Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(15)

Опубликована: Фев. 7, 2023

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via phosphoric acid-catalyzed formal (3+2) cycloadditions indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various were synthesized in good yields and excellent enantioselectivities (up to 87 % yield 96 ee). More importantly, class exhibited some degree cytotoxicity toward cancer cells was derived into phosphine ligands high catalytic activity. provides a strategy for using asymmetric organocatalysis realize applications such scaffolds medicinal chemistry catalysis.

Язык: Английский

---

Catalytic Asymmetric Synthesis of Atropisomers Featuring an Aza Axis

Accounts of Chemical Research, Год журнала: 2023, Номер 56(18), С. 2537 - 2554

Опубликована: Сен. 11, 2023

ConspectusAtropisomers bearing a rotation-restricted axis are common structural units in natural products, chiral ligands, and drugs; thus, the prevalence of asymmetric synthesis has increased recent decades. Research into atropisomers featuring an N-containing (N-X atropisomers) remains its infancy compared with well-developed C-C atropisomer analogue. Notably, N-X could offer divergent scaffolds, which extremely important bioactive molecules. The is recognized as both appealing challenging. Recently, we devoted our efforts to catalytic atropisomers, benzimidazole-aryl N-C indole-aryl hydrogen-bond-assisted pyrrole-pyrrole N-N pyrrole-indole indole-indole atropisomers. To obtain Buchwald-Hartwig reaction amidines or enamines was employed. Using Pd(OAc)2/(S)-BINAP Pd(OAc)2/(S)-Xyl-BINAP catalyst system, were readily obtained. address issue reduced stability diarylamine axis, six-membered intramolecular N-H-O hydrogen bond introduced scaffold. A tandem N-arylation/oxidation process used for phosphoric acid (CPA)-catalyzed N-aryl quinone For copper-mediated Friedel-Crafts alkylation/arylation developed. desymmetrization completed successfully via Cu(OTf)2/chiral bisoxazoline (CuOTf)·Tol/bis(phosphine) dioxide thereby achieving first N/N bipyrrole Asymmetric amination utilized provide bisindole excellent stereogenic control. This scaffold using de novo indole construction strategy. heterobiaryl substantially facilitated palladium-catalyzed transient directing group (TDG)-mediated C-H functionalization. Atropisomeric alkenylation, allylation, alkynylation accomplished Pd(OAc)2/l-tert-leucine system. Herein, summarize work on palladium-, copper-, CPA-catalyzed syntheses Furthermore, application molecule analogues axially ligands demonstrated. Subsequently, briefly discussed terms single crystals obtained rotational barriers. Finally, outlook provided.

Язык: Английский

---

Enantioselective Synthesis of N−N Biaryl Atropisomers through Iridium(I)‐Catalyzed C−H Alkylation with Acrylates

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(37)

Опубликована: Май 4, 2023

Abstract Enantioselective synthesis of N−N biaryl atropisomers is an emerging area but remains underexplored. The development efficient in great demand. Herein, the construction through iridium‐catalyzed asymmetric C−H alkylation reported for first time. In presence readily available Ir precursor and Xyl‐BINAP, a variety axially chiral molecules based on indole‐pyrrole skeleton were obtained good yields (up to 98 %) with excellent enantioselectivity 99 % ee). addition, bispyrrole could also be synthesized enantioselectivity. This method features perfect atom economy, wide substrate scope, multifunctionalized products allowing diverse transformations.

Язык: Английский

---

Enantioselective Synthesis of N‐N Atropisomers by Palladium‐Catalyzed C−H Functionalization of Pyrroles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(21)

Опубликована: Март 21, 2023

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies them lag far behind studies the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, first palladium-catalyzed enantioselective C-H activation pyrroles for synthesis atropisomers is presented. Structurally diverse indole-pyrrole possessing chiral axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, kinetic resolution trisubstituted heterobiaryls sterically demanding substituents was also achieved. Importantly, this versatile functionalization strategy enables iterative exquisite selectivity, expediting formation valuable, complex, atropisomers.

Язык: Английский

---

Cobalt-catalyzed atroposelective C−H activation/annulation to access N−N axially chiral frameworks

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 29, 2023

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, advanced material skeletons. anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report efficient method for enantioselective synthesis axially frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. reaction proceeds under mild conditions using Co(OAc)2·4H2O catalyst with salicyl-oxazoline (Salox) ligand O2 oxidant, affording variety products high yields enantioselectivities. This protocol provides approach facile construction atropisomers further expands range derivatives. Additionally, electrocatalysis, desired were also successfully achieved good excellent efficiencies

Язык: Английский

---

Enantioselective Strategies for The Synthesis of N−N Atropisomers

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(31)

Опубликована: Апрель 25, 2023

Axially chiral compounds have been always considered a laboratory curiosity with rare prospects of being applied in asymmetric synthesis. Things changed very quickly the last twenty years when it was understood important role and enormous impact that these medicinal, biological material chemistry. The synthesis atropisomers became rapidly expanding field recent reports on development N-N strongly prove how this research is hot topic open to new challenges frontiers This review focuses advances enantioselective highlighting strategies breakthroughs obtain novel stimulating atropisomeric framework.

Язык: Английский

---

Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 15, 2024

Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and ligands. One efficient method the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis atropisomers with simultaneous creation contiguous axial central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able synthesize structurally diverse pyrroles indoles vicinal or bearing 2,3-dihydropyrimidin-4-one moiety moderate good yields excellent enantioselectivities. Further synthetic transformations obtained derivative products demonstrated. reaction mechanism origin enantioselectivity understood through DFT calculations.

Язык: Английский

---

Atroposelective catalysis

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(7), С. 497 - 517

Опубликована: Июнь 18, 2024

Язык: Английский

---

Catalytic atroposelective synthesis of indolyl quinazolinones bearing N–N/C–C diaxes

Science China Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Язык: Английский

---

Synthesis of Atropisomeric Hydrazides by One‐Pot Sequential Enantio‐ and Diastereoselective Catalysis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(42)

Опубликована: Авг. 29, 2022

The first catalytic enantioselective and diastereoselective synthesis of atropisomeric hydrazides was achieved using a sequential catalysis protocol. This strategy is based on one-pot sequence two organocatalytic cycles featuring the enamine amination branched aldehydes followed by nitrogen alkylation under phase-transfer conditions. resulting axially chiral were obtained directly from commercially available reagents in high yields with good stereocontrol. permutation organocatalysts allowed easy access to all stereoisomers, enabling stereodivergent approach enantioenriched hydrazides.

Язык: Английский

---