Copper allylic alkylation

The Ag complex 121 in the presence of CuCl H O or CuCOTO CgHg catalyses the allylic alkylations of allyl phosphates by diaUcylzinc reagents with high enantiose-lectivity (Scheme 2.23). A copper complex 122 which is the precursor to the catalytic species was also isolated and structurally characterised (Figs. 2.21 and 2.22) [99]. 

Copper-catalyzed Asymmetric Allylic Alkylations with Alkylzinc Reagents 403... 

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

In light of these significant challenges, Evans and Leahy reexamined the rhodium-catalyzed allylic alkylation using copper(I) enolates, which should be softer and less basic nucleophiles [23]. The copper(I) enolates were expected to circumvent the problems typically associated with enolate nucleophiles in metal-allyl chemistry, namely ehmina-tion of the metal-aUyl intermediate and polyalkylation as well as poor regio- and stereocontrol. Hence, the transmetallation of the lithium enolate derived from acetophenone with a copper(I) hahde salt affords the requisite copper] I) enolate, which permits the efficient regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of a variety of unsymmetrical acychc alcohol derivatives (Tab. 10.3). 

Tab. 10.3 The scope of the regioselective rhodium-catalyzed allylic alkylation with copper(l) enolates.

Compared to the enantioselective allylic alkylation using soft nucleophiles, the reaction with Grignard reagents has received much less attention. The first enantioselective copper-catalyzed allylic alkylation with alkylmagnesium reagents was reported in 1995 by the groups of Backvall, van Koten and coworkers (Scheme 13). ... 

The utility of the copper/Taniaphos-catalyzed allylic alkylation was further illustrated in two subsequent reports. The application of aliphatic allylic bromides containing protected alcohols and amines leads to the efficient synthesis of bifunctional building blocks (Scheme 15) . ... 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

A regio- and stereocontrolled copper catalyzed allylic alkylation has been recently reported [219]. With the thiophenolate copper catalyst 150, the Grignard-coupling reaction provided only the y-allylated product in quantitative yield, albeit with modest enantioselectivity (Eq. 8E.33). 

Asymmetric allylboration, characteristics, 9, 197 Asymmetric allylic alkylation, allylic alcohols with copper, 11, 99 with iridium, 11, 105 with molybdenum, 11, 109 with nickel, 11, 102 with non-palladium catalysts, 11, 98 with platinum, 11, 103 reaction systems, 11, 112 with rhodium, 11, 104 with ruthenium, 11, 108 with tungsten, 11, 111... 

Figure 2.10 Allylic alkylation using copper complexes with functionalised NFIC.

Copper-catalyzed asymmetric allylic alkylations with organometalUc reagents used for small-ring openings, such as epoxides and aziridines, have gained interest. Illustrating... 

Copper salts such as CuCN, CuBr-SMc2 and CuCN-2LiCl were demonstrated to mediate the regioselective allylation, alkylation, and propargylation of the lithium anion of n-butylthiooxazole 128 providing 2,5-disubstituted systems 129. Desulfurization with deactivated W2-Raney nikel produced 5-substituted derivatives <03TL7395>. 

Evans and Leahy reported on a method for the rhodium-catalyzed allylic alkylation using copper enolates, generated by transmetalation of the corresponding lithium enolates (equation 19). These enolates are softer and less basic nucleophiles than lithium enolates and therefore problems typically associated with enolate nncleophiles in metal-allyl chemistry can be avoided. A copper(I) enolate, derived from acetophenone derivative 63, was used as nucleophile in a regio- and stereoselective rhodinm-catalyzed alkylation of the in situ activated allylic alcohol 62. Thereby, the synthesized ketone 64, a key intermediate in the total synthesis of (—)-sugiresinol dimethyl ether (65), was produced as the only detectable regioisomer with complete conservation of enantiomeric excess. 

Copper-catalyzed enantioselective allylic alkylation ring-opening reactions of oxiranes (and aziridines) with alkyl metals (e.g., dialkylzincs) has been reviewed by Pineschi <2004NJC657>. 

Chelucci, G., Muroni, D., Pinna, G. A., Saba, A., Vignola, D. Chiral 2-(2-phenylthiophenyl)-5,6,7,8-tetrahydroquinolines new N-S ligands for asymmetric catalysis. Palladium-catalyzed allylic alkylation and copper-catalyzed cyclopropanation reactions. J. Mol. Catal. A Chemical 2003, 191, 1-8. 

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