Acylpalladation alkynes

Coperet C, Negishi E (2002) Intramolecular Acylpalladation Intramolecular Acylpalladation Reactions with Alkenes, Alkynes, and Related Unsaturated Compounds. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 2519... 

Yet another important development in the area of Pd-catalyzed carbonylation is the development of acylpalladation and related carbonyl-Pd bond addition reactions. Acylpal-ladation may be defined as a process of acyl-Pd bond addition to alkenes and alkynes. Clearly, it is a kind of carbopalladation reaction. For practical reasons, however, it is discussed in Part VI together with other carbonylation reactions mentioned above. Tsuji and Hosaka " reported in 1965 what appears to be the first example of the perfectly alternating alkene-CO copolymerization (Scheme 8). Independently, Brewis and Hughes reported also in 1965 a Pd-catalyzed cyclic carbonylation of dienes with CO and methanol (Scheme 9). Although the exact mechanism of the initiation is unclear, these reactions... 

VI.4.1.1 Intramolecular Acylpalladation Reactions with Alkenes, Alkynes, and Related Unsaturated Compounds... 

All of the acylpalladation processes discussed above involve interaction of acylpalladium bonds with C=C bonds. The corresponding acylpalladation of C C bonds proved to be rather elusive. Thus, for example, attempts to observe cyclic acylpalladation of alkyne-containing iodobenzenes totally failed, even though the corresponding alkene derivatives undergo cyclic acylpalladationt (Scheme 23). The contrasting behavior of alkene and alkyne substrates is also schematically summarized in Scheme 23. 

A few bona fide examples of acylpalladation of alkynes were finally observed, as shown in Scheme 24.The hrst eqnation provides an example of the Type 11 Ac-Pd process, while the second one represents the Type 111 Ac-Pd process. The extents to which two potentially competing processes—cyclic acylpalladation and cyclic carbopal-ladation—occnr mnst largely be a fnnction of ring size, and the generalization shown at the bottom of Scheme 24 appears to be reasonable. 

Reactions of acylpalladium complexes involving acylpalladation with arenes or formally equivalent processes have been much less exploited compared with those involving acylpalladation with alkenes or alkynes discussed in the previous section, and to the best of our knowledge, their examples are limited to intramolecular reactions. A few reactions that may include the intramolecular acylmetallation with arenes are known in the case of a rhodium catalyst, but the products are limited to a narrow range of compounds such as indenones.t In contrast, the Pd-catalyzed carbonylation of 3-arylaUyl acetates or hahdes, most typically cinnamyl acetate, involving intramolecular acylpalladation with arenes results in the construction of 1-naphthol, which is a hiding member of cyclic aromatic ketones. The outline of the conversion is sketched in Scheme 1. In fact, this type of carbonylation-cyclization reaction (cyclocarbonylation) can be applied to the synthesis of a variety of fused aromatics, which is summarized in the following subsection. 

The intennolecular acylpalladation corresponds to the addition of an acyl-palladium bond onto a rr-bond system of another molecule this elementary step can also be referred to as an insertion (Scheme I). This produces another organopalladium complex, which can in principle participate in subsequent propagation or termination reactions. This excludes processes that involve alkoxycarbonylation (R— = R O—) and hydrocarbonyla-tion (R— = H—). This section will focus on nonpolymeric intermolecular reactions of acylpalladium complexes with different 7r-bond systems (alkenes, imines, dienes, and alkynes). 

After an arduous mechanistic investigation, the following reaction mechanism was proposed (Scheme 14) (i) generation of the acylpalladium complex, (ii) addition to the alkyne (acylpalladation), (iii) insertion of another molecule of CO, (iv) addition of the acylpalladium thus formed to the adjacent ketone, and (v-vi) isomerization into an alkoxypalladium intermediate, which readily hydrolyzes to give the butenolide 1 and regenerate the Pd(0) complex. 

There are other examples of carbonylation of terminal alkynes, which involve the in-termolecular reaction of an acylpalladium complex with an alkyne moiety, but they most probably also involve carbon-carbon bond formations via cross-coupling rather than acylpalladation (Scheme 21). 

A related example is also worth noting and involves the reaction of aryl iodides or vinyl triflates with 13 nnder carbonylative conditions to give 14 (43-83% yields) along with small amonnts of 15 (Scheme 24)P This reaction can in principle proceed by either acylpalladation or electrophilic activation of the alkyne moiety. Based on the mechanistic investigation of the noncarbonylative reaction, the electrophilic activation pathway seems to be the most likely mechanism. It is, however, interesting to see that small changes in the substrate can completely change the course of the reaction. 

Overall, the carbonylation of alkynes is rather complex, but it is possible to draw a general trend and to divide these processes into three classes depending on the alkyne (i) For most internal alkynes, the carbon-carbon bond-forming process can involve an acylpalladation step whether there is an isomerization or not. (ii) However, some of them may involve an electrophilic activation of the triple bond by the acylpalladium complex followed by nucleophilic attack and reductive elimination, (iii) On the other hand, terminal alkynes appear to undergo mostly cross-coupling for the first carbon-carbon bond formation. Aside from these mechanistic intricacies, it is important to point out that these processes usually involve incorporation of more than one molecule of CO and creation of two to three carbon-carbon bonds in one reaction, and they yield heterocycles in fair to good yields. Other multiple bond systems like alkenes, imines or dienes also provide nice entries to carbo- and heterocycles. The limitations are usually due to the necessary time balance between acylpalladation and the termination step to avoid polymeric or decarbonylation processes. 

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