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(OA… Show more
“…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…”
Section: Introductionmentioning
confidence: 99%
“…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.…”
Summary
Benzimidazolone constitutes the core structure of numerous pharmaceuticals, agrochemicals, inhibitors, pigments, herbicides, and fine chemicals. Amination of hydrocarbons is an attractive tool for the creation of nitrogen-containing products. However, the multiple steps, harsh conditions, and low atom efficiencies often present in these reactions remain challenging. We present a multicomponent synthesis of functional benzimidazolones from arylamines, dialkylamines, and alcohols, acting via the sequence of copper-catalyzed oxidative tandem C–H aminations and alkyl deconstructive carbofunctionalization. The catalytic transformation forms multiple bonds in one single operation, uses readily available feedstocks and a naturally abundant Cu/O
2
catalyst system, has broad substrate scope, avoids pre-installation of aminating agents and directing groups, and provides high chemo- and regioselectivity, resulting in direct functionalization of inert C–H and C–C bonds via single-electron oxidation-induced activation mode. This platform can be expected to provide structurally diverse products with interesting biological, chemical, and physical properties.
“…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…”
Section: Introductionmentioning
confidence: 99%
“…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.…”
Summary
Benzimidazolone constitutes the core structure of numerous pharmaceuticals, agrochemicals, inhibitors, pigments, herbicides, and fine chemicals. Amination of hydrocarbons is an attractive tool for the creation of nitrogen-containing products. However, the multiple steps, harsh conditions, and low atom efficiencies often present in these reactions remain challenging. We present a multicomponent synthesis of functional benzimidazolones from arylamines, dialkylamines, and alcohols, acting via the sequence of copper-catalyzed oxidative tandem C–H aminations and alkyl deconstructive carbofunctionalization. The catalytic transformation forms multiple bonds in one single operation, uses readily available feedstocks and a naturally abundant Cu/O
2
catalyst system, has broad substrate scope, avoids pre-installation of aminating agents and directing groups, and provides high chemo- and regioselectivity, resulting in direct functionalization of inert C–H and C–C bonds via single-electron oxidation-induced activation mode. This platform can be expected to provide structurally diverse products with interesting biological, chemical, and physical properties.
“…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.…”
Azaspirocyclic compounds have gained attention in chemistry and drug discovery fields. In this manuscript, the development of a Pd-catalyzed dearomative azaspirocyclization of bromoarenes bearing an aminoalkyl group with N-tosylhydrazones is described. The present method enables azaspirocyclization with the introduction of carbon substituents, achieving the convergent synthesis of 1-azaspirocycles. This method allowed furan, thiophene, and naphthalene cores to generate the corresponding 1-azaspirocycles. The obtained azaspirocycles from furans were further elaborated via an acid-catalyzed rearrangement to afford 1-azaspirocyclopentenones.
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“…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.…”
mentioning
confidence: 99%
“…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…”
Non-symmetric 1,3-substituted imidazopyridin-2-ones are a common structural scaffold found among many biologically active molecules. Herein we report an efficient, mild, and transition-metal free C-H amidation strategy to access such a pyrido-fused cyclic urea framework in good yields and with a broad functional group tolerance.
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