Preparation of differentially 1,3-disubstituted indolines by intramolecular carbolithiation

Cyclization vs. Cyclization/Dimerization in o-Amidostilbene Radical Cation Cascade Reactions: The Amide Question

“…A large number of biologically active compounds incorporate indole and indoline moieties, particularly those that possess C-2 phenyl or heteroaryl moieties [ 1 ]. A vast array of creative approaches to the indoline ring system have been reported recently, for example the 1,6-H transfer followed by the 5- exo -trigonal ring closure tactic that exploits o -nitrobenzaldehyde [ 2 ]; the 5- endo -trigonal ring closure of N -( o -bromophenyl)ene carbamates [ 3 ]; intramolecular carbolithiation [ 4 ]; reduction of indoles [ 5 ] and the thermal reaction of N -allylaniline and various alkoxyamines [ 6 ]. Creative bisindoline construction is also increasing in importance as recent developments clearly indicate.…”

Highly Enantioselective Synthesis of Chiral 3-Substituted Indolines by Catalytic Asymmetric Hydrogenation of Indoles

“…Notwithstanding 3-substituted indolines being important chiral constituents of a number of biologically active compounds (e.g., the Duocarmycins), , methods for the enantioselective formation of a chiral center at the 3-position have been scarce. Recently, Groth and Bailey reported the stereoselective syntheses of chiral 3-substituted indolines by asymmetric intramolecular carbolithiation. − This methodology suffers several disadvantages in that it requires an excess of chiral agent to deliver chiral products that never exceed 90% ee.…”

One-pot synthesis of highly substituted indolines

“…[1][2][3][4][5] A great number of methods have been developed for synthesis of this important class of compounds. These (Scheme 1) include reduction of indoles, [6][7][8][9][10][11][12][13][14][15][16][17][18] anionic, [19][20][21][22][23] radical, [24][25][26] and metal-mediated [27][28][29][30] intramolecular cyclizations, as well as several other approaches. [31][32][33] As part of our efforts in developing therapeutic agents for CNS diseases, we desired a convenient and versatile synthesis of 3,3-disubstituted indolines with potential substitution at alternate positions of the scaffold.…”