Reduction of Indolin‐2‐ones and Desulfurization of Indoline‐2‐thiones to Indoline and Indole Derivatives

Abstract

Reduction of indolin-2-ones with lithium aluminum hydride (LAH) or diisobutylaluminum hydride (DIBAL) and desulfurization of indoline-2-thiones with Raney -Ni were investigated. Treatment of indolin-2-ones 1 with LAH OT DIBAL yielded indoles 4 and/or indolines 3 in moderate-to-high yields depending on the substituents at N and C(3) of 1. Indoline-2-thiones 2 were desulfurized with Raney-Ni to give indoles 4 and/or indolines 3.

TaMe3Cl2‐Catalyzed Intermolecular Hydroaminoalkylation: A Simple Complex for Enhanced Reactivity and Expanded Substrate Scope

“…This intermediate can then undergo palladium‐catalyzed intramolecular amination to give 3‐methyl‐ N ‐phenylindoline in one pot in 66 % overall yield from commercially available precursors (Scheme ). This compares favorably with the reported synthesis of 20 by reduction of an indoline‐2‐thione intermediate in 37 % yield 10. This synthetic approach demonstrates the compatibility of d 0 Ta catalysts with late‐transition‐metal redox‐active catalysts for the development of one‐pot sequential syntheses that take advantage of the atom‐economic hydroaminoalkylation reaction.…”

“…This compares favorably with the reported synthesis of 20 by reduction of an indoline-2-thione intermediate in 37 % yield. [10] This synthetic approach demonstrates the compatibility of d 0 Ta catalysts with late-transition-metal redox-active catalysts for the development of one-pot sequential syntheses that take advantage of the atom-economic hydroaminoalkylation reaction.…”

Chemoselective sulfenylation and peptide ligation at tryptophan

“…Unfortunately, these conditions did not facilitate desulfurization, likely due to the relative strength of the carbon-sulfur bond in the 2-thiol indole moiety and signicant contributions of the indoline-2-thione tautomeric form. 45 On the basis of literature precedent for the reductive desulfurization of indoline-2-thiones, 46 we reasoned that standard metal-based reductive desulfurization protocols could be used to facilitate removal of the thiol auxiliary. Indeed, we were pleased to nd that treatment with Pd on Al 2 O 3 in buffer (6 M Gn$HCl/0.1 M Na 2 HPO 4 , adjusted to pH 5.8) in the presence of H 2 gas at 0 C 8 yielded cleanly desulfurized peptides (61-89% isolated yield) in under 4 h without any observable over-reduction of the Met, Trp, Tyr, or Phe residues (see Table 1 and Fig.…”

Untitled

“…Furthermore, overall conversion to the 1,2-dihydrospiro[3H-indole-3,4'-piperidines] 12 should be possible following literature procedures for similar compounds: reduction of the CO group of 1,2-dihydroindol-2-ones as mentioned before (Red-Al, toluene [7] or LiAlH 4 , Et 2 O [11]) and subsequent N-debenzylation (H 2 , Pd/C [12], or irradiation [13]) or, vice versa, N-debenzylation (Na, liq. NH 3 [14]) prior to reduction of the CO group [7].…”