Access to N-α-deuterated amino acids and DNA conjugates via Ca(II)-HFIP-mediated reductive deutero-amination of α-oxo-carbonyl compounds

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 20, 2025

The development of practical and selective strategies for deuterium incorporation to construct deuterated molecules, particularly deuterium-labeled amino acids, has become as a growing focus basic research, yet it remains formidable challenge. Herein, we present bioinspired calcium-HFIP-mediated site-selective reductive deutero-amination α-oxo-carbonyl compounds with amines. Utilizing d2-Hantzsch ester the source, this reaction attains remarkable deuteration efficiency (> 99% deuteration). It enables synthesis N-α-deuterated acid motifs wide range functionality, evidenced by over 130 examples. method exhibits compatibility diverse substrates, such peptides, drug natural products bearing different substituents. Moreover, application strategy in DNA-tagged acids/peptides been demonstrated. This work offers an efficient innovative solution chemistry holds substantial potential organic synthesis, medicinal chemistry, chemical biology.

Язык: Английский

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Iridium-Catalyzed Cyclative Indenylation and Dienylation through Sequential B(4)–C Bond Formation, Cyclization, and Elimination from o-Carboranes and Propargyl Alcohols

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(22), С. 9890 - 9895

Опубликована: Май 12, 2020

Described herein is the first iridium-catalyzed cyclative indenylation through sequential B(4)–C and intramolecular C–C bond formation from o-carboranes propargyl alcohols, leading to of B(4)-indenylated with excellent regioselectivity via direct B–H activation. Moreover, regioselective 1,3-dienylation has been accessed activation, dehydration, decarboxylation, producing B(4)-dienylated o-carboranes.

Язык: Английский

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Cobalt(III)-Catalyzed Diastereo- and Enantioselective Three-Component C–H Functionalization

ACS Catalysis, Год журнала: 2021, Номер 11(19), С. 11938 - 11944

Опубликована: Сен. 13, 2021

Catalytic enantioselective C–H functionalization has recently become a tool for the creation of stereogenic centers. The steep increase in molecular complexity multicomponent reactions matches very well with asymmetric functionalizations, but realization such processes remains large challenge. We describe diastereoselective and highly three-component catalyzed by an earth-abundant Co(III) complex equipped chiral cyclopentadienyl ligand (Cpx). transformation provides rapid access to substituted β-hydroxyketones using three readily accessible starting materials. outlined reactivity CpxCo(III) catalysis shows higher exploitable propensity selective additions across carbonyls contrast chemistry Rh(III).

Язык: Английский

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Recent progress in rare-earth metal-catalyzed sp² and sp³ C–H functionalization to construct C–C and C–heteroelement bonds

Organic Chemistry Frontiers, Год журнала: 2022, Номер 9(11), С. 3102 - 3141

Опубликована: Янв. 1, 2022

The review presents rare-earth metal-catalyzed C(sp 2 /sp 3 )–H functionalization accessing C–C/C–heteroatom bonds and olefin (co)polymerization, highlighting substrate scope, mechanistic realization, origin of site-, enantio-/diastereo-selectivity.

Язык: Английский

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Rapid and Mild Metal-Free Reduction of Epoxides to Primary Alcohols Mediated by HFIP

ACS Catalysis, Год журнала: 2022, Номер 12(6), С. 3309 - 3316

Опубликована: Фев. 25, 2022

The reduction of epoxides is a powerful tool to access anti-Markovnikov alcohols, but reported methods are poorly compatible with strongly electronically deactivated substrates. Here, we describe general method for the linear-selective styryl oxides incorporating strong electron-withdrawing groups. remains more traditional epoxide motifs, such as aliphatic and electron-rich styrene oxides. Other (hetero)cycles oxetanes, tetrahydrofurans, aziridines, cyclopropanes can also be reductively opened. This user-friendly reaction relies on combination Brønsted acid catalyst hexafluoroisopropanol solvent, thus, in contrast existing methods, it does not require anhydrous reagents or an inert atmosphere. generated primary alcohols conveniently functionalized situ by dehydrative Friedel–Crafts arylation without preactivation.

Язык: Английский

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HFIP-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes

Chemical Communications, Год журнала: 2020, Номер 57(8), С. 1050 - 1053

Опубликована: Дек. 21, 2020

Hexafluoroisopropanol (HFIP)-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes is developed.

Язык: Английский

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Trifluoroethanol as a Unique Additive for the Chemoselective Electrooxidation of Enamines to Access Unsymmetrically Substituted NH‐Pyrroles

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(5)

Опубликована: Дек. 1, 2021

An electrochemical method for the synthesis of unsymmetrically substituted NH-pyrroles is described. The synthetic strategy comprises a challenging heterocoupling between two structurally diverse enamines via sequential chemoselective oxidation, addition, and cyclization processes. A series aryl- alkyl-substituted were effectively cross-coupled from an equimolar mixture to synthesize various unsymmetrical pyrrole derivatives up 84 % yield. desired cross-coupling was achieved by tuning oxidation potential utilizing "magic effect" additive trifluoroethanol (TFE). Additionally, extensive computational studies reveal unique role TFE in promoting process regulating activation energies reaction steps through H-bonding C-H⋅⋅⋅π interactions. Importantly, developed protocol found be equally efficient homocoupling form symmetric pyrroles 92

Язык: Английский

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HFIP-Catalyzed Difluoroalkylation of Propargylic Alcohols to Access Tetrasubstituted Difluoroalkyl Allenes

Organic Letters, Год журнала: 2021, Номер 23(18), С. 7264 - 7269

Опубликована: Авг. 27, 2021

A hexafluoroisopropanol (HFIP)-catalyzed difluoroalkylation of propargylic alcohols with difluoroenoxysilanes to access structurally diverse tetrasubstituted difluoroalkyl allenes has been developed. This convenient procedure enables the rapid construction highly functionalized multisubstituted fluorinated in a mild and straightforward way. Furthermore, synthetic potential this methodology demonstrated by facile synthesis various interesting fluorine-containing molecules such as gem-difluorosubstituted dihydropyran, CF2H-allene, cyclopentanone derivatives.

Язык: Английский

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Synthesis of Unprotected β‐Arylethylamines by Iron(II)‐Catalyzed 1,2‐Aminoarylation of Alkenes in Hexafluoroisopropanol

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(9)

Опубликована: Дек. 21, 2022

β-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides direct entry to unprotected β-arylethylamines remarkable functional group tolerance, allowing key drug-oriented groups be installed two-step process. The use hexafluoroisopropanol as solvent combination an iron(II) catalyst proved essential reaching high-value nitrogen-containing molecules.

Язык: Английский

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Studies on the Origin of the Stabilizing Effects of Fluorinated Alcohols and Weakly Coordinated Fluorine-Containing Anions on Cationic Reaction Intermediates

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(3), С. 1814 - 1829

Опубликована: Янв. 12, 2022

Many synthetic methods that use fluorinated alcohols as solvents have been reported, and the found to be crucial success of these methods. In addition, there reports indicating adding a weakly coordinated fluorine-containing anion, such BF4-, PF6-, or SbF6-, can improve yields. The boosting effect is attributed mainly hydrogen bond activation. A few studies suggested very polar stabilize cationic reaction intermediates. However, how they do so why anions yields not studied in depth. Here, we used quaternary ammonium cations, phosphonium cation, triaryl-substituted carbocation models for short-lived intermediates possible interactions cations with SbF6-. On basis results, propose C-F dipoles E-F (where E B, P, Sb) stabilized by intermolecular charge-dipole interactions. We deduced same fashion thermodynamically

Язык: Английский

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