N‐arylcarbazole structures are important because of their prevalence in natural products and functional OLED materials. C−H amination of arenes has been widely recognized as the most efficient ...approach to access these structures. Conventional strategies involving transition‐metal catalysts suffer from confined substrate generality and the requirement of exogenous oxidants. Organocatalytic enantioselective C–N chiral axis construction remains elusive. Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N‐arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N‐arylcarbazoles in good yields with excellent enantiocontrol. This approach not only offers an alternative to metal‐catalyzed C–N cross‐coupling, but also brings about opportunities for the exploitation of structurally diverse N‐aryl atropisomers and OLED materials.
In the frame: Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N‐arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N‐arylcarbazoles in good yields with excellent enantiocontrol. This approach offers opportunities for the exploitation of structurally diverse N‐aryl atropisomers and OLED materials. CPA=chiral phosphoric acid.
Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed ...to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C−N bond formation while the resulting amine performs the nucleophilic addition to form the second C−N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N‐arylbenzimidazoles for their potential utilities in asymmetric catalysis.
A benzimidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis is presented. Two sets of conditions were developed to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol.
Functionalization of arenes represents the most efficient approach for constructing a core backbone of important aryl compounds. Compared with the well-developed electrophilic aromatic substitution ...and transition-metal-catalyzed C–H activation, nucleophilic aromatic substitution remains challenging because of the lack of a convenient route for rapid conversion of the σH adduct to other stable and versatile intermediates in situ. Guided by computational design, we were able to realize asymmetric nucleophilic aromatic substitution by introducing a nitroso group on naphthalene via chiral phosphoric acid catalysis. This strategy enables efficient construction of atropisomeric indole-naphthalenes and indole-anilines with excellent stereocontrol. Density functional theory (DFT) calculations provide further insights into the origins of enantioselectivity and the reaction mechanisms. The successful application in the synthesis of NOBINs (2-amino-2′-hydroxy-1,1′-binaphthyl) extends the utility of this strategy.
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•Computation-guided screening of functional groups for arene activation•Chemoselective C–H functionalization of 2-nitrosonaphthalene at an unconventional site•One-pot synthesis of optically active NOBINs by a solo organocatalytic system•Divergent access to two types of axially chiral arylindole frameworks
Highly efficient conversion of inexpensive and readily available arene materials into high-value-added chiral molecules is of great importance in modern synthetic chemistry given the enormous potential of such structures in functional materials, pharmaceuticals, and other relevant chemical industries. Organocatalytic nucleophilic aromatic substitution enabled by an azo group offers an effective approach to enantioselective functionalization of naphthalene C–H bonds featuring an intramolecular oxidation of an unstabilized σH adduct. Premised on density functional theory (DFT) calculations, nitroso has emerged as another promising activating and oxidative group, whose synthetic potential is substantiated in the atroposelective synthesis of several groups of representative biaryl atropisomers processed by a chiral phosphoric acid catalyst. The success of this reaction explicitly exemplifies the ability of computational tools to streamline organic synthesis with intensified robustness in the disclosed strategy.
Guided by computational design, Tan and colleagues disclose a chiral phosphoric-acid-catalyzed asymmetric functionalization of naphthalenes with nitroso as the activating and directing group. This nucleophilic aromatic substitution reaction allows divergent access to two types of axially chiral arylindole frameworks with wide substrate generality under excellent enantiocontrol and, more importantly, offers a facile approach to the privileged NOBIN (2-amino-2′-hydroxy-1,1′-binaphthyl) structures. DFT calculations illustrate the plausible reaction pathway and provide additional insights into the origins of enantioselectivity.
Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed ...to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C−N bond formation while the resulting amine performs the nucleophilic addition to form the second C−N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N‐arylbenzimidazoles for their potential utilities in asymmetric catalysis.
A benzimidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis is presented. Two sets of conditions were developed to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol.
N‐arylcarbazole structures are important because of their prevalence in natural products and functional OLED materials. C−H amination of arenes has been widely recognized as the most efficient ...approach to access these structures. Conventional strategies involving transition‐metal catalysts suffer from confined substrate generality and the requirement of exogenous oxidants. Organocatalytic enantioselective C–N chiral axis construction remains elusive. Presented here is the first organocatalytic strategy for the synthesis of novel axially chiral N‐arylcarbazole frameworks by the assembly of azonaphthalenes and carbazoles. This reaction accommodates broad substrate scope and gives atropisomeric N‐arylcarbazoles in good yields with excellent enantiocontrol. This approach not only offers an alternative to metal‐catalyzed C–N cross‐coupling, but also brings about opportunities for the exploitation of structurally diverse N‐aryl atropisomers and OLED materials.
Gerüstbau: Mit der ersten organokatalytischen Strategie wurden neuartige axial‐chirale N‐Arylcarbazolgerüste durch Zusammenfügen von Azonaphthalinen und Carbazolen synthetisiert. Das Substratspektrum ist breit, und man erhält atropisomere N‐Arylcarbazole in guten Ausbeuten bei exzellenter Enantiokontrolle. Dieser Ansatz bietet Möglichkeiten zur Erschließung von strukturell unterschiedlichen N‐Aryl‐Atropisomeren und OLED‐Materialien. CPA=chirale Phosphorsäure.
AIM： To clarify the incidence and nature of postoperative hyperbilirubinemia in patients after modern extracorporeal circulation, to analyze possible perioperative risk factors, and to elucidate the ...clinical significance of postoperative hyperbilirubinemia associated mortality and morbidity. METHODS： Between March 2005 and May 2006, three hundred and eighty six consecutive patients undergoing extracorporeal circulation surgery due to a variety of cardiac lesions were investigated prospectively. The incidence of postoperative hyperbilirubinemia was defined as a serum total bilirubin concentration of more than 51 μmol/L. Several perioperative parameters were compared by logistic regression between hyperbilirubinemia and non-hyperbilirubinemia patients to determine possible risk factors contributing to postoperative hyperbilirubinemia and mortality. RESULTS： Overall incidence of postoperative hyperbilirubinemia was 25.3% （98/386）. In patients with postoperative hyperbilirubinemia, 56.2% reached peak total bilirubin concentration on the first postoperative day, 33.5% on the second day, and 10.3% on the seventh day. Eighty percent of the increase of total bilirubin resulted from an increase of both conjugated and unconjugated bilirubin. Development of postoperative hyperbilirubinemia was associated with a higher mortality （P 〈 0.01）, longer duration of mechanical ventilation （P 〈 0.05） and longer ICU stay time （P 〈 0.05）. Preoperative total bilirubin concentration, preoperative right atrium pressure, numbers of valves replaced and of blood transfusion requirement were identified as important predictors for postoperative hyperbUirubinemia. CONCLUSION： Early postoperative hyperbilirubinemia after modern extracorporeal circulation is mainly caused by an increase in both conjugated and unconjugated bilirubin, and is associated with a high mortality. Important contributing factors are the preoperative total bilirubin concentration, preoperative severity of right atrial pressure, numbers of valve replacement procedures, and the amount of blood transfusion requirement during and shortly after surgery. We suggest that postoperative hyperbilirubinemia is a multifactorial process, which is caused by,both the impaired liver function of bilirubin transport and the increased production of bilirubin from haemolysis.
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