Wacker process natural products synthesis

The Wacker reaction is an important process at the industrial level but several applications of related reactions have been reported in natural products synthesis. 

When Wacker-type reactions are performed under a CO atmosphere, the (3-H elimination pathway can be suppressed in favor of CO insertion and subsequent nucleophilic cleavage of the acyl metal species.399 This alkoxycarbonylation process has found widespread utility, particularly in the synthesis of five- and six-membered oxacyclic natural products. For example, the THF core of tetronomycin was prepared by the Pd-catalyzed alkoxycarbonylation of 4-alkenol derivatives (Equations (117) and (118)), where stereocontrol was achieved by utilizing either the directing ability of a free hydroxyl or the conformational bias imposed by a bulky silyl ether.420 Additional examples making... 

Studies in the laboratory of M. Shibasaki toward the total synthesis of garsubellin A led to the stereocontrolled synthesis of the 18-ep/-tricyclic core of the natural product/ During the final stages of the synthetic sequence, the tetrahydrofuran ring was installed using a Wacker-type process. The reaction conditions insured that the acetonide protecting group was first removed and the Cl 8 secondary alcohol moiety served as the internal nucleophile to form the tricyclic product. 

Another prototypical example of the application of intermolecular oxypalladation to the synthesis of natural products and related compounds is shown in Scheme 3. Unlike the Wacker oxidation of alkenes to give ketones, the conversion of alkynes to ketones is a net nonredox process involving hydration of the triple bond. It should also be clearly noted that the observed high regioselectivity can most readily be explained in terms of intramolecular oxypalladation involving anchimeric participation by the cyclopentanone moiety followed by hydrolysis. 

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