Ti-Catalyzed Formal [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with 2-Azadienes to Access Aminobicyclo[2.1.1]hexanes

Organic Letters, Journal Year: 2024, Volume and Issue: 26(8), P. 1745 - 1750

Published: Feb. 20, 2024

Saturated bicyclic amines are increasingly targeted to the pharmaceutical industry as sp3-rich bioisosteres of anilines. Numerous strategies have been established for preparation bridgehead aminobicyclics. However, methods assemble bridge-amino hydrocarbon skeleton, which serves a meta-substituted arene bioisostere, limited. Herein, general approach access 2-aminobicyclo[2.1.1]hexanes (aminoBCHs) by titanium-catalyzed formal [2π + 2σ] cycloaddition bicyclo[1.1.0]butanes and 2-azadienes was developed. Simple derivatization aminoBCHs leads various medicinally agrochemically important analogues.

Language: Английский

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Catalytic Enantioselective Construction of an α-Thio-Substituted α-Aminonitriles-Bearing Tetrasubstituted Carbon Center

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(5), P. 3411 - 3419

Published: Feb. 16, 2024

Chiral unnatural amino acids (UAAs) are important structural units that commonly found in a wide range of natural products and bioactive molecules. α-aminonitriles, which one the most precursors for chiral α-amino acid synthesis, widely accessible via asymmetric Strecker reaction. However, construction α-heteroatom-substituted α-aminonitriles presents challenge due to lack reactivity electrophiles (ester, amide, thioamide, etc.) their ability as leaving groups. Therefore, practical robust approach enantioselective synthesis is highly desirable. We herein describe an efficient method preparation containing tetrasubstituted stereogenic carbon center. This protocol displayed broad substrate scope both reactants high yield with enantioselectivity. Several mechanistic studies revealed presence nitrile crucial enhancing controlling selectivity work not only provides N,S- N,Se-ketal motifs but also powerful strategy overcoming limitation synthesizable α-aminonitriles.

Language: Английский

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Recent Advances in Radical Coupling Strategies Enabled by 2‐Azaallyl Anions as Super‐Electron‐Donors

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(7), P. 1450 - 1466

Published: Feb. 14, 2024

Abstract Due to amine derivatives widely existing in numerous clinical medicines and bioactive compounds, their synthesis has received considerable attention over the past few decades. Traditional methods for of largely relied on reduction nitroarenes, amides, hydrazines, nitriles, azides. Recently, discovery 2‐azaallyl anions as super‐electron‐donors (SEDs) opened up new possibilities construction diverse carbon‐carbon carbon‐heteroatom bonds through radical coupling strategies. This breakthrough highlights potential generating radicals versatile intermediates organic synthesis. Then, hydrolysis product can easily separate corresponding derivatives. Thus, tremendous been paid C−H functionalization ketimines an alternative strategy Herein, we comprehensively summarize recent progress strategies enabled by SEDs. Their proposed mechanistic pathways, advantages, limitations are also discussed detail. 1. Introduction 2. C−C Bond Formation 2.1. Vinylation Ketimines 2.2. Arylation 2.3. Alkylation 2.3.1. Methylation 2.3.2. Other 3. C−X 3.1. C−P C−S Bonds 3.2. C−N C−O 4. Conclusions

Language: Английский

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Enantioselective modular synthesis of α-aryl-α-heteroaryl aminonitriles with parts per million organocatalyst loading: mechanistic investigation for stereochemical origins

Organic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

An enantioselective Friedel-Crafts reaction of iminonitriles gave chiral α-aryl-α-heteroarylaminonitriles in high yield with good enantioselectivity. Pyrrole and indole additions produced different stereochemistries under the same catalyst, explained by DFT.

Language: Английский

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Synthesis of Trifluoromethylated Alkenes via a Tandem Aldol/N-Acyloxyphthalimide-Assisted Decarboxylation Sequence

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

We have developed a metal-free approach for synthesizing E-trifluoromethylated alkenes from readily available aldehydes and the N-hydroxyphtalimide ester of trifluoropropionic acid. To address challenge defluorination, we conducted high-throughput screening reaction conditions. discovered that acid-base co-catalysis effectively suppresses thereby enhancing product yields. A key advantage our method is its reliance on inexpensive, commercially starting materials straightforward

Language: Английский

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Nickel-Catalyzed Enantioselective Hydrophosphinylation of 2-Azadienes to Access Enantioenriched α-Aminophosphine Oxides

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(16), P. 10887 - 10894

Published: Aug. 3, 2023

The practical synthesis of C-stereogenic α-aminophosphine oxides, which exhibit a wide range applications in medicinal chemistry, biochemistry, material science, and asymmetric catalysis, represents an unmet need. Herein, Ni/(S,S)-BenzP* catalyst system is developed for branched oxides through enantioselective Markovnikov addition H-phosphine to 2-azadienes. A variety readily available 2-azadienes undergo hydrophosphinylation with high enantioselectivities (up 99%) good yields 96%). These products can be hydrolyzed afford synthetically valuable chiral are key building blocks the bioactive compounds (such as phospholeucine synthesized herein), organocatalysts, ligands. Mechanistic studies suggest hydrofunctionalization process.

Language: Английский

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Thiocyanoalkylation of Alkenes via Dual Photoredox and Copper Catalysis

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Organic thiocyanates are commonly used as essential organic synthesis intermediates and widely present in various drug molecules bioactive molecules.

Language: Английский

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Enantioselective Synthesis of Aminals Via Nickel-Catalyzed Hydroamination of 2-Azadienes with Indoles and N-Heterocycles

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 30947 - 30957

Published: Oct. 30, 2024

New methods for the enantioselective synthesis of N-alkylated indoles and their derivatives are great interest because pivotal structural elements in biologically active molecules natural products. They also versatile intermediates organic synthesis. Among well-established asymmetric hydroamination methods, with indole-based substrates is a formidable challenge. This observation likely due to reduced nucleophilicity indole nitrogen. Herein, unique nickel-catalyzed enantio- branched-selective 2-azadienes structurally related N-heterocycles reported generation enantioenriched

Language: Английский

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