Stereodivergent synthesis of 1,4-dicarbonyls by traceless charge–accelerated sulfonium rearrangement

Science, Journal Year: 2018, Volume and Issue: 361(6403), P. 664 - 667

Published: Aug. 17, 2018

Four varieties of carbonyl sandwich Compounds with adjacent carbons sandwiched between two (C=O) centers turn up frequently in organic chemistry. When these central each have a substituent, there are four possible mutual geometries, all potentially distinct biochemical properties. Kaldre et al. present single method to access stereoisomer individually. The outcome depends on the straightforwardly tunable configuration sulfoxide group precursor, which guides rearrangement. versatility should facilitate selective 1,4-dicarbonyl motifs pharmaceutical research. Science , this issue p. 664

Language: Английский

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Stereodivergent Construction of Tertiary Fluorides in Vicinal Stereogenic Pairs by Allylic Substitution with Iridium and Copper Catalysts

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(33), P. 13066 - 13073

Published: July 25, 2019

Although much effort has been spent on the enantioselective synthesis of tertiary alkyl fluorides, compounds containing such a stereogenic center within an array stereocenters, particularly two vicinal ones, remains synthetic challenge, and no method to control configuration each independently reported. We describe strategy achieve stereodivergent centers, one fluorine atom, by forming connecting carbon-carbon bond with catalyst system comprising iridium complex that controls at electrophilic carbon copper nucleophilic fluorine-containing carbon. These reactions occur alkyl- aryl-substituted allylic esters unstabilized enolates azaaryl ketones, esters, amides in high yield, diastereoselectivity, enantioselectivity (generally >90% >20:1 dr, 97-99% ee). Access all four stereoisomers products demonstrates precise configurations independently. This methodology extends construction quaternary stereocenters similarly yield selectivity. DFT calculations uncover origin stereoselectivity enolate substitution.

Language: Английский

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Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd‐Catalyzed Asymmetric Dearomative Formal [3+2] Cycloaddition

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(8), P. 2134 - 2138

Published: Jan. 13, 2018

A stereodivergent synthesis of tetrahydrofuroindoles through palladium-catalyzed asymmetric dearomative formal [3+2] cycloaddition nitroindoles with epoxybutenes was developed. The polarity the solvent found to play a key role in diastereoselectivity. In toluene, good excellent yields (70-99 %), diastereoselectivity (87/13->95/5 d.r.), and enantioselectivity (85/15-94/6 e.r.) were obtained, regardless properties substituents on nitroindoles. acetonitrile, different diastereoisomer produced (75-98 %) stereoselectivity (78/22-93/7 d.r., 93/7-99/1 e.r.). Mechanistic studies conducted illustrate origin diastereodivergency. kinetic experiments indicate that rate-determining step this reaction is solvents. ESI-MS also support existence palladium complex intermediates catalytic cycle reaction.

Language: Английский

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Asymmetric [4+2] Annulation of C1 Ammonium Enolates with Copper‐Allenylidenes

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 56(19), P. 5212 - 5216

Published: March 31, 2017

Abstract An asymmetric catalytic decarboxylative [4+2] annulation of 4‐ethynyl dihydrobenzooxazinones and carboxylic acids has been established by cooperative copper nucleophilic Lewis base catalysis. A C1 ammonium enolate copper–allenylidene complex, each catalytically generated from different substrates, underwent a cascade propargylation lactamization process to yield optically active 3,4‐dihydroquinolin‐2‐one derivatives with excellent levels stereoselectivity (up 99 % ee , 95:5 d.r.).

Language: Английский

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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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Cooperative bimetallic catalysis in asymmetric allylic substitution

Organic & Biomolecular Chemistry, Journal Year: 2017, Volume and Issue: 15(46), P. 9747 - 9759

Published: Jan. 1, 2017

Synergistic catalysis is gaining increasing attention due to its advantages over traditional catalytic methodologies, such as improved activity, broader substrate scope, increased selectivity and lower cost. Methodologies involving the synergistic combination of metal catalysts organocatalysts have been intensively studied. Given clear benefits bimetallic catalyst systems consisting two distinct catalysts, cooperative has proved be successful for a number difficult asymmetric transformations. This review highlights recent advances in allylic substitution reactions. Strategies using chiral effect second achiral transformations are discussed. Additionally, several challenging reactions realized by employing different manner also covered.

Language: Английский

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Design and evolution of enzymes for non-natural chemistry

Current Opinion in Green and Sustainable Chemistry, Journal Year: 2017, Volume and Issue: 7, P. 23 - 30

Published: June 10, 2017

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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Organo/Transition-Metal Combined Catalysis Rejuvenates Both in Asymmetric Synthesis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(6), P. 2415 - 2437

Published: Jan. 20, 2022

Since its advent two decades ago, asymmetric organo/transition-metal combined catalysis (AOMC), including cooperative and relay catalysis, has leveraged redistribution of chemical bonds to build up molecular complexity enantio-differentiation form individual enantiomers with activations from versatile organocatalysts transition-metal complexes. The goal this perspective is provide readers the fundamental attributes AOMC─orthogonality, kinetics, mechanism, selectivity─to understand how an organocatalyst a complex would collaborate enable fruitful new reaction development what are intrinsic pathways unproductive events, such as catalyst self-quenching. In closing, future opportunities AOMC have been directed toward prediction effective combination, introducing enzyme focus on transient radical intermediate, animate area in years come.

Language: Английский

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