Simultaneous construction of axial and planar chirality by gold/TY-Phos-catalyzed asymmetric hydroarylation

Pei-Chao Zhang,Jiafeng He,Junliang Zhang,Zhiming Li,Hai-Hong Wu,Yin-Lin Li

doi:10.1038/s41467-021-24678-5

Abstract

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. Herein a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocenes derivatives is developed, which enable the simultaneous construction of axial and planar chirality. The here identified TY-Phos derived gold complex is responsible for the high yield, good diastereoselectivity (>20:1 dr), high enantioselectivities (up to 99% ee) and mild conditions. The catalyst system also shows potential application in the synthesis of chiral biaryl compounds. The cause of high enantioselectivity of this hydroarylation is investigated with density functional theory caculation.

Highlights

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge
To the best of our knowledge, simultaneous construction of multiple chiralities by asymmetric gold catalysis has not been reported so far, this hypothesis faced considerable challenges: (1) the universal and efficient asymmetric intramolecular desymmetric cyclization for the construction of planar ferrocene derivatives was not well developed (In the work of refs. 11,12, 10–20 mol% catalytic loading was used), (2) on the other hand, simultaneous construction of axial and planar chiral molecules via asymmetric catalysis has rarely been reported[52,53] and innate reluctance to undergo a related asymmetric desymmetric aromatization, and (3) the inherent difficulties to asymmetric gold catalysis, which stem from its linear coordination geometry and the outer-sphere nature of Au(I)-catalysis[44,45,46,47,48,49,50]
NMR yield with 80% ee and 3:1 diastereoselectivity. (S,S)-Ph-BPE (L2) could give the product 2aa in quite low enantioselectivity and conversion. (R)-BINAP (L3) furnished 2aa in 62% NMR yield with 51% ee and 5:1 d.r., and the dominant Brønsted acid (R)-CPA (L4) in the field of atroposelective synthesis of axially chiral molecules, cylohexanediamine-derived (S,S)-DACH-Phenyl Trost Ligand (L5), (R)-BI-DIME (L6), Binol-derived phosphor-amidite (Sa,R,R)-CPPA (L7), chiral oxazoline-phosphine ligand (R)-tBu-PHOX (L8), all have insufficient catalytic activity

Summary

Introduction

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. The groups of Alcarazo[1,14,16,18] and Tanaka[6,15,17] extensively studied the Au-catalyzed and Rh-catalyzed intramolecular alkyne hydroarylation to achieve enantioselective synthesis of axially chiral biaryls and helicenes, respectively (Fig. 1a).

Results

Conclusion