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

---

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

---

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

---

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones

ACS Catalysis, Год журнала: 2023, Номер 13(13), С. 8752 - 8759

Опубликована: Июнь 16, 2023

Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C–C bonds is well-known, C–N bond-containing relatively less explored, construction N–N has received only scant attention. Demonstrated herein N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to 3-amino quinazolinones. The NHC-catalyzed reaction quinazolinones containing a free N–H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished atropisomeric quinazolinone derivatives mild broad scope. Preliminary studies on experimental density functional theory-based rotational barrier determination are also presented.

Язык: Английский

---

Recent advances in the construction of axially chiral arylpyrroles

Science China Chemistry, Год журнала: 2023, Номер 66(9), С. 2480 - 2491

Опубликована: Авг. 9, 2023

Язык: Английский

---

Design and Catalytic Asymmetric Synthesis of Furan‐Indole Compounds Bearing both Axial and Central Chirality

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(8)

Опубликована: Дек. 29, 2023

Abstract In the chemistry community, catalytic asymmetric synthesis of furan‐based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing importance difficulty in constructing such frameworks. this work, we have realized first five‐five‐membered via organocatalytic (2+4) annulation achiral furan‐indoles with 2,3‐indolyldimethanols uncommon regioselectivity. By strategy, furan‐indole were synthesized high yields excellent regio‐, diastereo‐, enantioselectivities. Moreover, theoretical calculations conducted provide an in‐depth understanding reaction pathway, activation mode, origin selectivity.

Язык: Английский

---

Synthesis of Axially Chiral Biaryls through Cobalt(II)‐Catalyzed Atroposelective C−H Arylation

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(40)

Опубликована: Авг. 16, 2023

Highly efficient synthesis of axially chiral biaryl amines through cobalt-catalyzed atroposelective C-H arylation using easily accessible cobalt(II) salt and salicyloxazoline ligand has been reported. This methodology provides a straightforward sustainable access to broad range enantioenriched biaryl-2-amines in good yields (up 99 %) with excellent enantioselectivities % ee). The synthetic utility the unprecedented method is highlighted by its scalability diverse transformations.

Язык: Английский

---