Palladium catalysts indolines

Indolines are produced in good yield from 1-benzenesulfonylindoles by reduction with sodium cyanoborohydride in TFA at 0°C (Equation 5) (89TL6833). If acyl groups are present at C-2 or C-3 in the substrate, they are reduced to alkyl groups. Indole is also reduced to 2,3-dihydroindole by sodium cyanoborohydride and acetic acid or triethylamineborane and hydrochloric acid. An alternative method for preparing indolines involves treatment of indoles with formic acid (or a mixture of formic acid and ammonium formate) and a palladium catalyst (82S785). Reduction of the heterocyclic ring under acidic conditions probably involves initial 3-protonation followed by reaction with hydride ion. 

Tetrahydrocarbazoles and related fused systems have been accessed by a route relying on palladium-catalyzed tandem formation of alkenyl and aryl C-N bonds. For instance, the starting triflate 477 could be efficiently transformed into the target system 478 by amination with aniline (Equation 133) <2005AGE403>. Annulation of (2-triflyloxy)phenethyl carbonates with amides in the presence of a palladium catalyst has been used as a route to various N-substituted indoline derivatives <2005OL4777>. 

In recent years, there has been a considerable focus on the development of new reaction conditions that use only molecular oxygen as the co-oxidant and do not require DMSO solvent [19]. Considerable progress has been made through the use of palladium catalysts supported by pyridine or N-heterocyclic carbenes as ligands. For example, Stahl has demonstrated that the 2-allylaniline derivative 14 is transformed to indoline 15 in 79% yield upon treatment with 5 mol% IMesPd(TFA)2 and 10 mol% benzoic acid (Eq. (1.8)) 19d]. Stoltz has reported the conversion ofamide 16 to lactam 17 under similar reaction conditions (Eq. (1.9)) [19b]. Through elegant mechanistic studies Stahl has shown that the stereochemistry of the aminopalladation step is dependent on reaction conditions, and both syn- and antt-aminopalladation mechanistic pathways are accessible in oxidative amination reactions [20]. 

Members of the tetracyclic dibenzopyrrocoline alkaloid family can be prepared by the intramolecular ring closure of l-(o-halobcnzyl)-tetrahydroisoquinoline derivatives. (3.38.)47 The analogous transformation of dihydroisoquinolines (3.39.) proceeds probably through the isomeric enamine form obtained by the tautomeric shift of the double bond 48 The palladium-carbene catalyst system applied in these reactions was also effective in the preparation of indoline, indolizidine and pyrrolizidine derivatives 49... 

Representative compounds having a pyrrolidine or piperidine nucleus have been dehydrogenated in benzene solution under pressure at 250-350° over a nickel catalyst, e.g., l-( -amyl)-pyrrolidine to l-( -aniyl)-pyrrole (88%), indoline to indole (75%), and 1,2,3,4-tetrahydrocarbazole to carbazole (95%). Indole is also prepared by the dehydrogenation of its 2,3-dihydro derivative over palladium in boiling xylene (62%)." Partially hydrogenated alkylpyridines are dehydrogenated over palladized asbestos." 2,4-Diphenylpyrrole is synthesized by the selenium dehydrogenation of its 2,3-dihydro compound (46%). ... 

Oestxeich found that the direct arylation of indolines could be accomplished without over oxidation to the corresponding indole under palladium-catalysis with air (open flask), oxygen (balloon), or copper(II) acetate as the oxidant. Indolines can be unsubstituted or substituted as C2/C3 and the reaction performs well on gram scale (250, 18 examples, 18—90% isolated yield) (140L6020).A directed C2-functionalization/C7-alkenylation was discovered by Xu,Yi, and colleagues. With a rhodium catalyst, indole derivatives were functionalized with acetates at C2 (22 examples, 62—92% yield) the newly obtained products could be alkenylated at C7 with a rhodium/copper system (251,3 examples, 68—78% yield) (14CC6483). 

Additionally, the intramolecular cyclization of 2-halo-AT-allylanilines provides optional proeedures for indole derivative synthesis. Many transition metal eatalysts have been developed in this field, such as cobalt, nickel and palladium, but stoichiometric amounts of catalysts are needed. In 1987, a eatalytie version was developed by Laroek and Babu. In the pres-enee of a eatal54ie amount of Pd(OAe)2, indoles, indolines, oxindoles, qui-nolones, isoquinolines and isoquinolones were formed in high yields in short reaetion times under mild temperatures (Seheme 2.106). 

Sol and Serrano [108] employed a palladium/triphenylphosphane-based catalyst system in the intramolecular a-arylation of fl-(2-iodoanilino) esters, tiffording the corresponding indoline products in low to good yields (Scheme 8.60). [Pd(PPh3) j and potassium phenoxide as base were the conditions applied to obtain indoline-3-carboxylic acid derivatives. 

The synthesis of indolines through an intramolecular C-H amination reaction has been reported (S cheme 3.65) [71 ]. The reaction was catalyzed by a common palladium compound and promoted by an iodme(lll) reagent. This catalyst system generated good to excellent yields of the heterocycles at 60 °C. 

A palladium-catalyzed approach to the synthesis of polycyclic indolines has been developed using Pd(PPh3) as the catalyst (Scheme 3.70) [75]. The anthors screened a range of bases for activity toward the cyclization and fonnd that cesinm carbonate was the most effective. Using the optimized system, a great host of aryl halides were snccessfully converted into the target componnds in good to excellent yield. 

A possible reaction mechanism for the palladium-catalyzed cyclization of N-(2-fert-butylphenyl)acetamide is shown in Scheme 2.10. The acetanilide moiety acting as a directing group can coordinate to the palladium(II) catalyst, replacing the acetate ligand, and then the activation of the unactivated C-H bond of an alkyl group can take place to give intermediate. Subsequent reductive elimination of palladium(II) leads to the formation of indoline product. 

The inversion in alcohol has been attributed to the formation of hemiketals. Considering only the non-reacting solvents, the best correlation was established between the ee and the solvent basicity represented by the H-bond acceptor ability (P). Solvent acidity (a) did not play any significant role. The experimental results are validated by theoretical calculations. Palladium(ll) trifluoroacaetate-catalysed AH of 2-substituted 0 3-toluenesulfonamidoalkyl)indoles in the presence of (7 )-H8-BINAP as the chiral ligand and TsOH as the Brpnsted acid yielded chiral 2,3-disubstituted indolines with up to 91% Nitrobenzene is hydrogenated to aniline almost quantitatively with Pd-MCM-41 (g) catalyst in supercritical carbon dioxide. Experimental and DFT studies showed that a stepwise mechanism is operative. ... 

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