Carbopalladation alkenyl ethers

The nature of the alkene is important in determining reactivity. Indeed, electron-rich alkenes such as enamides, enoenamides, and alkenyl ethers are notably more reactive to carbopalladation. 

In the carbopalladation of alkenyl ethers it was found that stabilized carbanions added regioselectively to 2,3-dihydrofuran. When treated with PdCl2(MeCN)2 and 2 equiv of EtsN in 1 1 THF/DMF at room temperature (r.t.), addition at the oxygen-bearing carbon is observed along with migration of the double bond. This latter phenomenon appears to be the result of a series of elimination and readdition cycles by Pd—H (Scheme 4). 

As with alkenyl ethers, carbopalladation of enamidesf " takes place exclusively at the a-position. The j8-lactam 13, an intermediate in the synthesis of ( )-thienamycin 14, has been synthesized by this method with subsequent carbonylation by CO and MeOH (Scheme 9). 

Tietze and coworkers [60] observed a combination of a Heck reaction and a C-H-activation by treatment of the alkyne 6/1-111 with Pd°. These authors aimed at compound 6/1-112, but 6/1-110 was obtained as a single product in high yield (Scheme 6/1.29). It can again be assumed that after oxidative addition a cis-carbopalladation of the triple bond takes place to give an alkenyl Pd intermediate which undergoes the C-H-insertion into the neighboring naphthalene and not into the aryl ether moiety. 

Side chain introduction by carbopalladation has been utilized in a total synthesis of an-thramycin methyl ether (32) (Scheme Heck reaction of the alkenyl triflate 30 with acrylamide installs the necessary three-carbon chain in moderate yield. The desired alkene geometry and oxidation state are observed in the dienamide 31 with no need for protection of the primary amide. The organopalladium precursor can also be part of the side chain being introduced as illustrated in a synthesis of prostaglandin E2 33. ... 

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