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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Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 22, 2021

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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Photoinduced Copper‐Catalyzed Asymmetric Three‐Component Coupling of 1,3‐Dienes: An Alternative to Kharasch–Sosnovsky Reaction

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(42), P. 22956 - 22962

Published: Aug. 18, 2021

Abstract Kharasch–Sosnovsky reaction is one of the most powerful methods for allylic oxidation alkenes. However, inherent radical mechanism and use peroxides as both oxidants oxygen nucleophiles render dearth universal catalytic systems highly enantioselective variants limited scope. Herein, an alternative to asymmetric that utilized a chiral copper catalyst purple‐LED irradiation enable three‐component coupling 1,3‐dienes, oxime esters, carboxylic acids reported. This protocol features mild conditions, remarkable scope functional group tolerance evidenced by >80 examples utility in late‐stage modification pharmaceuticals natural products. Detailed mechanistic studies provide evidences radical‐based pathway.

Language: Английский

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Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 3915 - 3925

Published: Feb. 10, 2023

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit synthetic chemistry. Abundant applications free enantioenriched allyl alcohol and hydroxylamine motifs have made the asymmetric hydration hydroaminoxylation conjugated dienes from water hydroxylamine, respectively, intriguing efficient routes that have, however, unachievable thus far. A fundamental challenge is failure to realize transition-metal-catalyzed enantioselective C–O bond constructions via hydrofunctionalization dienes. Here, we perform comprehensive study toward stereoselective formal by synthesizing set new P,N-ligands identifying an aryl-derived oxime surrogate for both hydroxylamine. Asymmetric hydroalkoxylation with also elucidated. Furthermore, versatile derivatizations following provide indirect but concise hydrophenoxylation, hydrofluoroalkoxylation, hydrocarboxylation unreported Finally, ligand-to-ligand hydrogen transfer process proposed based on results preliminary mechanistic experiments.

Language: Английский

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Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2748 - 2756

Published: Jan. 12, 2024

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated great potential non-natural photoenzymes, all transformations are initiated by single-electron reduction substrate, with only one notable exception. Herein, we report an oxidation-initiated enantioselective hydrosulfonylation olefins using novel mutant gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known systems, our approach does not rely formation electron donor–acceptor complex between substrates and enzyme cofactor simplifies reaction system obviating addition regeneration mixture. More importantly, GluER variant exhibits high reactivity broad substrate scope. Mechanistic studies support proposed mechanism reveal that tyrosine-mediated HAT process is involved.

Language: Английский

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Photoinduced, Palladium-Catalyzed Enantioselective 1,2-Alkylsulfonylation of 1,3-Dienes

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(5), P. 3725 - 3732

Published: Feb. 21, 2024

The chiral allylic sulfonylated group is a unique structural motif embedded in range of natural products and pharmaceuticals. Notably, the synthesis structurally diverse derivatives via alkylsulfonylation 1,3-dienes remains underexplored because its inherent challenges stereocontrol regioselectivity. Herein, photoinduced, palladium-catalyzed enantioselective 1,2-alkylsulfonylation conjugated described. A wide variety alkyl bromides, 1,3-dienes, sodium sulfinates could be facilely coupled to generate value-added with high enantioselectivity. Finally, utility this difunctionalization protocol was demonstrated pharmaceutical analogue synthesis.

Language: Английский

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Palladium‐Catalyzed Asymmetric Hydrosulfonylation of 1,3‐Dienes with Sulfonyl Hydrazides

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(6), P. 2948 - 2951

Published: Oct. 23, 2020

A highly enantio- and regioselective hydrosulfonylation of 1,3-dienes with sulfonyl hydrazides has been realized by using a palladium catalyst containing monodentate chiral spiro phosphoramidite ligand. The reaction provided an efficient approach to synthetically useful allylic sulfones. Mechanistic studies suggest that the proceeds through formation allyl hydrazine intermediate subsequent rearrangement sulfone product. transformation product is enantioselectivity-determining step.

Language: Английский

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Enantioselective Addition of Pyrazoles to Dienes**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(36), P. 19660 - 19664

Published: June 19, 2021

We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic can be generated with excellent regioselectivity. Mechanistic studies support a pathway distinct from previous hydroaminations: Pd

Language: Английский

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A Palladium Complex as an Asymmetric π-Lewis Base Catalyst for Activating 1,3-Dienes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(12), P. 4809 - 4816

Published: March 18, 2021

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating electrons from d-orbitals empty antibonding orbitals double bonds (π*) via back-bonding. Thus, uncoordinated bond, as more reactive partner on basis principle vinylogy, directly attack imines, furnishing formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between imines with nucleophilic group is also compatible, trapping situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, activation, compatibility both conjugated neutral polyenes electron-deficient polyenes, elucidated control experiments density functional theory (DFT) calculations.

Language: Английский

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