Polycyclic indoline

Selenides are more readily cleaved by tin radicals than are thioethers. Two examples of the tin radical mediated cleavage of selenides are listed in Table 3.48 (Entries 8 and 9) more examples have been reported [768,773,821-823], The carbon-centered radicals initially formed by homolytic C-Se bond cleavage can either be directly reduced to the alkane by treatment with a tin hydride, or may add to multiple bonds before reduction. Entry 10 in Table 3.48 is an example of the formation of a polycyclic indoline through radical cyclization. Radical-mediated cleavage proceeds under mild,... 

Scheme 18.32 Synthesis of a library of bicyclic and polycyclic indolines.

Very recently, You and co-workers [21] have developed an elegant cascade FCA-Mannich process of indolyl enones to afford enantioenriched polycyclic indolines with the use of quinine-derived primary amine 6c as the catalyst (Scheme 9.7). Moreover, a-amino acid-derived 1,2-vicinal diamine 7 was proved to be efficient to catalyze the reaction of 4,7-dihydromdoles with a,p-unsaturated ketones [22]. 

Scheme 3 Reissig s synthesis of fused polycyclic indolines.

A hydroamination/N-sulfonyliminium cyclization cascade was carried out enantioselectively with gold and BINOL-phosphoric acid catalysts to generate fused indole 188. The method can also be extended to furnish lactams with up to 93% ee (13OL4330). Polycyclic indoline 189 was prepared via an indium/TFA-catalyzed tandem cycloannulation of P-oxodithioesters with tryptamine in yields up to 92% (130L1974). Dixon and colleagues utilized an enantioselective Michael addition/iminium ion cyclization of trypt-amine-derived ureas in the synthesis of tetracyclic indole 190 (22 examples, up to 78% yield and 96% ee) (130L2946). 

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. 

SCHEME 3.70 Palladium-catalyzed synthesis of polycyclic indolines [75]. 

This method has been used for the synthesis of 1-aryl and polycyclic isatins derived from phenoxazine, phenothiazine and dibenzoazepine as well as indoline. In the case of dimethoxyanilines, spontaneous cyclization to yield dimethoxyisatins in the absence of a Lewis acid has been observed, as exemplified in the synthesis of melosatin A, albeit in very low yield (Scheme 8). 

With the goal of producing different indoline-based functionalized polycyclic architectures and using such architectures in library generation, we developed a practical, enantio-controlled synthesis of an aminoindoline scaffold, (14) (Figure 17.7) [26]. This scaffold has several attractive features that make it extremely... 

Moreover, two indoline-Uke libraries were prepared (Scheme 1.6). A hydroxyindoline-derived scaffold 26 was used to prepare a tricyclic indoline-based library 27 by an IRORl split-and-mix approach on solid-support." A later indoline-alkaloid-like polycyclic library incorporated additional diversity, and the stereochemistry at the ring junction was controlled." ... 

Fused polycyclic iminoxyls with central system 5.12.2.1 5-Membered rings derivatives of indan, indoline, and fluorene... 

Brochu, J.L., Prakesch, M., Enright, GJ5., Leek, D.M., and Arya, P. (2008) Reagent-based, modular, tandem Michael approach for obtaining different indoline alkaloid-inspired polycyclic architectures. Journal of Combinatorial Chemistry, 10, 405-420. 

Oxidative annulations reaction of alkynes is one of the important methods to synthesize fused polycyclic heteroarenes [169-173]. Whereas the above examples show easy ruthenium catalysed insertions of alkynes into aromatic sp C-H bonds efforts have been made with related catalysts to perform the double insertion of alkynes into C-H and heteroatom-hydrogen bonds as a route to a variety of heterocycles. Chae S. Yi, has first shown, using ruthenium(ll) catalyst precursors [RuH(CO)(PCy3)2(NCMe)2]BF4 and preferably Ru3(CO)i2/NH4PF6, the alkenylation and double insertions of alkynes into C-H and N-H bonds for the transformation of indolines with terminal alkynes into quinoline derivatives [(Eq. 86)] [174, 175]. 

The tetrahydro-9a,4a-iminoethano-9/f-carbazole skeleton is a highly congested polycyclic ring system. It is the core structure of the indoline alkaloid akuammiline... 

In 2005, Ary a and co-workers reported on the stereocon-trolled solid-phase synthesis of a 90-membered library of indoline-alkaloid-like polycycles 41 and 42." These compounds are structurally related to a number of alkaloids such as vindoline, tabersonine, and yohimbine, and they could lead to compounds with similar or improved biological properties. Thus, chiral aminoindoline 36 was loaded via a silyl linker unit 37, deprotected, and reacted with an acid chloride to introduce the first point of diversity and to give 38. Treatment with piperidine removed the Fmoc group, and concomitant cyclization provided tricyclic... 

SCHEME 3.10. Solid-phase synthesis of indoline-alkaloid-like polycycles. 

Gan Z, Reddy PT, Quevillon S, Couve-Bonnaire S, Arya P. Stereocontrolled solid-phase synthesis of a 90-membered library of indoline-alkaloid-like polycycles from an enan-tioenriched aminoindoline scaffold. Angew. Chem. Int. Ed. 2005 44 1366-1368. 

Aniline derivatives have been used to synthesize the indoline system. A large variety of indoline alkaloid substructures are available in a very efficient way. Enamine derivatives such as 39 bearing electron withdrawing substituents on the olefinic double bond were transformed in high yields (Scheme 7). Two syn/anti isomers 41 and 42 were isolated. The isomeric ratio of the final products was influenced by a photostationary equilibrium between the substrates 39 and 40. The reaction was applied to the synthesis of a variety of derivatives of the alkaloid aspidospermidine." In this context, the cyclization products 43 were transformed into the polycyclic indole derivatives 44,45, and 46. Polycyclic indolone compounds 48 have been successfully produced by cyclization of enaminone derivatives 47 carrying a quinoline substituentIn these cases and contrary to the examples 41,42, and 43, the products 48 resulted from an oxidation of the cyclization product (also compare the formation of 30 in Scheme 5). 

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