Dehydropalladation intramolecular reactions

The complexity of this reaction scheme already points out the necessary time-balance between oxidative addition, CO insertion versus deinsertion (decarbonylation), acylpalladation, carbopaUadation, and dehydropalladation events to have a selective acylpallada-tion-type reaction. This has been more recently addressed by selecting acyl chlorides that could not readily undergo dehydropalladation, hence stabilizing the organopalladium intermediates to favor their intramolecular reaction with alkenes. For instance, Pd(OAc)2 catalyzes the reaction of benzoyl chloride derivatives with enol ethers (R = OEt, Scheme 3) to give the corresponding acylpalladation products typically in 40-77% yields. " ... 

Domino or cascade reactions provide valuable approaches, especially to various carbo- and heterocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, inter-intra-, as well as all-intramolecular reaction cascades, hi this section, the termination of these processes by alkenes, arenes, and related ir-bond systems such as alkynes and allenes will be described. A cascade Heck reaction is considered to consist of an oxidative addition of a heteroatom-carbon bond to palladium (starter), carbopalladation of a nonaromatic carbon-carbon double or triple bond without immediate dehydropalladation (relay), one, two, or more fimher car-bopalladation(s) of a carbon-carbon double or triple bond, and eventually ensuing dehydropalladation. Crucial for a cascade reaction of this kind to occur is the blockage or retardation of a dehydropalladation at one of the intermediate stages by using 1,1-disubsti-tuted alkenes and appropriately substimted cycloalkenes, bicycloalkenes, or alkynes as relays since they give kinetically stable alkyl- or alkenylpalladium intermediates, respectively. 

A different reaction mode was observed in the Pd-catalyzed co-cyclization of the 2-bromo-l-en-6-yne 76 and 4-octyne 77. After an intramolecular carbopalladation of the triple bond in 76, the formed alkenylpalladium bromide carbopalladates 77 and this is followed by another intramolecular carbopalladation or 67r-electrocyclization and dehydropalladation to yield the oligosubstituted indane derivative (Scheme 22). ... 

In more complex reaction cascades an additional alkyne-insertion step can occur. Thus starting with intramolecular carbopalladation of a vinyl iodide to a carbon-carbon triple bond, followed by two intramolecular alkene-insertion steps and termination with dehydropalladation, a palladium-catalyzed synthesis of l-(5 -methylbicyclo[3.1.0]hex-T-yl)-5,5-bis(carboethoxy)cyclo-hexadiene (52) starting from l-iodo-4,4-bis(carboethoxy)-ll-methyldodeca-l,ll-dien-6-yne (51) is achieved. ... 

Similar reaction sequences have been used in the synthesis of the vitamin D system103-108 and other polycyclic ring systems109 -113. Instead of carbanion capture of an alkyne-carbapalladation adduct, a subsequent insertion of an unsaturated unit also leads to dicarborative addition to alkynes. If used in intramolecular versions, polycyclic products are obtained61-63,114. In some cases more complicated cyclopropane formations are involved in these conversions if further insertions can lake place before dehydropalladation occurs45 64. 

A similar reaction of Ar-allyl-Ar-(2,3-allenyl)mesitylenesulfonamides 79A with aryl halides in dioxane afforded c/s-2-alkyl-3-(r-arylethenyl)-4-meth-ylenepyrrolidines 86 via carbopalladation-stereoselective intramolecular car-bopalladation-dehydropalladation (Scheme 41) [28]. Here the diastereose-lectivity may be determined by the unfavorable steric interaction between the pseudoaxial hydrogens and the aromatic group in intermediate 88, which would lead to the formation of the trans product 86 (Scheme 42). This chemistry has been extended to the carbon-tethered allenenes 89 (Scheme 43) [28]. In cases of more substituted C=C bonds, further cyclization with the aromatic ring from Arl was observed to afford fused tricyclic products 91 or tetracyclic products 92 (Scheme 44) [29]. 

Intramolecular amination of A/, AT-dimethylhydrazone of o-chlorophenylacetal-dehyde (73) offers a facile synthetic method of indoles. 1-Aminoindole 75 was prepared by intramolecular arylation of 73. For this reaction, (ferrocenyl)amino-phosphine VIII-3 was a better ligand than P(f-Bu)3. Al,Al-dimethylhydrazones have no hydrogen to be displaced, and the arylation is explained by isomerization to the enamine form 74. Another possibility may be insertion of C=N bond to Ar-Pd bond, followed by dehydropalladation. Similarly, the quinoline 77 was obtained by intramolecular amination of 2,6-dichlorophenylpropionaldehyde N,N-dimethylhydrazone (76) [55]. 

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. 

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