Catalytic Asymmetric Halogenation/Semipinacol Rearrangement of 3‐Hydroxyl‐3‐vinyl Oxindoles: A Stereodivergent Kinetic Resolution Process

Abstract

A highly enantioselective halogenation/semipinacol rearrangement of isatin‐derived allylic alcohols has been developed with a chiral N,N′‐dioxide/ScIII complex as catalyst. This strategy involved a pivotal stereodivergent kinetic resolution process and provided a facile and efficient entry to optically active halo‐substituted quinolone derivatives and quinoline alkaloids with a quaternary stereocenter simultaneously under mild reaction conditions. Based on the control experiments together with kinetic studies and DFT calculations, a possible catalytic cycle was proposed to illustrate the reaction process and enantiocontrol.

Two Green Protocols for Halogenative Semipinacol Rearrangement

“…10 Apparently, HSPR expands the synthetic utility of semipinacol rearrangement as illustrated in the total synthesis of natural products (i.e., lycoramine, galanthamine, and crinine). 10c−e Recent research efforts focused on the development of enantioselective HSPR by Tu (2005/2011), 11 Hennecke (2011), 12 Alexakis (2013−2015), 13 You (2014), 14 Ma (2014), 15 Yeung (2017), 16 and Feng and Cao (2021), 17 while the green chemistry of HSPR was rarely explored. A stoichiometric electrophilic halogenating agent is mechanistically required in HSPR because it is an oxidation process, and a halogen atom is present in the HSPR product.…”

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…In 2021, Feng and Cao described an enantioselective domino bromation/semipinacol rearrangement of isatin‐derived allylic alcohols 171 with NBS promoted at 30 °C in DCE by 10 mol% of a chiral scandium catalyst in situ generated from N,N’ ‐dioxide ligand 46 and Sc(OTf) 3 [50] . The process resulted in the formation of two types of chiral products, such as brominated dihydroquinoline‐2,4‐diones 172 arisen from an acyl‐migration, and bromo‐substituted dihydroquinoline‐2,3‐diones 173 generated from an aryl‐migration (Scheme 43).…”