Palladium acetate cyclizations

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

In a recent communication, the parent system 2 has been obtained in poor yields (16% and 10%, respectively) from the double cyclization of N-diphenyl-1,3-phenylenediamine either by using two equivalents of palladium acetate in refluxing acetic acid or by irradiation in methanol in the presence of a catalytic amount of iodine (00SC3651). All the available approaches sununarized so far were marred by harsh reactioi conditions or troublesome-to-prepare starting materials, leading to low overall yields of the desired products and difficulty in introducing sensitive substituents. 

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Perhydroindans (46) and (47) could be obtained in 73% yield from the carbonate (48) with only minor amounts of elimination product. The use of BSA and the triisopropyl phosphite-palladium acetate catalytic system provides further improvement. The low cisitrans selectivity in the formation of the first ring, and rapid subsequent cyclization account for the fact that the ratio of (46) to (47) is only 2 1 (Scheme 2.14). Even the presence of a bulky trialkylsiloxyl substituent adjacent to the vinyl sulfone moiety has only a minor influence on the cisitrans selectivity [24]. 

A novel route to indoles and quinolines has been developed by sequential Wiltig and Heck reactions <96CC2253>. Thus, treatment of o-bromo- or iodo-lV-lrifluoroaceiylanilines (86) with a stabilized phosphorane affords the corresponding enamines 87 as a mixture of isomers. Cyclization to 88 is effected by heating with palladium acetate, tri phenyl phosphine, and bu.se. 

The insertion of carbon monoxide into readily available 2-bromo-3-aminopropene derivatives can be effected by catalytic quantities of palladium acetate and triphenylphosphine high CO pressures are not required (Scheme 16).38 The /Mactam products presumably arise by palladation,carbonylation, and cyclization as depicted in Scheme 17.38 An extension of this approach to the synthesis of biologically interesting condensed /(-lactams can be expected. 

Dialkylindolines and 1,3-dialkylindoles are formed in poor yield (<10%) from the reaction of ethyl- or phenymagnesium bromide with 2-chloro-N-methyl-N-allylaniline in the presence of catalytic quantities of (bistriphenylphosphine)nickel dichloride.72 In a modification of this procedure, the allyl derivatives can be converted by stoichiometric amounts of tetrakis(triphenylphosphine)nickel into 1,3-dialkylindoles in moderate yield72 (Scheme 43) an initial process of oxidative addition and ensuing cyclization of arylnickel intermediates is thought to occur. In contrast to the nickel system,72 it has proved possible to achieve the indole synthesis by means of catalytic quantities of palladium acetate.73 It is preferable to use... 

An interestingly short total synthesis of quadrone was developed by Kende and coworkers who made application of Pd(II)-mediated cycloalkenylation of silyl enol ethers (Scheme LV) Their point of departure was 609 which was converted directly to 610, Reaction of this silyl enol ether with palladium acetate in acetonitrile gave predominantly 6JI which could be cyclized to 612. From this intermediate, it was possible to prepare the known keto acid. 

Cyclization ok Diphenyl Ethers to Dibenzofurans with Palladium Acetate under Acidic Conditions... 

The Heck reaction of dihydroindoles produces a mixture of cyclized products, the ratio of which can be controlled by varying the reaction conditions < 1998CEJ1554>. Hence, the < a ti-product is produced exclusively using palladium acetate as catalyst in the presence of silver carbonate and is isomerized to the endoA oms. i on exposure to camphor-sulfonic acid (CSA) at room temperature (Scheme 11). 

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>. 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

It has been shown that combination of bromoallylation reaction and Heck cyclization is a useful methodology for the preparation of a variety of fused bicyclic (3-lactams of nonconventional structure [95], Starting from acetates 164 and using palladium acetate as the palladium source, DMF as solvent, potassium carbonate as base, and triphenylphosphine, the reaction occurred. The reaction conditions were further optimized and typical results for the preparation of bicyclic (3-lactams 165-168 are summarized in Schemes 57. 

Cyclization of phenols 6 with the (acetoxypinene)palladium acetate complex 5 gives the enantiomeric 2,3-dihydro-2-vinylbenzofurans (R)-764. 

The asymmetric cyclization of 2[( )-3-pentenyl]phenol (1) performed with (f/3-pinene)palladium acetate (see Section 4.6.2.2.2.) in the presence of copper(II) acetate in methanol under an oxygen atmosphere, gives 3,4-dihydro-2-vinyl-27/-1 -benzopyran (2) in 64% yield and 25% ee87. The enantiomeric excess is determined by H-NMR analysis, in the presence of Eu(tfc)3, of methyl 3,4-dihydro-2//-1 -benzopyran-2-carboxylate, derived from 2 by oxidation with potassium permanganate, followed by esterification with diazomethane. 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

A novel Pd(I) complex has been obtained from the cyclization of diphenylacetylene with palladium acetate in methanol (12) ... 

The cyclization o-phenylenediamine with 2-butene-1,4-diol catalyzed by palladium acetate coordinated with (7 )-BINAP as the chiral ligand leads to optically active 1,2,3,4-tetrahydro-2-vinylquinoxaline with 19ee and 58% yield [117]. 

At the early stage of Heathcock s biomimetic total syntheses of discorhabdins [108], a 5-ejco Heck cyclization was employed for the synthesis of 3,6,7-functionalized indole. As highlighted in Scheme 42, when precursor 237 was exposed to catalytic palladium acetate, tri-o-tolylphosphine, and stoichiometric base, indole 238 was smoothly produced in 89% yield. Subsequently, the total syntheses of discorhabdin C (239) and discorhabdin E (240) were accomplished using indole 238 as the common intermediate. 

The intermediate 591a was also used in a synthesis of tabersonine. Alkylation of 591a by Z-l,3-di-iodopropene followed by elimination of the phenylselenyl group gave a ring C diene 594, which was cyclized by a reductive Heck reaction with palladium acetate, sodium formate, triphenyl-phosphine, and base, with formation of tabersonine (78) in 43% yield (Scheme 77) (346). 

In this case, the modified Heck reaction of amide 220 bearing fully protected functional groups, which was prepared from 5S,6S-bis(methoxy-methoxy)-4-(4f )-azidocyclohex-2-enone, is a key step. The protected amide 220 underwent intramolecular cyclization with palladium acetate in the presence of thallium(I) acetate and l,2-bis(diphenylphosphono)ethane... 

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