General chemoselective hindered amide coupling enabled by TCFH-catalytic Oxyma and transient imine protection
Qiuhan Li1, Sarah Napier1, Andrew N Singh2
1Process Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, USA. qiuhan.li@merck.com.
Abstract:
We report a general chemoselective strategy for amide bond formation with poorly nucleophilic amines in the presence of reactive primary alcohols or amines as the competing nucleophiles. The selectivity for less reactive amines over competing alcohols was achieved using TCFH and catalytic Oxyma as a highly reactive, inexpensive, and safe reagent combination. By temporarily masking more reactive amines as imines through the use of electron-deficient aldehydes, the hindered amines could be similarly coupled with high efficiency and selectivity.
More Related Videos
Related Concept Videos
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Amines to Alkenes: Cope Elimination
![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)

