Pd-catalyzed acylation

Pd-Catalyzed Acylation, Cyanation, and a-Substitution of Enolates and Related Derivatives 

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 [38] has been recognized as one of the most general and satisfactory methods of organometaUic acylation reactions, which is compatible with many heterofunctional groups, as eloquently demonstrated by a 

The Pd- and Ni-catalyzed acylation have been appHed to the syntheses of a fair number of natural products as shown in Table 3.17 [257]. 

---

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. 

SCHEME 81. Synthesis of amphidinolide T1 via Pd-catalyzed acylation of an alkylzinc derivative... 

For reviews of the Pd-catalyzed acylation and other cross-coupling reactions with a-hetero-substituted organic electrophiles, see ... 

The Pd-catalyzed acylation with acylanion equivalents has been achieved using a-alkoxyalkenylzincs [111] and 1-aryliminoalkylzincs [112]. 

Various Pd-catalyzed carbonylation reactions have often been referred to as carbonyla-tive cross-coupling reactions (Scheme 4). However, these reactions involving the formation of two C—C bonds with incorporation of CO clearly display a pattern of chemical transformation that is different from Scheme 1. So, these reactions are discussed in Parts VI and VIII. On the other hand, Pd-catalyzed acylation with acyl halides and related derivatives are examples of the reaction represented by Scheme 1, where is acyl, and they are therefore discussed in this Part (Sect. III.2.12.1), even if CO may be used to prevent decarbonylation. 

An interesting variant of Pd-catalyzed homoallyl-alkenyl coupling is Pd-catalyzed acylation (Sect. III.2.12.1) followed by carbonyl oleflnation shown in Scheme... 

Scheme 3.75 A plausible mechanism of Pd-catalyzed acylation of organometals [250].

Scheme 3.76 Representative examples of Pd-catalyzed acylation of organozinc derivatives with acyl chlorides.

Scheme 3.78 Application of Pd-catalyzed acylations of alkylzinc derivatives in the synthesis of amphidinolide T1 [256].

Scheme 1.39 Pd-Catalyzed acylation with aromatic aldehydes. DG = directing group.

Scheme 2-138. Pd-catalyzed acylation reactions of organozinc reagents.

L = P(4-MeOC6H4)3, PPha, dppf, PCys Scheme 3.49 Pd-catalyzed acylation reactions with boronic acids. 

---