Pd(II)/Ag(I)-Promoted One-Pot Synthesis of Cyclic Ureas from (Hetero)Aromatic Amines and Isocyanates

Abstract

A simple and facile one-pot reaction has been developed to afford a diverse range of N,N'-disubstituted benzimidazolones and imidazopyridinones containing two differently substituted N atoms. A cooperative Pd(II)/Ag(I) system promotes the sequential addition/intramolecular C-H amidation reaction of (hetero)aromatic amines and isocyanates, leading to the formation of two C-N bonds. A mechanism involving radical intermediates generated by single-electron transfer (SET) in the presence of a AgCO oxidant and Pd(OAc) Lewis acid is proposed. This protocol offers an operationally easy, simple, and robust approach with the use of readily available starting materials, good functional group tolerance, and high efficiency.

Synthesis of Multisubstituted Benzimidazolones via Copper-Catalyzed Oxidative Tandem C–H Aminations and Alkyl Deconstructive Carbofunctionalization

“…It is important to note that benzimidazolone constitutes the core structure of numerous pharmaceuticals, agrochemicals, inhibitors, pigments, herbicides, and fine chemicals (Monforte et al., 2010, Palin et al., 2008, Mastalerz and Oppel, 2012, Mir et al., 2012, Nale and Bhanage, 2015). To date, although there are a number of approaches reported for the synthesis of such compounds, including the cyclization of o -phenylenediamine with phosgene or CO surrogates (Scheme 2, path a), (Monforte et al., 2009, Kuethe et al., 2004, Diao et al., 2009) the cyclization of o -haloanilines involving C–N bond formation (paths b and c) (Zou et al., 2007, An et al., 2016), the oxidative aryl C–H amidation of N-disubstituted ureas (path d) (Beyer et al., 2001, Li et al., 2008, Yu et al., 2015), PhIO-induced Hofmann rearrangement of amides followed by intramolecular nucleophilic attack by an ortho -amino group (path e) (Łukasik and Wróbel, 2016), and the addition of anilines to isocyanates followed by intramolecular oxidative C–H amidation (path f) (Youn and Kim, 2016, Allen and Tidwell, 2013), to the best of our knowledge, the direct construction of benzimidazolones incorporated with additional functionalities from easily available feedstocks is still lacking. On the basis of our new observation, we herein present, for the first time, a multicomponent synthesis of functional benzimidazolones via tandem C–H aminations and alkyl deconstructive carbofunctionalization.

Scheme 2Existing Main Approaches for the Synthesis of Benzimidazolones

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“…Previous Work and the New Observation Scheme 2. Existing Main Approaches for the Synthesis of Benzimidazolones (paths b and c) (Zou et al, 2007;, the oxidative aryl C-H amidation of N-disubstituted ureas (path d) (Beyer et al, 2001;Li et al, 2008;Yu et al, 2015), PhIO-induced Hofmann rearrangement of amides followed by intramolecular nucleophilic attack by an ortho-amino group (path e) (Łukasik and Wró bel, 2016), and the addition of anilines to isocyanates followed by intramolecular oxidative C-H amidation (path f) (Youn and Kim, 2016;Allen and Tidwell, 2013), to the best of our knowledge, the direct construction of benzimidazolones incorporated with additional functionalities from easily available feedstocks is still lacking. On the basis of our new observation, we herein present, for the first time, a multicomponent synthesis of functional benzimidazolones via tandem C-H aminations and alkyl deconstructive carbofunctionalization.…”

Convergent Azaspirocyclization of Bromoarenes with N-Tosylhydrazones by a Palladium Catalyst

“…5a-5d One of the representative examples is the aza-Piancatelli reaction, which can transform furfuryl alcohols with a pendant aminoalkyl group to azaspirocyclopentenones under acidic conditions. 9,10 In most of the above cases, the substituents on the azaspirocycle should be installed before these dearomative reactions, resulting in a linear synthesis.…”

Transition-metal-free C–H amidation and chlorination: synthesis of N/N′-mono-substituted imidazopyridin-2-ones from N-pyridyl-N-hydroxylamine intermediates

“…To address this challenge, several routes to non-symmetric 1,3-substituted imidazopyridin-2-ones utilizing transition-metal catalysed coupling reactions have recently been reported (Scheme 1b). 13, 19-23 Keuthe et al synthesized such scaffolds from 3-iodo-2-chloropyridines utilizing a tandem chemo- and regioselective palladium-catalysed amination sequence. 19 Scott and co-workers prepared the desired pyrido-fused cyclic urea framework from tert -butyl (2-chloropyridin-3-yl)carbamates utilizing a one-pot Buchwald-Hartwig amination/intramolecular amidation strategy.…”

“…21 Furthermore, Youn has recently reported an elegant route for the synthesis of N , N ′-disubstituted imidazopyridinones containing two differently substituted N atoms from 3-aminopyridines and isocyanates via an intramolecular C–H amidation reaction. 23…”