A convenient photoredox‐catalyzed defluorinative trifluoromethylation of α‐trifluoromethyl alkenes and gem‐difluoroalkenes is developed. The reactions proceeded efficiently via trifluoromethyl ...radical addition followed by β‐fluorine elimination process, providing a new entry to multifluorinated alkenes in moderate to good yields with excellent stereoselectivity.
Indoles are one of the most ubiquitous subclass of N-heterocycles and are increasingly incorporated to design new axially chiral scaffolds. The rich profile of reactivity and N-H functionality allow ...chemical derivatization for enhanced medicinal, material and catalytic properties. Although asymmetric C-C coupling of two arenes gives the most direct access of axially chiral biaryl scaffolds, this chemistry has been the remit of metal catalysis and works efficiently on limited substrates. Our group has devoted special interest in devising novel organocatalytic arylation reactions to fabricate biaryl atropisomers. In this realm, indoles and derivatives have been reliably used as the arylation partners in combination with azoarenes, nitrosonapthalenes and quinone derivatives. Their efficient interaction with chiral phosphoric acid catalyst as well as the tunability of electronics and sterics have enabled excellent control of stereo-, chemo- and regioselectivity to furnish diverse scaffolds. In addition, indoles could act as nucleophiles in desymmetrization of 1,2,4-triazole-3,5-diones. This account provides a succinct illustration of these developments.
Axial chirality is historically epitomized by biaryl compounds containing rotationally impeded aryl-aryl linkage. As the field of atroposelective catalysis advances, the synthesis and application of ...less common scaffolds such as alkenes have now come to the fore. The manifestation of axial chirality in aryl alkenes was hypothesized in 1928 and the first resolution was achieved nearly a decade later. However, catalytic asymmetric construction of axially chiral open-chain alkenes appeared only in 2017 which ushered in a renewed focus on these structures. In principle, axially chiral alkenes possess an alkene group tethered at one end of the stereogenic axis, which greatly reduces the overall rigidity. To date, atropisomers with C (vinyl)-C (aryl) and C (vinyl)-heteroatom bond have been reported. Considering the rapid growth in the synthesis and synthetic utility of axially chiral open-chain alkenes, this review intends to provide a historical overview and discusses these new developments. It is hope that this timely discussion would motivate continued growth of this nascent field.
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The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings in terms of efficient synthetic access and skeletal variety. This account describes ...our strategies in answering these challenges within the organocatalytic context where the emergence of bifunctional catalysts such as chiral phosphoric acids (CPAs) has proven invaluable in controlling the sense of axial chirality. The wide occurrence of bi(hetero)aryl skeletons in privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating the intrinsic nucleophilicity of aromatic amines and alcohols. The first approach involves the design of an electron-withdrawing activating group which could associate with the catalyst for reactivity enhancement and selectivity control. The resonance of arenes offers the unique mechanistic possibility to select between activating sites. C2-Azo- and nitroso-substituted naphthalenes undergo atroposelective
- or
-arylation with (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads to regioselective activation by catalytic control alone or aided by substrate design. For instance, selective addition to nitroso nitrogen enables successive annulation initiated by the amine to yield axially chiral
-arylbenzimidazoles. In a biomimetic manner, a finely tuned catalyst could direct a
-selective nucleophilic approach in the atroposelective arylation of azobenzenes. The second strategy employs electrophilic arene precursors for arylation which occurs via rearomatization with central-to-axial chirality transfer. This enabled the arylation of (imino)quinones with indoles to access phenylindole atropisomers. By adapting this chemistry with an additional oxidation event to liberate the carbonyl functionalities, aryl-
-naphthoquinone and aryl-
-quinone atropisomers were attained. Along with the development of new arylation strategies, deriving new axially chiral structures has been another consistent theme of our research program. The atroposelective functionalization of alkynes provides broad entry to atropisomeric alkenes. The monofunctionalization of alkynes through the interception of an electrophilic vinylidene-quinone-methide (VQM) intermediate with 2-naphthols yielded the new EBINOL scaffolds. By designing an internal directing group, the atroposelective dihalogenation of alkynes was realized using abundant alkali halides despite their weak nucleophilicities and poor solubilities. The atroposelective
-alkylation of alkenes was pursued to prepare multifunctionalized alkene atropisomers that could be converted into 2-arylpyrroles with chirality transfer. The synthesis of
-aryl-1,2-azaborines containing a C-B chiral axis was accomplished where the CPA catalyst effects the desymmetrization and defines the configuration of the distal C-B bond. Inspired by the axially chiral scaffold of allenes, we leveraged the developed arene activation strategy to achieve
-addition and dearomatization of judiciously designed azobenzenes, which led to structurally novel cyclohexadienylidene-based hydrazones. To complement these structures, axially chiral cyclohexadienyl oxime ethers were also attained through CPA-catalyzed condensation between hydroxylamines and spiro4.5trienones.
The application of Suzuki–Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)‐C(alkene) axis ...is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine‐tuning of reaction parameters, we identified a highly active 3,3′‐triphenylsilyl‐substituted phosphite ligand to realize arene‐alkene Suzuki–Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl‐alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.
The construction of axially chiral acyclic aryl‐alkene skeletons via classic Suzuki–Miyaura reaction has been challenging compared to the biaryls. Rational optimization established an enabling 3,3′‐triphenylsilyl‐substituted phosphite ligand for asymmetric coupling of hindered aryl halides and vinyl boronates under mild conditions, affording the acyclic aryl‐alkenes in good yield, atroposelectivity and E/Z selectivity.
Z only: An atom‐economical synthetic route towards arylated Z‐enamides through double CH functionalization is described. The Z/E selectivity of the palladium‐catalyzed monoarylation is absolute ...(step A in scheme), and the molecular complexity of the products can be further endowed by a sequential second arylation, which requires the use of trifluoracetic acid (TFA; step B).
Stapling a G-quadruplex specific peptide Yaneva, Militsa Yavorova; Cheong, Vee Vee; Cheng, Jun Kee ...
Biochemical and biophysical research communications,
10/2020, Volume:
531, Issue:
1
Journal Article
Peer reviewed
Open access
G-quadruplex (G4) is a non-canonical four-stranded nucleic acid structure and the RHAU helicase has been identified to have high specificity for recognition of parallel-stranded G4s. We have designed ...and synthesized two stapled peptide analogues of the G4-specfic motif of RHAU, which preserve the G4 binding ability. Characterization of these peptides identified the stapled variants to exhibit higher helical formation propensity in aqueous buffer in comparison to the native RHAU sequence. Moreover, the stapled peptides exhibit superior enzymatic stability towards α-chymotrypsin. Our stapled RHAU peptides can serve as a new tool for targeting G4 nucleic acid structures.
The conceptually designed imidodiphosphorimidates (IDPis) have emerged as one of the most potent classes of chiral acid catalysts. They are characterized by enzyme‐like, highly confined active site ...and high acidity, which underlie their wide‐reaching applications as Brønsted acid catalysts and as precatalysts for silylium Lewis acids. Many carbon‐carbon and carbon‐heteroatom bond formation reactions that were deemed intractable could now be attained with spectacular reactivity and selectivity. Substrates that are small, unbiased and/or possess insufficient reactivity such as simple alkenes could now be engaged. The high structural confinement is particularly invaluable to control stereo‐ and chemoselectivity. The well‐defined steric environment offers unique opportunity to control high‐energy but structurally unbiased cation intermediates such as the norbonyl cations. Beyond practical appeals such as good scalability as well as ease and modularity of preparation, the extremely low pre‐catalyst loadings required to achieve high turnover and stereoselectivity have also come to define a new frontier in organocatalysis.
The extraordinary performance of IDPis in terms of reactivity and selectivity control pushes the boundaries of what can be accomplished with asymmetric acid catalysis. This article discusses their applications to realize various challenging carbon‐carbon and carbon‐heteroatom bond formations.
Atroposelective cross‐coupling is one of the most appealing routes to construct axially chiral binaphthyl molecules due to the modular and succinct nature. Although transition‐metal‐catalyzed ...cross‐couplings offer reliable synthetic means, alternative reaction modes that could be applied to broader substrate range without their pre‐functionalization is highly desirable. Herein we show that the application of chiral Brønsted acid catalyst as organocatalyst could accomplish cross‐coupling of 1‐azonaphthalenes and 2‐naphthols with high efficiency, exclusive C4‐selectivity as well as excellent enantioselectivity and functional group compatibility. The identification of acylimidazolinone auxiliary for azo activating group, effective remote catalyst control and arene resonance effect synergistically play key roles in the development of this method. The utility is further demonstrated by transformations of the products into other binaphthyl compounds with perfectly retained axial chirality.
By judicious development of acylimidazolinone as activating group and the use of a chiral Brønsted acid (CBA) catalyst, the cross‐coupling of 1‐azonaphthalenes with 2‐naphthols was realized with high efficiency, exclusive C4‐selectivity and excellent enantioselectivity. The reaction tolerates various functional groups and stereoretentive conversions of products to other binaphthyl compounds were found viable.
Azonaphthalenes have been verified as a class of effective arylation reagents in a variety of asymmetric transformations. Here a highly efficient approach to construct triaryl-substituted all-carbon ...quaternary stereocenters through chiral phosphoric acid-catalyzed enantioselective arylation of 3-aryl-2-oxindoles with azonaphthalenes is disclosed. This chemistry is scalable and displays excellent functional group tolerance, furnishing a series of 3,3-disubstituted 2-oxindole derivatives in good yields with excellent enantiocontrol. Preliminary mechanistic data suggest that the initially formed direct addition intermediate undergoes intramolecular annulation under acidic reaction conditions.
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