Abstract:Ring-opening hydroarylation of cyclopropanes is typically limited to substrates bearing a donor–acceptor motif. Here, the transformation is achieved for monosubstituted cyclopropanes by using catalytic Brønsted acid in hexafluoroisopropanol (HFIP) solvent.
“…On the contrary, lowering the temperature or loading amount of catalyst leaded to an increased proportion of 3 a (entry 6–9), and under the optimal conditions (entry 8), 3 a could be isolated in moderately high yield as the major product. We also optimized the reaction in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP), which is known to exhibit excellent performance in the nucleophilic ring opening of DACs . We found that 2 a could be obtained in high yield with a catalytic amount of TfOH in diluted solution (entry 12), which is consistent with the common principal of intramolecular reaction.…”
A unique intramolecular arylative ring opening of 2-biaryl substituted donor-acceptor cyclopropanes in the presence of triflic acid was found, furnishing 9H-fluorenes and 9,10-dihydrophenanthrenes. Chemoselectivity between both products is achieved by modification of the solvent, temperature, and amount of triflic acid. Representative large-scale experiments were also carried out successfully with good outcomes.Donor-acceptor cyclopropanes (DACs) are versatile building blocks in organic synthesis for assembling various classes of compounds. The typical cycloaddition of DACs with unsaturated compounds can be used to construct five-, six-, and sevenmembered carbocyclic and heterocyclic compounds. [1] The nucleophilic ring opening of DACs with a variety of heteroatomatic and carbon nucleophiles is demonstrated as a flexible tool to create CÀ X bonds. [1b-c,f-h,j,2] DACs, particularly 2-aryl cyclopropane-1,1-dicarboxylates, have high ring strain, and the corresponding cation and anion intermediates formed by heterolysis of the cyclopropane ring are relatively stable. As a result, DACs usually serve as 1,3-zwitterionic intermediates under the catalysis of Lewis acid or Brønsted acid, and proceed by nucleophilic addition at their C1 position (Scheme 1a). Recently, generation of 1,2-zwitterions from DACs under specified conditions was explored, [3] and some C2-addition reactions were reported (Scheme 1a). [4] Arylative ring opening of 2-aryl substituted DACs forms substituted diarylmethanes by C1-addition (Scheme 1b). Several arylative nucleophiles have been explored, including indoles, [5] benzo[b]furan, [6] electron-rich arenes, [7] polycyclic aromatic species, [7b,g,8] and arylboronic acids bearing electron-donating groups. [9] All of the arylative reactants are relatively reactive nucleophiles, and most of the arylation reactions are intermolecular. [10] However, it is well known that intramolecular reaction can be relatively easily achieved. Hence we assumed that the intramolecular arylative ring opening of DACs with less reactive arenes was possible. The intramolecular reactions would enlarge the limited range of nucleophiles in this type of reaction.With this perspective, we decided to test the intramolecular arylative ring opening of 2-(2'-biphenyl) cyclopropane-1,1dicarboxylate (1 a) to assess the nucleophilicity of the general aryl group (Table 1). When 1 a was treated with one equivalent of triflic acid (TfOH) at room temperature, the C1-addition product, 9H-fluorene 2 a, was indeed formed, but surprisingly, the C2-addition product, 9,10-dihydrophenanthrene 3 a, was obtained as the major product (entry 1). The proportion of 2 a increased with the increasing temperature (entry 2) or loading amount of TfOH (entry 3-5). An excellent yield (95%) of pure 2 a could be obtained when excess TfOH was used (entry 5). On the contrary, lowering the temperature or loading amount of [a]
“…On the contrary, lowering the temperature or loading amount of catalyst leaded to an increased proportion of 3 a (entry 6–9), and under the optimal conditions (entry 8), 3 a could be isolated in moderately high yield as the major product. We also optimized the reaction in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP), which is known to exhibit excellent performance in the nucleophilic ring opening of DACs . We found that 2 a could be obtained in high yield with a catalytic amount of TfOH in diluted solution (entry 12), which is consistent with the common principal of intramolecular reaction.…”
A unique intramolecular arylative ring opening of 2-biaryl substituted donor-acceptor cyclopropanes in the presence of triflic acid was found, furnishing 9H-fluorenes and 9,10-dihydrophenanthrenes. Chemoselectivity between both products is achieved by modification of the solvent, temperature, and amount of triflic acid. Representative large-scale experiments were also carried out successfully with good outcomes.Donor-acceptor cyclopropanes (DACs) are versatile building blocks in organic synthesis for assembling various classes of compounds. The typical cycloaddition of DACs with unsaturated compounds can be used to construct five-, six-, and sevenmembered carbocyclic and heterocyclic compounds. [1] The nucleophilic ring opening of DACs with a variety of heteroatomatic and carbon nucleophiles is demonstrated as a flexible tool to create CÀ X bonds. [1b-c,f-h,j,2] DACs, particularly 2-aryl cyclopropane-1,1-dicarboxylates, have high ring strain, and the corresponding cation and anion intermediates formed by heterolysis of the cyclopropane ring are relatively stable. As a result, DACs usually serve as 1,3-zwitterionic intermediates under the catalysis of Lewis acid or Brønsted acid, and proceed by nucleophilic addition at their C1 position (Scheme 1a). Recently, generation of 1,2-zwitterions from DACs under specified conditions was explored, [3] and some C2-addition reactions were reported (Scheme 1a). [4] Arylative ring opening of 2-aryl substituted DACs forms substituted diarylmethanes by C1-addition (Scheme 1b). Several arylative nucleophiles have been explored, including indoles, [5] benzo[b]furan, [6] electron-rich arenes, [7] polycyclic aromatic species, [7b,g,8] and arylboronic acids bearing electron-donating groups. [9] All of the arylative reactants are relatively reactive nucleophiles, and most of the arylation reactions are intermolecular. [10] However, it is well known that intramolecular reaction can be relatively easily achieved. Hence we assumed that the intramolecular arylative ring opening of DACs with less reactive arenes was possible. The intramolecular reactions would enlarge the limited range of nucleophiles in this type of reaction.With this perspective, we decided to test the intramolecular arylative ring opening of 2-(2'-biphenyl) cyclopropane-1,1dicarboxylate (1 a) to assess the nucleophilicity of the general aryl group (Table 1). When 1 a was treated with one equivalent of triflic acid (TfOH) at room temperature, the C1-addition product, 9H-fluorene 2 a, was indeed formed, but surprisingly, the C2-addition product, 9,10-dihydrophenanthrene 3 a, was obtained as the major product (entry 1). The proportion of 2 a increased with the increasing temperature (entry 2) or loading amount of TfOH (entry 3-5). An excellent yield (95%) of pure 2 a could be obtained when excess TfOH was used (entry 5). On the contrary, lowering the temperature or loading amount of [a]
“…Our group as well as many others have pointed out the enabling effect of solvents, such as hexafluoroisopropanol (HFIP) and nitromethane (MeNO 2 ), on Brønsted and Lewis acid catalyzed reactions through the formation of an H‐bond network. In the case of HFIP, we emphasized that the role of the catalysts was to significantly increase the acidity of an H‐bond cluster of HFIP, which was the true catalytically active species . Our reflections on the reactivity of arylboronic acids started during our investigations on the TfOH‐catalyzed arylative ring‐opening of unactivated cyclopropanes in HFIP (Table , entry 1.1) .…”
Section: Methodsmentioning
confidence: 99%
“…In the case of HFIP, we emphasized that the role of the catalysts was to significantly increase the acidity of an H‐bond cluster of HFIP, which was the true catalytically active species . Our reflections on the reactivity of arylboronic acids started during our investigations on the TfOH‐catalyzed arylative ring‐opening of unactivated cyclopropanes in HFIP (Table , entry 1.1) . We were puzzled by the reactivity of two catalyst systems typically used for activation of alcohols and oximes ( B1 and B3 ), as they were able to trigger the ring‐opening of phenylcyclopropane to generate product 1 (entries 1.2 and 1.5).…”
Boronic acid catalysis has emerged as am ild method for promoting aw ide variety of reactions. It has been proposed that the mode of catalysis involves Lewis acid or covalent activation of hydroxyl groupsb yb oron, but limited mechanistic evidencee xists. In this work, representative boronic acid catalyzedr eactions of alcohols and oximes have been reinvestigated. As eries of control experiments with boronic and Brønsted acids were interpreted along with correlations between their reactivity and their acidity measured by the Gutmann-Beckett method. Overall,i tw as concluded that the major modes of catalysis involvee ither dual H-bondc atalysis or Brønsted acid catalysis. Strong Brønsted acids were shown to be generated in situ from covalenta ssembly of the boronic acids with hexafluoroisopropanol, explaining why the solvent had such am ajor impact on the reactivity.T his new insight should guide the future development of boronic acid catalysis, where the diverse and solvent-specific nature of catalytic modes has been overlooked. Scheme1.Representative boronic acid catalyzed transformations of alcohols and oximes.
“…Another strategy to activate cyclopropanes takes advantage of their alkene-like reactivity, enabling electrophilic activation with Lewis acidic species. While efficacious protocols in this area have been recently disclosed 14–19 , the scope of the nucleophilic components remains limited. Notwithstanding the advances outlined above, the development of protocols for the selective ring-opening and functionalization of non-activated cyclopropanes is a problem that is largely unsolved.Fig.…”
Cyclopropanes represent a class of versatile building blocks in modern organic synthesis. While the release of ring strain offers a thermodynamic driving force, the control of selectivity for C–C bond cleavage and the subsequent regiochemistry of the functionalization remains difficult, especially for unactivated cyclopropanes. Here we report a photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enables the expedient construction of a host of structurally diverse β-amino ketone derivatives. Through one electron oxidation, the relatively inert aryl cyclopropanes are readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination is proposed to proceed through an SN2-like nucleophilic attack/ring-opening manifold. This protocol features wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins is described through a sequential cyclopropanation/oxo-amination.
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