Photosensitized O ₂ enables intermolecular alkene cyclopropanation by active methylene compounds

Science, Год журнала: 2023, Номер 381(6657), С. 545 - 553

Опубликована: Авг. 3, 2023

Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, highly energetic reagent requiring stringent safety precautions. Discovery alternative innocuous reagents remains ongoing challenge. Herein, we report simple photoredox-catalyzed intermolecular cyclopropanation unactivated alkenes active methylene compounds. proceeds neutral solvent under air or dioxygen (O 2 ) photoredox catalyst excited by blue light-emitting diode light iodine co-catalyst that either added molecular generated situ from alkyl iodides. Mechanistic investigations indicate photosensitized O plays vital role generation carbon-centered radicals both addition compounds to ring closure.

Язык: Английский

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Photocatalyzed Borylcyclopropanation of Alkenes with a (Diborylmethyl)iodide Reagent

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(38)

Опубликована: Авг. 2, 2023

Cyclopropane skeletons play a prominent role in the development of organic synthesis and pharmaceutical chemistry. Herein, we report design stable, multifunctional (diborylmethyl)iodide reagent (CHI(Bpin)2 ) for photoinduced cyclopropanation alkenes, providing an array 1,2-substituted cyclopropylboronates good yields. This α-haloboronic ester can be readily synthesized on multigram scale from commercially available starting materials. Furthermore, protocol displays high chemo- diastereoselectivity, excellent functional-group tolerance, allows late-stage borylcyclopropanation complex molecules. Mechanistic studies reveal that proceeds through radical addition/polar cyclization pathway mediated by photocatalyst fac-Ir(ppy)3 visible light.

Язык: Английский

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Advances in the Synthesis of Cyclopropylamines

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Cyclopropylamines are an important subclass of substituted cyclopropanes that combine the unique electronic and steric properties with presence a donor nitrogen atom. In addition to their in diverse array biologically active compounds, cyclopropylamines utilized as synthetic intermediates, particularly ring-opening or cycloaddition reactions. Consequently, synthesis these compounds has constituted significant research topic, evidenced by abundant published methods. widely used Curtius rearrangement, classical cyclopropanation methods have been adapted integrate function (Simmons-Smith reaction, metal-catalyzed reaction diazo on olefins, Michael-initiated ring-closure reactions) advances enantioselective synthesis. More recently, specific developed for preparation aminocyclopropane moiety (Kulinkovich reactions applied amides nitriles, cyclopropenes, involving C-H functionalization, ...). The topic this review is present different cyclopropylamine derivatives, aim covering methodological best possible, highlighting scope, stereochemical aspects future trends.

Язык: Английский

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Donor‐Acceptor Cyclopropanes: Activation Enabled by a Single, Vinylogous Acceptor

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(1)

Опубликована: Ноя. 2, 2022

A novel class of highly activated donor-acceptor cyclopropanes bearing only a single, vinylogous acceptor is presented. These strained moieties readily undergo cycloadditions with aldehydes, ketones, thioketones, nitriles, naphth-2-ols and various other substrates to yield the corresponding carbo- heterocycles. Diastereocontrol can be achieved through choice catalyst (Brønsted or Lewis acid). The formation tetrahydrofurans was shown enantiospecific when chiral are employed. series mechanistic kinetic experiments conducted elucidate plausible catalytic cycle rationalize stereochemical outcome.

Язык: Английский

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Catalytic Diastereo‐ and Enantioselective Cyclopropanation of gem‐Dihaloalkanes and Terminal Olefins

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(28)

Опубликована: Май 11, 2023

Chiral cyclopropane derivatives are essential in synthetic chemistry and drug discovery. Their synthesis commonly relies on asymmetric cyclopropanation of diazo compounds, potentially explosive needing stabilizing substituents. Thus, catalytic transformations non-stabilized carbenes or carbenoids remain a formidable challenge. Herein, we report the unprecedented chromium-catalyzed readily available gem-dihaloalkanes terminal olefins. Distinct from previous approaches, serve as suitable precursors for carbenoids, furnishing various functionalized chiral cyclopropanes. Mechanistic studies, including radical trapping, non-linear effect, UV/Vis spectroscopy, provide insights into process, featuring radical-polar crossover.

Язык: Английский

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Reductive Cyclopropanation through Bismuth Photocatalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22140 - 22144

Опубликована: Авг. 5, 2024

We present here a catalytic method based on low-valent Bi complex capable of cyclopropanation double bonds under blue LED irradiation. The catalysis features various unusual Bi-based organometallic steps, namely, (1) two-electron inner sphere oxidative addition Bi(I) to CH2I2, (2) light-induced homolysis the Bi(III)–CH2I bond, (3) subsequent iodine abstraction-ring-closing, and (4) reduction Bi(III) with an external reducing agent close cycle. Stoichiometric experiments support proposed mechanism. This protocol represents unique example reductive photocatalytic process bismuth radical catalysis.

Язык: Английский

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Chiral Bismuth‐Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C−H Functionalization Nexus

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(45)

Опубликована: Сен. 14, 2022

Heterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3-disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in C-H functionalization reactions too. Because of the confined ligand sphere about derived donor/acceptor carbenes, insertions into unhindered methyl groups kinetically favored, although methylene units also react excellent levels induction; even gaseous ethane is a suitable substrate. Moreover, many functional both partners tolerated. The resulting products synthetically equivalent outcome traditional ester alkylation, allylation, benzylation, propargylation and aldol therefore constitute valuable nexus more conventional chemical logic.

Язык: Английский

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A Carbene Relay Strategy for Cascade Insertion Reactions

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(45)

Опубликована: Сен. 19, 2023

Abstract Insertion reactions that involve stabilized electrophilic metallocarbenes are of great importance for installing α‐heteroatoms to carbonyl compounds. Nevertheless, the limited availability carbene precursors restricts introduction only a single heteroatom. In this report, we describe new approach based on an I (III) /S (VI) reagent promotes cascade insertion heteroatoms. This is achieved by sequentially generating two α‐heteroatom‐substituted metal carbenes in one reaction. We found mixed ylide reacts efficiently with transition catalyst and X−H bond (where X=O, N). transformation leads sequential formation sulfoxonium‐ X‐substituted Rh‐carbenes, enabling further another Y−H bond. Remarkably, wide range symmetrical unsymmetrical α,α‐ O , ‐, N ‐subsituted ketones can be prepared under mild ambient conditions. addition, successfully demonstrated other cascades, such as CN/CN double amidation, C−H/C−S insertion, C−S/Y−H Y=S, N, O, C). Notably, latter cascades enabled simultaneous installation three functional groups α‐carbon compounds step. These demonstrate versatility our approach, allowing synthesis esters multiple using common precursor.

Язык: Английский

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Recent Advances in Enantioselective Reactions of Terminal Unactivated Alkenes

Chinese Journal of Chemistry, Год журнала: 2023, Номер 42(7), С. 760 - 776

Опубликована: Ноя. 21, 2023

Comprehensive Summary α ‐Olefins as aliphatic terminal alkenes could be obtained easily from numerous contemporary synthetic reactions well petrochemical industry, and also found in natural products. Compared to the attaching directing groups or activating group, catalytic asymmetric reaction of unactivated presents great challenges due weak electron effect small steric hindrance effect. This review mainly summarizes latest progress olefins since 2016. Key Scientists image

Язык: Английский

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Activity‐Based Protein Profiling Identifies Protein Disulfide‐Isomerases as Target Proteins of the Volatile Salinilactones

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 2, 2024

Abstract The salinilactones, volatile marine natural products secreted from Salinispora arenicola , feature a unique [3.1.0]‐lactone ring system and cytotoxic activities through hitherto unknown mechanism. To find their molecular target, an activity‐based protein profiling with salinilactone‐derived probe is applied that disclosed the disulfide‐isomerases (PDIs) as dominant mammalian targets of thioredoxin (TRX1) secondary target. inhibition disulfide‐isomerase A1 (PDIA1) TRX1 confirmed by biochemical assays recombinant proteins, showing (1 S ,5 R )‐salinilactone B more potent than its )‐configured enantiomer. salinilactones bound covalently to C53 C397, catalytically active cysteines isoform PDIA1 according tandem mass spectrometry. Reactions model substrate demonstrated cyclopropyl group opened attack thiol at C6. Fluorophore labeling experiments showed cell permeability salinilactone‐BODIPY (dipyrrometheneboron difluoride) conjugate co‐localization PDIs in endoplasmic reticulum. study one first pinpoint target for microbial product, it demonstrates can achieve high selectivity despite small size intrinsic reactivity.

Язык: Английский

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