Stereodivergent Pd/Cu Catalysis for the Dynamic Kinetic Asymmetric Transformation of Racemic Unsymmetrical 1,3-Disubstituted Allyl Acetates

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(18), P. 8097 - 8103

Published: April 19, 2020

A stereodivergent Pd/Cu catalyst system has been developed for the unprecedented dynamic kinetic asymmetric transformation (DyKAT) of racemic unsymmetrical 1,3-disubstituted allylic acetates with prochiral aldimine esters. series α,α-disubstituted α-amino acids bearing vicinal stereocenters were easily prepared excellent enantioselectivities (up to >99% ee) and diastereoselectivities >20:1 dr). Moreover, all four stereoisomers product can be readily obtained simply by switching configurations two chiral metal catalysts. Furthermore, present work highlights power synergistic catalysis consisting common bidentate ligands synthesis.

Language: Английский

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Stereodivergent Synthesis of Tertiary Fluoride-Tethered Allenes via Copper and Palladium Dual Catalysis

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(19), P. 7285 - 7291

Published: May 10, 2021

Herein we describe a protocol for the unprecedented stereodivergent synthesis of tertiary fluoride-tethered allenes bearing stereogenic center and axis via Cu/Pd synergistic catalysis. A broad scope conjugated enynes are coupled with various α-fluoroesters in high yields diastereoselectivities generally >99% ee. In addition, four stereoisomers allene products ensure precise access to corresponding fluorinated hydrofurans novel axial-to-central chirality transfer process.

Language: Английский

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Enantio- and Diastereodivergent Construction of 1,3-Nonadjacent Stereocenters Bearing Axial and Central Chirality through Synergistic Pd/Cu Catalysis

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(32), P. 12622 - 12632

Published: Aug. 5, 2021

In contrast to the widely explored methods for asymmetric synthesis of molecules bearing a single stereocenter or adjacent stereocenters, concurrent construction 1,3-stereogenic centers in an enantio- and diastereoselective manner remains challenge, especially acyclic systems. Herein, we report diastereodivergent 1,3-nonadjacent stereocenters allenyl axial central chirality through synergistic Pd/Cu-catalyzed dynamic kinetic allenylation with racemic allenylic esters. The protocol is suitable wide range substrates including challenging esters less sterically bulky substituents provided chiral products high levels diastereoselectivities (up >20:1 dr >99% ee). Furthermore, several representative transformations involving axial-to-central transfer were conducted, affording useful structural motifs containing nonadjacent manner.

Language: Английский

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Synergistic Pd/Amine-Catalyzed Stereodivergent Hydroalkylation of 1,3-Dienes with Aldehydes: Reaction Development, Mechanism, and Stereochemical Origins

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(29), P. 10948 - 10962

Published: July 15, 2021

Metal-hydride-catalyzed hydroalkylation of 1,3-dienes with enolizable carbonyl compounds is an atom- and step-economical method for preparing chiral molecules allylic stereocenters. Although high diastereo- enantioselectivities have been achieved many coupling partners, aldehydes not yet used this purpose because they are less stable than other under basic conditions the potential to rapidly epimerize at α-position. Moreover, stereodivergent reactions access complementary diastereomers vicinal stereocenters challenging. Herein, we describe a synergistic palladium/amine catalyst system that allowed us achieve first aldehydes. By choosing appropriate combination palladium amine catalysts, could obtain either syn or anti products, therefore provides highly enantioselective α,β-vicinal Density functional theory calculations revealed mechanism involving PdH formation migratory insertion into alkene, followed by C–C bond formation. The origin stereoselectivities was investigated means distortion/interaction analysis.

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 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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Stereodivergent Synthesis of Enantioenriched 2,3-Disubstituted Dihydrobenzofurans via a One-Pot C–H Functionalization/Oxa-Michael Addition Cascade

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(23), P. 8583 - 8589

Published: June 1, 2021

A one-pot rhodium-catalyzed C–H functionalization/organocatalyzed oxa-Michael addition cascade reaction has been developed. This methodology enables the stereodivergent synthesis of diverse 2,3-disubstituted dihydrobenzofurans with broad functional group compatibility in good yields high levels stereoselectivity under exceptionally mild conditions. The full complement stereoisomers chiral and 3,4-disubstituted isochromans could be accessed at will by appropriate permutations two catalysts. current work provides a rare example catalysts independently controlling contiguous stereogenic centers subsequently via two-step single operation.

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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