ACS catalyst: Miura group reported the Rh (III) - catalyzed cyclization of C-H / N-H with ethylene carbonate as acetylene substitute

Polycyclic heteroaryl frameworks are widely found in many natural compounds and common functional molecules Therefore, it has become a research hotspot for chemists to develop a new and efficient synthesis method of fused ring skeleton Transition metal catalyzed C-H activation and subsequent epoxidation with alkynes or their equivalents have become effective tools for the synthesis of heterocycles (scheme1a) However, most of these reactions are only suitable for internal alkynes Because the unsubstituted vinyl segments cannot be installed by catalytic method, the practical value of the coupling reaction is greatly reduced In addition, stoichiometric external oxidants are usually needed for the above reactions to ensure the circulation of catalyst, which will also lead to the formation of by-products In order to realize the catalytic preparation of vinyl condensed aromatic compounds, appropriate acetylene substitutes must be used Recently, vinyl acetate and α - chloroacetaldehyde were used as acetylene equivalents to install vinyl segments (scheme 1b) However, these equivalents are limited to coupling with n-alkoxyamide and oxime Recently, the Masahiro Miura group of Osaka University in Japan reported the ring reaction of C-H / N-H catalyzed by RH (III) with ethylene carbonate as acetylene substitute Ethylene carbonate is used as internal oxidant to regenerate Rh (III) species in situ The related research results were published on ACS catalyst (DOI: 10.1021 / acscalal 9b04254) (source: ACS catalyst.) at first, the author used n-methoxybenzamide (1a) and vinyl carbonate (2) as model substrates to study the reaction In the presence of rhodium catalyst and 1.0 equivalent 2, the target product 3A (Table 1, entry 1) can be obtained in 78% yield Then the author screened the conditions of temperature and catalyst, and found that when the amount of 2 increased to 2 equivalent, the yield increased slightly; when the temperature decreased to 70 ° C, the yield increased further, and 3a was separated from the reaction with 86% yield (Table 1, entry 7) (source: ACS catalyst.) under the optimal reaction conditions, the author first investigated the scope of application of amide (scheme 2) In addition to hydroxamate 1a, n-alkylsec amides can form corresponding Isoquinolinone 3b-3d in high yield The corresponding cyclization product 3E - 3H can be obtained from the substrates with various substituents in the yield of 60% - 90% Fused or heterocyclic amides are also suitable substrates, and Isoquinolinone 3I - 3K is obtained in good yield (source: ACS catalyst.) the possible mechanism of the cyclization coupling reaction is shown in scheme 3 The amide guiding group is coordinated with the cationic Cp * Rh (III) species, thus forming a five membered rhodium ring a through the activation of the proximal C-H bond The ethylene carbonate is transferred and inserted into rh-c bond to form a seven membered metal ring B According to the literature, the author speculates that intermediate B is eliminated by C-N bond reduction and C-O bond oxidation addition to form compound C After β - oxygen elimination, the corresponding coupling products and the active Rh (III) complex were released Another secondary pathway is that intermediate B may undergo β - oxygen elimination and decarboxylation reaction to form alkoxide complex D The protonation of intermediate D produces the target product through the corresponding aldehyde intermediate (source: ACS catalyst.) in order to prove the universality of the reaction system, the author used the C-H / N-H oxidation cyclization method to synthesize various n-heteroaromatics (scheme 4) Under slightly adjusted reaction conditions, acetanilide 4 can be used to prepare a variety of indole 5 (scheme 4a) in one step 2-arylbenzimidazole was also compatible with the reaction system, and the corresponding fused ring product 7 (scheme 4b) was obtained in good yield In addition, Isoquinolinone and a variety of imine derivatives can be successfully cyclically coupled with vinyl carbonate, and polycyclic products 9 and 11 (scheme 4C and 4D) can be obtained in good yields, respectively (source: ACS catalyst.) in a word, the author developed Rh (III) - catalyzed cyclization coupling reaction with vinyl carbonate as acetylene substitute The remarkable characteristics of the reaction system are: (1) no pre functionalization is needed to directly obtain the unsubstituted vinyl group fused cyclic compounds; (2) no extra external oxidants or bases are needed in the catalytic conversion process In addition, the C-H / N-H oxidation cyclization reaction can also be used to prepare a variety of n-heteroaromatics.