Organozinc compounds, coupling with

An organozinc compound that occupies a special niche in organic synthesis is iodo-methylzinc iodide (ICH2ZnI). It is prepared by the reaction of zinc-copper couple [Zn(Cu), zinc that has had its surface activated with a little copper] with diiodomethane in diethyl ether. 

Organozinc compounds are also useful in palladium-catalyzed coupling with aryl and alkenyl halides. Procedures for arylzinc,156 alkenylzinc,157 and alkylzinc158 reagents have been developed. The ferrocenyldiphosphine dppf has been found to be an especially good Pd ligand for these reactions.159... 

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 cross-coupling reaction of thiomethylpyrimidines 99 with organozinc compounds 100 in the presence of palladium was found to produce pyrimidines 101 in good to excellent yields <00SL905>. 

Recent notable improvements by Knochel and co-workers include iron-catalyzed cross-coupling reactions of various acid chlorides 148 with dialkylzinc reagents (Equation (24))324 as well as the iron-catalyzed arylation of aroyl cyanides 149 with Grignard reagents (Equation (25)).3 5 In the first case Knochel s reaction conditions tolerate ester groups on the organozinc compounds, while in the latter case ester, aryl alkyl ether, cyano, and chloro functionalities on the aromatic moieties are compatibles with the reaction conditions. 

Carbon dioxide instead of aldehydes can be involved in Ni(0)-promoted reductive coupling reactions (Equations (76) and (77) Scheme 90).434,434a 434c A stoichiometric amount of Ni(COD)2/DBU reacts with C02 and dienes, alkynes, or allenes to afford a metallacycle intermediate. This metallacycle reacts with organozinc compounds or aldehydes in one-pot to give carboxylic acid derivatives. As shown in Scheme 90, double carboxylation occurs in the presence of dimethylzinc, where the stereochemical outcome is opposite to that of the reaction with diphenylzinc. 

Some synthetically important allenylmetallics, such as allenylzinc and allenylin-dium reagents, are prepared from allenylpalladium intermediates. These reactions are discussed in appropriate sections of this chapter. This section covers the reactions of allenylpalladium compounds without further transmetallation. Allenylpalladium complexes can be prepared from propargylic halides, acetates, carbonates, mesylates, alcohols and certain alkynes [83-87], The allenylpalladium compound prepared from 3-chloro-3-methyl-l-butyne has been isolated and characterized spectroscopically (Eq. 9.106) [83], It was found to couple with organozinc chlorides to produce homologated allenes quantitatively (Eq. 9.107). 

The reactivity of these organozinc compounds depends on the experimental protocol. The coupling reaction of these compounds with various substrates is thus more efficient when the organozinc compound is prepared in the presence of the substrate. This suggests the formation of an R—Zn intermediary species which would be more reactive than the classical organozinc compound RZnX. 

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). 

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