Enantioselective Construction of Spiroindolines with Three Contiguous Stereogenic Centers and Chiral Tryptamine Derivatives via Reactive Spiroindolenine Intermediates

Abstract

The highly efficient synthesis of the enantioenriched spiroindolines by iridium-catalyzed asymmetric allylic dearomatization and reduction is presented. Spiroindolines containing three contiguous stereogenic centers were obtained with excellent diastereo- and enantioselectivity. In addition, a chiral tryptamine derivative could be easily accessed in good yield with excellent ee value through an unprecedented dearomatization/retro-Mannich/hydrolysis cascade reaction of an indole derivative.

Catalytic Asymmetric Dearomatization by Transition-Metal Catalysis: A Method for Transformations of Aromatic Compounds

“…Although an allylic dearomatization of C2-substituted N-Bn-tethered indol-3-yl allylic carbonate 16 under conditions similar to those shown above still proceeded, leading to aza-spiroindolenine 17 instead of undergoing any type of migration, the latter could be reduced by LiAlH 4 in one pot to give aza-spiroindoline 18 bearing three contiguous stereogenic centers in high yield and stereochemical control. 28 Notably, when an electron-rich arene was installed at the a position of the nitrogen atom (16, Ar = 4-MeC 6 H 4 ), the corresponding aza-spiroindolenine species became less stable, and a retro-Mannich reaction and hydrolysis occurred via intermediate I during the purification process. Finally, a chiral tryptamine derivative 19 was furnished after acyl protection of the free amino group.…”

“…Further Transformations Based on the Migration ReactivityOriginally reported by the You group 28,29. Scheme 5.…”

Functionalized Spiroindolines with Anticancer Activity through a Metal‐Free Post‐Ugi Diastereoselective One‐Pot Cascade Reaction

“…The cost-effective and environment-friendly conditions, short reaction steps, and simple work-ups are still desirable. [6] …”

Iridium‐Catalyzed Enantioselective Synthesis of Pyrrole‐Annulated Medium‐Sized‐Ring Compounds

“…We envisaged that pyrrole-annulated medium-sized-ring compounds could be constructed by an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis reaction sequence (Scheme 1). [10,11] Firstly,i ridium-catalyzed allylic [*] L. Huang [12] Herein, for the first time we report ah ighly enantioselective synthesis of pyrrole-annulated medium-sized rings by an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis sequence. We began our studies by investigating the reaction of 1a with aw ell-developed catalytic iridium system consisting of [Ir(COD)Cl] 2 and ap hosphoramidite ligand.…”