Carboxylic acids oxypalladation

The unsaturated hydroxy carboxylic acid 152 was converted to the dilactone 153 via domino oxypalladation and carbonylation [63]. The y-lactone 156 was prepared by intramolecular oxycarbonylation of the alkenediol 154. The intermediate 155 is formed by the oxypalladation, and subsequent intramolecular carbonylation affords the lactone 156. The reaction was applied to the synthesis of tetrono-mycin [64]. The oxycarbonylations of alkenol and alkanediol can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCl2, and have been applied to syntheses of a number of natural products. 

The use of other oxygen nncleophiles such as acetic acid or alcohols also results in oxypalladation. Subsequent 8-Pd-H elimination produces vinyl acetates or vinyl ethers. However, these are not necessarily the final products. When acetic acid is used as the nucleophile, ally lie acetates often become the major product. In the case of alcohols, another alcohol reacts with the resulting vinyl ether to give an acetal (Scheme 2). Focusing on such product compositions, the oxypalladation of alkenes with carboxylic acids and alcohols followed by dehydropalladation is described here. 

D. OXYPALLADATION OF ALKYNES WITH CARBOXYLIC ACIDS AND ALCOHOLS... 

In summary, oxypalladation of unsaturated carbon-carbon bonds followed by Pd—H elimination has been studied extensively with aUcenes using carboxylic acids and alcohols, but not much with alkynes. The chirality generated by this type of... 

The oxidative addition reactions to alkenes promoted or catalyzed by PdCl2(CH3CN)2 have been classified based on the nature of the attacking species. Oxygen nucleophiles such as water, alcohols and carboxylic acids undergo oxypalladation, while ammonia, amines and their derivatives are typical nucleophiles for aminopalladation. Carbopalladation with active methylene compounds is also discussed The palladium-catalyzed intramolecular hetero- and carbopalladation of olefins is extensively used as the ring-forming step in the synthesis of a variety of heterocyclic and carbocyclic systems, and representative examples are provided. 

Thereafter, a serial of palladium-catalyzed intramolecular C-ff activation of allylic C-H bonds (Scheme 2.4) was reported by White [9], who first developed a novel route for accessing chiral syn-l,2-amino alcohols enabled through the discovery of a Pd/sulfoxide-catalyzed diastereoselective allylic C-H activation reaction of chiral homoallylic Af-tosyl carbamates. The author discovered that the addition of bis-sulfoxide ligands (L-1) to Pd(OAc)2 promoted allylic C-H cleavage of a-olefins versus oxypalladation in the presence of weak oxygen nucleophiles (i.e., carboxylic acids). Evidences presented that the mechanism proceeds via Pd(ll)/sulfoxide-promoted allylic C-H cleavage to furnish a n-allylic palladium intermediate followed by counterion-promoted functionalization with the tethered Af-tosyl carbamate nucleophile. 

The palladium(II)-catalyzed olefin carbonylation reaction was first reported more than 30 years ago in studies by Stille and co-workers and James et al. The reaction of carbon monoxide with cis- and tra 5-but-2-ene in methanol in the presence of palladium(II)-chloride and copper(II)-chloride yielded threo- and eryt/zro-3-methoxy-2-methyl-butanoate, respectively. The transformation that was based on the well-known Wacker process for oxidation of ethylene into acetaldehyde in water " is now broadly defined as the Pd(II)-catalyzed oxycarbonylation of the unsaturated carbon-carbon bonds. This domino reaction includes oxypalladation of alkenes, migratory insertion of carbon monoxide, and alkoxylation. Since the development of this process, several transformations mediated by palladium(II) compounds have been described. The direct oxidative bisfunctionalization of alkenes represents a powerful transformation in the field of chemical synthesis. Palladium(II)-promoted carbonylation of alkenes in the presence of water/alcohol may lead to alkyl carboxylic acids (hydrocarboxylation), diesters [bis(aIkoxycarbonyla-tion)], (3-alkoxy carboxylic acids (alkoxy-carboxylation), or (3-alkoxy esters (alkoxy-carbonylation or alkoxy-alkoxy-carbonylation). Particularly attractive features of these multitransformation processes include the following ... 

The Pd-catalyzed coupling reaction of the propargyl acetate 53 and 4-pentynoic acid (54) in the presence of potassium bromide produced the unsaturated exo-enol lactone 55 [66], The reaction proceeded via oxypalladation of the triple bond of 54 with an allenylpalladium intermediate, which was formed from Pd(0) and 53 and the carboxylate as shown in Scheme 3.30. 

The unsaturated exc-enol lactone 175 was obtained by the coupling of the propargylic acetate 172 with 4-pentynoic acid (173) in the presence of potassium bromide using tris(2-furyl)phosphine (TFP) as a ligand (Scheme 11-47). Oxypalladation of the triple bond of 4-pentynoic acid (173) with allenylpalladium and the carboxylate as shown by 174 is the first step, and the subsequent reductive elimination affords the lactone 175. The E olefinic bond is formed because the oxypalladation is a trans addition [42]. 

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