Litcius/Paper detail

Two Catalytic Annulation Modes via Cu-Allenylidenes with Sulfur Ylides that Are Dominated by the Presence or Absence of Trifluoromethyl Substituents

Malla Reddy Gannarapu, Jun Zhou, Bingyao Jiang, Norio Shibata

2020iScience16 citationsDOIOpen Access PDF

Abstract

We disclose the Cu-catalyzed enantioselective synthesis of 3-methyl-3-propargyl-indolines, which contain a quaternary stereogenic carbon center, via the decarboxylative [4 + 1] annulation of 4-methyl-4-propargyl-benzoxazinanones with variety of sulfur ylides. The reaction proceeds predominantly through a γ-attack at the Cu-allenylidene intermediates by sulfur ylides to provide the corresponding indolines in good yield and high enantioselectivity (up to 91% ee). In contrast, the reaction of 4-trifluoromethyl-4-propargyl-benzoxazinanones with sulfur ylides delivers 3-trifluoromethyl-2-functionalized indoles in good to high yield via an unexpected α-attack at the Cu-allenylidene intermediates. Control over the α/γ-attack at the Cu-allenylidene intermediates by the same interceptors was achieved for the first time by the use of trifluoromethyl substituents.

Topics & Concepts

TrifluoromethylPropargylAnnulationStereocenterChemistryEnantioselective synthesisYield (engineering)SulfurCatalysisMedicinal chemistryOrganic chemistryMaterials scienceAlkylMetallurgyCatalytic Alkyne ReactionsCyclopropane Reaction MechanismsCatalytic C–H Functionalization Methods