Copper-Catalyzed Synthesis of Axially Chiral Biaryls with Diaryliodonium Salts as Arylation Reagents.

Ji-Wei Zhang,Bin Tan,Shao-Hua Xiang,Shaoyu Li

doi:10.3390/molecules26113223

Ji-Wei Zhang, Bin Tan + Show 2 more

Open Access

https://doi.org/10.3390/molecules26113223

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Abstract

NOBIN and BINAM derivatives harboring biaryl frameworks are recognized as a class of important atropisomers with versatile applications. Here, we present an efficient synthetic route to access such compounds through copper-catalyzed domino arylation of N-arylhydroxylamines or N-arylhydrazines with diaryliodonium salts and [3,3]-sigmatropic rearrangement. This reaction features mild conditions, good substrate compatibility, and excellent efficiency. The practicality of this protocol was further extended by the synthesis of biaryl amino alcohols.

Highlights

Chiral biaryl frameworks constitute the core structure of a wide range of natural products and biologically active molecules
NOBIN and BINAM derivatives have been involved in metal catalysis [5,6,7], organocatalysis [8,9], photocatalysis [10], and even heterogeneous catalysis [11] for effective chirality induction
For NOBIN and its derivatives, they could be accessed from other binaphthyl compounds such as BINOL or BINAM [14,15,16]

Summary

Introduction

Chiral biaryl frameworks constitute the core structure of a wide range of natural products and biologically active molecules. For NOBIN and its derivatives, they could be accessed from other binaphthyl compounds such as BINOL or BINAM [14,15,16] In these synthetic processes, excess noble metal reagents, harsh conditions, or expensive reagents were commonly required to achieve satisfactory efficiency [17]. Tu and coworkers successfully constructed enantioenriched 3,3 -disubstituted NOBINs by aerobic oxidative cross-coupling utilizing a novel Cu/SPDO catalytic system [24]. Our group developed an efficient coupling approach for the synthesis of NOBINs via a palladium-catalyzed highly site-selective C-H arylation reaction of N-Boc-2naphthylamines with diazoquinones under mild conditions [25]. D: 20 May 2021 extensive attenqtiuoenns ftrloym, Dthine gsy[n2t2h]etaicnrdesCeaarrcrhecioram[m2u3n]iptyr.ovided a series of improved approaches to ed: date the synthetic efficiency and applicability in large-scale preparations and inhibit in er’s Note: MDPI stays neuble homo-coupling by-products. FFigiguurere2. 2O.uOr ustrrasttergaietsegfoiressyfnotrhessyisnotfhNesOisBIoNf dNerOivBaItiNvesdveiraivcoaptipveer-scavtiaalyczoedppdoemr-icnaotaarlyylzaetidondomino aannddre[a3r,r3a]n-gseigmmenatt. ropic rearrangement

Optimization of Reaction Conditions

Control Experiments and Plausible Mechanism

Conclusions