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

Qi Tong,

Ren-Feng Xiu,

Jiahe Chen

et al.

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

Dearomative ring expansion of thiophenes by bicyclobutane insertion DOI
Huamin Wang, Huiling Shao, Ankita Das

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 75 - 81

Published: July 6, 2023

Skeletal ring enlargement is gaining renewed interest in synthetic chemistry and has recently focused on insertion of one or two atoms. Strategies for heterocyclic expansion through small-ring remain elusive, although they would lead to the efficient formation bicyclic products. Here, we report a photoinduced dearomative thiophenes by bicyclo[1.1.0]butanes produce eight-membered rings under mild conditions. The value, broad functional-group compatibility, excellent chemo- regioselectivity were demonstrated scope evaluation product derivatization. Experimental computational studies point toward photoredox-induced radical pathway.

Language: Английский

Citations

118
Skeletal Editing: Interconversion of Arenes and Heteroarenes DOI Creative Commons
Ben W. Joynson, Liam T. Ball

Helvetica Chimica Acta, Journal Year: 2023, Volume and Issue: 106(3)

Published: Jan. 13, 2023

Abstract Skeletal editing involves making specific point‐changes to the core of a molecule through selective insertion, deletion or exchange atoms. It thus represents potentially powerful strategy for step‐economic modification complex substrates and is perfect complement methods such as C−H functionalization that target molecular periphery. Given their ubiquity in biologically active compounds, ability perform skeletal on – therefore interconvert between aromatic heterocycles especially valuable. This review summarizes both recent key historical examples applied interconversion rings; we anticipate it will serve highlight not only innovative enabling nature current methods, but also tremendous opportunities still exist field.

Language: Английский

Citations

115
Skeletal Editing of Pyrimidines to Pyrazoles by Formal Carbon Deletion DOI
G. Logan Bartholomew, Filippo Carpaneto, Richmond Sarpong

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(48), P. 22309 - 22315

Published: Nov. 28, 2022

A method for the conversion of pyrimidines into pyrazoles by a formal carbon deletion has been achieved guided computational analysis. The pyrimidine heterocycle is most common diazine in FDA-approved drugs, and are diazole. An efficient to convert would therefore be valuable leveraging chemistries unique access diversified pyrazoles. One known, though it proceeds low yields requires harsh conditions. transformation reported here under milder conditions, tolerates wide range functional groups, enables simultaneous regioselective introduction N-substitution on resulting pyrazole. Key success this one-carbon room-temperature triflylation core, followed hydrazine-mediated skeletal remodeling.

Language: Английский

Citations

109
Skeletal Editing of (Hetero)Arenes Using Carbenes DOI
Zhaohong Liu, Paramasivam Sivaguru, Yongquan Ning

et al.

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(42)

Published: May 26, 2023

Abstract (Hetero)arenes continue to prove their indispensability in pharmaceuticals, materials science, and synthetic chemistry. As such, the controllable modification of biologically significant (hetero)arenes towards diverse more‐potent complex molecular scaffolds through peripheral skeletal editing has been considered a challenging goal organic Despite many excellent reviews on ( i. e ., C−H functionalization) (hetero)arenes, editings via single atom insertion, deletion, or transmutations have received less attention review literature. In this review, we systematically summarize state‐of‐the‐art reactions using carbenes, with focus general mechanistic considerations applications natural product syntheses. The potential opportunities inherent challenges encountered while developing these strategies are also highlighted.

Language: Английский

Citations

77
Skeletal editing of pyridines through atom-pair swap from CN to CC DOI Creative Commons
Qiang Cheng,

Debkanta Bhattacharya,

Malte Haring

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(5), P. 741 - 748

Published: Jan. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Language: Английский

Citations

60
Tunable molecular editing of indoles with fluoroalkyl carbenes DOI
Shaopeng Liu, Yong Yang, Qingmin Song

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(6), P. 988 - 997

Published: March 5, 2024

Language: Английский

Citations

46
Ring expansion of indene by photoredox-enabled functionalized carbon-atom insertion DOI
Fu‐Peng Wu, Chetan C. Chintawar, Rémy F. Lalisse

et al.

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(3), P. 242 - 251

Published: Jan. 9, 2024

Language: Английский

Citations

39
Dearomatization of Pyridines: Photochemical Skeletal Enlargement for the Synthesis of 1,2-Diazepines DOI

Elise Boudry,

Flavien Bourdreux,

Jérôme Marrot

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2845 - 2854

Published: Jan. 18, 2024

In this report, we developed a unified and standardized one-pot sequence that converts pyridine derivatives into 1,2-diazepines by inserting nitrogen atom. This skeletal transformation capitalizes on the in situ generation of 1-aminopyridinium ylides, which rearrange under UV light irradiation. A thorough evaluation key parameters (wavelength, reaction conditions, activating agent) allowed us to elaborate simple, mild, user-friendly protocol. The model was extrapolated more than 40 examples, including drug derivatives, affording unique 7-membered structures. Mechanistic evidence supports transient presence diazanorcaradiene species. Finally, pertinent transformations products, ring contraction reactions form pyrazoles, were conducted paved way broad application

Language: Английский

Citations

34
Regiodivergent Ring-Expansion of Oxindoles to Quinolinones DOI Creative Commons

Hendrik L. Schmitt,

Den Martymianov,

Ori Green

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 4301 - 4308

Published: Feb. 9, 2024

The development of divergent methods to expedite structure–activity relationship studies is crucial streamline discovery processes. We developed a rare example regiodivergent ring expansion access two regioisomers from common starting material. To enable this regiodivergence, we identified distinct reaction conditions for transforming oxindoles into quinolinone isomers. presented proved be compatible with variety functional groups, which enabled the late-stage diversification bioactive as well facilitated synthesis drugs and their derivatives.

Language: Английский

Citations

20
Interrogation of Enantioselectivity in the Photomediated Ring Contractions of Saturated Heterocycles DOI
Sojung F. Kim, Jordan P. Liles, Michaelyn C. Lux

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding single heteroatom from ring, this transformation builds desirable C(sp3)–C(sp3) bonds in the contracted products; however, origins enantioselectivity remain poorly understood. In work, has been explored across an expanded structurally diverse substrate scope, revealing wide range enantioselectivities (0–99%) using two distinct CPA catalysts. Mechanistic investigations support rate-determining excitation that generates short-lived achiral intermediates are intercepted by enantiodetermining closure. The effects competitive uncatalyzed reactivity light-driven reversibility closure on have elucidated. Statistical models were built regressing scope against key structural features products for both resultant suggested factors influence response each catalyst enabled rational modification pharmaceutically relevant target molecule to improve enantioselectivity. Finally, density functional theory (DFT)-based transition state analysis identified noncovalent interactions with correlated unique selectivity-relevant uncovered through statistical modeling. Our findings not only offer comprehensive insight into system but should also aid future development related CPA-catalyzed reactions.

Language: Английский

Citations

4