ABSTRACT
We have demonstrated a Pd(0)-catalyzed Heck/C(sp3)-H activation cascade for the synthesis of spirocyclopropyl oxindoles in high yields from easily accessible ortho-bromoacrylamides. The formation of spirocyclopropyl oxindole is guided by an unconventional four-membered palladacycle through C(sp3)-H activation. The reaction exhibits a wide range of substrate scope and operates efficiently with a mere 0.5 mol % of Pd-catalyst. In addition, the use of microwave conditions facilitates rapid completion of the reaction. Furthermore, this spirocyclopropanation strategy can be coupled with [3 + 2] cycloaddition to produce spiropyrrolidine oxindoles, offering a valuable approach for the preparation of alkaloids such as (±)-horsfiline and (±)-coerulescine.
ABSTRACT
Herein, we have demonstrated an operationally simple Pd-catalyzed double-Heck reaction between N-(o-bromoaryl)acrylamide derivatives and α-fluoro/trifluoromethyl acrylates to enable monofluoro/trifluoromethyl alkene tethered 3,3-disubstituted oxindoles in a stereoselective manner. Remarkably, the reaction proceeds well without any external ligand in an open-air atmosphere. Control experiments and spectroscopic analysis are performed to understand the reaction mechanism.
ABSTRACT
Metal- and additive-free, photoinduced decarboxylative radical alkylation-cyclization of CF3-acrylamides with alkyl redox-active esters provided the corresponding quaternary CF3-oxindole derivatives in good yields. Notably, diaryliodonium salts also efficiently participated in the arylation-cyclization of CF3-acrylamides in environmentally benign H2O as a solvent. The present approach has been extended for the concise synthesis of CF3-attached indoline alkaloid analogues, i.e., CF3-(±)-desoxyeseroline, CF3-(±)-esermethole, and CF3-(±) progesterone receptor antagonists. The preliminary mechanistic studies revealed that the reaction is likely to proceed through initial photoexcitation of redox-active ester/diaryliodonium salts followed by the SET process with acrylamide.
