Pd-catalyzed Cope rearrangement

A chelation-assisted Pd-catalyzed Cope rearrangement was proposed in the reaction of phenanthroline to generate isoquinolinone derivatives (Eq. 12.78).177 The use of aqueous media and ligands enables a double-Heck reaction on a substrate favoring alkene insertion over (J>-hydride elimination. 

Although the sulfonamide 7 appears to be prochiral, in fact its two most stable conformations are bent, and enantiomers of each other, with a significant barrier for interconversion. Katsuhiko Tomooka of K oishu University separated Tetrahedron Lett. 2008, 49, 6327) the enantiomers of 7, then carried the enantiomercially-pure 7 on, by Pd-catalyzed Cope rearrangement, to 8 and so to (-)-Kainic Acid 9. 

The rearrangements of various allylic compounds catalyzed by both Pd(II) and Pd(0) are treated in this section[491]. Related reactions such as the Carroll rearrangement are treated in Section 2.10.1 and the Pd(II)-catalyzed Cope rearrangement is treated in Chapter 5, Section 3. 

The mechanism of the PdCh-catalyzed Cope rearrangement has been studied by use of the partially deuterated 1.5-diene 53[46], The coordination of Pd(II) activates the alkene, and cyclization (carbopalladation) takes place to... 

Several transition metal ions and complexes, especially Pd(II) salts, have been found to catalyze Cope rearrangements.207 The catalyst that has been adopted for synthetic purposes is PdCl2(CH3CN)2, and with it the rearrangement of 14 to 15 and 16 occurs at room temperature, as contrasted to 240° C in its absence.208 The catalyzed reaction shows enhanced stereoselectivity and is consistent with a chairlike TS. 

Pd(II)-catalyzed Cope rearrangement [225] occurs at room temperature, via chairlike transition states. A plausible mechanism is cyclization-induced rearrangement. Both the addition and fragmentation steps are assisted by the introduction and removal... 

Cope rearrangement (10, 31). The Pd(II)-catalyzed Cope rearrangement of chiral 1,5-dienes occurs with virtually complete 1,4-transfer of chirality.1 Example ... 

In this latter reaction mode, which is observed much more rarely than /3-dehydropal-ladation, a wide variety of ligands can be coupled to each other with the formation of new C—C, C—H, C— N, C—O, and C—Hal bonds. This section does not cover the numerous cascade couplings in which a number of successive intramolecular additions of 2 onto double bonds is eventually completed by /3-dehydropalladationt as well as the numerous [2 -I- 2 -I- 2] and [4 + 2] cyclotri- and cyclodimerizations of alkynes, enynes, and related compounds. " The Pd(0)-catalyzed Cope rearrangement also will not be considered here, as it proceeds via bis(i7 -allyl)palladium(ll) intermediates. The carbopalladation reactions of aUenes, which have been reviewed recently, are covered in Sect. IV.7. (For new examples see also refs. [10]-[12]). On the other hand, the numerous Pd-catalyzed formal [3 + 2] cycloadditions of trimethylenemethane (TMM) complexes may be classified as carbopalladations of alkenes without subsequent dehydropalladation. As the subject of this section has partially been covered in several newly published reviews, " the attention here will be on the most recent and interesting communications. 

Discovered in 1966/ " the Pd(II)-promoted" and Pd(II)-catalyzed " Cope rearrangement has become an important tool in synthetic endeavors. Catalysis of the Cope rearrangement by palladium salts such as PdCl2 provides rate enhancements as high as 10 while also offering higher levels of stereoselectivity than their thermal counterparts.In one of the early examples described by Overman, a predominant contributor in this area, 72 was smoothly converted to 73 in the presence of PdCl2(PhCN)2 at room temperature." ... 

The Pd(Il)-catalyzed Cope rearrangement has been applied extensively in synthetic efforts. One example which warrants mention is the... 

Another recently reported variant of the palladium catalyzed Cope rearrangement utilizes Pd(0) to effect the transformation. In this case, the reaction is presumed to proceed through a bis-(ri -allyl)Pd(II) intermediate via insertion of Pd(0) into a non-strained C-C bond. 

Pd(ll)-catalyzed Cope rearrangement most probably proceeds through a Pd-bound six-membered carbenium ion intermediate to afford the [3,3] rearranged products. A donor substituent is required at either C-2 or C-5 of 1,5-dienes for the rearrangement in order to stabilize the carbenium cation. 

Pd(0)-catalyzed Cope rearrangement proceeds through a bis(7r-allyl)palladium(II) intermediate to afford the [1,3] and [3,3] rearranged products. The electron-withdrawing groups are required at the allylic position of 1,5-dienes to stabihze the bis(7r-allyl)palla-dium(II) intermediate, which is generated by the oxidative insertion of Pd(0) into the C—C cr-bond. 

In a clever application of the hetero-Cope rearrangement, Martin used a Pd-catalyzed coupling of W-arylhydroxamates 362 with vinyl acetate to set up the [3,3] sigmatropic rearrangement 363 to 364 and final cyclization 364 to 365 [432-435]. Applications of this novel indole ring... 

The dissociative mechanism of the Cope rearrangement casually mentioned above222 can be illustrated by two examples of Pd-catalyzed reactions. The migration of an allyl group from carbon to carbon in the pyridine system 466 occurs in the presence of a Pd° catalyst236. Refluxing dilute solutions of precursors 466 (R1, R2 = H, Me) in toluene for 7 h or in n -heptane for 24 h gave derivatives 468. The pyridine allyl ether 469 was also... 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

Aza-Cope rearrangement.7 This reaction proceeds readily when catalyzed by Pd(0) and a strong protic acid, particularly trifluoroacetic acid or methanesul-fonic acid. This isomerization is involved in a direct synthesis of S,e-unsaturated imines from allylamines with carbonyl compounds (equation I). The unsaturated... 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

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