Chiral Bifunctional Phosphine Ligand Enables Gold-Catalyzed Asymmetric Isomerization and Cyclization of Propargyl Sulfonamide into Chiral 3-Pyrroline

Abstract

This work details an asymmetric gold-ligand cooperative catalysis that transforms readily accessible chiral/achiral propargylic sulfonamides into chiral 3pyrrolines. A bifunctional biphenyl-2-ylphosphine ligand featuring a chiral tetrahydroisoquinoline fragment is essential for the observed metal−ligand cooperation and the asymmetric induction. 2,5-cis-3-Pyrrolines are formed with excellent diastereoselectivities in a "matched" scenario. The "mismatched" scenario by using the ligand enantiomer delivers 2,5-trans-3-pyrrolines with >5/1 diastereoselectivity. The synthetic utilities of this chemistry are demonstrated.

Asymmetric Photoaerobic Lactonization and Aza-Wacker Cyclization of Alkenes Enabled by Ternary Selenium–Sulfur Multicatalysis

“…This compound class has been intensively investigated, inter alia, for their salient role in biologically active natural compounds and pharmaceuticals . Throughout the last 25 years, numerous synthetic protocols for the assembly of chiral 3-pyrroline scaffolds have been reported. − Most prominent tactics include asymmetric intramolecular S N reactions, concerted and consecutive cycloadditions, hydroaminations, Mizoroki–Heck reactions, and ring-closing metatheses . Surprisingly, despite the overwhelming progress made in this field, there are no catalytic oxidative enantioselective cycloaminations on record to form 2-substituted 3-pyrroline rings directly .…”

Asymmetric gold catalysis enabled by specially designed ligands

“…103 Furthermore, in 2021, X. Cheng and L. Zhang utilised the S-isomer of ligand L11 for the gold-catalysed asymmetric synthesis of 3-pyrrolines (11e) from readily available propargylic sulfonamides (11d) (Scheme 11C). 104 The reactions worked fairly well with chiral and achiral propargylic sulfonamides to produce the desired pyrrolines in high diastereo-and enantioselectivity (up to >50 : 1 d.r. and up to 94% ee).…”

Recent progress in the homogeneous gold-catalysed cycloisomerisation reactions

“…In 2021, Zhang 31 et al developed a metal–ligand-promoted protocol for synthesising chiral 3-pyrrolines with excellent diastereoselectivity using biphenyl-2-ylphosphine as a chiral ligand with an Au( i ) catalyst (Scheme 18).…”