Deoxytrifluoromethylation of Alcohols

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(27), С. 11961 - 11968

Опубликована: Июль 5, 2022

Deoxy-functionalization of alcohols represents a class reactions that has had profound impact on modern medicine. In particular, deoxyfluorination is commonly employed as means to incorporate high-value fluorine atoms into drug-like molecules. Recently, the trifluoromethyl (CF3) group garnered attention from medicinal chemists due its ability markedly improve pharmaceutical properties small-molecule drug candidates. To date, however, there remains no general accomplish analogous deoxygenative trifluoromethylation alcohols. We report herein copper metallaphotoredox-mediated direct deoxytrifluoromethylation, wherein alcohol substrates are activated in situ by benzoxazolium salts for C(sp3)-CF3 bond formation.

Язык: Английский

---

Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

Chemical Society Reviews, Год журнала: 2022, Номер 51(17), С. 7358 - 7426

Опубликована: Янв. 1, 2022

Transition metal catalysis has contributed immensely to C-C bond formation reactions over the last few decades, and alkylation is no exception. The superiority of such methodologies traditional evident from minimal reaction steps, shorter times, atom economy while also allowing control regio- stereo-selectivity. In particular, hydrocarbonation alkenes grabbed increased attention due its fundamental ability effectively selectively synthesise a wide range industrially pharmaceutically relevant moieties. This review attempts provide scientific viewpoint systematic analysis recent developments in transition-metal-catalyzed various C-H bonds using simple activated olefins. key features mechanistic studies involved these transformations are described briefly.

Язык: Английский

---

Electrophotochemical Ce-Catalyzed Ring-Opening Functionalization of Cycloalkanols under Redox-Neutral Conditions: Scope and Mechanism

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(30), С. 13895 - 13902

Опубликована: Июль 21, 2022

Selective cleavage and functionalization of C–C bonds in alcohols is gaining increasing interest organic synthesis biomass conversion. In particular, the development redox-neutral catalytic methods with cheap catalysts clean energy utmost interest. this work, we report a versatile method for ring-opening cycloalkanols by electrophotochemical (EPC) cerium (Ce) catalysis. The EPC-Ce-enabled catalysis allows different ring sizes to be cleaved while tolerating broad range functional groups. Notably, presence chloride as counteranion electrolyte, protocol selectively leads formation C–CN, C–C, C–S, or C–oxime instead C–halide bond after β-scission. A preliminary mechanistic investigation indicates that redox-active Ce catalyst can tuned electro-oxidation photo-reduction, thus avoiding use an external oxidant. Spectroscopic characterizations (cyclic voltammetry, UV–vis, electron paramagnetic resonance, X-ray absorption fine structure) suggest Ce(III)/Ce(IV) pathway transformation, which Ce(IV)-alkoxide involved.

Язык: Английский

---

Photoinduced Ligand-to-Metal Charge Transfer (LMCT) of Fe Alkoxide Enabled C–C Bond Cleavage and Amination of Unstrained Cyclic Alcohols

Organic Letters, Год журнала: 2022, Номер 24(3), С. 977 - 982

Опубликована: Янв. 14, 2022

We report an alkoxy radical process for the C-C bond cleavage and functionalization of unstrained tertiary secondary cyclic alcohols. In absence a chlorine atom, readily available iron catalysts [Fe(OBu-t)3 or Fe(acac)3/t-BuONa] facilitate formation via direct ligand-to-metal charge transfer Fe alkoxide further enable ring opening amination The remote amino carbonyl compounds could be obtained with broad scope in up to excellent yields under mildly redox-neutral system. Light-driven electron transfer, formation, subsequent β-scission were keys transformation.

Язык: Английский

---

Identification of Alkoxy Radicals as Hydrogen Atom Transfer Agents in Ce-Catalyzed C–H Functionalization

Journal of the American Chemical Society, Год журнала: 2022, Номер 145(1), С. 359 - 376

Опубликована: Дек. 20, 2022

The intermediacy of alkoxy radicals in cerium-catalyzed C–H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)–alkoxide complexes have synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified as the sole heteroatom-centered radical species generated ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom (HAT) verified kinetic analysis, density functional theory (DFT) calculations, reactions under strictly chloride-free conditions. These experimental findings establish critical role Ce-LMCT catalysis definitively preclude involvement chlorine radical. This study also reinforced necessity a high relative ratio alcohol vs Ce for selective alkoxy-radical-mediated HAT, seemingly trivial changes can lead to drastically different mechanistic pathways. Importantly, previously proposed radical–alcohol complex, postulated explain alkoxy-radical-enabled selectivities this system, examined scrutiny ruled out regioselectivity studies, experiments, high-level calculations. Moreover, peculiar selectivity generation LMCT homolysis heteroleptic analyzed back-electron (BET) may regulated efficiency formation ligand-centered radicals.

Язык: Английский

---