HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

Llopis, Natalia; Baeza, Alejandro

doi:10.3390/molecules25153464

Cited by 10 publications

(9 citation statements)

References 31 publications

(57 reference statements)

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“…Dissolution in HFIP mediated the synthesis of tetrahydrofurans from epoxides and electron-rich alkenes (Scheme ). Other protic solvents such as water, i -PrOH, and TFE primarily provided hydrolyzed epoxide byproducts and low yields of the desired tetrahydrofuran.…”

Section: Cyclization Reactionsmentioning

confidence: 99%

HFIP in Organic Synthesis

et al. 2022

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1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability to stabilize ionic species, transfer protons, and engage in a range of other intermolecular interactions. The use of this solvent has exponentially increased in the past decade and has become a solvent of choice in some areas, such as C–H functionalization chemistry. In this review, following a brief history of HFIP in organic synthesis and an overview of its physical properties, literature examples of organic reactions using HFIP as a solvent or an additive are presented, emphasizing the effect of solvent of each reaction.

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Section: Cyclization Reactionsmentioning

confidence: 99%

HFIP in Organic Synthesis

et al. 2022

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“…35,36 However, Llopis and Baeza have reported catalyst-free conditions, simply by warming in HFIP solvent. 37 Although the scope is limited to aryl-substituted epoxides, the yields are modest, and the diastereoselectivity is generally low, metal-catalyzed versions of this transformation also share these limitations. 35,36 The reactions of styrene ( 25)…”

Section: © Author(s)mentioning

confidence: 99%

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Dover¹,

McDonald²

2021

Arkivoc

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Ring-opening reactions of epoxides with carbon nucleophiles are valuable transformations for constructing functionalized carbon-carbon bonds. Epoxide ring-opening methods typically require Lewis acidic additives and/or strong nucleophiles to overcome the activation barrier for these reactions. Fluorinated alcohol solvents present a desirable alternative, enhancing the efficacy of these reactions with weak and neutral carbon nucleophiles by promoting electrophilic activation of the epoxide. We present here a thorough review of the literature regarding epoxide ring-opening reactions with carbon nucleophiles in fluorinated alcohol solvents, concluding with a few recent examples with aziridines.

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“…This methodology aims to enable access to functionalized tetrahydrofurans, commonly found in naturally occurring bioactive substances spanning diverse classes such as lignans, acetogenins, ionophores, and macrolides . Notable examples include (+)-fragransin A2, caloxylane, and amphidinolide F (Figure ).…”

mentioning

confidence: 99%

Iron-Carbene Initiated O–H Insertion/Aldol Cascade for the Stereoselective Synthesis of Functionalized Tetrahydrofurans

Kafle,

Ghosh,

Hunter

et al. 2024

ACS Catal.

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Given its earth abundance, cost-effectiveness, and ecofriendly qualities, iron serves as a promising alternative to precious metals in catalysis. This article presents an iron carbene-initiated cascade approach for synthesizing highly substituted tetrahydrofurans at the gram scale. This cascade reaction utilizes readily accessible β-hydroxyketones and diazo compounds and works with iron catalyst loading as low as 5 mol %. This reaction proceeds through an O−H insertion into diazo-derived iron carbenes, followed by an intramolecular aldol reaction to access functionalized tetrahydrofurans in high yields and diastereoselectivity. The versatile nature of this domino sequence accommodates diverse β-hydroxyketones and diazo compounds, streamlining access to synthetically challenging spiroethers. Furthermore, this cascade process offers a route to enantiopure tetrahydrofurans by utilizing a diazo ester bearing a chiral auxiliary, 8-phenylmenthol. Postmodifications of the tetrahydrofuran product provide access to various analogues, including a medicinally relevant oxetane motif. Density functional theory (DFT) calculations substantiate a stereospecific mechanism wherein the intramolecular aldol reaction proceeds via a fused six-and five-membered iron−oxygen transition-state complex, yielding the contrathermodynamic cis-aldol product.

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HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

Cited by 10 publications

References 31 publications

HFIP in Organic Synthesis

HFIP in Organic Synthesis

Fluorinated alcohols: powerful promoters for ring-opening reactions of epoxides with carbon nucleophiles

Iron-Carbene Initiated O–H Insertion/Aldol Cascade for the Stereoselective Synthesis of Functionalized Tetrahydrofurans

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