Coupling of organozinc compounds

The use of transition metal catalysts, especially those containing Pd and Ni, has converted otherwise unreactive or sluggishly reactive organozincs into highly reactive reagents for their reactivity towards various common electrophiles. This includes carbonyl addition reactions of organozinc reagents, which are catalyzed by Pd complexes. 

The coupling of organozinc reagents with thioesters in the presence of palladium catalyst is known as the Fukuyama coupling.  

The Ni-catalyzed reaction of ( )-l-aIkenylalanes and ( )-l-alkenylzirconium derivatives with aryl halides (ArX) gave the corresponding cross-coupled products in good yields, as shown in Table 5.1. 

Among all the alkenyl metals selected, Zn, Zr and A1 give best results for the Pd-catalyzed cross-coupling reactions of alkenyl metals. 

The Negishi reaction is utilized to construct substituted pyrimidines and purines. 

---

Scheme 5.2-20 Pd-catalyzed cross-coupling of organozinc compounds (Negishi cross-coupling)...

For transition metal-catalyzed cross-coupling of organozinc compounds, see the appropriate transition metal (Ni page 382, Section 20 Pd page 386, Section 21 Cu page 392, Section 22). 

The palladium-catalyzed coupling of organozinc compounds with thioesters to form ketones. This reaction tolerates a variety of functional groups due to the low reactivity of the organozinc reagents. 

R = alkenyl, aryl, allyl, benzyl, propargyl R = alkenyl, aryl, alkynyl, alkyl, benzyl, allyl The Negishi Coupling was the first reaction that allowed the preparation of unsymmetrical biaryls in good yields. The versatile nickel- or palladium-catalyzed coupling of organozinc compounds... 

The cross-coupling of organozinc compounds has been accomplished using a number of metal enolate complexes, namely Rh(acac)(H2C=CH2)2 (6) , Co(acac)3 (30) °, Ni(acac)2 (47) , Li(acac) (107) and Cr(acac)3 (108) . For instance, complex 47 proved to be an extremely effective catalyst system for the Negishi cross-coupling of arylzinc halides (109) with aryl (110), heteroaryl and alkenyl halides, triflates and nonaflates to give the corresponding biaryl compounds (111) (equation 30). The solvent played an important role in these reactions and optimal conditions were found with 8 1 mixtures of THF and A-ethylpyrrolidinone (nep). Only 0.05 mol% of the nickel complex... 

The Negishi cross-coupling reaction is the nickel- or palladium-catalyzed coupling of organozinc compounds with various halides or triflates (aryl, alkenyl, all nyl, and acyl). 

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 first examples of microwave-assisted cross-couplings with organozinc compounds were recently reported [47]. In addition, the first high-speed synthesis of aryl boronates (Suzuki coupling reactants) has been performed under the action of single-mode irradiation with an in-situ-generated palladium carbene catalyst [48],... 

The isoprenylation of isovaleraldehyde led to the product in 68% isolated yield, higher than with a conventional procedure using zinc dust in DMF, or refluxing THF. The same procedure was used for the coupling reaction of allylic bromides with aldehydes and ketones, via the preliminary formation of organozinc compounds coming from the reaction between the electrolytic zinc and allylic bromides12. 

In addition, the organozinc compound obtained from ethyl 4-bromobutanoate reacts under similar conditions to those described previously, with 4-bromoacetophenone, to give the corresponding product in good yield15. The preparation of organozinc compounds and their cross-coupling with aryl halides can be carried out in one step (equation 7). 

In all events, the activation/reduction of RX occurs at potential values higher than that observed for the Znn/Zn(s) couple. As a consequence, the electrochemical synthesis of organozinc compounds can be achieved by nickel-catalyzed processes. 

Alkenylation and Arylation of Organozinc Compounds (Negishi Couplings) and of Functionalized Organozinc Compounds... 

D. Cross-coupling Reactions of Organozinc Compounds in the Presence of... 

The past decade has seen extensive development of cross-coupling reactions of organozinc compounds and organic halides catalyzed by nickel or palladium catalysts. Although nickel-based catalysts are more reactive with respect to the organic halide partner, the number of failures with these catalysts and the greater selectivity realized with palladium-based catalysts have resulted in the almost exclusive use of the latter group of catalysts for these reactions. 

---