Sulfenylnitrene-mediated nitrogen-atom insertion for late-stage skeletal editing of N -heterocycles

Science, Journal Year: 2025, Volume and Issue: 387(6729), P. 102 - 107

Published: Jan. 2, 2025

Given the prevalence of nitrogen-containing heterocycles in commercial drugs, selectively incorporating a single nitrogen atom is promising scaffold hopping approach to enhance chemical diversity drug discovery libraries. We harness distinct reactivity sulfenylnitrenes, which insert transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors over broad temperature range (−30 150°C). This compatible with diverse functional groups, including oxidation-sensitive functionalities such as phenols thioethers, has been applied various natural products, amino acids, pharmaceuticals. Furthermore, we have conducted mechanistic studies explored regioselectivity outcomes through density theory calculations.

Language: Английский

---

Design of rigid chiral bipyridine-2NO tetradentate ligands: application in asymmetric catalysis

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(5), P. 1314 - 1321

Published: Jan. 1, 2024

A new class of chiral bipyridine-2NO ligands, which incorporate the advantages both bipyridine skeleton and pyrroloimidazolone-based N -oxide moiety, was developed.

Language: Английский

---

Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 12692 - 12699

Published: Sept. 14, 2023

Accomplished herein is a rearrangement strategy for the highly efficient assembly of synthetically cumbersome while medicinally significant 2-amino-3-formyl chromones via palladium-catalyzed ring-opening, rearrangement, and cyclization process. Such sequence enables formation one C(sp2)–O bond C(sp2)–C(sp2) bond, reconstruction benzo-γ-pyrone moiety in single operation, thus producing difunctionalized chromone-incorporated derivatives. The reaction proceeds shorter time (30 min 3-iodochromones most cases) atom- step-economical manner. synthetic application current protocol further demonstrated by late-stage modification pharmaceuticals their intermediates, gram-scale reactions, transformations functional groups, as well synthesis bioactive molecules drugs. Mechanistic studies indicate that nucleophilic ring-opening process moiety, phenoxy anion intermediate, an intramolecular might be involved present system.

Language: Английский

---

Total Syntheses of Highly Oxidized Natural Products^†

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Comprehensive Summary Natural products with high oxidation states and complex chemical skeletons exhibit diverse bioactivities due to their unique interactions biological targets. The state is characterized by the presence of multiple oxygen‐containing functional groups such as hydroxyl groups, carbonyl epoxides that are usually tough construct selectively. In recent years, thanks development efficient strategies sophisticated methodologies, significant advancements have been made in total syntheses highly oxidized natural (HONPs). this review, we highlight examples HONPs focusing on tetrodotoxin (TTX) its derivatives, steroidal alkaloids, sesquiterpenes, diterpenoids since 2019. Key Scientists 2005, Yang group applied thioureas ligands Pauson−Khand reaction for synthesis triterpene products. methodological advances achieved a series topologically structural features following years. 2009, Baran established pioneering “two‐phase” approach terpenes, an innovative strategy has inspired numerous field. 2011, Xu Theodorakis (−)‐jiadifenolide, sesquiterpene from Illicium . 2012, Li 6π electrocyclization containing aromatic rings. 2014, Inoue introduced α‐alkoxy bridgehead radical, facilitating unified ryanodane diterpenoids. subsequent radical‐based convergent were employed assembling HONPs. developed type ΙΙ [5+2] reaction, which can be efficiently featuring bridged ring systems. Reisman presented pattern analysis guided synthetic designs complex, isoryanodane diterpenes. 2017, Gao reported photoenolization/Diels‐Alder (PEDA) constructing related polycyclic rings elevated states. 2018, Ding unprecedented oxidative dearomatization‐induced (ODI) cycloaddition/pinacol‐ 1,2‐acyl migration cascade assemble oxygenated bicyclo[3.2.1]octane system, was subsequently grayanane same year, Gui explored “bioinspired” strategic transformations enabled rapid construction core framework steroid terpenoid 2020, Luo successfully synthesized several HONPs, including (−)‐batrachotoxinin, (−)‐zygadenine, diterpenoids, employing elegant strategies. 2021, Zhang site‐specific photochemical desaturation late‐stage skeletal reorganization strategies, enabling divergent sesquiterpenes. 2022, Jia first (−)‐principinol C, accomplished six More recently, Trauner concise tetrodotoxin, particularly strategy.

Language: Английский

---

Skeletal Reorganization of Saturated Six-Membered Aza-cycles to Sulfonated Pyrrolidines under Redox-Neutral Conditions

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Ring contraction in skeletal reorganization strategies is one of the most intriguing yet surprisingly challenging transformations. Herein, we report for first time a ring tandem sulfonation between saturated six-membered N-heterocyclic nitroxides and sulfonyl hydrazides to access sulfonated pyrrolidine derivatives by an electrochemical redox cascade under redox-neutral metal-free conditions, which unavailable via conventional synthetic approaches. This benign approach has been further demonstrated gram-scale preparation pharmaceutical molecule synthesis mild conditions.

Language: Английский

---

Phen-2NO, a new C₂-symmetric rigid-featured tetradentate ligand, and its application in the asymmetric alkylation reaction of indoles

New Journal of Chemistry, Journal Year: 2024, Volume and Issue: 48(15), P. 6670 - 6675

Published: Jan. 1, 2024

A new class of C 2 -symmetric rigid-featured chiral phen ligands that provide the N , O -tetradentate coordination moiety and two additional -dioxides were rationally designed developed.

Language: Английский

---

Design and Synthesis of Rigid‐Featured Tertiary Amine‐Derived C₂‐Symmetric Chiral Furan‐N,N′‐dioxide Ligands

European Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 26(42)

Published: Aug. 19, 2023

Abstract To expand the chemical space of chiral N ‐oxides and furan‐containing ligands, herein we designed synthesized a new class rigid‐featured tertiary amine‐derived C 2 ‐symmetric furan‐ , N′ ‐dioxide (Fu‐2NO) ligands from optically pure l ‐prolinamides/hydroxylprolinamides in operationally simple two steps up to 57 % overall yield. The newly developed Fu‐2NO possesses pyrroloimidazolone‐based as non‐flat walls, afforded opportunity for fine‐tuning ligand electronic conformational properties by judicious choice substituent nonligating nitrogen atom. More importantly, can tolerate air moisture such that no special handling is needed their storage, be applied Ni(II)‐catalyzed asymmetric Friedel‐Crafts alkylation reaction indole.

Language: Английский

---

Sulfenylnitrene-Mediated Nitrogen-Atom Insertion into Pyrroles, Indoles, and Imidazoles

Published: Feb. 12, 2024

In this study, we harness the distinct reactivity of sulfenylnitrenes, which insert a single nitrogen atom to transform readily available pyrroles, indoles, and imidazoles into synthetically challenging pyrimidines, quinazolines, triazines, respectively. Our additive-free method for skeletal editing employs easily accessible, benchtop-stable sulfenylnitrene precursors as source atom. This chemical approach is compatible with free diverse functional groups, including oxidation-sensitive functionalities like phenol thioether. Additionally, facilitates selective incorporation various natural products, amino acids, pharmaceuticals. Furthermore, have conducted mechanistic studies explored regioselectivity outcomes through DFT calculations.

Language: Английский

---

Copper-Catalyzed Enantioselective Synthesis of Spirohydroindoles by Ethoxyformylmethylene Oxindole and Iminoester 1,3-Dipole Cycloaddition: An Examination of Associated Biological Activities

ACS Omega, Journal Year: 2024, Volume and Issue: 9(23), P. 24406 - 24414

Published: May 28, 2024

A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(

Language: Английский

---

Heteroatom-Controlled Three-Component [4 + 3] or [3 + 2] Annulation of Isatin-Derived Azomethine Ylide with Azadiene: Selective Synthesis of Spirooxindole-diazepines and Density Functional Theory Studies

Organic Letters, Journal Year: 2024, Volume and Issue: 26(41), P. 8945 - 8950

Published: Oct. 9, 2024

A novel three-component [4 + 3] annulation reaction of isatin-derived azomethine ylides with azadienes was developed for the first time to efficiently synthesize spirooxindole-diazepines incorporating a benzothiophene moiety under catalyst-free conditions. Effects heteroatom azadiene on chemoselectivity investigated. With use bearing benzofuran as substrate, dominant pathway changed an α-[3 2] annulation. When indenone used, distinct γ-[3 observed. Density functional theory calculations revealed that delicate balance between kinetic accessibility and thermodynamic driving force controlled competition different reactions.

Language: Английский

---