Organozinc compounds acylation

CoBr2 is a very efficient catalyst for acylation of organozinc compounds with aliphatic and aromatic acid chlorides,... 

Acylation of organozinc reagents. Reaction of acyl chlorides with organozinc compounds catalyzed by palladium-phosphine complexes provides a general synthesis of ketones. The organozincs are readily available by treatment of the corresponding organo-lithium with ZnCh. Alkenylzinc compounds and a,p-unsaturated acyl chlorides react with retention of the stereochemistry. Isolated yields of ketones are 55-90%. 

Organozinc compounds can be prepared by direct metallation of organic halides with zinc metal. The procedure makes the coupling reaction more convenient. A mixture of alkyl halide, acyl chloride, and zinc metal upon stirring in the presence of palladium catalyst at room temperature gives the desired ketone.f - " While direct metallation can be carried out efficiently when the zinc-copper couple is used in some cases, the presence of copper ion sometimes prevents the coupling reaction with acyl chloride.f ... 

Palladium-catalyzed coupling reactions of organozinc compounds with acyl halides are the fastest and mildest among the known methods using a variety of organometallic compounds. 

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). 

Pd-catalyzed cross-coupling reactions of organozinc compounds with alkenyl and aryl halides can be carried out under mild conditions and are the fastest among all reactions using various organometallics. The reaction with acyl hahdes is not an exception. Usually, the reaction is completed at lower than room temperature within a couple of hours [38,251 - 25 3]. As organozinc compounds are coordinatively unsaturated and sterically less bulky, the transmetallation step is facilitated [29] ... 

The Pd-catalyzed acylation of organozincs was reported in 1983144, and it has since been widely employed as one of the most satisfactory methods of acylation of organometals20. Even in cases where ,/J-unsaturated carbonyl compounds are the products, their subsequent conjugate addition reactions do not appear to be competitive. Among recent examples of its application to the synthesis of natural products, the synthesis of amphidi-nolides Tl, , T4 and T5 by Fiirstner and coworkers213 is particularly noteworthy (Scheme 81). 

Even the very efficient enantioselective catalysts used in organozinc addition reactions to carbonyl compounds failed to catalyze the corresponding addition reactions to nonactivated imines such as A-silyl-, A-phenyl-, or iV-benzyl-imines. However, enantioselective additions of diaUcylzinc compounds to more activated imines, like iV-acyl- or iV-phosphinoyl-imines, in the presence of catalytic or stoichiometric amounts of chiral (see Chiral) aminoalcohols, have been recently reported. For example, in presence of 1 equiv of (A,A-dibutylnorephedrine) (DBNE) diethylzinc reacts with masked A-acyl imines like A-(amidobenzyl)benzotriazoles, to give chiral A-(l-phenylpropyl)amides with up to 76% e.e. (equation 68). 

Organozinc addition reactions to unsaturated systems lead to an intermediate zinc compound which is in most cases further hydrolyzed to give the corresponding protonated organic compound. This intermediate can also be trapped by reaction with electrophiles (see Electrophile) (E+) such as aldehydes, acyl chlorides, organic halides, silyl halides, and so on. Depending on the nature of the electrophile (see... 

The scope of the Negishi reaction is broad, similar to that of Stille and Suzuki cross-coupling. The reaction seems to work if R = aryl, vinyl, alkynyl, acyl, allyl, benzyl, homoallyl (-CH2-CH2-CH=CH2) and homobenzyl (-CH2-CH2-Ph), or even primary alkyl, and if X = I, Br, or OTf (Cl works, but often sluggishly). Correspondingly, R = aryl, vinyl, alkynyl, allyl, benzyl, and primary alkyl. The organozinc reagent may either be used as a preformed compound, such as R2Zn... 

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