Palladium catalyzed reactions alkoxycarbonylation

In studies using tetrahydropyran formation as part of a synthesis of frenolicin and other naphthoquinone antibiotics50 53, this reaction proceeds with high stereoselectivity. Thus, palladium-catalyzed intramolecular alkoxycarbonylation of various 6-hydroxyaIkenes (e.g., 1) leads to 2,6-disubstituted tetrahydropyrans 2 with up Lo 97 % diastereoselectivity. The configuration of the exocyclic stereocenter depends on the E or Z geometry of the substrate double bond34... 

Although chloroaromatics generally display lower reactivity in palladium-catalyzed reactions, the presence of the heteroatom in heteroaryl chlorides can activate the C—Cl bond in G-2 and C-4 positions. Accordingly, alkoxycarbonylation of S7 in the presence of the Pd(OAc)2/dppp catalyst followed by the annulation of the cyclopen-tanone ring was used for the construction of the tricyclic ring system (S9) during the total synthesis of the anticancer drug irinotecan [80]. 

Very high regioselectivities (> 99.5% iso) were obtained, using PdCl2(PhCN)2 in combination with (+)-neomethyldiphenylphosphine and toluene-j9-sulfonic acid, under mild conditions (70 °C and 10 bar). More recently, the palladium-catalyzed alkoxycarbonylation and amido-carbonylation of aryl bromides and iodides in [bmim][BF4] and [bmim][PF6] has been described. Enhanced reaction rates were observed compared to conventional media and the ionic liquid-catalyst could be recycled. 

It has been demonstrated that fluorovinylzinc reagents undergo stereoselective palladium-catalyzed coupling reactions with aryl (e.g., formation of 2 " ), vinyl (e.g., formation of heteroaryl, alkanoyl. and alkoxycarbonyl halides. Fluorovinylzinc reagents also undergo allyl-ation (e.g., formation of 4 ), halogenation, oxidative dimerization, and protonation reactions. ... 

A useful synthesis of ( )-j -ethoxycarbonylvinylsilanes by palladium-catalyzed regio- and stereospecific hydroesterification (EtOH -I- CO) (or carboethoxylation) of trimethylsilylacetylenes has been reported recently [210]. Alkoxycarbonyl or carbonyl functionalization of vinylsilanes are useful synthetic intermediates [211, 212]. The use of PdCl2(dppf) as a catalyst (with SnCl2 2 H2O as cocatalyst) is found to be superior and gives excellent yields. A key step in the reaction is thought to involve hydropalladation to give 60 or 61. The preference for 60 to 61 is understood... 

Carbonylphosphine complexes of zero-valent palladium are considerably less stable and more reactive than their Ni counterparts. Most common triphenyl-phosphine complexes of Pd are excellent catalysts for various carbonylation reactions of aryl iodides and bromides [15,129-131 ]. It is conceivable that the palladium-catalyzed alkoxycarbonylation of ArCl proceeds via a mechanism similar to that proposed for the analogous reactions of bromo- and iodoarenes (Scheme 5) [45,159,160,161]. 

Palladium-catalyzed alkoxycarbonylations represent another class of transition metal catalyzed oxycarboration reactions37. This reaction type was recognized early as proceeding via trans addition, while dicarbonylations (see Section 1.5.8.3.3.) involve overall cix addition38 43-95. 

This reaction type can also be applied to tetrahydrofuran formation and its stereoselectivity is markedly influenced by substituents on the chain and at the double bond49,3 -56. Starting from 5-hydroxy-l-heplenes 3, palladium-catalyzed alkoxycarbonylation leads to 2.5-disubstituted tetrahydrofurans 4 in good yield. Tetrahydrofuran formation is sterically unselective when the substituent R1 at the double bond is hydrogen or methyl however, when R1 is a methoxy group, formation of an isomer of type 4A is highly favored (d.r. >95 5)49,55. 

Synthetic approaches that have been developed or extended in the review period and have the potential for general use include radical alkoxycarbonylation to give 4-alkoxycarbonylpyridazines (Section 6.01.5.6) preparation of 4(5)-aminopyridazines by direct amination with ammonia or amide ions followed by oxidation (Section 6.01.5.4.3) C—C bond formation by palladium catalyzed coupling reactions of pyridazine O-triflates (Section 6.01.7.12.2) and halopyridazines (Section... 

With the same reaction as that of alkoxycarbonylation, the first palladium-catalyzed amidation reaction of aryl-X compounds was again developed by Heck and his group. They demonstrated that by carbonylation reactions, secondary and tertiary amides are conveniently produced [118]. More specifically, (hetero)aryl bromides and vinyl iodides were reacted with primary or secondary amines under atmospheric CO pressure at 60-100 °C in the presence of 1.5 mol% PdX2(PPh3>2. Stoichiometric amounts of a tertiary amine were required to neutralize the formed acid if weakly basic amines were used as nucleophiles. 

Tanaka and his associates demonstrated for the first time how to use non-volatile ionic liquids (ILs) as solvents in palladium-catalyzed carbonylations [163], In the case of alkoxycarbonylation of bromobenzene, higher yields were obtained when 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4] was used as the reaction medium compared with standard conditions. And the selectivity for the monocarb-onylation of iodobenzene with t -PrOH or Et2NH was significantly enhanced by [bmim][BF4]. After separation of the products, the solvent-catalyst system was easily recycled and exhibited catalytic activity up to seven times. Since then the replacement of traditional solvents with quaternary ammonium halides, imidazoli-um- or pyridinium-derived ILs has gained increasing importance [164—173]. Recently, the phosphonium salt IL trihexyl(tetradecyl)phosphonium bromide has proven to be an effective reaction medium for various carbonylation reactions of aryl and vinyl bromides or iodides under mild conditions (Scheme 2.17) [174]. 

Like alkoxycarbonylation, aminocarbonylation, and hydroxycarbonylation, the palladium-catalyzed reductive carbonylation reaction was originally discovered by Schoenberg and Heck in 1974 [15]. In the presence of a relatively large amount of [PdX2(PPh3)2l as a catalyst under 80-100 bar of synthesis gas and at 80-150 °C, aryl and vinyl bromides or iodides were converted into the corresponding aldehydes in good yields (Table 3.1). 

There is an impressive number of publications on the application of transition metal-catalyzed carbonylation reactions in total synthesis. In 1980 Tsuji and colleagues applied palladium-catalyzed alkoxycarbonylation in the synthesis of Zearalenone [22] and Curvularin [23]. Starting from the corresponding aryl iodides or benzyl chlorides and alcohols, the parent molecules for Zearalenone and Curvularin were prepared in good yields and finally transferred to the target products by a few more steps (Scheme 10.1). 

After a long period of neglect of hydroformylation of fatty acid compounds derived from renewable resources, it is once again in the focus of research. In comparison to the pioneering time, smoother reaction conditions have been identified. Also, related methods such as palladium-catalyzed alkoxycarbonylation of fatty acid esters are attracting more and more attention [64]. This methodology mainly produces a,m-diesters, which cannot be produced in good yields by hydroformylation to date. 

Addition of element-element compounds to alkynes has been reviewed.Other insertions of alkynes into palladium-hydride bonds have been identified in Drent s palladium-catalyzed alkoxycarbonylation of alkynes palladium(ii)-alkenyl complexes have been invoked to account for the observed H/D exchange when conducted in GH3OD and to identify the pathway (i.e., through migratory insertion into Pd-H and formation of acyl species by carbonylation) of the overall reaction. ... 

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-... 

Gabriele et al. reported an unprecedented multicomponent domino reaction to functionalized indoles based on the combination between an initial nucleophilic attack step on an imine moiety and a palladium-catalyzed oxidative heterocycliza-tion/alkoxycarbonylation process [84] (Scheme 6.61). Initially, condensation of aldehyde and alkynylanilines 220 would generate 2-alkynylaniline imines 221 in the presence 4-A molecular sieves. Subsequent nucleophilic addition of ROH to the imine group of 221 followed by a Pdl -catalyzed oxidative 5-endo-dig cycliza-tion/alkoxycarbonylation would afford the final products 222 in moderate to good yields. 

Leighton et al. described an effective and nuld palladium-catalyzed tandem alkene addition/carbonylation procedure in the synthesis of leucascandrolide A [50]. Intramolecular alkoxycarbonylation of diol 65 under Semmelhack conditions proceeded efficiently to provide the desired 2,6-cis-tetrahydropyran 66 in 75 % yield with a dr of >10 1 (Scheme 22). Reaction optimization showed that use of benzonitrile as a cosolvent leads to cleaner and more efficient reactions. The functional group tolerance and chemoselectivity of the reaction simplified the protecting group strategy. 

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

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