Intramolecular oxidative functionalization, palladium-catalyzed

In the second approach an ailylsiiane was employed as carbon nucleophile in the side chain. Ailylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function. Palladium-catalyzed reaction of ailylsiiane 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... 

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%. 

A common pathway in palladium-catalyzed oxidation reactions is that the 7r-olefin complex formed reacts with a nucleophile, either external or coordinated, and the new organometallic intermediate may then undergo a number of different reactions (Scheme l) (i) an intramolecular hydride shift leads to ketone formation (ii) a )6-elimination results in the formation of a vinyl functionalized olefin (iii) an oxidative cleavage of the palladium-carbon bond produces a 1,2-functionalized olefin and (iv) an insertion reaction, exemplified by insertion of an olefin, leads to formation of a new palladium-carbon bond, which may be cleaved according to one of the previous processes ()6-elimination or oxidative cleavage). In all cases palladium has removed 2 electrons from the organic molecule, which becomes oxidized. These electrons, which end up on Pd(0), are in turn transferred to the oxidant and Pd(II) is regenerated, in this way a palladium(II)-catalyzed oxidation is realized. 

The intramolecular Fujiwara-Moritani/oxidative Heck reaction was applied to the synthesis of functionalized benzo[fe]furans and dihydrobenzo[h]furans in 50-80% yields, and 15 examples are given in the article <04AG(E)6144->. Ionic liquid ([bmimJBF4) was found to be an effective solvent for the PdCl -catalyzed intramolecular Heck reaction to realize benzofurans <04TL6235>. Another palladium-catalyzed intramolecular Heck reaction between vinyl triflate and benzo[(j]furan was utilized to construct the seven-membered ring based (-)-frondosin B <04T9675>. 

The formation of several 2-aminobenzothiazoles via palladium-catalyzed, direct intramolecular oxidative C-H functionalization was recently demonstrated by Batey at the University of Toronto. The substrates used were A -aryl thioureas which in the presence of an interesting co-catalytic Pd(PPh3)4/Mn02 system under oxygen atmosphere, yielded the desired products. In terms of the mechanism, this transformation proceeded presumably through electrophilic palladation, suggested by the higher reactivity of the more electron-deficient substrates. 

A direct and easy palladium-catalyzed C-H bond oxidative cyclization for the synthesis of polycyclic aromatic hydrocarbons (PAHs) was reported. The intramolecular palladium-catalyzed direct oxidative C-H bond functionalization for the C-O bond formation was demonstrated, which... 

The isotope effect was also studied in the palladium-catalyzed cyclization of substrates 15 to form oxindoles 16 via C—H bond functionalization (Scheme 11.5) [34]. Whereas, no kinetic isotope effect was observed in the competitive reaction of 15a and 15a-d5, an intramolecular primary isotope effect of 4 was found in the cyclization of the ortho-monodeuterated substrate 15a-di. The absence of any inter-molecular isotope effects suggests that the first step, the oxidative addition, is both slow and rate-determining overall. Although different mechanistic scenarios were considered, the significant intramolecular isotope effect shows that the palladation... 

Evano and colleagues disclosed a modular indole synthesis via the intramolecular carbocupration of N-aryl-ynamides (124 125) (130L3122).A series of indole derivatives was prepared by Jiao via the palladium-catalyzed aerobic oxidative intramolecular hydroamination and C-H functionalization of N-alkynylanilines (13T4408). Suh reported a microwave-assisted synthesis of 3-functionalized indoles via an intramolecular arene-alkene coupling of o-iodoanilino enamines (13T7211). 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

The palladium-catalyzed synthesis of functionalized indoles through intramolecular nitrogen-carbon(sp ) bond formation has been reported (Scheme 3.55) [61], This was an oxidative cycloisomerization process, and the authors found that molecular oxygen (1 atm) was an effective oxidant for the process. The substrate scope for this reaction was quite... 

A cascade reaction including oxidative functionalization of the indole intermediates at the C3 position is shown in Scheme 19.87. The Zhu group reported a palladium-catalyzed synthesis of tetracyclic indoles 328 by intramolecular diamina-tion of alkynylanilines 327 bearing a benzamide moiety [160]. The reaction would be initiated by the coordination of both alkyne and amide, followed by deprotonation to form the intermediate 329. An anti addition of the dimethylamino group of 329... 

In 2008, Ruck et al. developed a novel and efficient synthetic route to spiro-fused indance-oxindoles 9 by a palladium-catalyzed tandem Heck/C—H functionalization reaction [8] (Schone 6.2). Oxidative addition of the aryl bromide 8 to the palladium complex is followed by the intramolecular Heck insertion process through 5-exo-trig cycUzation to afford primary alkylpaUadium species 11. Reaction at the highlighted C—H bond provides six-monbered paUadacycle 12, and subsequent reductive elimination generates spiro-fused iudauce-oxindoles 9. 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

After investigation of the palladium-catalyzed cascade cyclization/Suzuki coupling reactions of 1,6-enynes, Zhu and Zhang turned their attention to the analog 1,2,7-triene 333 for the synthesis of various functionalized five-membered cycles 334/335 [115] (Scheme 6.88). Oxidative addition of allyl hahides or carbonates to Pd(0) generates 7i-allylpalladium species 336, followed by intramolecular cycUzation to form vinylpalladium complex 337. Subsequent transmetallation with aryl boronic acids... 

Joyce LL, Batey RA. Heterocycle formation via palladium-catalyzed intramolecular oxidative C—H bond functionalization an efficient strategy for the synthesis of 2-aminobenzo-thiazoles. Org. Lett. 2009 11 2792-2795. 

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