Nanjing University Shi Zhuangzhi Team's Research on ACS Cent. Sci. – Novel Applications of Josiphos

Nanjing University Shi Zhuangzhi Team's Research on ACS Cent. Sci. – Novel Applications of Josiphos

The team led by Prof. Zhuangzhi Shi from Nanjing University reports a breakthrough in ACS Central Science: Copper-Catalyzed Asymmetric Cyclizative Sulfinamidation: Forging Indole-Based Stereogenic Sulfur(IV) Centers and Atropisomeric Chirality. This work addresses the underexplored chemical space of chiral S(IV)-containing sulfinamides, which are critical intermediates in drug design due to their balanced stability and reactivity. By employing Josiphos as a key ligand, the team achieves enantioselective synthesis of indole sulfinamides with exceptional selectivity and functional group tolerance.

Reaction Optimization

Substrate Scope

Key Advantages of Josiphos Ligand:

1. Superior Enantiocontrol:

Josiphos dramatically enhances enantioselectivity, increasing product ee from 17–26% (with other ligands) to 92–95% after optimization.

2. Broad Substrate Compatibility:

The CuBr-Josiphos system stabilizes active catalytic species, accommodating diverse o-alkynylanilines with alkyl, aryl, heterocyclic, halogen, ether, or ester groups while maintaining high stereoselectivity.

3. Facile Post-Functionalization:

Products generated via Josiphos catalysis undergo efficient transformations, and all transformations preserve high enantioselectivity and diastereoselectivity:

l Deprotection with methanesulfonic acid → Primary

sulfinamides

l Reaction with trichloroisocyanuric acid → Sulfonyl

imidoyl chlorides

l Halogen-magnesium exchange/Sonogashira coupling →

Allylated/cyanated derivatives

Literature details

Authors: Xiaowu Fang,#Fengrui Xiang,# Yue Zhao, and Zhuangzhi Shi*

Title: Copper-Catalyzed Asymmetric Cyclizative Sulfinamidation: Forging Indole-Based Stereogenic Sulfur(IV) Centers and Atropisomeric Chirality

DOI: 10.1021/acscentsci.5c00909