Isomerization palladium-mediated

Palladium-mediated cydization based on the reactivity of o-alkynyl or alkenyl-phenyl isonitriles have been developed [105]. On the basis of their earlier studies on the three-component synthesis of allyl aryl cyanamides [106], Yamamoto and co-workers reported a palladium-catalyzed three-component coupling reaction of 2-alkynylisocyanobenzenes 122 with allyl methyl carbonate and trimethylsilylazide leading to N-cyanoindoles 125 [107]. One of the key steps of the proposed mechanism is the formation of 7i-allylpalladium carbodiimide 123 and its isomerization to rc-allylpalladium cyanamide complex 124 (Scheme 8.50). 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

A remarkable product selectivity is also observed in the case of methylenecyclopropanes with geminal diphenyl substitution. Whereas under nickel catalysis [Ni(cod)2 at SO-TO C] 18 is selectively dimerized to tra7w-l,l,6,6-tetraphenyldispiro[2.1.2.1]octane, which can be obtained in 28% yield at a conversion of 40%, substrate 18 reacts in a completely different manner with palladium(O) catalysts derived from (t/ -allyl)( -cyclopentadienyl)palladium(II) and triisopropylphosphane. Besides isomerization to 19, proceeding at temperatures above 85 °C, the monospiro derivative 20 is formed as the major product. Additionally, minor amounts of a formal [3 + 3] dimer 21 can be isolated. The latter probably arises from a palladium-mediated, stoichiometric reaction as the yield of 21 could not be improved under any conditions in catalytic runs. On prolonged heating, thermal isomerization of the methylenecyclopropanes to form... 

Palladium-mediated hydroformylation of several terminal and internal olefins was also investigated by the Beller group (Scheme 5.30) [138]. Rapid isomerization already took place when 1-octene was stirred at room temperature in the presence of the catalyst without any hydrogen pressure. Within 1 h, 1-octene was almost completely equilibrated to produce a mixture of internal olefins. Hydroformylation trials at 40 or 80 bar syngas pressure and at 80 or 100 °C revealed the strong influence of these parameters on the success of the reaction. 

It is worth noting that under these conditions, the 1-substituted vinylstannane behaved well (1-substituted vinylstannanes tend to behave poorly in Stille reactions due to steric hindrance) and that no isomeric mixture of products was obtained (palladium mediated couplings on famesyl substrates had led in the past to isomeric mixtures of products). The newly formed carbon C(sp )-C(sp ) bond resulted from the attack at the less hindered terminus of the 7t-allyl intermediate (which is a usual trend in this type of couplings). 

A palladium-mediated bisallylic substitution leading to spirocarbocycles has been reported to involve cleavage of carbon-carbon allylic bonds allowing the isomerization of vinylcyclopentenes into cycloheptadienes (Scheme 137). ... 

Furukawa et al. reported the total synthesis of murrayaquinone A (107) by a palladium(II)-mediated oxidative cyclization of the corresponding 2-arylamino-5-methyl-l,4-benzoquinones. 2-Anilino-5-methyl-l,4-benzoquinone (842) was prepared starting from 2-methyl-l,4-benzoquinone 841 and aniline 839, along with the regio-isomeric 2-anilino-6-methyl-l,4-benzoquinone (844). The oxidative cyclization of 2-anilino-5-methyl-l,4-benzoquinone (842) with stoichiometric amounts of palla-dium(ll) acetate provided murrayaquinone A (107) in 64% yield. This method was also applied to the synthesis of 7-methoxy-3-methylcarbazole-l,4-quinone (113) starting from 3-methoxyaniline (840) (623). Seven years later, Chowdhury et al. reported the isolation of 7-methoxy-3-methylcarbazole-l,4-quinone (113) from the stem bark of Murraya koenigii and named it koeniginequinone A (113) (49) (Scheme 5.101). 

In accessing chiral allyl vinyl ethers for Claisen rearrangement reactions, Nelson et al. employed the iridium-mediated isomerization strategy. Thus, the requisite enantioenriched diallyl ether substrate 28 was synthesized via a highly enantioselective diethylzinc-aldehyde addition protocol10 (Scheme 1.1k). The enantioselective addition of Et2Zn to cinnamaldehyde catalyzed by (—)-3-exo-morpholinoisobomeol (MIB 26)11 provided an intermediate zinc alkoxide (27). Treatment of 27 with acetic acid followed by 0-allylation in the presence of palladium acetate delivered the 28 in 73% yield and 93% ee. Isomerization of 28 with a catalytic amount of the iridium complex afforded the allyl vinyl ether... 

If the substrate lacks a hydrogen suitable for p elimination and there is another alkene present in the molecule, the a-alkyl palladium intermediate can follow a Heck pathway to form a bicyclic structure in a tandem reaction sequence. Once again, the final step is a palladium-hydride-mediated isomerization to give the endocyclic alkene. 

An intramolecular Pd-mediated Heck-type approach to 3-pyrrolin-2-ones has been disclosed by Yang and Shea (1995MI1 Scheme 30). Treatment of N-allyl-2-bromoacetamide 152 with palladium acetate and triphenylphos-phine in acetonitrile gives 4-methyl-3-pyrrolin-2-one 153 by a 5-exo-trig cyclization onto a terminal alkene, reductive elimination, and isomerization... 

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