Carbene‐Catalyzed Asymmetric Construction of Atropisomers

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(50), P. 26026 - 26037

Published: July 16, 2021

Atropisomeric molecules have found proven applications and shown promising potential in chemistry medicine. The design of N-heterocyclic carbene (NHC) catalyzed reactions to construct atropisomerically enriched has emerged as an important research topic recent years. These include kinetic resolutions, asymmetric desymmetrizations, central-to-axial chirality conversions, cycloadditions. This Minireview evaluates summarizes the progress NHC-based organic catalysis for access atropisomers, briefly states our personal perspectives on future advancement this topic. NHC provided rich unique reaction modes that led success synthesis central-chiral molecules. It is expected similar could also be achieved developing prepare atropisomeric molecules, including those not easily accessible by other methods.

Language: Английский

---

Direct α-Acylation of Alkenes via N-Heterocyclic Carbene, Sulfinate, and Photoredox Cooperative Triple Catalysis

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(13), P. 4903 - 4909

Published: March 24, 2021

N-Heterocyclic carbene (NHC) catalysis has emerged as a versatile tool in modern synthetic chemistry. Further increasing the complexity, several processes have been introduced that proceed via dual catalysis, where NHC organocatalyst operates concert with second catalytic moiety, significantly enlarging reaction scope. In biological transformations, multiple is generally used to access complex natural products. Guided by strategy, triple studied recently, three different modes are merged single process. this Communication, direct α-C–H acylation of various alkenes aroyl fluorides using NHC, sulfinate, and photoredox cooperative reported. The method allows preparation α-substituted vinyl ketones moderate high yields excellent functional group tolerance. Mechanistic studies reveal these cascades through sequential radical addition/coupling/elimination contrast known operate two sets interwoven cycles, process, all cycles interwoven.

Language: Английский

---

Diastereodivergent Desymmetric Annulation to Access Spirooxindoles: Chemical Probes for Mitosis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4199 - 4207

Published: Feb. 13, 2023

Spirooxindoles have emerged as promising architectures for engineering biologically active compounds. The diastereodivergent construction of unique scaffolds this type with full control continuous chiral centers including an all-carbon quaternary stereogenic center is yet to be developed. Here, we report unprecedented desymmetric [3 + 3] annulation oxabicyclic alkenes enals enabled by N-heterocyclic carbene (NHC)/Rh cooperative catalysis, leading a series enantiomerically enriched spirooxindole lactones excellent enantioselectivities (up >99% ee) and diastereoselectivities >95:5 dr). combined catalyst system comprises rhodium complex that controls the configuration at electrophilic carbon NHC nucleophilic oxindole-containing carbon; thus, four stereoisomers products can readily obtained simply switching configurations two catalysts. Transformations spirooxindoles delivered synthetically useful Importantly, those arrested mammalian cells in mitosis exhibited potent antiproliferative activities against HeLa cells. Significantly, both absolute relative exert prominent effects on bioactivities, underscoring great importance catalytic asymmetric synthesis beyond creating tools exploration structure–activity relationships.

Language: Английский

---

N‐Heterocyclic Carbene‐Catalyzed Atroposelective Annulation for Access to Thiazine Derivatives with C−N Axial Chirality

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(17), P. 9362 - 9367

Published: Feb. 4, 2021

Abstract A catalytic atroposelective cycloaddition reaction between thioureas and ynals is developed. This features the first NHC‐catalyzed addition of to acetylenic acylazolium intermediates eventually set up C−N axial chirality with excellent optical purities. The obtained axially chiral thiazine derivative products bear multiple functional groups are feasible for further transformations.

Language: Английский

---

Light‐Driven Carbene Catalysis for the Synthesis of Aliphatic and α‐Amino Ketones

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(33), P. 17925 - 17931

Published: June 7, 2021

Single-electron N-heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C-C bonds. Guided by density functional theory and mechanistic analyses, we report light-driven aliphatic α-amino ketones using single-electron NHC operators. Computational experimental results reveal that reactivity key radical intermediate is substrate-dependent can be modulated through steric electronic parameters NHC. Catalyst potential harnessed in visible-light driven generation an acyl azolium species undergoes selective coupling with various partners to afford diverse ketone products. This methodology showcased direct late-stage functionalization amino acids pharmaceutical compounds, highlighting utility

Language: Английский

---

1,4-Alkylcarbonylation of 1,3-Enynes to Access Tetra-Substituted Allenyl Ketones via an NHC-Catalyzed Radical Relay

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(21), P. 13363 - 13373

Published: Oct. 19, 2021

Reactions involving allenyl ion intermediates have been widely applied in the synthesis of functionalized allenes, but reactions radicals less studied and limited successful examples realized mainly by transition metal catalysis. We herein demonstrate generation N-heterocyclic carbene (NHC) organocatalysis their applications three-component radical relay 1,4-alkylcarbonylation 1,3-enynes without participation. This strategy could accommodate a collection different alkyl precursors such as CF3I, halides, cycloketone oxime esters, aliphatic carboxylic acid derived redox-active enabling convenient pathway to access range synthetically challenging tetra-substituted ketones with high regioselectivity. The key success this protocol relied on Csp-C(O)sp2 radical–radical coupling NHC-bound ketyl radicals, constructing ketone motifs highly efficient reaction pathway.

Language: Английский

---

Catalytic, Metal-Free Amide Synthesis from Aldehydes and Imines Enabled by a Dual-Catalyzed Umpolung Strategy under Redox-Neutral Conditions

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(21), P. 12960 - 12966

Published: Oct. 22, 2020

The synthesis of amides is a long-term theme in chemistry and related areas. use readily available cost-effective precursors for straightforward amide with atom economy under mild conditions attractive yet challenging. Herein, we report the direct from aldehydes imines 100% atom-economical manner. redox-neutral C–N bond-forming process was enabled by dual catalysis visible light an N-heterocyclic carbene (NHC) at room temperature. This protocol features unprecedented umpolung to generate N-centered radicals. Mechanistic investigations reveal this reaction undergoes nontrivial radical–radical coupling between radical C-centered forge bond. operationally simple tolerates wide range functional groups, providing rapid access aromatic or aliphatic without producing any byproduct.

Language: Английский

---

Cooperative N-heterocyclic Carbene and Iridium Catalysis Enables Stereoselective and Regiodivergent [3 + 2] and [3 + 3] Annulation Reactions

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(7), P. 3810 - 3821

Published: March 12, 2021

A cooperative N-heterocyclic carbene (NHC)/iridium catalysis has been developed to achieve highly stereoselective and regiodivergent [3 + 2] 3] annulation reactions of 2-indolyl allyl carbonates with enals. The use the NHC catalyst introduced switchable homoenolate enolate intermediates from common enal precursor via a simple adjustment reaction conditions in predictable manner. This protocol furnishes two types biologically important products, pyrrolo[1,2-a]indoles pyridine[1,2-a]indoles, high diastereo- enantioselectivities (up >20:1 dr >99% ee). Notably, all four stereoisomers these products vicinal stereocenters could be afforded through permutations enantiomers chiral catalysts. Mechanistic investigations further computational density functional theory calculations give an explanation origin regioselectivity. In addition, NHC-enolate intermediate generated formylcyclopropanes was also compatible this catalytic system thus arsenal optically pure pyrrolo[1,2-a]indole enriched.

Language: Английский

---

Carbene-Catalyzed Atroposelective Annulation and Desymmetrization of Urazoles

Organic Letters, Journal Year: 2021, Volume and Issue: 23(10), P. 3991 - 3996

Published: May 12, 2021

An NHC-catalyzed atroposelective reaction between ynals and urazoles is disclosed. The establishes a chiral C–N axis via an [3 + 2] annulation/desymmetrization process. Our allows efficient access to axially heteroatom-rich urazole derivatives with potential applications in bioactive molecules catalysis.

Language: Английский

---

Radical Relay Trichloromethylacylation of Alkenes through N-Heterocyclic Carbene Catalysis

Organic Letters, Journal Year: 2021, Volume and Issue: 23(18), P. 7242 - 7247

Published: Aug. 31, 2021

N-Heterocyclic carbene catalysis enabling vicinal trichloromethylacylation of alkenes using tetrachloromethane and aldehydes has been developed. The reaction involves single electron transfer from the enolate form Breslow intermediate to generate persistent intermediate-derived ketyl radical a transient trichloromethyl radical. After addition an alkene, prolonged alkyl is preferentially captured by over leading atom product.

Language: Английский

---