were determined (34) from reactions at room temperature of d- and/or /-menthyl diazoacetate (MDA) with styrene (Table 1), which allows direct comparison with results from both the Aratani (A-Cu) and Pfaltz (P-Cu) catalysts (19, 24). Cyclopropane product yields ranged from 50 to 75%, which were comparable to those obtained with chiral copper catalysts, but enantiomeric excesses were considerably less than those reported from use of either P-Cu or A-Cu. Furthermore, these reactions were subject to exceptional double diastereoselectivity not previously seen to the same degree with the chiral copper catalysts. Although chiral oxazolidinone ligands proved to be promising, the data in Table 1 suggested that steric interactions alone would not sufficiently enhance enantioselectivities to advance RI12L4 as an alternative to A-Cu or P-Cu. 

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. 

In contrast to enone 281, the enantiomers of the corresponding /-butyl-substituted Michael acceptor 284 show different rates and enantioselectivities in their reaction with organozinc reagents and chiral copper catalysts. In all... 

Similar to the conjugate addition, the focus of the last decade has been put on the development of chiral copper catalysts for enantioselective S -substitutions of prochiral substrates.197,197a,197b 271,285 These represent a useful alternative for the preparation of those substitution products which cannot be obtained by anti-stereoselective copper-promoted or -catalyzed SN2 -substitution of chiral substrates (see Section 9.12.2.1.2). The first reported example for such a transformation is the reaction of the allyl acetate 333 with //-butylmagnesium bromide in the presence of 15 mol.% of the copper arenethiolate 334 which gave the substitution product 335 with exclusive y-selectivity and 50% ee (Equation (18)),286 286a... 

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]. 

Cyclic and acyclic enol derivatives 480 can be asymmetrically aziridinated with (A -tosylimino)iodobenzene 481 using a chiral copper catalyst prepared in situ from [Cu(MeCN)4]PF6 and the optically active ligand 479. Collapse of the aminal (i.e., 482) leads to the formation of enantiomerically enriched Q-amino carbonyl compounds 483, although ee s to date are modest <2000EJ0557>. Similarly, dienes can be selectively aziridinated using the chiral Mn-salen complex 484 to give vinyl aziridines 486 in scalemic form (Scheme 124) <2000TL7089>. 

H2O2 in methanol. Aryl methyl ketones can be dibrominated (ArCOCHa ArCOCHBr2) in high yields with benzyltrimethylammonium tribromide. Active methylene compounds are chlorinated with NCS and Mg(C104)2. " Similar chlorination in the presence of a chiral copper catalyst led to cx-chlorination with modest enantioselectivity. 

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... 

Catalytic enantioselective Henry reactions are known, such as the use of a chiral copper catalyst or a zinc catalyst. The Henry reaction of nitro-methane an a chiral aldehyde under high pressure gives the p-nitro alcohol with excellent enantioselectivity. ... 

Thienamycin and its derivatives are exciting new antibiotics. Then-clinical use is limited, however, by their susceptibility to the kidney enzyme dehydropeptidase I. Reversible inhibition of this enzyme is provided by cilastatin [11]. The preparation of the S-cyclopropane portion [10] of cilastatin is achieved (16) by decomposition of ethyl diazoacetate in isobutylene [9] in the presence of the chiral copper catalyst R-7644. The product [10] is obtained in 92% e.e. and then further processed to cilastatin. Cilastatin is now marketed in combination with the thienamycin derivative imipenem as a very-broad-spectnim antibiotic. 

Enantioselective cyclopropanation reactions with chiral copper catalysts are discussed in Section 1.2.1.2.4.2.6.3.2. 

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