Spiro Indane-Based Phosphine-Oxazolines as Highly Efficient P,N Ligands for Enantioselective Pd-Catalyzed Allylic Alkylation of Indoles and Allylic Etherification.

Zhongxuan Qiu,Kun Yang,Dawei Teng,Rui Sun

doi:10.3390/molecules24081575

Zhongxuan Qiu, Kun Yang + Show 2 more

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https://doi.org/10.3390/molecules24081575

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Abstract

A series of indane-based phosphine-oxazoline ligands with a spirocarbon stereogenic center were examined for palladium-catalyzed asymmetric allylic alkylation of indoles. Under optimized conditions, high yields (up to 98%) and enantioselectivities (up to 98% ee) were obtained with a broad scope of indole derivatives. The ligand was determined to be the most efficient P,N-ligand for this reaction. Moreover, the ligand was also efficient for Pd-catalyzed asymmetric allylic etherification with hard aliphatic alcohols as nucleophiles.

Highlights

As a typical heterocyclic structural subunit, the indole scaffold is highly prevalent in biological compounds, pharmaceuticals, natural products and material science [1,2,3,4,5]
The chiral phosphine-oxazoline ligands L1–L4 were synthesized according to the literature [36]
We investigated the ability of four representative spiro phosphine-oxazoline ligands L1–L4 for

Summary

Introduction

As a typical heterocyclic structural subunit, the indole scaffold is highly prevalent in biological compounds, pharmaceuticals, natural products and material science [1,2,3,4,5]. The synthesis and functionalization of chiral indole derivatives is meaningful. It is found that many 3-substitued indoles are important intermediates of natural products, such as (−)-agroclavine and (−)-aurantioclavine (Figure 1). Because of the biologically significant activities, including treatment of migraine headaches, antagonists, antiviral activity and agonist, functionalization of indoles on C-3 position has attracted much attention [6]. Enantioselective alkylation of indoles at the C-3 position by the Friedel–Crafts reaction with Lewis acid as the catalyst has been explored extensively [7,8,9,10]. High catalyst loading (10 %mol) is usually needed to obtain satisfactory yields and enantioselectivites

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Conclusion