Exploring the Chemistry of Spiroindolenines by Mechanistically-Driven Reaction Development: Asymmetric Pictet–Spengler-type Reactions and Beyond

Accounts of Chemical Research, Год журнала: 2020, Номер 53(4), С. 974 - 987

Опубликована: Апрель 10, 2020

ConspectusThe Pictet–Spengler reaction is a fundamental named in organic chemistry, and it the most straightforward method for synthesis of tetrahydro-β-carbolines, core structure embedded numerous alkaloids. Spiroindolenines are often proposed as possible intermediates reactions. However, whether spiroindolenine species an intermediate mechanism asymmetric remains unclear. Questions about role regarding include following: Can be formed effectively under conditions? If so, what its fate? Is delivery enantioenriched tetrahydro-β-carboline product related to intermediate? Previous studies these questions have not reached consensus. Therefore, elucidating will advance field synthetic chemistry.The first highly enantioselective spiroindolenines that same molecular scaffold key was accomplished by Ir-catalyzed intramolecular allylic substitution indol-3-yl carbonate. In this reaction, piperidine, pyrrolidine, or cyclopentane ring can introduced conjunction with indolenine structure.Spiroindolenines were found undergo ring-expansive migration reactions when treated catalytic amount acid, leading tetrahydro-β-carbolines tetrahydrocarbazoles. Comprehensive DFT calculations Born–Oppenheimer dynamics simulations provided insight into process. It has been stereochemistry strongly correlated electronic properties migratory group along acidity catalyst. Close interactions between positively charged electron-rich indole favor stereospecificity migration. Furthermore, continuous mechanistic spectrum obtained on basis two readily accessible energetic parameters derived from computed energies competing transition states relative species. This theoretical model provides unified understanding which further supported rationally designed prototype Chemically stereochemically controllable achieved multiple potential groups available.The reactivity also explored beyond A one-pot dearomatization/stereoconvergent allows facile racemic starting materials. An unprecedented six- seven-membered vinyliminium moiety involved reactive group. facilitates stereoselective thermodynamically challenging indole-annulated rings. process interrupted. The electrophilic released retro-Mannich captured inter- nucleophile, thus providing new entries structurally diverse polycyclic derivatives.Therefore, probed manipulating turn, insights gained herein aid chemical transformations toward various target molecules. study serves vivid example positive interplay experimental investigations chemistry.

Язык: Английский

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Visible-light-induced intramolecular charge transfer in the radical spirocyclisation of indole-tethered ynones

Chemical Science, Год журнала: 2019, Номер 11(5), С. 1353 - 1360

Опубликована: Дек. 13, 2019

Indole-tethered ynones form an intramolecular electron donor–acceptor complex that can undergo visible-light-induced charge transfer to promote thiyl radical generation from thiols. This initiates a novel chain sequence, based on dearomatising spirocyclisation with concomitant C–S bond formation. Sulfur-containing spirocycles are formed in high yields using this simple and mild synthetic protocol, which neither transition metal catalysts nor photocatalysts required. The proposed mechanism is supported by various mechanistic studies, the unusual initiation mode represents only second report of use synthesis.

Язык: Английский

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Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[b]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition

Angewandte Chemie International Edition, Год журнала: 2018, Номер 57(37), С. 12121 - 12125

Опубликована: Июль 14, 2018

Abstract A highly enantio‐ and diastereoselective formal (4+3) cycloaddition of 1,3‐diene‐1‐carbamates with 3‐indolylmethanols in the presence a chiral phosphoric acid catalyst is reported. The approach described herein provides efficient access to 6‐aminotetrahydrocyclohepta[b]indoles good yields mostly complete diastereoselectivity excellent levels enantioselectivity (>98:2 dr up 98 % ee). Mild reaction conditions, facile scale‐up, versatile derivatization highlight practicality this methodology. mechanistic study suggests that occurs stepwise fashion, after formation an ion pair between catalytic phosphate intermediate carbocation.

Язык: Английский

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Asymmetric Dearomatization of Indole by Palladium/PC‐Phos‐Catalyzed Dynamic Kinetic Transformation

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(49), С. 21991 - 21996

Опубликована: Сен. 2, 2020

Abstract A palladium‐catalyzed intermolecular dynamic kinetic asymmetric dearomatization of 3‐arylindoles with internal alkynes was developed the use achiral Xantphos and chiral sulfinamide phosphine ligand ( PC‐Phos ) as co‐ligands. This method could deliver various spiro[indene‐1,3′‐indole] compounds in good yields (up to 95 % yield) up 98 ee . The salient features transformation include readily available substrates, ease scale‐up versatile functionalization products. mechanistic experiments gave some insights on active intermediates.

Язык: Английский

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Enantioselective Allylation of Alkenyl Boronates Promotes a 1,2-Metalate Rearrangement with 1,3-Diastereocontrol

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(13), С. 4921 - 4927

Опубликована: Март 23, 2021

Alkenyl boronates add to Ir(π-allyl) intermediates with high enantioselectivity. A 1,2-metalate shift forms a second C–C bond and sets 1,3-stereochemical relationship. The three-component coupling provides tertiary boronic esters that can undergo multiple additional functionalizations. An extension trisubstituted olefins three contiguous stereocenters.

Язык: Английский

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Unified Mechanistic Understandings of Pictet-Spengler Reactions

Chem, Год журнала: 2018, Номер 4(8), С. 1952 - 1966

Опубликована: Июль 15, 2018

Язык: Английский

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Palladium-catalyzed allylic alkylation dearomatization of β-naphthols and indoles withgem-difluorinated cyclopropanes

Chemical Communications, Год журнала: 2020, Номер 57(10), С. 1262 - 1265

Опубликована: Дек. 22, 2020

A palladium-catalyzed allylic alkylation dearomatization of β-naphthols and indoles withgem-difluorinated cyclopropanes has been developed for the first time.

Язык: Английский

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Iridium-Catalyzed Intramolecular Asymmetric Allylic Alkylation of Hydroxyquinolines: Simultaneous Weakening of the Aromaticity of Two Consecutive Aromatic Rings

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(8), С. 3114 - 3119

Опубликована: Фев. 12, 2018

Intramolecular asymmetric allylic alkylation reactions of 5- and 7-hydroxyquinoline derivatives were realized by a chiral Ir/NHC catalyst. A series functionalized cyclic enones afforded in excellent yields (up to 99%) high enantioselectivity 97% ee). Theoretical computations revealed that the aromaticity two consecutive rings hydroxyquinoline substrates is significantly weakened. highly efficient formal synthesis (-)-gephyrotoxin was accomplished based on this method.

Язык: Английский

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Controllable Syntheses of Spiroindolenines and Benzazepinoindoles via Hexafluoroisopropanol-Mediated Redox-Neutral Cascade Process

Organic Letters, Год журнала: 2019, Номер 21(16), С. 6225 - 6230

Опубликована: Июль 30, 2019

The pharmaceutically intriguing spiroindolenines incorporating tetrahydroquinoline were constructed via a hexafluoroisopropanol-promoted redox-neutral cascade cyclization from readily available starting materials. benzazepinoindole skeletons could also be facilely accessed one-pot sequential operation. Distinctive features of these transformations include their controllable access the two privileged skeletons, high efficiency, simple operation, and mild reaction conditions.

Язык: Английский

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Organocatalytic Asymmetric One‐Step Desymmetrizing Dearomatization Reaction of Indoles: Development and Bioactivity Evaluation

Angewandte Chemie International Edition, Год журнала: 2018, Номер 58(1), С. 216 - 220

Опубликована: Ноя. 13, 2018

Abstract An organocatalytic one‐step desymmetrizing dearomatization reaction of indoles with in situ formed vinylidene ortho ‐quinone methides is reported. A set [6‐6‐5] and/or [5‐6‐5] fused indoline heterocycles were obtained excellent yields diastereoselectivities (>20:1 d.r.) and enantioselectivities (up to 99 % ee ). Moreover, some the products screened against a panel cancer cell lines, one was identified inhibit proliferation all tested cells, but showed marginal effects non‐cancerous cells. The methodology provides platform for synthesis new leading compounds antitumor activity.

Язык: Английский

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