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.
Pnictogen-bonding catalysis based on σ-hole interactions has recently attracted the attention of synthetic chemists. As a proof-of-concept for asymmetric pnictogen-bonding catalysis, we report herein ...an enantioselective transfer hydrogenation of benzoxazines catalyzed by a novel chiral antimony cation/anion pair. The chiral pnictogen catalyst library could be rapidly accessed from triarylstibine with readily available mandelic acid analogues, and the catalyst displays remarkable efficiency and enantiocontrol potency even at 0.05 mol % loading. Moreover, the properties of the catalyst and the mechanistic insights have been investigated by nonlinear effect studies, 1H NMR, LC-MS, and control experiments.
Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic ...element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.
By a simple stereoselective condensation with remote chirality control, axial chirality could be introduced to the symmetric anthrone backbones that comprise mostly sp2‐hybridized carbons. The generated oxime ether functionality enables their transformation with axial‐to‐point chirality conversion via Beckmann rearrangement into enantioenriched dibenzo‐fused seven‐membered N‐heterocycles.
Abstract
Chiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially optically enriched ...1,1-diboron compounds, has been greatly inhibited by the lack of direct synthetic protocols. Therefore, it is very challenging to develop a simple and effective strategy to obtain chiral 1,1-diborylalkanes. Herein, we develop an enantioselective copper-catalyzed cascade double hydroboration of terminal alkynes and highly enantioenriched
gem
-diborylalkanes were readily obtained. Our strategy uses simple terminal alkynes and two different boranes to construct valuable chiral
gem
-bis(boryl) alkanes with one catalytic and one ligand pattern, which represents the simplest and most straightforward strategy for constructing such chiral
gem
-diborons.
Aspongdopamines A and B (1 and 2), unusual adducts composed of N-acetyldopamine and adenine were isolated from the insect Aspongopus chinensis. Compounds 1 and 2 are positional isomers both isolated ...as racemates. Chiral separation assisted by 14-step total synthesis and computation including vibrational circular dichroism calculations allowed us to unambiguously assign the absolute configurations of eight stereoisomers. Renal fibrosis inhibition of the stereoisomers was evaluated in TGF-β1-induced rat kidney epithelial cells.
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.
Despite the increased importance of C-glycosides in biochemistry, the strategy for creating the C-glycosidic bond stereoselectively has received less attention than that for its O- and ...N-counterparts. We describe here a β-C-glycosylation of oxazol-5(4H)-ones which are the direct precursors of amino acids. For a wide variety of glycal donors and glycosyl acceptors, this chemistry could be accomplished with excellent efficiency and exquisite chemoselectivity without exogenous bases in most cases. The excellent stereocontrol at the anomeric center originates from the steric hindrance imposed by the bulky phosphine ligand.
Strategies for site-selective C–H difunctionalization on N-alkyl activated azaarenes have attracted considerable attention as a powerful tool in heterocyclic chemistry. By employing graphene oxide ...(GO) as a heterogeneous cocatalyst, the visible light-induced site-selective difunctionalizations of pyridiniums/quinoliniums provided a distinct and straightforward synthetic route toward C4- and C2-selective phosphonation of the pyridinone/quinolinone/quinolone cores. Furthermore, the site-selectivity on quinoliniums could be successfully switched from C4 to C2 by changing the base and solvent. This coordination of catalysis systems drove the regioselective phosphonyl radical and phosphoryl anion addition to N-alkyl activated azaarenes, respectively, and subsequent oxidation with air as the terminal oxidant. In vitro antitumor studies showed that complex 3c participated in mitochondria-mediated pathways on the apoptosis of HeLa cells to 42.2% (21 μM). Phosphorus-based organocatalyst 4e, as one of the optical materials, offered efficient tuning of the emission and quantum yields.
We herein present an electrochemical method for the dehydrogenative cross-coupling of
-(4-hydroxyphenyl)-sulfonamides and 2-naphthols. This transformation provides a direct and scalable approach to a ...wide range of
-symmetric 2,2'-bis(arenol)s with moderate to high yields under mild conditions. Preliminary attempts with the asymmetric variant of this reaction were also performed with ≤55% ee for the synthesis of 2,2'-bis(arenol)s. Control experiments were conducted to propose a plausible mechanism for the reaction.
This report describes a highly efficient β-selective C-glycosylation of bicyclic galactals with 2-oxindoles through a palladium-catalyzed decarboxylative pathway. A variety of substrates representing ...both glycosyl donors and acceptors could be transformed in greater than 90% yields under mild reaction conditions. The decarboxylation intermediate of galactal could serve as an efficient base to deprotonate the enol tautomer of 2-oxindole and enhance its nucleophilicity. The β-selective nucleophilic addition at the anomeric center originates from the steric hindrance imposed by the palladium and bulky ligand.
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