<i>N</i>-Iodosuccinimide-Mediated Dimerization of 2-Alkynylnaphthols: A Highly Diastereoselective Construction of Bridged Polycyclic Compounds via Vinylidene <i>ortho</i>-Quinone Methide Intermediate

Tan, Yu; Zhao, Zhengxing; Chen, Zhili; Huang, Shengbing; Jia, Shiqi; Peng, Lei; Xu, Da; Qin, Wenling; Yan, Hailong

doi:10.1021/acs.orglett.0c01458

Cited by 19 publications

(4 citation statements)

References 55 publications

(10 reference statements)

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“…First, the generation of VQM is thermodynamically unfavorable, but its reverse reaction is feasible [8] . Second, VQM is extremely active and easily leads to self‐destruction or side reactions [7h] . In previous studies, density functional theory (DFT) calculations predicted a low barrier (5.3 kcal mol −1 ) for the reversion of the tri‐ substituted VQM intermediate to the precursor, [8a] translating to a half‐life time of t 1/2 =0.84 ns at room temperature.…”

Section: Methodsmentioning

confidence: 99%

An Isolable Vinylidene ortho‐Quinone Methide: Synthesis, Structure and Reactivity

Liu

Huang

et al. 2022

Angewandte Chemie

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Commonly, an elusive intermediate is generated from a precursor and then trapped and consumed in a reaction. Vinylidene ortho‐quinone methides (VQMs) have been demonstrated as transient axially chiral intermediates in asymmetric catalysis due to their orthogonal π‐bonds forming an allene motif. The current understanding of VQMs is primarily based on time‐resolved absorption, trapping experiments and computational studies. Herein, we report the first isolation and comprehensive characterization of a VQM, including crystallographic analysis. The disturbed aromaticity of the VQM led to its high reactivity as an electrophile or a 4π‐component capable of asymmetric dearomatization of an electron‐deficient phenyl group. Notably, the VQM could be isolated in enantiomerically enriched form, and the subsequent transformation was stereospecific, indicating that the generation of the VQM was involved in the enantiodetermining step. This study paves the way for the direct application of VQMs as starting materials.

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Section: Methodsmentioning

confidence: 99%

An Isolable Vinylidene ortho‐Quinone Methide: Synthesis, Structure and Reactivity

Liu

Huang

et al. 2022

Angewandte Chemie

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“…One intriguing question is whether the chiral VQMs can be realized from 2‐alkynylnaphthols by using carbon electrophiles, such intermediates containing new carbon‐carbon bonds would be captured intramolecularly to provide a rapid cyclization to access axially chiral molecules (Scheme 1, b), thus offering an intermolecular cycloaddition strategy to enhance molecular complexity and diversity (model C ). Notably, the enantioselective intermolecular cycloaddition of alkynylnaphthols is an unmet synthetic challenge, only one preliminary result with 20 % ee was reported at the allene ketone part (model B ) [10] . To the best of our knowledge, there is no report on the enantioselective cycloaddition reaction of alkynylnaphthols with diploes via in situ generation of carbon‐based VQMs.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, the enantioselective intermolecular cycloaddition of alkynylnaphthols is an unmet synthetic challenge, only one preliminary result with 20 % ee was reported at the allene ketone part (model B). [10] To the best of our knowledge, there is no report on the enantioselective cycloaddition reaction of alkynylnaphthols with diploes via in situ generation of carbon-based VQMs.…”

Section: Introductionmentioning

confidence: 99%

Modular Construction of Heterobiaryl Atropisomers and Axially Chiral Styrenes via All‐Carbon Tetrasubstituted VQMs

et al. 2022

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Here we report a new type of chiral all-carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2-alkynylnaphthols to o-quinone methides or imines, which can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl-2H-chromenes bearing axially and centrally chiral elements and axially chiral quinone-naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols with o-quinone methides proceeded via a [2+2] cycloaddition, followed by a retro-4π-electrocyclization and a 6π re-cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [2+4] cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.

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“…The disturbed aromaticity of highly resonance-stabilized arenes imparts high reactivity to the intermediates, which can be exploited in downstream reactions . Vinylidene ortho -quinone methide (VQM) is such a reactive intermediate with broad applications in the asymmetric syntheses of polycyclic skeletons, atropisomers, helicenes, and molecule-bearing multiple stereogenic elements . The common thread in VQM chemistry is the in situ generation of an elusive axially chiral VQM intermediate from an appropriate precursor in the presence of a chiral catalyst (Figure a), and the plethora of reactivity is harnessed through a judicious precursor design and suitable catalyst system .…”

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confidence: 99%

Mechanistic Features of Asymmetric Vinylideneortho-Quinone Methide Construction and Subsequent Transformations

Chang

Liu

et al. 2023

ACS Catal.

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Vinylidene ortho-quinone methide (VQM), an elusive dearomatized intermediate, is widely used in asymmetric catalysis. Due to its transient nature, the current understanding of VQM was largely acquired based on computational studies and trapping experiments. Herein, the enantioselective construction of stable VQM intermediates by an organocatalyzed bromination was achieved. Kinetic studies, control experiments, and nonlinear effects were realized to obtain insights into the two sequential mechanistic events in VQM-involved reactions. The results elucidated that the stereocontrol was enforced by one catalyst molecule in the generation of the axially chiral VQM, but the subsequent transformation was independent of the catalyst. The efficiency of the VQM as axially chiral synthetic reagents was demonstrated by its reactions with carboxylic acids, cyclo-1,3-diones, and nitrone. In all cases, the VQM reacted smoothly to provide the axially chiral esters and ethers via an axial-to-axial chirality transfer, as well as the chiral α-bromo ketones through an axial-to-central chirality conversion. The properties of the isolated VQM exhibited its high potential in organic chemistry.

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N-Iodosuccinimide-Mediated Dimerization of 2-Alkynylnaphthols: A Highly Diastereoselective Construction of Bridged Polycyclic Compounds via Vinylidene ortho-Quinone Methide Intermediate

Cited by 19 publications

References 55 publications

An Isolable Vinylidene ortho‐Quinone Methide: Synthesis, Structure and Reactivity

An Isolable Vinylidene ortho‐Quinone Methide: Synthesis, Structure and Reactivity

Modular Construction of Heterobiaryl Atropisomers and Axially Chiral Styrenes via All‐Carbon Tetrasubstituted VQMs

Mechanistic Features of Asymmetric Vinylideneortho-Quinone Methide Construction and Subsequent Transformations

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