N- and O-arylation of pyridin-2-ones with diaryliodonium salts: base-dependent orthogonal selectivity under metal-free conditions.

Masami Kuriyama,Shimpei Ono,Kosuke Yamamoto,Osamu Onomura,Kotone Katagiri,Yusuke Abe,Natsumi Hanazawa

doi:10.1039/d0sc02516j

Masami Kuriyama, Shimpei Ono + Show 5 more

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https://doi.org/10.1039/d0sc02516j

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Abstract

Metal-free N- and O-arylation reactions of pyridin-2-ones as ambident nucleophiles have been achieved with diaryliodonium salts on the basis of base-dependent chemoselectivity. In the presence of N,N-diethylaniline in fluorobenzene, pyridin-2-ones were very selectively converted to N-arylated products in high yields. On the other hand, the O-arylation reactions smoothly proceeded with the use of quinoline in chlorobenzene, leading to high yields and selectivities. In these methods, a variety of pyridin-2-ones in addition to pyridin-4-one and a set of diaryliodonium salts were accepted as suitable reaction partners.

Highlights

Carbon–heteroatom bond forming reactions are one of the fundamental transformations in organic synthesis.[1]
As a metal-free process, Mukaiyama achieved the N-arylation with organobismuth reagents.7a While Gaunt reported the preparation of 2-phenoxypyridine with the use of diphenyliodonium uoride,7c Mo developed the metal-free O-arylation of 6-substituted pyridin-2-ones.7b The utilization of appropriate catalysts and reagents is a promising approach to control chemoselectivity for ambident nucleophiles,[9,10] and the orthogonal selectivity in arylation reactions of N,O-nucleophiles has been realized with transition-metal catalysts to give simple and useful methods.[11]
The chemoselectivity in the formation of arylated aminophenols largely depended on the kind of catalyst metals,11a while bidentate ligands for a copper catalyst played key roles in the selective arylation of aminoalcohols (Scheme 1a).11b Buchwald found that copper catalysts had the ability to switch the selectivity for the N- and O-arylation of pyridin-2-one with aryl iodides (Scheme 1b).[12]

Summary

Introduction

Carbon–heteroatom bond forming reactions are one of the fundamental transformations in organic synthesis.[1]. The examination of organic bases proved that the reaction conditions with pyridine gave the O-phenylated product 4aa with a high selectivity despite a low yield, while the highly selective formation of the N-phenylated product 3aa was observed with a high yield in the presence of DIPEA (entries 2–3). The use of pyridine and 2,6-lutidine gave the O-phenylated product 4aa in moderate yields with good selectivites, and 2,6-lutidine led to a slightly better result (entries 1–2).

Results

Conclusion