Rhodium-catalyzed asymmetric 1,4-addition reactions of aryl boronic acids with nitroalkenes: reaction mechanism and development of homogeneous and heterogeneous catalysts.

Hiroyuki Miyamura,Kohei Nishino,Shū Kobayashi,Tomohiro Yasukawa

doi:10.1039/c7sc03025h

Hiroyuki Miyamura, Kohei Nishino + Show 2 more

Open Access

https://doi.org/10.1039/c7sc03025h

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Abstract

Asymmetric 1,4-addition reactions with nitroalkenes are valuable because the resulting chiral nitro compounds can be converted into various useful species often used as chiral building blocks in drug and natural product synthesis. In the present work, asymmetric 1,4-addition reactions of arylboronic acids with nitroalkenes catalyzed by a rhodium complex with a chiral diene bearing a tertiary butyl amide moiety were developed. Just 0.1 mol% of the chiral rhodium complex could catalyze the reactions and give the desired products in high yields with excellent enantioselectivities. The homogeneous catalyst thus developed could be converted to a reusable heterogeneous metal nanoparticle system using the same chiral ligand as a modifier, which was immobilized using a polystyrene-derived polymer with cross-linking moieties, maintaining the same level of enantioselectivity. To our knowledge, this is the first example of asymmetric 1,4-addition reactions of arylboronic acids with nitroalkenes in a heterogeneous system. Wide substrate generality and high catalytic turnover were achieved in the presence of sufficient water without any additives such as KOH or KHF2 in both homogeneous and heterogeneous systems. Various insights relating to a rate-limiting step in the catalytic cycle, the importance of water, role of the secondary amide moiety in the ligand, and active species in the heterogeneous system were obtained through mechanistic studies.

Highlights

Asymmetric synthesis is crucial in ne chemical production, such as the synthesis of drugs, biologically active compounds, and natural products
We report the development of asymmetric 1,4-addition reactions of aryl boronic acids with nitroalkenes with a high catalytic turnover and excellent enantioselectivity using both homogeneous metal complex and heterogeneous metal nanoparticle systems of chiral diene ligand 4c without any additives, such as KOH and KHF2
A family of chiral dienes with bicyclo[2,2,2]hexadiene structure were developed independently by Hayashi et al and Carreira et al They have been widely used for transition metal-catalyzed asymmetric reactions, Rh-catalyzed asymmetric 1,4addition-type reactions.[52–55]

Summary

Introduction

Asymmetric synthesis is crucial in ne chemical production, such as the synthesis of drugs, biologically active compounds, and natural products. As a strategy to convert homogeneous catalysis to heterogeneous catalysis, the use of heterogeneous metal nanoparticle catalysts is of great interest because of their reusability, robustness and high reactivity.[22,23,24,25] Recently, several organic transformations originally catalyzed by homogeneous catalysts have been successfully converted to heterogeneous metal nanoparticle catalysis.[26,27] Asymmetric organic synthesis with heterogeneous metal nanoparticle systems using chiral ligands as “chiral modi ers” have been investigated, especially in asymmetric hydrogenation reactions pioneered by Orito et al.[28,29] Several mechanistic studies, even including theoretical calculations, have been conducted for Orito-type reactions.[30,31,32,33,34,35] In contrast, asymmetric C–C bond formation reactions using heterogeneous metal nanoparticle systems is a very limited and developing eld, and their reaction mechanisms are obscure in contrast to matured asymmetric hydrogenation reactions.[27,36–43] In this context, we have developed chirally modi ed rhodium and bimetallic nanoparticle systems based on a polymer-incarcerated (PI) strategy, in which polystyrene derivatives with cross-linking moieties (Fig. 1a) are used to immobilize metal nanoparticles.[44–48]. This is the rst heterogeneous system for this asymmetric transformation, and we have found various insights into the reaction mechanism, especially that are different from asymmetric 1,4-addition reactions with a,b-unsaturated carbonyl compounds

Results and discussion

Discussion of proposed reaction mechanism

Conclusion