Palladium catalysts oxidative cyclization

In an extension of this work, the Shibasaki group developed the novel transformation 48—>51 shown in Scheme 10.25c To rationalize this interesting structural change, it was proposed that oxidative addition of the vinyl triflate moiety in 48 to an asymmetric palladium ) catalyst generated under the indicated conditions affords the 16-electron Pd+ complex 49. Since the weakly bound triflate ligand can easily dissociate from the metal center, a silver salt is not needed. Insertion of the coordinated alkene into the vinyl C-Pd bond then affords a transitory 7t-allylpalladium complex 50 which is captured in a regio- and stereocontrolled fashion by acetate ion to give the optically active bicyclic diene 51 in 80% ee (89% yield). This catalytic asymmetric synthesis by a Heck cyclization/ anion capture process is the first of its kind. 

The reaction mechanism was considered to be oxidative cyclization, and pal-ladacyclopentene 32 was formed. Reductive elimination then occurs to give cyclobutene 33, whose bond isomerization occurs to give diene 28. The insertion of alkyne (DMAD) into the carbon palladium bond of 32 followed by reductive elimination occurs to give [2+2+2] cocyclization product 27. Although the results of the reactions of E- and Z-isomers of 29 with palladium catalyst 26a were accommodated by this pathway, Trost considered the possibility of migration of substituents. Therefore, 13C-labeled substrate 25 13C was used for this reaction. 

Palladium-catalyzed, Wacker-type oxidative cycHzation of alkenes represents an attractive strategy for the synthesis of heterocycles [139]. Early examples of these reactions typically employed stoichiometric Pd and, later, cocat-alytic palladium/copper [140-142]. In the late 1970s, Hegedus and coworkers demonstrated that Pd-catalyzed methods could be used to prepare nitrogen heterocyles from unprotected 2-allylanilines and tosyl-protected amino olefins with BQ as the terminal oxidant (Eqs. 23-24) [143,144]. Concurrently, Hosokawa and Murahashi reported that the cyclization of allylphenol substrates can be accomplished by using a palladium catalyst with dioxygen as the sole stoichiometric reoxidant (Eq. 25) [145]. 

The proposed mechanism is given in Scheme 15. Initially the dissociation of water, maybe trapped by the molecular sieve, initiates the catalytic cycle. The substrate binds to the palladium followed by intramolecular deprotonation of the alcohol. The alkoxide then reacts by /i-hydride elimination and sets the carbonyl product free. Reductive elimination of HOAc from the hydride species followed by reoxidation of the intermediate with dioxygen reforms the catalytically active species. The structure of 13 could be confirmed by a solid-state structure [90]. A similar system was used in the cyclization reaction of suitable phenols to dihydrobenzofuranes [92]. The mechanism of the aerobic alcohol oxidation with palladium catalyst systems was also studied theoretically [93-96]. 

Trost and Tanoury found an interesting skeletal reorganization of enynes using a palladium catalyst.In this reaction, the second product is derived from a metathesis reaction (Equation (5)). It was speculated that the reaction would proceed by oxidative cyclization of enynes with the palladium complex followed by reductive elimination and then ring opening. To confirm this reaction mechanism, they obtained a compound having a cyclobutene ring, which was considered to be formed by the reductive elimination (Equation (6)). 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

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%... 

Several benzologs of furan and thiophene are conveniently formed by procedures of ring closure over dehydrogenation catalysts. o-Ethylphenol is cyclized at 620° over a palladium catalyst to benzofuran (11%). Chromium oxide on alumina at 450° converts o-ethylthiophenol to benzo-thiophene (42%). Alkyl groups in the alpha and beta positions are obtained by suitable variation of structure in the alkyl side chain. For the... 

A new oxidative cyclization of propargylic acetates to 1,3-dioxolanes has been achieved using a palladium(ll) catalyst with carbon monoxide in methanol (Equation 48) <2002TL6587, 2006T2545>. 

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... 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

Chemo- and regioselective synthesis of naphtho[2,3-c]chromenes result from the palladium-catalyzed reaction of 2-haloaryl aUenes with 2-alkynyl-phenols in refluxing 1,4-dioxane (Scheme 18) (14CC5891). Another palladium catalyst was involved in the intramolecular oxidative cyclization of 3-allyl-2 -hydroxyflavones to afford chromone[2,3-c]-2f/-chromenes in good... 

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