Organozincs acylation

Reactions of Organozinc Reagents with Acyl Halides, Anhydrides, and Other... 

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

Scheme 2.42. Synthesis of 2-substituted indoles by acylation of functionalized organozinc reagents.

In 1997, Dunn and Jackson reported on a new approach to the synthesis of di- and tripeptides with unnatural amino acids by converting di- and tripeptides into organozinc reagents and coupling them with aryl iodides or acyl chlorides in the presence of Pd2(dba)3 and either PPhs or P(o-tol)3 under mild reaction conditions, with no loss of optical purity. " The synthesis of jS- and y-amino acids in an analogous fashion was reported shortly after (Scheme 12). " ... 

SCHEME 115. Palladium-catalyzed acylation reactions of organozincs... 

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). 

A few interesting variants of the Pd-catalyzed acylation of organozincs have been developed. In one such variant, thiol esters are employed in place of acyl chlorides214. Another is the Ni-catalyzed reaction of organozincs with cyclic anhydrides215 shown in Scheme 82. this desymmetrization reaction can be made highly enantioselective, it would become a significant tool for asymmetric synthesis. 

The acylpalladium is formed by CO insertion as the intermediate of the carbonylation. They can be prepared directly by the oxidative addition of acyl chlorides to Pd(0). Thus ketones can be prepared by the reaction of acyl halides with organozinc reagents and organostannanes. Benzoacetate (490) is obtained by the reaction of benzoyl chloride with the Reformatsky reagent 489 [243], The macrocyclic keto lactone 492 is obtained by intramolecular reaction of the alkenylstannane with acyl chloride in 491 [244]. 

Organozinc halides and diorganozincs can be successfully acylated and ally-lated using catalytic ammounts of transition metal salts like CoBr2, FeCl3.25 With trisubstituted double bonds, the substitution reaction occurs with Sn2 selectivity and complete retention of the double bond geometry (Scheme 10.10).25... 

Table 11.2 Pd catalysed reaction of organozincs with acyl chlorides ...

Palladium catalysed acylation of organozincs preparation of S-nonyn-2-one45... 

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