Triethylamine Enables Catalytic Generation of Oxidopyrylium Ylides for [5+2] Cycloadditions with Alkenes: An Efficient Entry to 8‐Oxabicyclo[3.2.1]octane Frameworks

Toda, Yasunori; Shimizu, Masahiro; Iwai, Toshihiro; Suga, Hiroyuki

doi:10.1002/adsc.201800290

Cited by 14 publications

(5 citation statements)

References 62 publications

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“…These regio-and stereoselectivities are similar to those reported for the cycloaddition of the parent 2unsubstituted oxidopyrylium species. 8,14 DFT calculations of a model reaction involving methyl vinyl ether instead of n-butyl vinyl ether suggest that TSs for endo-products are lower than TSs for exo-products (Figure S2, Supporting Information). The predicted relative rate for the formations of endo-4abMe and endo-5abMe is 2.8:1, which is in good accordance with the experimentally observed product distribution (endo-4ab/endo-5ab = 2.4:1).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The stereochemistry was assigned by analogy to the reported compound. 14 DFT calculations suggest that exomode intramolecular cycloaddition is kinetically more favored than the endo mode intramolecular cycloaddition (Figure S5, Supporting Information), and the corresponding cycloaddition of an oxidopyrylium intermediate with a less flexible acrylate substituent is much less favorable (Figure S6, Supporting Information).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

et al. 2022

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Trifluoromethylation of furfural using the Ruppert−Prakash reagent (TMSCF 3 ) and subsequent photo-Achmatowicz reaction afforded 6-hydroxy-2-(trifluoromethyl)-2H-pyran-3(6H)-one. After acetylation, the resultant 6-acetoxy-2-(trifluoromethyl)-2H-pyran-3(6H)-one was transformed into various 1-(trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-one derivatives through a base-mediated oxidopyrylium [5 + 2] cycloaddition. The reactivity and selectivity of the 2-trifluoromethylated oxidopyrylium species toward [5 + 2] cycloaddition were analyzed using density functional theory calculations.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

et al. 2022

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“…Recent studies have shown that the catalytic and/or enantioselective mode of type I [5 + 2] cycloadditions can be achieved by bases, which provides insight for developing catalytic enantioselective type II [5 + 2] cycloadditions . In addition, there are only two examples of the generation of the oxidopyrylium ylide by acid promotion. , Therefore, the catalytic enantioselective modes of type I and type II [5 + 2] cycloadditions by acids are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Total Synthesis of Natural Products with Bridged Bicyclo[m.n.1] Ring Systems via Type II [5 + 2] Cycloaddition

Min

Liu

2020

Acc. Chem. Res.

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Conspectus Natural products containing bridged ring systems are widely identified and show significant biological activity. The development of efficient synthesis reactions and strategies to construct bridged ring systems is a long-standing but very significant challenge in organic chemistry. In 2014, our group developed a unique type II [5 + 2] cycloaddition reaction that provides a facile and direct methodology for constructing highly functionalized bridged bicyclo[4.3.1], bicyclo[4.4.1], bicyclo[5.4.1], bicyclo[6.4.1], and other bicyclo[m.n.1] systems containing a strained bridgehead double bond. In this Account, we summarize the methodology development and report the results of application of our unique strategy for the total synthesis of several natural products with bridged ring systems (i.e., cyclocitrinol, cerorubenic acid-III, and vinigrol) during the past 5 years in our laboratory. In the first part, we introduce the logic behind the design and discovery of type II [5 + 2] cycloadditions. The substrates can be easily synthesized by a modular approach, followed by base-promoted group elimination under heat to form an oxidopyrylium ylide, which can undergo cycloaddition under relatively mild conditions with a variety of double bonds to generate bridged bicyclo[m.n.1] frameworks in high yield. The diastereocontrol and unique endo selectivity of this methodology are favorable for further application to the synthesis of complex natural products. In the second part, we highlight our endeavors in the total synthesis of several different types of molecules bearing bridged ring systems using our methodology. The bridged bicyclo[4.4.1] system is the core structure of two different types of natural products, cyclocitrinol and cerorubenic acid-III, that can be efficiently constructed by type II [5 + 2] cycloadditions. The development of suitable strategies and methods for site-selective cleavage of the C–O bond of the oxa-[3.2.1] ring system in the products of type II [5 + 2] cycloadditions is also discussed and highlighted during the syntheses. Moreover, the bridged bicyclo[5.3.1] system is the core structure of vinigrol, which can be constructed through a novel ring contraction sequence of the bicyclo[5.4.1] system formed by a type II [5 + 2] cycloaddition. By combining with a ring contraction cascade, we believe that type II [5 + 2] cycloadditions have the potential to be used as a unified approach to constructing natural products containing bridged bicyclo[m.n.1] frameworks.

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“…5 Building upon the seminal work of Hendrickson, 7 Sammes, 8 and Wender, 9 recent examples in the literature illustrate the expanding utility of oxidopyrylium-based [5 + 2] cycloadditions. 5a, 10 Although several strategies toward the generation of oxidopyrylium intermediates (i.e., C) have been disclosed, conversion of acetoxypyranones 7 (i.e., B) derived from oxidative Achmatowicz 11 rearrangement 12 of furfuryl alcohols (i.e., A) has endured as a practical and versatile route (Figure 2), particularly since the development of intramolecular variants by Sammes. 8 In our previous work, we reported preliminary investigations of the formation and cycloaddition of oxidopyrylium intermediates 13 toward a novel oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C 3 ) en route to caged polycyclic bis-ethers.…”

Section: ■ Introductionmentioning

confidence: 99%

Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C³) Sequences: Scope, Limitation, and Computational Investigations

et al. 2018

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Oxidopyrylium-alkene [5 + 2] cycloaddition conjugate addition cascade (C) sequences are described. Intramolecular cycloadditions involving terminal alkenes, enals, and enones were investigated. Substrates with tethers of varying lengths delivered five- and six-membered carbocycles and heterocycles thus demonstrating the scope and limitation of the cycloaddition-conjugate addition cascade. Several experiments and theoretical calculations provide evidence for the proposed mechanistic pathway.

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Triethylamine Enables Catalytic Generation of Oxidopyrylium Ylides for [5+2] Cycloadditions with Alkenes: An Efficient Entry to 8‐Oxabicyclo[3.2.1]octane Frameworks

Abstract: Scheme 1. Synthetic Access to 8-Oxabicyclo[3.2.1]octane Frame works via Oxidopyrylium Ylides.

Cited by 14 publications

References 62 publications

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

Total Synthesis of Natural Products with Bridged Bicyclo[m.n.1] Ring Systems via Type II [5 + 2] Cycloaddition

Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C³) Sequences: Scope, Limitation, and Computational Investigations

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Triethylamine Enables Catalytic Generation of Oxidopyrylium Ylides for [5+2] Cycloadditions with Alkenes: An Efficient Entry to 8‐Oxabicyclo[3.2.1]octane Frameworks

Abstract: Scheme 1. Synthetic Access to 8-Oxabicyclo[3.2.1]octane Frame works via Oxidopyrylium Ylides.

Cited by 14 publications

References 62 publications

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

Combined Computational and Experimental Study on [5 + 2] Cycloaddition of 2-Trifluoromethylated Oxidopyrylium Species Leading to 1-(Trifluoromethyl)-8-oxabicyclo[3.2.1]oct-3-en-2-ones

Total Synthesis of Natural Products with Bridged Bicyclo[m.n.1] Ring Systems via Type II [5 + 2] Cycloaddition

Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C3) Sequences: Scope, Limitation, and Computational Investigations

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Oxidopyrylium-Alkene [5 + 2] Cycloaddition Conjugate Addition Cascade (C³) Sequences: Scope, Limitation, and Computational Investigations