Pseudo‐Stereodivergent Synthesis of Enantioenriched Tetrasubstituted Alkenes by Cascade 1,3‐Oxo‐Allylation/Cope Rearrangement

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(18), P. 7083 - 7088

Published: Feb. 19, 2020

The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction another element, that is, Z/E configuration involving a polysubstituted alkene group, into optically active stereoisomers, not recognized yet. Disclosed here is pseudo-stereodivergent synthesis highly enantioenriched tetrasubstituted architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives, under cooperative catalysis tertiary amine chiral iridium complex. success motif relies on 1,3-oxo-allylation reaction between N-allylic ylides π-allyliridium complex intermediates by ligand substrate control, followed stereoselective concerted 3,3-Cope rearrangement process.

Language: Английский

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

Angewandte Chemie, Journal Year: 2020, Volume and Issue: 133(12), P. 6619 - 6626

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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Boron Catalysis in the Transformation of Carboxylic Acids and Carboxylic Acid Derivatives

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 26(1)

Published: Nov. 26, 2022

Abstract Carboxylic acids, amides, and esters are ubiquitous motifs in functional organic molecules. However, the reactivities of these high oxidation state carbonyl compounds far lower than ketones aldehydes, catalysts applicable to transform this class limited. On other hand, boron have found various applications transformation by taking advantage unique properties derived from their vacant p ‐orbitals. The continuous advancement catalysis has realized several unprecedented direct transformations carboxylic past decade. In review, representative achievements summarized according reaction types focusing on non‐activated esters.

Language: Английский

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Coordination‐Controlled Nickel‐Catalyzed Benzylic Allylation of Unactivated Electron‐Deficient Heterocycles

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(22)

Published: March 4, 2022

Heterocycles are widespread in pharmaceuticals but methods for their transition metal-catalyzed functionalization remain limited. This report describes a general, mild, and effective nickel-catalyzed benzylic allylation benzylation of 14 types heterocyclic aromatic compounds, including pyridines, pyrazines, pyrimidines, pyridazines, triazines, benzimidazoles, oxazoles, thiazoles, as well 3,3-dimethyl-indoles. The exquisite selectivity sites at the 2-position is hypothesized to be controlled by coordination nitrogen Zn(TMP)2 subverting generally presumed pKa 's protons. Furthermore, broad range substrates, diversity electrophiles, excellent functional group compatibility suggest its future application synthesis complex molecules library diversification drug discovery.

Language: Английский

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

Angewandte Chemie, Journal Year: 2021, Volume and Issue: 133(47), P. 25134 - 25144

Published: Oct. 11, 2021

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

Angewandte Chemie, Journal Year: 2022, Volume and Issue: 134(21)

Published: March 11, 2022

Abstract Carbon–fluorine bond activation of the trifluoromethyl group represents an important approach to fluorine‐containing molecules. While selective defluorinative functionalization reactions CF 3 ‐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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Diastereodivergent Aldol‐Type Coupling of Alkoxyallenes with Pentafluorophenyl Esters Enabled by Synergistic Palladium/Chiral Lewis Base Catalysis

Angewandte Chemie, Journal Year: 2022, Volume and Issue: 134(33)

Published: June 17, 2022

Abstract 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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Highly Regio‐ and Enantioselective Cu/Pd Co‐Catalyzed Allylic Alkylation of α‐pyridyl‐α‐fluoroesters: Construction of Quaternary C−F Stereocenters

Chemistry - An Asian Journal, Journal Year: 2023, Volume and Issue: 18(11)

Published: April 8, 2023

New methods for preparation of chiral alkyl fluorides have been studied intensively in recent years due to the favorable physicochemical and biological properties those structures. Herein, we describe regio- enantioselective allylic alkylation α-pyridyl-α-fluoroesters with allyl acetates promoted by Cu/Pd synergistic catalysis, constructing carbon- fluorine quaternary stereocenters. In this co-catalytic system, palladium catalyst mainly constructed C-C bond, while copper controlled enantioselectivity. A series aryl- aliphatic-substituted are applied, giving corresponding products high yield, excellent enantioselectivity, E/Z (up 98% 98 : 2 er, E/Z>20 1).

Language: Английский

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Enantioselective Tertiary Electrophile (Hetero)Benzylation: Pd‐Catalyzed Substitution of Isoprene Monoxide with Arylacetates**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(51), P. 26495 - 26499

Published: Oct. 20, 2021

The enantioselective generation of quaternary carbon centers remains challenging but is growing importance for the preparation functional molecules. Metal catalyzed allylic alkylations tertiary electrophiles can provide access to these substructures remain generally incompatible with organometallic benzyl nucleophiles. Here we demonstrate that electron-deficient arylacetates serve as nucleophile surrogates generate enantioenriched acyclic molecules containing a center via two-step substitution-decarboxylation process using isoprene monoxide. Products are often obtained in >90 % ee commercially available catalyst. An array electron-withdrawing groups on arylacetate moiety tolerated. lactone generated by initial substitution reaction be used further stereoselective transformations prepare vicinal stereocenters.

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, Journal Year: 2022, Volume and Issue: 134(36)

Published: June 28, 2022

Abstract 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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