Enantioselective carbopalladation

The syn addition of the adducts suggests a mechanism different from that observed in rhodium-catalyzed alcoholysis and aminolysis reactions. Mechanistic investigations from the Tautens laboratory have revealed that the most likely mechanism involves an enantioselective carbopalladation followed by a (3-alkoxide elimination to afford the ring-opened product." ... 

Based on a /rarcr-acetoxypalladation of the triple bond, Lu has developed a highly enantioselective (up to 87% ee) synthesis of 7-butyrolactones with Pd(n) catalysis (Scheme 73).280 Following the initial /ra/w-acetoxy-palladation, a plausible mechanism for this sequence involves an intramolecular carbopalladation of the pendant olefin, and deacetoxypalladation instead of the common /3-hydride elimination in the final step. 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Negishi E, Wang G, Zhu G (2006) Palladium-Catalyzed Cyclization via Carbopalladation and Acylpalladation. 19 1-48... 

A highly enantioselective intramolecular AHR of the cyclohexadienone 322 to give 324 with 96% ee in 100% conversion was carried out using the chiral phosphoamidite-type ligand (III-IO), which is monodentate. The stereogenic center was not created at the site of C—C bond formation, but instead the cyclohexadienone was desymmetrized. The use of Cy2MeN as a base gave the best result. It should be added that the carbopalladation product 323 has no jS-H syn to Pd, and hence the cyclized product 324 was formed by syn y3-H elimination after epimerization [132]. 

With 1,1-disubstituted alkenes, diastereoselective and/or enantioselective cycUc carbopalladation can, in principle, be achieved. Whereas the latter has not yet been demonstrated for the cyclic carbopalladation-carbonylative termination processes, its diastereoselective version promises to provide an attractive method for the synthesis of chiral natural products. 

An example of the use of an intermolecular carbopalladation in complex molecule synthesis is the preparation of a PAF (platelet activating factor) antagonist (Scheme 11). In the key step, an intermolecular Heck reaction of 2-naphthyl triflate with 2,3-dihydrofuran 71 yields 2-naphthyl-2,3-dihydrofuran 72 in 52% yield with excellent enantioselectivity. The reaction presumably occurs via the cationic manifold and the alkene is isomerized by a hy-dropalladation/dehydropalladation reaction. The minor product 2,5-dihydrofuran 73 is obtained in 26% yield with modest enantioselectivity favoring the opposite absolute configuration at the key center. Critical to the reaction is the use of the sterically demanding and highly basic proton sponge [l,8-bis(dimethylamino)naphthalene] as the base. It is... 

The final step in a reaction sequence after a carbopalladation can also be ctqtture on an acetate anion, or carbon monoxide followed by another nucleophile. ° f The former reaction in an enantioselective version has been used to prepare the key intermediates 34 and 36 en route to the sesquiterpene capnellenol (Scheme 10), but with moderate... 

In 2007, Ln s group developed a cationic Pd(II)-catalyzed elegant carbopalladation of alkynoates 108 using arylboronic acids followed by enantioselective intramolecular addition to ketones of the resulting vinylpalladinm species [45] (Scheme 6.27). 

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