Nickel‐Catalyzed Enantioselective Synthesis of 2,3,4‐Trisubstituted 3‐Pyrrolines

The development of synthetic methods to produce highly functionalized chiral 3‐pyrrolines is of indisputable importance because of their prevalence in natural and synthetic bioactive molecules. Unfortunately, previous general cycloaddition approaches using allenoates, could not synthesize 3,4‐disubs...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-07, Vol.61 (29), p.e202203494-n/a
Main Authors: Tambe, Shrikant D., Ka, Cheol Hyeon, Hwang, Ho Seong, Bae, Jaehan, Iqbal, Naeem, Cho, Eun Jin
Format: Article
Language:English
Subjects:
Asymmetric Catalysis
Chemical synthesis
Chiral Ligands
Chirality
Cyclization
Cycloaddition
Enantiomers
Nickel
Production methods
Pyrroline
Stereoselectivity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development of synthetic methods to produce highly functionalized chiral 3‐pyrrolines is of indisputable importance because of their prevalence in natural and synthetic bioactive molecules. Unfortunately, previous general cycloaddition approaches using allenoates, could not synthesize 3,4‐disubstituted 3‐pyrrolines. Herein, an original approach to yield 2,3,4‐trisubstituted 3‐pyrrolines with chirality at the 2‐position is presented. A NiII/Fc‐i‐PrPHOX catalytic system facilitated a redox‐neutral highly stereoselective process that exhibited an enantioselectivity of up to 99 %. Enantioenriched 3‐pyrrolines can be converted to other valuable classes of N‐heterocycles. A nickel‐catalyzed regio‐ and enantioselective arylative cyclization process of alkyne‐tethered N‐sulfonamide acrylates with (hetero)arylboronic acids was developed for the synthesis of chiral 2,3,4‐trisubstituted 3‐pyrrolines (up to 99 % ee). A series of computational studies supported the syn/anti rotation of alkenyl‐Ni intermediate and the excellent enantioselectivity.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202203494