Regio‐ and Stereoselective Cascade of β,γ‐Unsaturated Ketones by Dipeptided Phosphonium Salt Catalysis: Stereospecific Construction of Dihydrofuro‐Fused [2,3‐b] Skeletons

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(36), P. 19860 - 19870

Published: July 2, 2021

Abstract Chiral (dihydro)furo‐fused heterocycles are significant structural motifs in numerous natural products, functional materials and pharmaceuticals. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor synthetic chemistry. Herein, we develop effective, modular method by a dipeptide‐phosphonium salt‐catalyzed regio‐ stereoselective cascade reaction of readily available linear β,γ‐unsaturated ketones aromatic alkenes, affording wide variety structurally fused heterocyclic molecules high yields excellent stereoselectivities. Moreover, mechanistic investigations revealed that the bifunctional phosphonium salt controlled stereoselectivities this reaction, particularly proceeding through initial ketone α‐addition followed O ‐participated substitution; multiple hydrogen‐bonding interactions between Brønsted acid moieties catalyst nitro group alkene were crucial asymmetric induction. Given generality, versatility, efficiency method, anticipate it will have broad utilities.

Language: Английский

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Recent Advances in Phosphonium Salt Catalysis

Advanced Synthesis & Catalysis, Journal Year: 2021, Volume and Issue: 363(8), P. 2023 - 2036

Published: Feb. 5, 2021

Abstract Quaternary phosphonium salts have been extensively used in organic synthesis as Lewis acid organocatalysts. This review covers recent applications of acidic catalysts for Mannich, Strecker, and Friedel‐Crafts reactions the formation C−C bonds, annulation reactions, etc., allowing construction structurally diverse synthetically useful architectures. magnified image

Language: Английский

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Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 18, 2022

Abstract Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure−activity relationship studies, also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting broad use. Here, we report a general modular method constructing these N -bridged [3.3.1] ring systems via cascade process bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety substrates bearing assortment functional groups (59 examples) compatible with this protocol. Other features include [3 + 2] cyclization/ring-opening/Friedel-Crafts pathway, excellent reactivities stereoselectivities, easily starting materials, step economy scalability. The obtained enantioenriched showed potential preliminary anticancer activities. Insights gained from our studies expected advance efforts towards the synthesis challenging even unprecedented chiral PNPs, offering opportunities bioactive small-molecule discovery.

Language: Английский

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Design and Application of Peptide‐Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: July 6, 2023

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer has proven to be powerful strategy for the stereoselective preparation diverse optically active molecules. However, there still remain numerous forbidding issues reactivity and selectivity in such well-known organocatalysis system. Accordingly, development new high-performance catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes prominent endeavours family peptide-mimic multiple hydrogen-bonding donors their applications plethora enantioselective synthesis during past few years. Hopefully, this minireview will pave way further developing much more efficient privileged ligands/catalysts featuring exclusively catalytic ability asymmetric synthesis.

Language: Английский

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Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides

Organic Letters, Journal Year: 2021, Volume and Issue: 23(21), P. 8600 - 8605

Published: Oct. 21, 2021

An enantioselective dearomative 1,3-dipolar cycloaddition of 2-nitrobenzothiophenes and isatin-derived azomethine ylides with a bifunctional hydrogen-bonding thiourea catalyst was established, giving polyheterocyclic compounds in excellent results (up to 99% yield, >20:1 dr for all cases up ee). The enantioselectivity could be reversed by the squaramide containing same chiral source as catalyst. DFT calculations revealed origin observed stereochemistry reversal enantioselectivity.

Language: Английский

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Access to S-Stereogenic Free Sulfoximines via Bifunctional Phosphonium Salt-Catalyzed Desymmetrization of Bisphenols

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(22), P. 13902 - 13912

Published: Nov. 1, 2021

Sulfur-stereogenic sulfoximines particularly with a free N-H unit exhibit intriguing chemical and biological activities, thus have received continuous attention from chemists. However, there are currently no examples of guiding catalytic asymmetric strategies available to directly access these molecules. Herein, we disclose an efficient practical protocol for the direct enantioenrichment sulfoximines, via bifunctional phosphonium salt-catalyzed desymmetrization triggered by Atherton–Todd reaction together further extended nucleophilic acyl substitution-type reaction. A series bearing assortment aromatic groups (70 examples) tolerated in this incidentally involving minority kinetic resolution (KR). The desymmetrized products can be easily transformed into chiral sulfoxides other classes active sulfur-stereogenic compounds. Mechanistic studies provided insights pathway suggesting desymmetrization/KR synergic process, also offered support on hydrogen-bonding interactions as key elements successful stereocontrol.

Language: Английский

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Synergistic Catalysis between a Dipeptide Phosphonium Salt and a Metal‐Based Lewis Acid for Asymmetric Synthesis ofN‐Bridged [3.2.1] Ring Systems

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(38)

Published: June 29, 2022

Abstract We present an unprecedented synergic catalytic route for the asymmetric construction of fluorinated N ‐bridged [3.2.1] cyclic members tropane family via a bifunctional phosphonium salt/silver co‐catalyzed cyclization process. A broad variety substrates bearing assortment functional groups are compatible with this method, providing targeted compounds seven‐membered ring and four contiguous stereocenters in high yields excellent stereoselectivities. The gram‐scale preparations, facile elaborations preliminary biological activities products demonstrate application potential. Moreover, both experimental computational mechanistic studies revealed that proceeded “sandwich” reaction model multiple weak‐bond cooperative activations. Insights gained from our expected to advance general efforts towards synthesis challenging chiral heterocyclic molecules.

Language: Английский

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Catalytic asymmetric dearomative [4 + 2] annulation of 2-nitrobenzofurans and 5H-thiazol-4-ones: stereoselective construction of dihydrobenzofuran-bridged polycyclic skeletons

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(22), P. 6330 - 6336

Published: Jan. 1, 2021

An organocatalytic asymmetric dearomative [4 + 2] annulation of 2-nitrobenzofurans and 5 H -thiazol-4-ones is developed for the construction dihydrobenzofuran-bridged polycyclic skeletons with good results.

Language: Английский

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Electron-rich benzofulvenes as effective dipolarophiles in copper(i)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides

Chemical Science, Journal Year: 2023, Volume and Issue: 14(20), P. 5460 - 5469

Published: Jan. 1, 2023

A series of benzofulvenes without any electron-withdrawing substituents were employed as 2π-type dipolarophiles for the first time to participate in Cu(i)-catalyzed asymmetric 1,3-dipolar cycloaddition (1,3-DC) reactions azomethine ylides. An intrinsic non-benzenoid aromatic characteristic from serves a key driving force activation electron-rich benzofulvenes. Utilizing current methodology, wide range multi-substituted chiral spiro-pyrrolidine derivatives containing two contiguous all-carbon quaternary centers formed good yield with exclusive chemo-/regioselectivity and high excellent stereoselectivity. Computational mechanistic studies elucidate origin stereochemical outcome chemoselectivity, which thermostability these products is major factor.

Language: Английский

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Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1163 - 1163

Published: March 5, 2024

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions affords a series benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis versatile derivatizations demonstrate the potential synthetic application protocol. A plausible mechanism is also proposed account for observed process. work represents first instance N-triggered 2-nitrobenzofurans.

Language: Английский

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