Recent advances in chemical dearomatization of nonactivated arenes

Chemical Society Reviews, Journal Year: 2018, Volume and Issue: 47(21), P. 7996 - 8017

Published: Jan. 1, 2018

Dearomatization reactions provide a synthetic connection between readily available, simple aromatic starting materials and more saturated intermediates of greater molecular complexity utility. The last decade has witnessed steady increase in the development dearomative methods, providing new approaches to high-value building blocks natural products. This review highlights advances both area dearomatization methodologies for most chemically inert arenes applications such strategies.

Language: Английский

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The High Chemofidelity of Metal-Catalyzed Hydrogen Atom Transfer

Accounts of Chemical Research, Journal Year: 2018, Volume and Issue: 51(11), P. 2628 - 2640

Published: Nov. 8, 2018

ConspectusThe implementation of any chemical reaction in a structurally complex setting (King, S. M. J. Org. Chem. 2014, 79, 8937) confronts defined barriers: steric environment, functional group reactivity, product instability, and through-bond electronics. However, there are also practical barriers. Late-stage reactions conducted on small quantities material run inevitably at lower than optimal concentrations. Access to late-stage limits extensive optimization. Impurities from past can interfere, especially with catalytic reactions. Therefore, which one rely the front lines synthesis campaign emerge crucible total as robust, dependable, widely applied. Trost conceptualized "chemoselectivity" reagent's selective or reactive site preference others (Trost, B. Science 1983, 219, 245). Chemoselectivity tolerance be evaluated quickly using robustness screens (Collins, K. D. Nat. 2013, 5, 597). A may characterized by its "chemofidelity", that is, reliable molecular context. For example, ketone reduction an electride (dissolving metal conditions) exhibits high chemofidelity but low chemoselectivity: it usually works, many other groups reduced similar rates. Conversely, alkene coordination chemistry effected π Lewis acids exhibit chemoselectivity 245) chemofidelity: highly for alkenes sensitive substitution pattern (Larionov, E. Commun. 50, 9816). In contrast, undergo reliable, diverse hydrogen atom transfer hydrides generate carbon-centered radicals. Although potential applications this chemistry, tolerance, rates, ease execution have led rapid deployment campaigns. Its success derives chemofidelity, dependable reactivity environments patterns. Metal hydride H (MHAT) convert diverse, simple building blocks more stereochemically functionally dense products (Crossley, W. Rev. 2016, 116, 8912). When is returned metal, MHAT considered radical equivalent Brønsted acid catalysis—itself broad paradigm. This Account summarizes our group's contributions method development, reagent discovery, mechanistic interrogation. Our earliest contribution area—a stepwise hydrogenation chemofidelity—has found application problems. More recently, we reported first examples dual-catalytic cross-couplings merger cycles nickel catalysis. With time, anticipate will become staple synthesis.

Language: Английский

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Selective Arene Hydrogenation for Direct Access to Saturated Carbo‐ and Heterocycles

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(31), P. 10460 - 10476

Published: Jan. 31, 2019

Arene hydrogenation provides direct access to saturated carbo- and heterocycles thus its strategic application may be used shorten synthetic routes. This powerful transformation is widely applied in industry expected facilitate major breakthroughs the sciences. The ability overcome aromaticity while controlling diastereo-, enantio-, chemoselectivity central use of preparation complex molecules. In general, multisubstituted arenes yields predominantly cis isomer. Enantiocontrol imparted by chiral auxiliaries, Brønsted acids, or transition-metal catalysts. Recent studies have demonstrated that highly chemoselective transformations are possible. Such methods underlying strategies reviewed herein, with an emphasis on synthetically useful examples employ readily available

Language: Английский

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Photoredox-Enabled Dearomative [2π + 2σ] Cycloaddition of Phenols

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2789 - 2797

Published: Jan. 18, 2024

Dearomative photocycloaddition of monocyclic arenes is an appealing strategy for comprehending the concept "escape from flatland". This brings replacement readily available planar aromatic hydrocarbon units with a 3D fused bicyclic core sp3-enriched carbon units. Herein, we outline intermolecular approach dearomative phenols. In order to circumvent ground-state aromaticity and construct conformationally restrained building blocks, bicyclo[1.1.0]butanes were chosen as coupling partners. renders straightforward access bicyclo[2.1.1]hexane unit cyclic enone moiety, which further contributed synthetic linchpin postmodifications. Mechanistic experiment advocates plausible onset both reactants, depending on redox potential.

Language: Английский

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Enantioselective sulfur(VI) fluoride exchange reaction of iminosulfur oxydifluorides

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(3), P. 353 - 362

Published: Feb. 14, 2024

Language: Английский

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Visible‐Light‐Induced Dearomatizations

European Journal of Organic Chemistry, Journal Year: 2019, Volume and Issue: 2020(10), P. 1259 - 1273

Published: Sept. 26, 2019

The dearomatization of aromatic compounds is an important synthetic strategy used in accessing complex three‐dimensional structures from simple precursors. This minireview aims to provide overview recent advancements this area, with a specific focus on visible‐light‐mediated dearomative transformations. Compared the conventional high‐energy ultraviolet (UV) light‐promoted processes, not only these new approaches offer milder reaction conditions accommodate wider variety substrates sensitive functionalities, but also enable use photocatalysts and other promoters, significantly expanding space. Application transformations synthesis bioactive are discussed.

Language: Английский

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Chemical Equivalent of Arene Monooxygenases: Dearomative Synthesis of Arene Oxides and Oxepines

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(22), P. 10125 - 10131

Published: May 8, 2020

Direct epoxidation of aromatic nuclei by cytochrome P450 monooxygenases is one the major metabolic pathways arenes in eukaryotes. The resulting arene oxides serve as versatile precursors to phenols, oxepines, or trans-dihydrodiol-based metabolites. Although such compounds have an important biological and chemical relevance, lack methods for their production has hampered access utility. Herein, we report a general arenophile-based strategy dearomative synthesis oxides. mildness this method permits sensitive monocyclic without any noticeable decomposition phenols. Moreover, enables direct conversion polycyclic heteroarenes into corresponding oxepines. Finally, these studies provided connection between simple complex small organic molecules via

Language: Английский

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Chemoselective 1,2‐Reduction and Regiodivergent Deuteration of Chromium‐Bound Arenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(18)

Published: Feb. 23, 2023

Herein, a general strategy for chemo- and regioselective 1,2-reduction of chromium-bound arenes was developed, thus providing rapid access to 1,3-cyclohexadienes. Selective arene activation via π-complexation along with the use mild hydride Ph3 SiH can overcome inherently low reactivity π-bonds while tolerating various reduction-sensitive functional groups. Its versatility further enables regiodivergent deuteration. Using different sequences (non)deuterated acid reagents, deuterated positions as well degrees deuterium incorporation be controlled precisely, which leads large previously inaccessible chemical space 1,3-cyclohexadiene isotopologues. A reasonable mechanism proposed based on intermediate capture control experiments. The synthetic value this selective demonstrated in formal total synthesis (±)-galanthamine (±)-lycoramine.

Language: Английский

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Recent Advances in Dearomative Partial Reduction of Benzenoid Arenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 14, 2024

Abstract Dearomative partial reduction is an extraordinary approach for transforming benzenoid arenes and has been well‐known many decades, as exemplified by the dehydrogenation of Birch hydroarylation Crich addition. Despite its remarkable importance in synthesis, this field experienced slow progress over last half‐century. However, a revival observed with recent introduction electrochemical photochemical methods. In Minireview, we summarize advancements dearomative arenes, including dihydrogenation, hydroalkylation, arylation, alkenylation, amination, borylation others. Further, intriguing utilization synthesis natural products also emphasized. It anticipated that Minireview will stimulate further arene transformations.

Language: Английский

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Photochemical dearomative skeletal modifications of heteroaromatics

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(12), P. 6600 - 6624

Published: Jan. 1, 2024

Dearomatization has emerged as a powerful tool for rapid construction of 3D molecular architectures from simple, abundant, and planar (hetero)arenes. The field evolved beyond simple dearomatization driven by new synthetic technology development. With the renaissance photocatalysis expansion activation mode, last few years have witnessed impressive developments in innovative photochemical methodologies, enabling skeletal modifications dearomatized structures. They offer truly efficient useful tools facile highly complex structures, which are viable natural product synthesis drug discovery. In this review, we aim to provide mechanistically insightful overview on these innovations based degree alteration, categorized into dearomative functionalization editing, highlight their utilities.

Language: Английский

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