Asymmetric copper catalysts

The first catalytic, asymmetric aziridination of an alkene in good yield and high enantioselectivity was recently reported56. Thus styrene (63) was treated with [N-(p-toluenesulphonyl)imino]phenyliodinane (64) and an asymmetric copper catalyst to yield (/ )-Ar-(p-toluenesulphonyl)-2-phenylaziridine [(/ )-65] in 97% yield with an ee of 61%, the catalyst being the complex formed in situ in chloroform from the chiral bis[(5 ) 4-ferf-butyloxazoline] [(S,S)-66] and copper triflate (CuOTf)56, the reaction proceeding by way of a nitrene transfer57. 

Allylic oxidation (acyloxylation) can also be achieved with copper catalysts and stoichiometric amounts of peresters or an alkylhydroperoxide in a carboxylic acid as solvent [108], via a free radical mechanism (Fig. 4.40). The use of water-soluble ligands [109] or fluorous solvents [110] allows recycling of the copper catalyst. In view of the oxidants required, this reaction is economically viable only when valuable (chiral) products are obtained using asymmetric copper catalysts [111-113]. The scope of the reaction is rather limited however. 

Asymmetric copper catalysts arc less efficient. Low optica) yields were obtained with chiral phosphine liijpinds, and these experimems wctc significant in proving the formation of copper carbenoids rather than free carbenes in the copper catalyzed decomposition of diaio compounds. From a practical point of view, however, the optical yield was too low to be of much interest. The best results with copper catalysts were those obtained by Aratani [36] using complex (36). 

Compared to tlie intensive and successfrd development of copper catalysts for asymmetric 1,4-addition reactions, discussed in Cbapt. 7, catalytic asymmetric al-lylic substitution reactions have been tlie subjects of only a few studies. Diflictilties arise because, in tlie asymmetric y substitution of unsymniettical allylic electto-pb des, tlie catalyst bas to be capable of controlling botli tegioselectivity and enan-tioselectivity. 

Chelucci et al. [41] synthesized further chiral terpyridines derived from (-)-yd-pinene, (-i-)-camphor, and (-l-)-2-carene and tested their ability to chelate copper or rhodium for the asymmetric cyclopropanation of styrene. The copper catalysts were poorly efficient and selective in this reaction. The corresponding rhodium complexes led to the best result (64% ee) with the ligand derived from (-l-)-2-carene (ligand 33 in Scheme 17). 

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). 

Later, several other copper catalysts bearing dinitogen ligands [bipyridine derivatives (76),232,233 diamines (77),234 bis(azaferrocene) (78),235 bisferrocenyldiamine (79),159 and bis(oxazoyl) binaphthyl (80)236] have been introduced (Scheme 62), but asymmetric induction by them does not exceed that by complex (75). 

Subsequently, Lowenthal and co-workers,3 la,9 Evans et al.,31b and Muller et al.98 reported chiral bis(oxazoline) ligands 185, 186, and 83 as shown in Figure 5-12. The gem-dimethyl [(bis)oxazoline] 83-coordinated copper catalyst is the most widely used ligand. The catalyst is prepared in situ by mixing ligand 83 with an equal molar amount of CuOTf. Asymmetric cyclopropanation of isobutylene with ethyl diazoacetate (EDA) gives ethyl 2,3-dimethylcyclopro-pane carboxylate with >99% ee. 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

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. 

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... 

Carbenoids derived from the aryldiazoacetates are excellent donor/acceptor systems for the asymmetric cyclopropanation reaction [22]. Methyl phenyldiazoacetate 3 cyclopropanation of monosubstituted alkenes catalyzed by Rh2(S-DOSP)4 is highly diaster-eo- and enantioselective (Tab. 14.5) [22]. Higher enantioselectivities can be obtained when these reactions are performed at -78°C, as the catalyst maintains high solubility and activity at this temperature. The phenyldiazoacetate system has been evaluated using many popular rhodium(II) and copper catalysts the rhodium(ll) prolinates have proven to be superior catalysts for this class of carbenoids [37, 38]. 

In contrast to the intermolecular cyclopropanation, the dirhodium tetraprolinates give modest enantioselectivities for the corresponding intramolecular reactions with the do-nor/acceptor carbenoids [68]. For example, the Rh2(S-DOSP)4-catalyzed reaction with al-lyl vinyldiazoacetate 32 gives the fused cyclopropane 33 in 72% yield with 72% enantiomeric excess (Eq. 4) [68]. The level of asymmetric induction is dependent upon the substitution pattern of the alkene cis-alkenes and internally substituted alkenes afford the highest asymmetric induction. Other rhodium and copper catalysts have been evaluated for reactions with vinyldiazoacetates, but very few have found broad utility [42]. 

Ferrocene-derived ligand (l ,S)-Josiphos, which is widely used for catalytic asymmetric hydrogenation reactions, is also a good catalyst for the asymmetric copper-catalyzed 1,4-addition. Reaction in f-BuOMe in the presence of 6 mol% of this ligand gives products with up to 98%. ... 

The Kyoto group hoped to obtain more definitive evidence for the existence of carbene species bound covalently to copper. If such a species did exist, the use of an optically active copper catalyst should show some asymmetric induction in the cyclopropanation reaction. Indeed,... 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and <5-lactones, respectively (equations 137 and 138)198 205. The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of E-alkenes in bicyclic y-lactone formation198. Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enandoselectivity in intramolecular cyclopropanation (equation 139)194. On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations201. In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140)206. 

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). 

Asymmetric amplification, 551,700-712 in carbonyl-ene reaction, 551 in diethylzinc addition, 702 Asymmetric autoinduction, 713 Asymmetric aziridination, 317-322 mechanism of, 320 with copper catalysts, 317-321... 

An efficient way to create, enantioselectively, all-carbon quaternary centres, by the unprecedented asymmetric conjugate addition of Grignard reagents to enones has been developed using a copper catalyst and a chiral diaminocarbene ligand of the corresponding salt (19) or (20).87... 

One of the earliest examples of such catalysis was demonstrated in 1966 by the Japanese chemist Hitosi Nozaki, who reacted styrene and ethyl diazoacetate in the presence of a chiral Schiffbase-Cu11 complex [72-74], Although the initial enantios-electivity was modest (<10% ee), the principle was proven. Some years later, the companies Sumitomo and Merck used similar copper catalysts for asymmetric cyclopropanation on a multikilogram scale, in the production of various insecticides and antibiotics [75]. One of Nozaki s PhD students at that time was Rioji Noyori, who later developed the BINAP asymmetric hydrogenation catalysts for which he received the 2001 Nobel Prize in Chemistry [7[. 

Asymmetric oxidative coupling polymerization of hydroxynaphthalene derivatives was investigated by Habaue and Okamoto et al. First, they studied the oxidative coupling polymerization of optically active 3,3/-hydroxy-2,2/-dimethoxy-1,1 -binaphthalene with copper catalysts bearing chiral ligands under an oxygen atmosphere (Scheme 41) [166]. The obtained polymers had molecular weights of 3100-5200. When the polymerization of (J )-monomer... 

They next studied the asymmetric oxidative polymerization of achiral 2,3-dihydroxynaphthalene (Scheme 42). The polymerization of this monomer with CuCl2-(-)-sparteine complex resulted in a low yield and gave a low molecular weight oligomer, whereas the polymerization with CuCl-(S)-Phbox quantitatively gave a polymer with Mn of 10 600-15 300. The enantioselectiv-ity attained in this polymerization, however, was estimated to be low, with 43% ee from the model reaction [169]. When vanadyl sulfate (VOSO -Phbox complex was used instead of the copper catalyst system, the enantioselectivity was improved up to 80% ee [170]. Asymmetric cross-coupling polymerization of two kinds of naphthol derivatives was also reported [171,172]. 

Highly efficient catalytic asymmetric cyclopropanation can be effected with copper catalysts complexed with ligands of type 2.3 These bis(oxazolines) are prepared by reaction of dimethylmalonyl dichloride with an a-amino alcohol. As in the case of ligands of type 1, particularly high stereoselectivity obtains when R is /-butyl. Cyclopropanation of styrene with ethyl diazoacetate catalyzed by copper complexed with... 

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