Journal Article

Catalytic Asymmetric Cyclizative Rearrangement of Anilines and Vicinal Diketones to Access 2,2‐Disubstituted Indolin‐3‐ones

He, Yu‐Ping, Wu, Hua, Wang, Zi‐Qi, Li, Xing‐Zi, Quan, Rui

2024

Overview

The efficient synthesis of chiral 2,2‐disubstituted indolin‐3‐ones is of great importance due to its significant synthetic and biological applications. However, catalytic enantioselective methods for de novo synthesis of such heterocycles remain scarce. Herein, a novel cyclizative rearrangement of readily available anilines and vicinal diketones for the one‐step construction of enantioenriched 2,2‐disubstituted indolin‐3‐ones is presented. The reaction proceeds through a self‐sorted [3+2] heteroannulation/regioselective dehydration/1,2‐ester shift process. Only chiral phosphoric acid is employed to promote the entire sequence and simplify the manipulation of this protocol. Various common aniline derivatives are successfully applied to asymmetric synthesis as 1,3‐binuclephiles for the first time. Remarkably, the observed stereoselectivity is proposed to originate from an amine‐directed regio‐ and enantioselective ortho‐Csp2‐H addition of the anilines to the ketones. A range of synthetic transformations of the resulting products are demonstrated as well. Anilines are successfully applied to a catalytic asymmetric cyclizative rearrangement (CACR) sequence, which enables straightforward access to 2,2‐disubstituted indolin‐3‐ones in high yield and enantiopurity with adequate structural diversity. A high regio‐ and stereoselective ortho‐carbon addition of anilines to ketones is the key to the success of this overall sequence.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: 1,2‐rearrangement / Acids / anilines / Carbon / Catalysis / indolin‐3‐ones / organocatalysis / quaternary stereocenter / Solvents