Photocatalyzed Enantioselective Functionalization of C(sp³)–H Bonds

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(2), С. 1209 - 1223

Опубликована: Янв. 3, 2024

Owing to its diverse activation processes including single-electron transfer (SET) and hydrogen-atom (HAT), visible-light photocatalysis has emerged as a sustainable efficient platform for organic synthesis. These provide powerful avenue the direct functionalization of C(sp3)–H bonds under mild conditions. Over past decade, there have been remarkable advances in enantioselective bond via combined with conventional asymmetric catalysis. Herein, we summarize involving discuss two main pathways this emerging field: (a) SET-driven carbocation intermediates are followed by stereospecific nucleophile attacks; (b) photodriven alkyl radical further enantioselectively captured (i) chiral π-SOMOphile reagents, (ii) stereoselective transition-metal complexes, (iii) another distinct stereoscopic species. We aim key reaction design, catalyst development, mechanistic understanding, new insights into rapidly evolving area research.

Язык: Английский

---

Metal-catalyzed asymmetric reactions enabled by organic peroxides

Chemical Society Reviews, Год журнала: 2024, Номер 53(5), С. 2326 - 2349

Опубликована: Янв. 1, 2024

This review summarizes the advances in metal-catalyzed asymmetric reactions enabled by organic peroxides that have been found to exhibit multifunctionalities, for instance, applied as stoichiometric reactants, reagents, or catalytic amount reagents.

Язык: Английский

---

Beyond conventional: Role of chiral metal–organic frameworks in asymmetric scenarios

Nano Today, Год журнала: 2024, Номер 56, С. 102227 - 102227

Опубликована: Март 18, 2024

Язык: Английский

---

Remote site-selective arene C–H functionalization enabled by N-heterocyclic carbene organocatalysis

Nature Catalysis, Год журнала: 2024, Номер 7(8), С. 900 - 911

Опубликована: Июль 11, 2024

Язык: Английский

---

One-Step Synthesis of β-Alkylidene-γ-lactones via Ligand-Enabled β,γ-Dehydrogenation of Aliphatic Acids

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(28), С. 12924 - 12933

Опубликована: Июль 8, 2022

Ligand-enabled Pd-catalyzed regioselective α,β-dehydrogenation of carbonyl compounds via β-methylene C–H activation has recently emerged as a promising transformation. Herein, we report the realization β,γ-dehydrogenation and subsequent vinyl olefination reactions free carboxylic acids, thus providing unique method for structural diversification aliphatic acids containing α-quaternary centers through sequential functionalizations two β-C–H bonds one γ-C–H bond. This tandem dehydrogenation–olefination–lactonization reaction offers one-step preparation β-alkylidene-γ-lactones, which are often difficult to prepare conventional methods, from inexpensive abundant acids. A variety such isosteviol grandiflorolic acid natural products, olefins compatible with reported protocol. The newly designed bidentate oxime ether-pyridone morpholine-pyridone ligands crucial this proceed. Notably, these also enable preferential methylene over previously reported, competing process methyl bond olefination.

Язык: Английский

---

Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C–H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(42), С. 19542 - 19558

Опубликована: Окт. 13, 2022

Reactions that enable selective functionalization of strong aliphatic C–H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific bond by catalyst control. Herein we describe the catalytic site- stereoselective γ-lactonization unactivated primary in carboxylic acid substrates. The system relies on chiral Mn activates aqueous hydrogen peroxide promote intramolecular lactonization under mild conditions, via carboxylate binding metal center. exhibits high enables oxidation γ-C–H even presence intrinsically weaker priori more reactive secondary tertiary ones at α- β-carbons. With substrates bearing nonequivalent bonds, factors governing have been uncovered. Most remarkably, manipulating absolute chirality catalyst, methyl groups gem-dimethyl structural units rigid cyclic bicyclic acids achieved with unprecedented levels diastereoselectivity. Such control has successfully exploited late-stage natural products such as camphoric, camphanic, ketopinic, isoketopinic acids. DFT analysis points rebound type mechanism initiated 1,7-HAT from bound substrate highly MnIV-oxyl intermediate, deliver carbon radical lactonizes through transfer. Intramolecular kinetic deuterium isotope effect 18O labeling experiments provide support this mechanistic picture.

Язык: Английский

---

Hydrogen-bond-acceptor ligands enable distal C(sp3)–H arylation of free alcohols

Nature, Год журнала: 2023, Номер 622(7981), С. 80 - 86

Опубликована: Сен. 6, 2023

Язык: Английский

---

Enantioselective remote methylene C−H (hetero)arylation of cycloalkane carboxylic acids

Science, Год журнала: 2024, Номер 384(6697), С. 793 - 798

Опубликована: Май 16, 2024

Stereoselective construction of γ- and δ-stereocenters in carbonyl compounds is a pivotal objective asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote γ-C−H (hetero)arylations free cycloalkane carboxylic acids, which are essential carbocyclic building blocks organic The reaction establishes γ-tertiary α-quaternary stereocenters simultaneously up to >99% enantiomeric excess, providing access wide range cyclic synthons bioactive molecules. sequential editing two methylene C–H bonds can be achieved by using with opposite configuration construct carbocycles containing three centers. Enantioselective δ-C−H (hetero)arylation also realized establish particularly challenging classical methodologies.

Язык: Английский

---

Enantioselective functionalization of unactivated C(sp3)–H bonds through copper-catalyzed diyne cyclization by kinetic resolution

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

Опубликована: Март 12, 2024

Site- and stereoselective C-H functionalization is highly challenging in the synthetic chemistry community. Although of vinyl cations has been vigorously studied C(sp

Язык: Английский

---

Versatile Copper-Catalyzed γ-C(sp³)–H Lactonization of Aliphatic Acids

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17311 - 17317

Опубликована: Июнь 13, 2024

Site-selective C(sp3)–H oxidation is of great importance in organic synthesis and drug discovery. γ-C(sp3)–H lactonization free carboxylic acids provides the most straightforward means to prepare biologically important lactone scaffolds from abundant inexpensive acids; however, a versatile catalyst for this transformation with broad substrate scope remains elusive. Herein, we report simple yet broadly applicable scalable γ-lactonization reaction aliphatic enabled by copper combination Selectfluor as oxidant. This exhibits compatibility tertiary, benzylic, allylic, methylene, primary γ-C–H bonds, affording access wide range structurally diverse lactones such spiro, fused, bridged lactones. Notably, exclusive γ-methylene C–H cycloalkane acetic was observed, giving either fused or γ-lactones that are difficult other methods. δ-C–H only favored presence tertiary bonds. The synthetic utility methodology demonstrated late-stage functionalization amino acids, molecules, natural products, well two-step total (iso)mintlactones (the shortest reported date).

Язык: Английский

---