Amides carbopalladation

The author believed that Pd(ll)/Pd(0) process occurs via coordination of the metal center to the amide, carbopalladation, and reductive elimination to form... 

The palladium(0)-catalyzed cyclization of amide-allenes via a carbopalladation has been developed by several groups. The reaction proceeds through the carbopalladation of the allene moiety with an organopalladium species (R-Pd-X), generated by oxidative addition of R-X to palladium(O), and subsequent reductive elimination of the resultant 7r-allylpalladium intermediate.47,47a 47f... 

Various examples of intramolecular stereoselective carboamination have been reported28 "30. Asymmetric synthesis of key intermediates for capnellenols is achieved via a Heck-type intramolecular carbopalladation of an alkene with a vinyl halide and amide anion capture in the presence of Chiraphos- or BINAP-modified palladium catalysts31. 

Other possible relays are mostly alkynes, which, after carbopalladation, undergo a surprisingly clean reductive demetallation with formic acid salts (Scheme 2). At this point it is crucial that the catalyst cocktail has the appropriate composition, as yields under different conditions can vary substantially. The high degree of regioselectivity starting from propynoic acid amides has been attributed to coordination with the amide functionality. 

With specially structured alkenes, such as norbomadiene, it is feasible to observe the in-termolecular version of the carbopalladation-carbonylative lactonization tandem process, as shown in Scheme This also represents a rare example in which the termination step involves lactonization. Althongh a single example of termination by lartamiyatinn is shown in Eq. 6 of Scheme 13, there does not appear to be any example in which termination involves intermolecular amidation. 

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. ... 

A unique example of direct olefination of a cyclopropane was also disclosed by the Yu lab [21]. An electron-deficient arylamide was employed as directing group, as the previously employed oxazoline or hydroxamic acid was unreactive in the alkenylation. The proposed mechanism for the reaction involves an amide-directed C-H insertion of the Pd(II) catalyst into the cyclopropane methylene C-H bond of 9, followed by olefin carbopalladation and p-hydride elimination to provide intermediate 10 (Scheme 3a). Pd(0) is re-oxidized back to Pd(II) by Ag(I)/Cu(II), and a tandem 1,4-addition between the amide moiety of 10 and the acrylate provides the corresponding y-lactam 11 as the sole isolated product, fii the presence of an... 

Carbopalladation of dienes yields 7r-allylpalladium intennediates capable of capturing nucleophiles. An example of this type of reaction in natural product synthesis is the conversion of the aryl iodide 168 into pentacycle 169. After 6-exo carbopalladation the free phenol is captured by the resultant Tr-allylpaUadium intermediate to yield aUyUc ether 169 en route to (-)-morphine 120. The domino reaction closes a srx-membered ring, forges a quaternary center, and forms a five-membered furan ring. The reaction sequence has also been effectively reversed in a construction of (+)-y-lycorane 172. Treatment of aUylic benzoate 170 with a palladium catalyst in the presence of sodium hydride triggers tt-allylpalladium formation and intramolecular amide capture. rr-Allylpalladium formation occurs with inversion, as does reaction with the pendant amide, resulting in a net retentive 1,3-transposition of stereochemical information. Subsequent addition of base and thermolysis induces 6-exo intramolecular carbopalladation to yield alkene 171. 

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