Fused indoline

Studies on asymmetric annulation of the precursor 203 resulted in development of reaction conditions for the construction of the fused indoline system 204 (Equation 64). Similar cyclization of a substrate containing a longer chain gave a corresponding indoline fused to a six-membered ring <2002TA1351>. 

Table 5.3 Palladium/NHC-catalyzed asymmetric synthesis of fused indolines reported by Kundig. ...

Almost at the same time as the first report of the Kiindig group in 2011, Kagan and co-workers realized an asymmetric synthesis of chiral indoline scaffolds via Pd°/bisphosphine catalyzed C(sp )—H bond functionalization. They briefly investigated a number of chiral ligands (R,R)-L16 gave the cyclization product in best results (Scheme 5.35). They also employed this method to synthesize cyclohexyl fused indolines in promising yields (up to 97%) and enantioselectivity (up to 93% ee). 

A large series of substituted and fused indoles was reported by Maiti and co-workers via the palladium-catalyzed annulation of aniline 124 with styrene (125).The reaction is suspected to proceed by ori/ro-palladation, olefin coordination, and P-migratory insertion from readily and commercially available anilines and olefins. The diversity of obtainable-substituted products is highlighted by fused indoline 127, fused indole 128 (as a single regioisomer), 2,3-disubstituted indole 129, and 2-substituted indole 130 (14AG(I) 11895). 

Wu reported a diastereoselective [3+2]-cycloaddition reaction that delivers fused indoline products in good to excellent yields with high regiocon-trol (e.g., 208). Density functional theory calculations suggest the reaction may proceed via the hydroxyaUyl cation derived from 207, rather than the corresponding oxyallyl cation. Additionally, it is suggested that O-alkylated products are formed initially and isomerize to the observed indolines. The utility of the method was demonstrated by concise syntheses of the core structures of vincorine, isocorymine, and aspidophylline A. (14JA6288). 

Nakanishi M, Katayev D, Besnard C, Kiindig EP (2011) Fused indolines by palladium-catalyzed asymmetric C-C coupling involving an unactivated methylene group. Angew Chem Int Ed 50(32) 7438-7441... 

Scheme 25 Synthesis of highly fused indoline derivatives...

Recently, Wang and co-workers reported the first asynunetric inverse-electron-demand aza-Diels-Alder reactirai of indoles with in situ formed azoalkenes catalyzed by a Cu(I)/Bu-Phosfeirox complex (Scheme 35) [60]. The current methodology provides an expedient access to highly functionalized [2,3]-fused indoline... 

SCHEME 62 Multicomponent synthesis of spiro-fused indolin-2-ones (110, 111 and 112) in PEG. 

SCHEME 3.26 Silver-promoted synthesis of fused indolines [26]. Me... 

Scheme 8.27 Synthesis of fused indolines from 2-ethynylarylmethylenecyclopropane with sulfonyl azide.

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