Palladium-catalyzed oxidative cyclization

Palladium-catalyzed oxidative cyclization of aryl homoallyl ethers affords 4-methyl-2//-chromenes in moderate yield. The reaction is proposed to proceed via activation of the alkene by coordination to Pd(ll) followed by intramolecular nucleophilic attack by the arene. Subsequent [1-hydride elimination and isomerization then affords 4-methyl-27/-chromenes (Scheme 13). Electron-rich aryl homoallyl ethers give the best yield and good regio-selectivity is observed for the reaction of unsymmetrical arenes <2005OL3355>. 

Fix et al. reported the palladium-catalyzed oxidative cyclization of aminoalkenes.132b The reaction of the aminoalkenes 176 having a methyl group on the olefin moiety gave the 2-vinylpyrrolidines 177, while the reaction of the aminoalkene 178 having a terminal olefin gave a mixture of the cyclic enamines 179 and 179 (Schemes 58 and 59). 

Remote asymmetric induction in palladium-catalyzed oxidative cyclizations of this type can be achieved with chiral 2,6-heptadienoates89. 

A palladium-catalyzed oxidative cyclization of tertiary enamines 7 to pyrroles 8 using copper acetate was reported by Guan and co-workers. Trifluo-roacetic acid as a stoichiometric additive was proven to be integral to the improvement of yield. The mechanism is proposed to go through electrophilic paUadation on the C—H of a tertiary enamine under acidic conditions which tri ers a cascade to form pyrroles 8. This method was used to synthesize a range of differentially functionalized 1,3,4-tri-substituted pyrroles (14OL3360). 

Gabriele, B., Salerno, G. and Cassoni, S. (2005) Heteroqfdic derivative syntheses by palladium-catalyzed oxidative cyclization-alkoxycarbonylation of substituted y-oxoalkynes. The Journal of Organic Chemistry, 70, 4971 979. no Gabriele, B., Salerno, G., Fazio, A. and Campana, F.B. (2002) Unprecedented carbon dioxide effect on a Pd-catalysed oxidative carbonylation reaction a new synthesis of pyrrole-2-acetic esters. Journal of the Chemical Society, Chemical Communications, 1408-1409. m Gabriele, B., Salerno, G., Fazio, A. and Veltri, L (2006) Versatile synthesis of pyrrole-2-acetic esters and (pyridine-... 

Besides six-membered heterocycles, the construction of five-membered analogs by C-H olefination of phenol derivatives has also been reported. In 2011, Wang and coworkers reported a palladium-catalyzed oxidative cyclization of 3-phenoxy acrylates to construct benzofurans via an intramolecular aromatic C-H olefination (Scheme 3.13) [31]. In the presence of 5 mol% Pd(OAc)2/PPh3 and 2.0 equiv. of CF3C02Ag, benzofurans were obtained in good yields in... 

As foretold in the introduction, ring formation via attack on a double bond in the endo-trig mode is not well exemplified. The palladium(II) catalyzed oxidative cyclization of o-aminostyrenes to indoles has been described (78JA5800). The treatment of o-methyl-selenocinnamates with bromine in pyridine gives excellent yields of benzoselenophene-2-carboxylates (Scheme 10a) (77BSF157). The base promoted conversion of dienoic thioamides to 2-aminothiophenes is another synthetically useful example of this type (Scheme 10b) (73RTC1331). 

An intramolecular palladium-catalyzed tandem cyclization of dienamides 67 in which the amide nucleophile adds twice has been developed (equation 29)60. This reaction constitutes a formal [4+1] cycloaddition and provides a new route to pyrrolizidine and indolizidine alkaloids. Reaction of dienamides 67 in the presence of catalytic amounts of Pd(OAc)2 and CUCI2/O2 as the oxidant afforded bicyclic compounds 68 in good yields. The pyrrolizidine derivative 68 (R = Me, n = 1) was transformed to the alkaloid ( )-heliotridane. 

Addition of the arylamines 117 to 2-methoxy-3-methyl-l,4-benzoquinone 118 affords regioselectively the 5-arylamino-2-methoxy-3-methyl-l,4-benzo-quinones 119 (Scheme 37). Palladium(II)-catalyzed oxidative cyclization leads to the carbazole-l,4-quinones 28 [135,136],previously obtained by the iron-mediated approach (cf. Scheme 14). Regioselective addition of methyllithium to the quinones 28 provides carbazomycin G 29a and carbazomycin H 29b [96,135]. Reduction of 29a with lithium aluminum hydride followed by elimination of water on workup generates carbazomycin B 23a [135]. Addition of heptylmag-... 

One year later, we extended the aforementioned palladium(II)-catalyzed approach to a series of 6-oxygenated carbazole alkaloids, glycozoline (86), glycozolinine (glycozolinol) (91), glycomaurrol (92), micromeline (100), and methyl 6-methoxycarbazole-3-carboxylate (104) (547). The palladium(0)-catalyzed coupling of 4-bromoanisole (670) and p-toluidine (1028), followed by palladium(II)-catalyzed oxidative cyclization, afforded directly glycozoline (86). 

Palladium acetate has also been used to catalyze oxidative cyclizations to produce the related dihydroindole in dimethylacetamide (DMA) in moderate yields <1997BMEL749> (Equation 68). Similar cyclizations have been reported to occur in the presence of manganese dioxide and nitrobenzoic acid <1997TL7207>. 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

Scheme 15.16 Palladium(ll)-catalyzed oxidative cyclization to 4-methoxy-2-methyl-5H-benzo[fo]carbazole-6,l 1-dione.

Addition of aniline to 2-methoxy-3-methyl-l,4-benzoquinone affords the anilino-substituted benzoquinone with complete regioselectivity. Optimization of the palladium(II)-catalyzed oxidative cyclization to 3-methoxy-2-methylcarbazol-l,4-quinone was achieved by varying the different reaction parameters. The best yield of the product was obtained using 30 mol% of the palladium(II) catalyst. Using 5 mol%... 

Tab. 15.3 Palladium(ll)-catalyzed oxidative cyclization of 5-arylamino-2-methyl-l,4-benzoquinones.

A Pd-catalyzed oxidative cyclization of phenols with oxygen as stoichiometric oxidant in the noncoordinating solvent toluene has been developed for the synthesis of dihydrobenzo[ ]furans (Equation 136). Asymmetric variants of this Wacker-type cyclization have been reported by Hayashi and co-workers employing cationic palladium/2,2 -bis(oxazolin-2-yl)-l,l -binaphthyl (boxax) complexes <1998JOC5071>. Stoltz and co-workers have reported ee s of up to 90% when (—)-sparteine is used as a chiral base instead of pyridine <2003AGE2892, 2005JA17778>. Attempts to effect such a heteroatom cyclization with primary alcohols as substrates, on the other hand, led to product mixtures contaminated with aldehydes and alkene isomers, which is in contrast to the reactions with the Pd(ii)/02 system in DMSO <1995TL7749>. 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

Trend, R. M., Ramtohul, Y. K., Ferreira, E. M., Stoltz, B. M. Palladium-catalyzed oxidative Wacker cyclizations in nonpolar organic solvents with molecular oxygen A stepping stone to asymmetric aerobic cyclizations. Angew. Chem., Int. Ed. Engl. 2003,42, 2892-2895. 

Condensation of 1 with 3,4-dimethoxybenzyl cyanide afforded the epimeric cyano alcohols 2, which on alkaline hydrolysis gave the epimeric y -lactones 3 in 64% yield. Treatment of 3 with crotyl bromide afforded the a,a-disubstituted lactone 4. Acid-catalyzed debenzy-lation of 4 afforded the alcohol 5, which on sequential saponification, periodate cleavage and reduction gave the lactone 7 via 6. Palladium-catalyzed oxidation of 7 afforded 8, which underwent intramolecular cyclization to produce 9 in 66% yield. Treatment of 9 with methylamine gave 10 (41%) and 11 (7%) however, the former can be cyclized into the latter in 85% yield. Reduction of 11 furnished 12 in 77% yield. 

Much research interest in the synthesis of carbazoles is directed at the preparation of natural products. The total syntheses of murrayafoline A 153 and murrayanine have been reported <04S2499>. The key step included a regioselective cycloaddition between oxazolidinone 150 and acrolein which led to benzoxazol-2-one 151 after DDQ oxidation. Ring opening of the oxazol-2-one ring of 151 followed by methylation provided A-phenylaniline 152. A palladium-catalyzed intramolecular cyclization of the latter then produced the natural product 153. Finally, venerable iron-mediated chemistry has been utilized in the total synthesis of furoclausine A 154 <04SL528> and 6-chlorohyellazole 155 <04SL2705>. 

In 2003, Stoltz at CalTech described a palladium-catalyzed oxidative Wacker cyclization of o-allylphenols such as 55 in nonpolar organic solvents with molecular oxygen to afford dihydrobenzofurans such as 56.44 Interestingly, when (-)-sparteine was used in place of pyridine, dihydrobenzofuran 56 was produced asymmetrically. The ee reached 90% when Ca(OH)2 was added as an additive. Stoltz considered it a stepping stone to asymmetric aerobic cyclizations. In 2004, Mufiiz carried out aerobic, intramolecular Wacker-type cyclization reactions similar to 55—>56 using palladium-carbene catalysts.45 Hiyashi et al. investigated the stereochemistry at the oxypalladation step in the Wacker-type oxidative cyclization of an o-allylphenol. Like o-allylphenol, o-allylbenzoic acid 57 underwent the Wacker-type oxidative cyclization to afford lactone 58.47... 

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