Synthesis of Cyclopropenols Enabled by Visible‐Light‐Induced Organocatalyzed [2+1] Cyclization

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(10)

Published: Jan. 7, 2022

Although the synthesis of common cyclopropenes has been well studied, access to cyclopropenols is rather limited. Herein, we report first α-trifluoromethylated via 2+1 cycloaddition reactions between alkynes and trifluoroacylsilanes, enabled by visible-light-induced organocatalysis. The novel ambiphilic donor-acceptor carbenes derived from trifluoroacetylsilanes reacted efficiently with both activated non-activated alkynes. reaction features simple operation, mild conditions, broad substrate scope good functional group tolerance. synthetic potential highlighted gram-scale cyclopropanols through combination cyclization high diastereoselective hydrogenation in one pot.

Language: Английский

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Diastereoselective Transfer of Tri(di)fluoroacetylsilanes‐Derived Carbenes to Alkenes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(25)

Published: April 13, 2022

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet-metal-carbene intermediates. However, previous transition-metal-catalyzed with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible-light-induced transition-metal-free terminal trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic aliphatic as well electron-deficient are suitable substrates for highly cis-selective [2+1] cyclization reaction. A combination experimental computational studies identified triplet carbenes being key intermediates in this transformation. The gram scale late-stage functionalization demonstrated synthetic potential strategy.

Language: Английский

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Metal-Catalyzed Transformations of Cyclopropanols via Homoenolates

Bulletin of the Chemical Society of Japan, Journal Year: 2020, Volume and Issue: 94(1), P. 265 - 280

Published: Sept. 28, 2020

Abstract Metal homoenolates represent uniquely useful organometallic intermediates in synthetic chemistry, allowing umpolung synthesis of β-functionalized carbonyl compounds. While siloxycyclopropanes had been established as reliable precursors to homoenolates, often stoichiometric, for diverse carbon–carbon bond forming reactions, unprotected cyclopropanols have emerged alternative and attractive catalytically generated, carbon–heteroatom bond-forming reactions. This review article provides an overview the development such homoenolate transformations, classified with respect metals involved cyclopropane ring opening.

Language: Английский

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Nickel-Catalyzed Carbonylation of Cyclopropanol with Benzyl Bromide for Multisubstituted Cyclopentenone Synthesis

Organic Letters, Journal Year: 2022, Volume and Issue: 24(14), P. 2699 - 2704

Published: April 7, 2022

Herein, we reported a Ni-catalyzed carbonylation of cyclopropanol with benzyl bromide to afford multisubstituted cyclopentenone under 1 atm CO. The reaction proceeds through cascade bromides, followed by generation nickel homoenolate from cyclopropanols via β-C elimination 1,4-diketones, which undergoes intramolecular Aldol condensation furnish highly substituted derivatives in moderate good yields. exhibits high functional group tolerance broad substrate scope.

Language: Английский

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Enantio- and Diastereoenriched Enzymatic Synthesis of 1,2,3-Polysubstituted Cyclopropanes from (Z/E)-Trisubstituted Enol Acetates

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(29), P. 16176 - 16185

Published: July 11, 2023

In nature and synthetic chemistry, stereoselective [2 + 1] cyclopropanation is the most prevalent strategy for synthesis of chiral cyclopropanes, a class key pharmacophores in pharmaceuticals bioactive natural products. One extensively studied reactions organic chemist's arsenal, cyclopropanation, largely relies on use stereodefined olefins, which can require elaborate laboratory or tedious separation to ensure high stereoselectivity. Here, we report engineered hemoproteins derived from bacterial cytochrome P450 that catalyze 1,2,3-polysubstituted regardless stereopurity olefin substrates used. Cytochrome P450BM3 variant P411-INC-5185 exclusively converts (Z)-enol acetates enantio- diastereoenriched cyclopropanes model reaction delivers leftover (E)-enol acetate with 98% stereopurity, using whole Escherichia coli cells. was further single mutation enable biotransformation α-branched ketones levels enantioselectivity while simultaneously catalyzing excellent activities selectivities. We conducted docking studies molecular dynamics simulations understand how active-site residues distinguish between substrate isomers enzyme perform these distinct transformations such Computational suggest observed diastereoselectivities are achieved through stepwise pathway. These biotransformations streamline readily available mixtures (Z/E)-olefins, adding new dimension classical methods.

Language: Английский

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Ti-Catalyzed Diastereoselective Cyclopropanation of Carboxylic Derivatives with Terminal Olefins

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(17), P. 7889 - 7900

Published: April 20, 2022

Cyclopropanols and cyclopropylamines not only serve as important structural motifs in medicinal chemistry but also show diverse reactivities organic synthesis. Owing to the high ring strain energy, development of a general protocol from stable readily available starting materials afford these cyclopropyl derivatives remains compelling challenge. Herein, we describe that Ti-based catalyst can effectively promote diastereoselective syntheses cyclopropanols widely accessible carboxylic (acids, esters, amides) with terminal olefins. To best our knowledge, this method represents first example direct converting alkyl acids into cyclopropanols. Distinct conventional studies Ti-mediated cyclopropanations reactive Grignard reagents nucleophiles or reductants, utilizes Mg Me2SiCl2 turn over Ti catalyst. Our exhibits broad substrate scope good functional group compatibility is amenable late-stage synthetic manipulations natural products biologically active molecules.

Language: Английский

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Ring‐Opening Cross‐Coupling/Cyclization Reaction of Cyclopropanols with Organic Compounds

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(32)

Published: Aug. 23, 2023

Abstract Cyclopropanols, due to their particular chemistry, can participate in various synthetic reactions with retention or cleavage of the strained three‐membered ring. Direct cross‐coupling ring‐opening reaction such molecules access organic compounds, as ketones has great importance medicinal chemistry and material sciences. Hence, coupling reaction/cyclization cyclopropanols for constructing new valuable presence a transition metal catalyst under metal‐free conditions is described this context. The features are discussed, mechanisms challenging highlighted.

Language: Английский

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Metallaphotoredox-Mediated Decarboxylative Cross-Coupling of α-Oxy Morpholine Carboxylic Acids and (Hetero)Aryl Halides

Organic Letters, Journal Year: 2023, Volume and Issue: 25(23), P. 4219 - 4224

Published: June 6, 2023

A decarboxylative C(sp2)–C(sp3) cross-coupling reaction of α-oxy carboxylic acids using dual nickel/photoredox catalysis has been developed for the synthesis complex morpholines and other saturated heterocycles, affording direct entry to scaffolds interest in drug discovery. This chemistry can be applied coupling an array (hetero)aryl halides α-heteroatom acids, providing C(sp2)–C(sp3)-coupled products modest excellent yields enabling access intermediates that further derivatized multivector architectures.

Language: Английский

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Photocatalytic O‐ to S‐Rearrangement of Tertiary Cyclopropanols

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(17)

Published: Feb. 29, 2024

Abstract Despite the importance of heteroatom‐substituted cyclopropane derivatives in drug design and organic synthesis, cyclopropanethiols remain critically underexplored. Inspired by wide use Newman‐Kwart rearrangement to access valuable thiophenols from phenol feedstocks, we report development a photocatalytic approach for efficient ambient temperature aliphatic O ‐ S ‐rearrangement on tertiary cyclopropanol derivatives. After demonstrating that range cyclopropanethiols—that are difficult other methods—can be obtained with this strategy, show these rearranged products can easily hydrolyzed further derivatized. We conclude study mechanistic findings enabled an initial extension toward classes alcohols.

Language: Английский

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TEMPO Mediated Cyclopropanols Ring Opening C−N Cross‐Coupling with Nitrogen Nucleophiles

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(10), P. 1678 - 1684

Published: April 28, 2023

Abstract A feasible and umpolung strategy for the synthesis of structurally diverse β ‐amino ketones has been achieved through TEMPO mediated C−N coupling cyclopropanols with nitrogen nucleophiles. Mechanism studies indicated that in situ generated enones derived from are key intermediates play multiple roles, including radical initiator, trapping reagent, a porter ‐hydrogen an base. This protocol features broad substrate scope, good scalability to excellent yields provides alternative complementary approach important ketone scaffolds under metal additive‐free conditions. magnified image

Language: Английский

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