Intramolecular palladium-catalyzed allylic

The allylic chloride offers a useful dual control of stereoselectivity in the allylic substitution since the chloride can be replaced with either retention (via a Pd(0)-catalyzed reaction) or inversion (via a nornial 8 2 reaction or a Cu(I)-catalyzed reaction). This was used in cyclic systems to obtain stereoselective cis- and rra72.s-annulation reactions [86,87]. The reaction starts with the transformation of cyclohexa-1,3-diene to cis- and trans-62 via chloroacetate 58 (Scheme 8-21) [78,88]. Subsequent transformation of cis- and trans-62 to cis- and trans-63, respectively, followed by an intramolecular palladium-catalyzed allylic substitution (syn) afforded the cis- and franj-annulated products [86]. 

This one-step transformation of an alkene to an allylic acetate compares well with other methods of preparation such as hydride reduction of a, 8-unsaturated carbonyl compounds followed by esterification. The scope and limitations of the reaction have been investigated. The allylic acetoxylation proceeds via a TT-allylpalladium intermediate, and as a result, substituted and linear alkenes generally give several isomeric allylic acetates. With oxygen nucleophiles the reaction is quite general, and reactants and products are stable towards the reaction conditions. This is normally not yet the case with nitrogen nucleophiles, although one intramolecular palladium-catalyzed allylic amination mechanistically related to allylic acetoxylation has been reported. ... 

In the last synthesis from this series,the (5)-conhgured a-hydroxyphosphonate building block 70 was required (Scheme 47.17). In this case, the desired carbonate could be obtained directly from the enzymatic kinetic resolution as it was the unreactive enantiomer. The synthesis involved similar key steps as before, namely, a cross metathesis, followed by a stereospecific intramolecular palladium-catalyzed allylic substitution that furnished the furan ring in 78. In contradistinction to the previous syntheses, the phosphonate group was not removed by ozonolysis, but instead it was employed in the Wittig reaction, to produce fragments 80 and 81 for the synthesis of amphidinolides F and C. 

Syn- and ft -l,5-allylic diols 224 undergo stereospecific intramolecular palladium-catalyzed cyclizations to afford syn- or //-2,6-disubstituted 3,6-dihydropyrans the stereochemistry of the 3,6-dihydropyran product is defined by that of the starting diol (Scheme 64) <2005TA1299>. 

Scheme 14 A domino of twofold palladium-catalyzed allylation and reductive intramolecular cross-coupling reaction with subsequent cycloaddition [65]...

A one-pot procedure for the palladium-catalyzed allylation/cyclization of o-alkynyltrifluoroacetanilides 57a [57] and o-alkynylphenols 57b [58] was developed by Cacchi et al. (Scheme 20). This method provides a valuable tool for the synthesis of 2-substituted-3-allylindoles 58a and 2-substituted-3-allylbenzofurans 58b. It was reported that reaction proceeded through the formation of X-allyl derivatives, which form 7r-allylpalladium species 59. A subsequent rearrangement of 59 would then lead to the 7r-allylpalladium species 60. Intramolecular nucleophilic attack of the hetero atom across the activated carbon-carbon triple bond in 60, followed by reductive elimination of Pd(0) gives the products 58. A similar reaction was reported by Balme et al. [59]. 

Palladium-catalyzed allyl rearrangements can be considered special cases of allyl substitutions that occur intramolecularly. Hence, via the forma-... 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

Due to the insolubility of anions in BTF (see Sect. 3.8), a palladium catalyzed allylic substitution reaction using the malonate anion [67] could not be tried. However, an intramolecular version using tosylcarbamate as nucleophile (11.4)... 

A palladium-catalyzed allylation of indoles with allyl carbonates furnished 3-alkylated indoles <04OL3199>. An intramolecular variation with indolyl carbonates provided a novel synthesis of tetrahydro-p-carbolines and pyrazinoll,2-a indoles. 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The palladium-catalyzed allylation takes place with retention of the configuration [76] and requires the cis-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of 0-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

More recently, Alper and colleagues described a convenient protocol for the synthesis of substituted benzazepine derivatives (Scheme 2.44) [286]. This protocol is based on the sequential palladium-catalyzed allylic amination and a subsequent intramolecular carbonylation reaction. The substrates were obtained by a Baylis-HiUman reaction. 

Homoallylic alcohol 9 is readily prepared by palladium-catalyzed directed cyanoboration followed by Suzuki-Miyaura cross-coupling (Scheme 5.15) [15]. Palladium-catalyzed allyl transfer from 9 to aryl bromide results in removal of the hydroxymethyl directing group and concomitant formation of 3,4-diaryl-2-butenenitrile albeit the lack of regio- and stereospecificity. The overall transformation proposes a concept of intramolecular reaction with a carbon tether removable through retro-allylation. 

In the second approach55 an allylsilane was employed as carbon nucleophile in the side chain. Allylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function57. Palladium-catalyzed reaction of allylsilane 57 with LiCl under similar conditions as used for the other intramolecular 1,4-oxidations afforded 58 (equation 22). Interestingly, the carbochlorination over the diene was highly 1,4-syn... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

Another approach is based on the palladium-catalyzed intramolecular carbocyclization of the allylic acetate moiety with the alkene moiety (Scheme 96). After the formation of a 7t-allylpalladium complex, with the first double bond the intramolecular carbometallation of the second double bond occurs to form a new C-C bond. The fate of the resulting alkylpalladium complex 393 depends on the possiblity of /3-elimination. If /3-elimination is possible, it generates a metallated hydride and furnishes the cycloadduct 394. This cyclization could be viewed as a pallada-ene reaction, in which palladium replaces the hydrogen atom of the allylic moiety.231... 

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho-... 

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