We have previously reported the first formal hydroamination of enamines for the synthesis of chiral 1,2‐diamines. Here, we describe: (i) the discovery, optimization, and substrate expansion of this ...reaction; (ii) a novel and straightforward protocol for the “click‐type” synthesis of enamines in quantitative yield utilizing sodium sulfate in a dual role as an ancillary and dehydrating agent without the need for workup or purification; (iii) the application of this methodology to the first enantioselective synthesis of orthogonally protected 1,1′‐(1‐(4‐fluorophenyl)ethane‐1,2‐diyl) piperazines, a scaffold for rapid lead optimization in drug discovery; (iv) a computational investigation into the mechanism and rationalization of the enantioselectivities of the reaction.
Chiral 1,2‐diamines are an important structural motif in organic synthesis, and can be prepared by an efficient Cu−H catalyzed asymmetric hydroamination of enamines. The applicability of the hydroamination protocol is demonstrated by an asymmetric synthesis of a MC‐4 receptor antagonist. The origin of the excellent enantioselectivity is investigated using DFT calculations.
A unique Pd‐catalyzed approach for asymmetric (4+1) annulations via cascade allylation and transient σ‐alkyl‐Pd(II) initiated methylene Csp3−H activation is reported. The enolate fragment derived ...from the decarboxylation of vinyl methylene carbonate is crucial to stabilize the key intermediate. These reactions enable the synthesis of various useful dihydrobenzofurans with excellent enantioselectivity, typically >95 : 5 er, and exclusive (Z)‐stereoselectivity. Compared with the well‐established annulations via Heck‐type C−H activations, this protocol showcases a conceptually new way to generate σ‐alkyl‐Pd(II) species that could initiate challenging asymmetric Csp3−H activations.
A unique catalytic approach for asymmetric (4+1) annulations via cascade allylation and transient σ‐alkyl‐Pd(II) initiated methylene Csp3−H activation is reported. Comparing to the well‐established annulations via Heck‐type C−H activations, this protocol showcases a conceptually new way to generate σ‐alkyl‐Pd(II) species which could initiate challenging asymmetric Csp3−H activations.
A PdII‐catalyzed, domino enantioselective desymmetrizative coupling of 7‐azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three ...covalent bonds and two contiguous stereocenters with excellent enantio‐ and diastereo‐selectivity. The resulting functionalized indole‐dihydronaphthalene‐amine conjugates served as an appealing platform to streamline the diversity‐oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non‐covalent interactions contributed to the observed enantioselectivity.
A palladium‐catalyzed enantioselective desymmetrizative coupling of prochiral 7‐azabenzonorbornadienes with readily available alkynylanilines afforded dihydronaphthalenes via concomitant generation of three covalent bonds. The methods also allows to build two stereocenters and an indole motif in a highly diastereo‐ and enantioselective as well as atom‐economic manner.
This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N′‐bisindoles via chiral phosphoric acid‐catalyzed formal (3+2) cycloadditions of indole‐based ...enaminones as novel platform molecules with 2,3‐diketoesters, where de novo indole‐ring formation is involved. Using this new strategy, various axially chiral N,N′‐bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N,N′‐bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiral N,N′‐bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.
An organocatalytic enantioselective synthesis of axially chiral N,N′‐bisindoles has been established via chiral phosphoric acid‐catalyzed formal (3+2) cycloaddition of indole‐based enaminones with 2,3‐diketoesters. This study provides a new strategy for the highly selective synthesis of axially chiral N,N′‐bisindoles and shows the successful application of such skeletons in medicinal and synthetic chemistry.
Abstract
Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α‐heteroatoms to carbonyl compounds. Nevertheless, the limited availability ...of carbene precursors restricts the introduction of only a single heteroatom. In this report, we describe a new approach based on an I
(III)
/S
(VI)
reagent that promotes the cascade insertion of heteroatoms. This is achieved by sequentially generating two α‐heteroatom‐substituted metal carbenes in one reaction. We found that this mixed I
(III)
/S
(VI)
ylide reacts efficiently with a transition metal catalyst and an X−H bond (where X=O, N). This transformation leads to the sequential formation of a sulfoxonium‐ and an X‐substituted Rh‐carbenes, enabling further reactions with another Y−H bond. Remarkably, a wide range of symmetrical and unsymmetrical α,α‐
O
,
O
‐, α,α‐
O
,
N
‐, and α,α‐
N
,
N
‐subsituted ketones can be prepared under mild ambient conditions. In addition, we successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S double insertion, and C−S/Y−H double insertion (where Y=S, N, O, C). Notably, the latter two cascades enabled the simultaneous installation of three functional groups to the α‐carbon of carbonyl compounds in a single step. These reactions demonstrate the versatility of our approach, allowing for the synthesis of ketones and esters with multiple α‐heteroatoms using a common precursor.
A new class of axially chiral styrene‐based thiourea tertiary amine catalysts, which have unique characteristics such as an efficient synthetic route, multiple chiral elements, and multiple ...activating groups, has been rationally designed. These new chiral catalysts have proven to be efficient organocatalysts, enabling the chemo‐, diastereo‐, and enantioselective (2+4) cyclization of 2‐benzothiazolimines with homophthalic anhydrides in good yields (up to 96 %) with excellent stereoselectivities (all >95:5 dr, up to 98 % ee). More importantly, theoretical calculations elucidated the important role of an axially chiral styrene moiety in controlling both the reactivity and enantioselectivity. This work not only represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, but also gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
A new class of axially chiral styrene‐based organocatalysts has been rationally designed. They enable the chemo‐, diastereo‐ and enantioselective (2+4) cyclization of 2‐benzothiazolimines. This work represents the first design of styrene‐based chiral thiourea tertiary amine catalysts and the first catalytic asymmetric (2+4) cyclization of 2‐benzothiazolimines, and it gives an in‐depth understanding of axially chiral styrene‐based organocatalysts.
Tremendous effort has been devoted to developing novel near‐infrared (NIR) emitters and to improving the performance of NIR organic light‐emitting diodes (OLEDs). Os(II) complexes are known to be an ...important class of NIR electroluminescent materials. However, the highest external quantum efficiency achieved so far for Os(II)‐based NIR OLEDs with an emission peak wavelength exceeding 700 nm is still lower than 3%. A new series of Os(II) complexes (1–4) based on functional pyrazinyl azolate chelates and dimethyl(phenyl)phosphane ancillaries is presented. The reduced metal‐to‐ligand charge transfer (MLCT) transition energy gap of pyrazinyl units in the excited states results in efficient NIR emission for this class of metal complexes. Consequently, NIR OLEDs based on 1–4 show excellent device performance, among which complex 4 with a triazolate fragment gives superior performance with maximum external quantum efficiency of 11.5% at peak wavelength of 710 nm, which represent the best Os(II)‐based NIR‐emitting OLEDs with peak maxima exceeding 700 nm.
A series of highly efficient near‐infrared (NIR) Os(II) complexes based on functional pyrazinyl azolates and PPhMe2 ancillaries is reported. Remarkably, organic light‐emitting diodes using Os(II) emitter 4 exhibit excellent performance with a maximum external quantum efficiency up to 11.5% at a peak wavelength of 710 nm.
Catalytic asymmetric construction of chiral indole‐fused rings has become an important issue in the chemical community because of the significance of such scaffolds. In this work, we have ...accomplished the first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols by using indoles and 2‐naphthols as suitable reaction partners under the catalysis of chiral phosphoric acids, constructing enantioenriched indole‐fused six‐membered and seven‐membered rings in high yields with excellent enantioselectivities. In addition, this approach is used to realize the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which are found to show promising anticancer activity. More importantly, theoretical calculations of the reaction pathways and activation mode offer an in‐depth understanding of this class of indolylmethanols. This work not only settles the challenges in realizing catalytic asymmetric cycloadditions of indolyldimethanols but also provides a powerful strategy for the construction of enantioenriched indole‐fused rings.
The first catalytic asymmetric (4+2) and (4+3) cycloadditions of 2,3‐indolyldimethanols enable the construction of enantioenriched indole‐fused rings in high yields with excellent enantioselectivities. This approach led to the first enantioselective construction of challenging tetrahydroindolocarbazole scaffolds, which show promising anticancer activity. Theoretical calculations offer an in‐depth understanding of this class of indolylmethanols.
A novel enantioselective Tsuji–Trost‐type cross coupling reaction between gem‐difluorinated cyclopropanes and N‐unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is ...presented herein. This transformation streamlined the diversity‐oriented synthesis (DOS) of optically active α‐quaternary α‐amino acid esters bearing a linear 2‐fluoroallylic motif, which served as an appealing platform for the construction of other valuable enantioenriched compounds. The key intermediates were confirmed by HRMS detection, while DFT calculations revealed that the excellent enantioselectivity was attributed to the stabilizing non‐covalent interactions between the Pd(II)‐π‐fluoroallyl species and the Ni(II)‐Schiff base complex.
A robust palladium/nickel/chiral aldehyde synergistic relay system was developed for the enantioselective ring‐opening functionalization of gem‐difluorinated cyclopropanes with N‐unprotected amino acid esters, enabling the efficient assembly of α‐quaternary α‐amino acid esters bearing a linear 2‐fluoroallylic motif in a highly enantioselective manner.
Formation of a single‐component charge‐transfer complex (SCCTC) is unveiled in solid state of an intermolecular charge‐transfer molecule ...2‐(4‐(1‐phenyl‐1H‐phenanthro9,10‐dimidazol‐2‐yl)phenyl)anthracene‐9,10‐dione (PIPAQ). Intermolecular donor–acceptor interactions between two PIPAQ molecules is the primary driving force for self‐association and contributes to intermolecular charge transfer. The SCCTC character is fully verified by crystallographic, photophysical, electron spin resonance, and vibrational characterizations. The PIPAQ‐based SCCTC is first applied in light‐emitting devices as an emissive layer to realize efficient deep‐red/near‐infrared electroluminescence. This work provides new insights into SCCTC and represents an important step toward their applications in optoelectronic devices.
Dimeric single‐component charge‐transfer complexes (SCCTCs) by self‐complexation of a donor–π–acceptor molecule (PIPAQ) are revealed and fully investigated, wherein the strong intermolecular charge transfer leads to unprecedented deep‐red/near‐infrared emission. The SCCTCs can be formed in thin films and applied in electroluminescence devices to realize high efficiencies via a thermally activated delayed fluorescence channel.
