Stereodivergent Synthesis of Enantioenriched γ‐Butyrolactones Bearing Two Vicinal Stereocenters Enabled by Synergistic Copper and Iridium Catalysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(47), P. 24930 - 24940

Published: Oct. 11, 2021

By virtue of a fundamentally new reaction model azomethine ylide serving as two-atom synthon, we present the first example stereodivergent preparation γ-butyrolactones via synergistic Cu/Ir-catalyzed asymmetric cascade allylation/lactonization, and all four stereoisomers bearing two vicinal stereocenters are accessible with excellent diastereoselective enantioselective control. The chiral IrIII -π-allyl intermediate was separated characterized to understand origin regio- stereoselectivity initial C-C bond formation process. Control experiments shed some light on catalyst/substrate catalyst/catalyst interactions in this dual catalytic system rationalize related kinetic/dynamic kinetic resolution process different catalyst combinations. enantioenriched γ-butyrolactone products were converted into an array structurally complex molecules organocatalysts that otherwise inaccessible.

Language: Английский

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Stereodivergent Construction of 1,4‐Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(36)

Published: June 28, 2022

An unprecedented hydroalkylation of racemic allylic alcohols and ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with a copper-catalyzed Michael addition in one-pot procedure. The current method enables efficient preparation highly functionalized δ-hydroxyesters bearing 1,4-nonadjacent stereocenters good yields high levels diastereoselectivity excellent enantioselectivity under mild conditions. full complement four stereoisomers products could be readily accessed orthogonal permutations two chiral metal catalysts. work highlights power for stereodivergent construction that were otherwise inaccessible.

Language: Английский

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Diastereodivergent Synthesis of β‐Amino Alcohols by Dual‐Metal‐Catalyzed Coupling of Alkoxyallenes with Aldimine Esters

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(12), P. 6545 - 6552

Published: Dec. 4, 2020

Abstract Both syn ‐ and anti ‐β‐amino alcohols are common structural motifs in natural products, drug molecules, chiral ligands catalysts. However, the currently available methods for synthesizing these limited to generate only one diastereoisomer. Therefore, development of a unified method stereoselective access complementary diastereomers would be highly desirable. Herein, we report dual‐metal‐catalyzed diastereodivergent coupling alkoxyallenes with aldimine esters. By carefully selecting two metals appropriate ligands, could synthesize both alcohol high enantioselectivity diastereoselectivity from same set starting materials. Furthermore, stereodivergent syntheses all four stereoisomers β‐amino achieved. We demonstrated synthetic utility this by concisely mycestericins F G.

Language: Английский

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Organic Superbases in Recent Synthetic Methodology Research

Chemistry - A European Journal, Journal Year: 2020, Volume and Issue: 27(13), P. 4216 - 4229

Published: Aug. 26, 2020

Abstract Organic superbases are a distinct and increasingly utilized class of Brønsted base that possess properties complementary to common inorganic bases. This Concept article discusses recent applications commercial organic in modern synthetic methodologies. Examples the advantages three areas highlighted, including discovery new base‐catalyzed reactions, optimization reactions require stoichiometric base, high‐throughput experimentation technology.

Language: Английский

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Diastereodivergent Aldol‐Type Coupling of Alkoxyallenes with Pentafluorophenyl Esters Enabled by Synergistic Palladium/Chiral Lewis Base Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(33)

Published: June 17, 2022

As a fundamental and synthetically useful C-C bond formation reaction, the aldol reaction is one of most versatile transformations in organic synthesis. However, despite extensive research on asymmetric versions unified method for stereoselective access to complementary syn anti diastereomeric products remains be developed. In this study, we developed synergistic palladium/chiral Lewis base system that overcomes inherent diastereoselectivity bias reactions and, as result, allowed us achieve first diastereodivergent coupling alkoxyallenes with pentafluorophenol esters. Computational studies suggest mechanism involving an intermolecular protonative hydropalladation pathway rather than palladium-hydride migratory insertion pathway. The origin stereochemistry catalysis rationalized by DFT calculations.

Language: Английский

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Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 4, 2023

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium-catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2-position) reported in literature, current reaction achieve nonadjacent (1,3-position) proper combination two chiral catalysts different enantiomers.

Language: Английский

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Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(7)

Published: Oct. 20, 2021

Abstract Alkyl fluorides modulate the conformation, lipophilicity, metabolic stability, and pKa of compounds containing aliphatic motifs and, therefore, have been valuable for medicinal chemistry. Despite significant research in organofluorine chemistry, synthesis alkyl fluorides, especially chiral remains a challenge. Most commonly, are prepared by formation C−F bonds (fluorination), numerous strategies nucleophilic, electrophilic, radical fluorination reported recent years. Although to access C−C bond (monofluoroalkylation) inherently convergent complexity‐generating, they studied less than methods based on fluorination. This Review provides an overview developments (enantioenriched or racemic) secondary tertiary monofluoroalkylation catalyzed transition‐metal complexes. We expect this contribution will illuminate potential monofluoroalkylations simplify complex suggest further directions growing field.

Language: Английский

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Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α‐Fluoroketones

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(50)

Published: Oct. 19, 2022

The development of mild, efficient, and enantioselective methods for preparing chiral fluorinated compounds has been a long-standing challenge. Herein, we report promiscuous cyclohexanone monooxygenase (CHMO) the photoinduced synthesis α-fluoroketones via reductive dehalogenation α,α-halofluoroketones. Wild-type CHMO from Acinetobacter sp. possesses this ability innately; however, yield stereoselectivity are low. A structure-guided rational design improved remarkably. Mechanistic studies molecular simulations demonstrated that catalyzes novel electron transfer (ET)/proton (PT) mechanism, distinct previously reported reductases with similar promiscuity. This methodology was expanded to various substrates, desirable were obtained in high yields (up 99 %) e.r. values 99:1).

Language: Английский

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Asymmetric Defluoroallylation of 4‐Trifluoromethylpyridines Enabled by Umpolung C−F Bond Activation**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(21)

Published: March 11, 2022

Carbon-fluorine bond activation of the trifluoromethyl group represents an important approach to fluorine-containing molecules. While selective defluorinative functionalization reactions CF3 -containing substrates have been achieved by invoking difluorocarbocation, difluorocarboradical, or difluoroorganometallic species as key intermediates, transformations via fluorocarbanion mechanism only limited success. Furthermore, enantioselective transformation remained a formidable challenge. Here we report reaction 4-trifluoromethylpyridines involving difluoro(pyrid-4-yl)methyl anion intermediate, which was developed based upon our previous studies on N-boryl pyridyl chemistry. In particular, asymmetric defluoroallylation and -pyrimidines could be using Ir-catalysis forge difluoroalkyl-substituted chiral center.

Language: Английский

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Iridium‐Catalyzed Chemo‐, Diastereo‐, and Enantioselective Allyl‐Allyl Coupling: Accessing All Four Stereoisomers of (E)‐1‐Boryl‐Substituted 1,5‐Dienes by Chirality Pairing

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 31, 2023

Here, we report a highly chemo-, diastereo-, and enantioselective allyl-allyl coupling between branched allyl alcohols α-silyl-substituted allylboronate esters, catalyzed by chiral iridium complex. The esters can be chemoselectively coupled with electrophiles, affording diverse set of enantioenriched (E)-1-boryl-substituted 1,5-dienes in good yields, excellent stereoselectivity. By permuting the catalysts substrates, efficiently selectively obtained all four stereoisomers bearing two consecutive centers. Mechanistic studies via density functional theory calculations revealed origins diastereo- chemoselectivities, indicating pivotal roles steric interaction, β-silicon effect, rapid desilylation process. Additional synthetic modifications for preparing variety compounds containing contiguous centers are also included.

Language: Английский

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