Copper-phosphoramidite catalyst

Pineschi and Feringa reported that chiral copper phosphoramidite catalysts mediate a regiodivergent kinetic resolution (RKR) of cyclic unsaturated epoxides with dialkylzinc reagents, in which epoxide enantiomers are selectively transformed into different regioisomers (allylic and homoallylic alcohols) [90]. The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7.45 and 7.46,... 

When an alkyl and an alkoxy moiety are present at the 4-position of the dienone (Scheme 7.17(b)), desymmetrization during the 1,4-addition produces two stereocenters in a single step. The chiral copper-phosphoramidite catalyst derived from... 

Feringa and coworkers have developed a copper phosphoramidite catalyst system that accesses the diastereomeric anti products in the alkylative ring opening... 

Kinetic Resolution and Desynnnetrization. A variety of substituted 2-cyclohexenones are obtained in enantiomerically pure form employing chiral copper phosphoramidite catalyst for kinetic resolution (eq 5) (> 99% ee at 52% conversion, selectivity S > 200). The enantioselective desymmetrization of methylidene epoxycycloalkanes is also reported. ... 

For the transfer of arj l and alkenyl groups to enones, Hayashi s procedure, employing the corresponding boronic adds and a rhodium-BINAP catalyst, is the method of choice at present [24, 25]. For the transfer of alkyl groups to cydic enones the use of dialkylzinc reagents in the presence of copper-phosphoramidite catalysts is superior. Although the first examples of hi ly enantiosdective 1,4-ad-ditions of R Zn reagents to nitroalkenes have been reported, similar catalytic methods for numerous other dasses of a, -unsaturated compounds still need to be devdoped. 

The copper-catalysed conjugate addition process is not limited to the use of Grignard reagents and dialkylzincs. Some success has been achieved using trimethylaluminium as nucleophile and up to 97% ee has been obtained in the addition to 2-cyclohexenones using copper-phosphoramidite catalysts. ... 

For related relevant work, see a,p-unsaturated ketimines/NFIC-copper(I) catalysts [21], a,p-unsaturated imines/phosphoramidite-copper(I) catalyst [22], in situ-formed a,p-unsaturated aldimmes/phosphine-copper(I) catalysts [23], and a,p-unsaturated esters/NHC-copper(I) catalysts [24, 25],... 

In 1996, Feringa and co-workers (164) reported the use of binaphthol-derived phosphoramidite 232a as a ligand for the copper-catalyzed conjugate addition. Addition of 2 equiv of 232a to Cu(OTf)2 forms an effective catalyst for the selective... 

The presence of two ligands in the active catalyst is proposed on the basis of the optimum ligand-to-copper ratio of 2 and the nearly identical selectivities of monodentate and bidentate phosphoramidites in the 1,4-addition of Et2Zn to 2-cydohexenone [45]. 

A number of structurally very different copper complexes were employed as catalysts. The copper complex of binaphthol-derived phosphoramidite 32 and the Schiff base complex 53 (derived from salicylaldehyde and phenylglycine) gave promising results in a screening reaction between 52 and MeMgBr, and 53 was chosen as the candidate for optimization. The effect of solvent (THF or Et20),... 

Meanwhile, copper salt catalyzed asymmetric conjugate addition of dialkylzincs has been developed. Alexakis and coworkers reported the catalytic addition of diethylzinc to cyclohexenone using copper salt111. Feringa and coworkers developed a marvelous phosphoramidite (49)112. In the presence of 49 and Cu(OTf)2, diethylzinc adds to cyclohexenone in >98% . Recently, asymmetric addition of diphenylzinc using 49 has been reported113. Nowadays, compounds 50114, 51115, 52116, 53117 and 54118 are known as highly enantioselective catalysts. 

It is evident from the previous examples that most copper catalysts have been applied only to simple, unsubstituted Michael acceptors so far. Only very recently, chiral, substituted cyclohex-2-enones were used as substrates for copper-catalyzed enantioselective 1,4-additions with phosphoramidites as the chiral ligand. Thus, highly enantioselective kinetic resolutions of several 4- or 5-substituted cyclohex-2-enones were reported by Feringa and co-workers.236,236a In contrast to these Michael acceptors, the corresponding 6-substituted cyclohex-2-enones possess a stereogenic center which can be... 

Finally, when aziridines bear a 2-alkenyl substituent, they can engage in an SN2 reaction with dialkylzinc reagents using copper catalysts. Enantioselectivity can also be induced by including a chiral ligand, such as the binaphthyl phosphoramidite 174. For example, the aziridinyl cyclohexane 175 provided exclusively the trans-, 4 adduct with 83% ee upon treatment with dimethylzinc in the presence of copper(II) triflate and ligand 174 <03TL8559>. 

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