Palladium-mediated carbonylation

Another compound 9 with three heterocyclic rings linearly fused (5 5 5) with two heteroatoms has been prepared from 1,1 -carbonyl diindole 297 <2001T5199>. Palladium-mediated coupling of the 2- and 2 -positions of 297 afforded the 1,1 -carbonyl-2,2 -biindolyl 9. 1,1 -Carbonyl diindole 297 was in turn obtained in 41% yield from 1,1 -carbonyldiimidazole 296 by reaction with indole in DMSO at 125 °C. The palladium-catalyzed coupling step afforded the desired product 9 in low yield and required a stoichiometric amount of palladium acetate. Therefore, it was felt prohibitively expensive. Addition of various co-oxidants (Ac20, Mn02, and Cu(OAc)2, etc) to make the reaction catalytic in palladium did not result in any improvement of the yield of 18 (Scheme 53). 

Isoindolin-l-ones can also be prepared by the palladium-mediated carbonylation of o-bromo(aminoalkyl)benzenes (Scheme 50).86 This amidation... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

Several examples have been reported of the use of palladium-mediated oxidation reactions of alcohols and alkyl halides. Palladium(II) acetate in the presence of iodobenzene converts primary and secondary alcohols into carbonyl compounds under solid-liquid two-phase conditions [20], However, other than there being no further oxidation to carboxylic acids, the procedure has little to commend it over other methods. It is relatively slow with reaction times in the order of 2 days needed to achieve yields of 55-100%. 

Palladium(0)-mediated couplings continue to show utility for iodoimidazole functionalizations, as illustrated in several reports of synthesis of (lR,2S,3R)-acetyl-4(5)-[(l,2,3,4)-tetrahydroxybutyl]imidazole (58) [95TL5969], and the trihydroxybutyl analogs [95JOC2378]. In contrast, 1,2-disubstituted imidazoles undergo palladium-mediated carbonylation, in the presence of alkenes, to afford 4-alkenoylimidazoles (59) [96JACS493]. 

Scheme 2.6 Allylatioti via an allyl carbonyl derivative followed by palladium-mediated CO2 extrusion.

Oxidative coupling was used to form alkyl- and alkoxy-substituted phenanthrenedione products lOOa-d (Table 22) [73]. These compounds can be obtained by other methods, albeit in much lower yields. In this instance, oxidative coupling proceeds even with carbonyl-substituted arenes, and VOF3 gives much better results than thallium- or palladium-mediated coupling procedures. 

Hydrophenylation of enones. A remarkable catalytic effect exerted by SbClj has been observed in the palladium-mediated transfer of a phenyl group from sodium tetraphenylborate to enones, furnishing j8-phenyl-carbonyl compounds. 

An efficient synthetic methodology was developed in which the palladium-mediated intramolecular carbonylative annulation of o-alkynylphenols was employed to construct benzo[l>]furo[3,4-d]furan-l-ones by a tandem reaction. Several densely functionalized alkynyl- phenols were cyclized into their respective substituted benzo[fc]furo[3,4-d]furan-l-ones in good yields under conditions of a combination of PdCljfPPh,), dppp and CsOAc in acetonitrile at 55°C under a balloon pressure of CO. An example is depicted below <01OL1387>. 

The nucleophilic addition to polyene (e.g., alkene, diene, arene) and polyenyl (e.g., allyl, cyclopentadienyl) ligands has contributed significantly to the numerous and unique applications organometallic reagents have in organic synthesis. The catalytic oxidation of olefins to carbonyl compounds (e.g., the palladium-mediated conversion... 

In 1980 Fujiwara and colleagues described for the first time a palladium-mediated oxidative carbonylation of arenes to benzoic acids [9—11]. The direct carboxylations of benzene, toluene, anisole, chlorobenzene, furan, and thiophene were carried out under CO and in the presence of Pd(OAc)2- 2-43 % of the corresponding benzoic acids were formed as the terminal products. Later on, the reaction was performed with a catalytic amount of palladium salts using tert-... 

The examples of oxidative carbonylations of alkynes were reported on in 1964. Here, Tsuji et al. described the palladium-mediated transformation of acetylene into muconyl chloride, fumaryl and maleic acid chloride (Scheme 8.15) [77]. Later on, they used diphenylacetylene as a substrate for the synthesis of lactones in the presence of alcohol and HCl [78, 79]. 

Scheme 8.15 Palladium-mediated oxidative carbonylation of alkynes...

Scheme 8.30 Palladium-mediated oxidative carbonylation towards lactones...

N- [4-[ 1 -Ethyl-2-(2,4-diaminofuro[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glu-tamic acid as an antifolate was synthesized by Gangjee and colleagues [107], and palladium-catalyzed alkoxycarbonylation of aryl triflate was applied. A palladium-mediated carbonylative C-H activation was developed by Sames and team and applied in the total synthesis of teleocidin B4 core (Scheme 10.24) [108]. 

Recently, transition metals and particularly palladium have found an increased use in C-synthesis. Reactions such as aromatic cyanation, the Stille-coupling reactions, and palladium-mediated carbonylation reactions using [ C] carbon monoxide are opening up new labeling pathways. 

The Tp ligands have been successfirUy used to prepare the stable copper carbonyl complexes as [Cu(Tp)(CO)]. Recently a solution of CuTp has been employed to improve the solubihty of CO that upon release from the complex has been used in low-pressure, one-pot palladium-mediated carbonylation reactions for the production of C-radiolabeled amides and ureas. The coordination chemistry oftris(3-R-5-R -pyrazolyl)borate ligands bearing different substituents (Tp , Tp ", "ppPhos.Me ... 

Kealey S, Miller PW, Lomg NJ, Plisson C, Martarello L, Gee AD. Copper(I) scorpionate complexes and their apphcation in palladium-mediated [ C]carbonylation reactions, (. hem Commun. 2009 3696—3698. 

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