Copper organozinc reagents

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

Lack of cooling during preparation of the Simmons-Smith organozinc reagent caused the reaction to erupt. The possibly pyrophoric nature of organozinc compounds and the presence of ether presents a severe fire hazard [1]. An alternative, safer method of activating the zinc for the reaction involves use of ultrasonic irradiation rather than the copper-zinc couple [2]. 

The presence of Cu(i) or Cu(n) salts in the aforementioned reactions is critical. It is believed that organozinc reagents undergo transmetallation with copper species to yield more reactive complexes.301 A proposed301 catalytic cycle (Scheme 118) suggests that the alkyl group transferred to the enone from the copper metal in a bimetallic intermediate 207. 

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. 

The related zinc cuprates formed from diorganozinc reagents and copper(I) cyanide also undergo smooth SN2 substitution reactions with propargyl oxiranes in the presence of phosphines or phosphites (Scheme 2.12). These transformations can also be performed with catalytic amounts of the copper salt since no direct reaction between the organozinc reagent and the substrate interferes [31, 34], and therefore should also be applicable to functionalized organozinc compounds. 

Copper-Catalyzed Conjugate Addition of Functionalized Organozinc Reagents to a,p-Unsaturated Ketones Preparation of Ethyl 5-(3-Oxocyclohexyljpentanoate. 

Scheme 6.42. Copper-catalyzed allylic substitution of mesylate 197 with an organozinc reagent.

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

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. 

I 7 Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents Tab. 7.4. Conjugate additions to 2,5-cyclohexadienone monoacetals and ethers. 

For enantioselective copper catalyzed addition of organozinc reagents to imines, see [97-116]. Enantioselective Ni-catalyzed alkyne, imine, triethylborane 3-component coupling has been reported, but modest selectivities (51-89% ee) are observed. For this method, vinylation is accompanied by ethyl transfer [149]... 

---