Catalytic Enantioselective Primary C–H Borylation for Acyclic All-Carbon Quaternary Stereocenters

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(2), С. 1635 - 1643

Опубликована: Янв. 5, 2024

Creating a perfect catalyst to operate enzyme-like chiral recognition has been long-sought aim. A challenging example in this context is constructing acyclic all-carbon quaternary stereogenic centers by transition metal-catalyzed enantioselective C–H activation. We now report highly iridium-catalyzed primary borylation of α-all-carbon substituted 2,2-dimethyl amides enabled tailor-made bidentate boryl ligand (CBL). The success the current transformation attributed CBL/iridium catalyst, which confined pocket. This protocol provides diverse array stereocenters with excellent enantiocontrol and distinct structural features. Computational study reveals that steric hindrance CBL could regulate type dominant orbital interaction between substrate, crucial conferring high induction.

Язык: Английский

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2-Aminophenanthroline Ligands Enable Mild, Undirected, Iridium-Catalyzed Borylation of Alkyl C–H Bonds

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(11), С. 7124 - 7129

Опубликована: Март 8, 2024

The catalytic, undirected borylation of alkyl C–H bonds typically occurs at high reaction temperatures or with excess substrate, both, because the low reactivity bonds. Here we report a new iridium system comprising 2-anilino-1,10-phenanthroline as ligand that catalyzes little to no induction period and rates. This superior activation profile 2-aminophenanthroline-ligated catalysts leads broader scope, including reactions sensitive substrates, such epoxides glycosidic acetals, enhanced diastereoselectivity, higher yields borylated products. These also enable alkanes, amines, ethers room temperature for first time. Mechanistic studies imply facile N-borylation under conditions complexes containing N-boryl aminophenanthrolines are competent precatalysts reaction.

Язык: Английский

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Direct C–H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(14), С. 9755 - 9767

Опубликована: Март 26, 2024

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development reactions that complement address limitations existing methods for introduction aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable direct C–H hydroxylation mildly acidic N-heteroarenes benzenes. This protocol employs alkoxide base catalyze X-transfer from sacrificial 2-halothiophene oxidants aryl substrates, forming SNAr-active intermediates undergo nucleophilic hydroxylation. Key process use 2-phenylethanol inexpensive hydroxide surrogate that, after substitution rapid elimination, provides hydroxylated arene styrene byproduct. Use simple 2-halothiophenes allows 6-membered 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends scope electron-deficient benzene substrates. Mechanistic studies indicate reversible, suggesting deprotonation, halogenation, steps operate synergy, manifesting unique selectivity trends not necessarily dependent on most position. The utility method further demonstrated through streamlined target molecule syntheses, examples regioselectivity contrast alternative methods, scalable recycling thiophene oxidants.

Язык: Английский

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Electrochemical generation of aryl radicals from organoboron reagents enabled by pulsed electrosynthesis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(31)

Опубликована: Май 16, 2024

Aryl radicals play a pivotal role as reactive intermediates in chemical synthesis, commonly arising from aryl halides and diazo compounds. Expanding the repertoire of sources for radical generation to include abundant stable organoboron reagents would significantly advance chemistry broaden their reactivity profile. While traditional approaches utilize stoichiometric oxidants or photocatalysis generate these reagents, electrochemical conditions have been largely underexplored. Through rigorous mechanistic investigations, we identified fundamental challenges hindering generation. In addition high oxidation potentials aromatic compounds, electrode passivation through grafting, homocoupling radicals, decomposition issues were identified. We demonstrate that pulsed electrosynthesis enables selective efficient by mitigating challenges. Our discoveries facilitated development first conversion potassium trifluoroborate salts into C-P bonds. This sustainable straightforward oxidative approach exhibited broad substrate scope, accommodating various heterocycles chlorides, typical substrates transition-metal catalyzed cross-coupling reactions. Furthermore, extended this methodology form C-Se, C-Te, C-S bonds, showcasing its versatility potential bond formation processes.

Язык: Английский

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The role of silicon in drug discovery: a review

RSC Medicinal Chemistry, Год журнала: 2024, Номер 15(10), С. 3286 - 3344

Опубликована: Янв. 1, 2024

This review aims to highlight the role of silicon in drug discovery.

Язык: Английский

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Enantioselective Total Syntheses of Vallesamidine and Schizozygane Alkaloids

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

A general streamlined strategy for the enantioselective total syntheses of schizozygane family natural products and related alkaloid vallesamidine is described. Specifically, a catalytic enantioconvergent cross-coupling sets quaternary stereogenic center in pluripotent intermediate adorned with an olefin three orthogonal carboxylate groups, upon which modularity synthesis relies. late-stage oxidative lactamization alkyne instrumental first-generation alkaloids. In second-generation approach, novel application van Leusen reaction generation lactams pivotal to accessing alkaloids from common intermediate. The strategies outlined here are expected enable detailed biological investigations as well facilitate access provide solutions modification bioactive

Язык: Английский

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Ir-Catalyzed, Nitrogen-Directed C(sp³)–H and C(sp²)–H Borylation with a Spiro-Fluorene-Indenoindenyl Ligand

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 4061 - 4068

Опубликована: Фев. 21, 2025

Язык: Английский

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Copper-Catalyzed C–B(sp³) Bond Formation through the Intermediacy of Cu–B(sp³) Complex

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

The vast majority of transition metal (TM) catalyzed borylative transformations rely on TM-B(sp2) complexes. Contrastingly, the chemistry TM-B(sp3) species and their potential in catalytic borylation remain surprisingly underdeveloped, due probably to lack suitable boron(sp3) reagents. Herein, we employ our recently developed sp2-sp3 diboron reagent successfully enable a copper-catalyzed hydroboration allenes for C-B(sp3) bond formation. A comprehensive mechanistic study, including isolation structural characterization Cu-B(sp3) complex, substantiates presence intermediate cycle.

Язык: Английский

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C–H borylation: a tool for molecular diversification

Organic Chemistry Frontiers, Год журнала: 2023, Номер 11(3), С. 929 - 953

Опубликована: Дек. 19, 2023

Iridium-catalyzed C–H activation and borylation has become as a powerful synthetic tool in the past few decades because of widespread applicability versatility organoboron compounds.

Язык: Английский

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Electrochemical meta-C–H sulfonylation of pyridines with nucleophilic sulfinates

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

Опубликована: Авг. 28, 2024

Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well materials science, a direct meta-selective C-H functionalization is paramount importance, but such reactions remain limited highly challenging. In general, established methods for meta rely on utilization tailored electrophilic reagents to realize intrinsic polarity match. Herein, we report complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation through redox-neutral dearomatization-rearomatization strategy by tandem dearomative cycloaddition/hydrogen-evolution electrooxidative sulfonation resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, facile late-stage modification, have been demonstrated, which further contributes practicality adaptability this approach.

Язык: Английский

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