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. 2022 Dec 21;14(3):485-490.
doi: 10.1039/d2sc06225a. eCollection 2023 Jan 18.

Streptocyanine as an activation mode of amine catalysis for the conversion of pyridine rings to benzene rings

Tatsuya Morofuji  1 , Shota Nagai  1 , Airi Watanabe  1 , Kota Inagawa  1 , Naokazu Kano  1
Affiliations

Streptocyanine as an activation mode of amine catalysis for the conversion of pyridine rings to benzene rings

Tatsuya Morofuji et al. Chem Sci. .

Abstract

Amine catalysts have emerged as an invaluable tool in organic synthesis. Iminium, enamine, and enamine radical cation species are representative activation modes of amine catalysis. However, the development of new amine catalysis activation modes that enable novel synthetic strategies remains highly desirable. Herein, we report streptocyanine as a new amine catalysis activation mode, which enables the skeletal editing of pyridine rings to benzene rings. N-Arylation of pyridines bearing an alkenyl substituent at the 3-position generates the corresponding N-arylpyridiniums. The resulting pyridinum reacts with a catalytic amount of piperidine to afford a streptocyanine intermediate. Catalytically generated streptocyanine forms a benzene ring via a ring-closing reaction, thereby releasing the amine catalyst. Consequently, the alkene moiety in the starting pyridines is incorporated into the benzene ring of the products. Pyridiniums bearing various alkene moieties were efficiently converted to formyl-substituted benzene derivatives. Mechanistic studies support the postulation that the present catalytic process was intermediated by streptocyanine. In this reaction system, streptocyanine could be regarded as a new activation mode of amine catalysis.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Reaction of secondary amines (a) with carbonyl compounds, (b) with N-arylpyridiniums.
Fig. 2
Fig. 2. Working hypothesis for streptocyanine catalysis and its application to skeletal editing of pyridine rings to benzene rings. Ar = 2,4-dinitrophenyl.
Scheme 1
Scheme 1. Scope of benzene ring formation via amine-catalyzed activation of pyridine rings. Pyridinium 1 (0.1 mmol), piperidine (0.02 mmol), K2CO3 (0.2 mmol), H2O (10 mmol), and THF were stirred in a pressure tube under argon atmosphere. Ar = 2,4-dinitrophenyl. Ad = adamantyl.
Scheme 2
Scheme 2. Conversion of pyridiniums to various benzene derivatives using an amine catalyst. Pyridinium 1 (0.1 mmol), piperidine (0.02 mmol), K2CO3 (0.2 mmol), H2O (10 mmol), and THF were stirred in a pressure tube under argon atmosphere. Ar = 2,4-dinitrophenyl. a The reaction was carried out at 40 °C for 16 hours.
Scheme 3
Scheme 3. Formal synthesis of an anti-microtube agent. (a) 4′-Fluoroacetophenone, NaOH, MeOH/H2O, r.t., 17 h. (b) 2,4-(NO2)2C6H3OTs, toluene, reflux, 20 h. (c) Piperidine (20 mol%), K2CO3, H2O, THF, 120 °C, 42 h. Ar = 2,4-dinitrophenyl.
Scheme 4
Scheme 4. Mechanistic studies. (a) Reaction of N-arylpyridinium 6 with 0.5 equiv. of piperidine. (b) HRMS analysis. Ar = 2,4-dinitrophenyl.
Scheme 5
Scheme 5. Plausible reaction mechanism for benzene ring formation via amine-catalyzed skeletal-editing of the pyridine ring in pyridiniums.
See this image and copyright information in PMC

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