Catalytic Enantioselective Synthesis of Acyclic Quaternary Centers: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Acyclic Enol Carbonates

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(32), С. 10109 - 10112

Опубликована: Июль 26, 2018

The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted acyclic enol carbonates providing linear α-quaternary ketones is reported. Investigation into the reaction revealed that use an electron-deficient phosphinooxazoline ligand renders enolate geometry starting material inconsequential, with same enantiomer product obtained in level selectivity regardless ratio enolates. As a result, general method toward all-carbon quaternary stereocenters has been developed.

Язык: Английский

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Chemo- and Enantioselective Pd/B Hybrid Catalysis for the Construction of Acyclic Quaternary Carbons: Migratory Allylation of O-Allyl Esters to α-C-Allyl Carboxylic Acids

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(18), С. 5899 - 5903

Опубликована: Апрель 24, 2018

We describe herein the asymmetric synthesis of α-allyl carboxylic acids containing an α-quaternary stereocenter by a chiral hybrid catalyst system comprising palladium and boron complexes. The reaction proceeded through palladium-catalyzed ionization α,α-disubstituted O-allyl esters for generation π-allyl complex as electrophile, boron-catalyzed enolization carboxylate part acid-derived enolates nucleophile, enantioselective coupling between thus-generated nucleophile electrophile. Proper combinations ligands catalysts were crucial. chemoselectively at α-position acid group.

Язык: Английский

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Brønsted acid and Pd–PHOX dual-catalysed enantioselective addition of activated C-pronucleophiles to internal dienes

Chemical Science, Год журнала: 2019, Номер 10(19), С. 5176 - 5182

Опубликована: Янв. 1, 2019

We describe the development of Pd–PHOX-catalysed enantioselective couplings internal dienes with malononitrile and other activated C-pronucleophiles.

Язык: Английский

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Quaternary β^2,2‐Amino Acids: Catalytic Asymmetric Synthesis and Incorporation into Peptides by Fmoc‐Based Solid‐Phase Peptide Synthesis

Angewandte Chemie International Edition, Год журнала: 2017, Номер 57(3), С. 818 - 822

Опубликована: Ноя. 23, 2017

Abstract β‐Amino acid incorporation has emerged as a promising approach to enhance the stability of parent peptides and improve their biological activity. Owing lack reliable access β 2,2 ‐amino acids in setting suitable for peptide synthesis, most contemporary research efforts focus on use 3 ‐ certain 2,3 acids. Herein, we report catalytic asymmetric synthesis into by Fmoc‐based solid‐phase (Fmoc‐SPPS). A quaternary carbon center was constructed palladium‐catalyzed decarboxylative allylation 4‐substituted isoxazolidin‐5‐ones. The N−O bond products not only acts traceless protecting group β‐amino but also undergoes amide formation with α‐ketoacids derived from Fmoc‐protected α‐amino acids, thus providing expeditious α‐β ‐dipeptides ready Fmoc‐SPPS.

Язык: Английский

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Stereoselective Electrophilic Chlorination of β,β-Disubstituted Enesulfinamides with Chloramine-T: Asymmetric Synthesis of Acyclic α,α-Disubstituted α-Chlorinated Carbonyl Surrogates

Organic Letters, Год журнала: 2024, Номер 26(9), С. 1851 - 1856

Опубликована: Фев. 22, 2024

Enamine and iminium ion-mediated asymmetric organocatalysis was not successful in achieving highly stereoselective α-chlorination of acyclic α,α-disubstituted carbonyls. To address this limitation, an alternative method developed, which involved the use geometry-defined persubstituted enesulfinamides to intercept electrophilic chlorinating reagent. This approach enables construction challenging α-chlorinated ketimines with a high degree stereoselectivity. The chloramine-T, cost-effective stable chlorine source rarely utilized chlorination, plays crucial role superior stereocontrol.

Язык: Английский

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Nickel-catalyzed enantioselective allylic alkylation of lactones and lactams with unactivated allylic alcohols

Chemical Science, Год журнала: 2018, Номер 9(9), С. 2547 - 2551

Опубликована: Янв. 1, 2018

Reported is the first nickel-catalyzed enantioselective allylic alkylation of lactones and lactams to provide products bearing an all-carbon quaternary stereocenter.

Язык: Английский

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Cyclometalated Iridium–PhanePhos Complexes Are Active Catalysts in Enantioselective Allene–Fluoral Reductive Coupling and Related Alcohol-Mediated Carbonyl Additions That Form Acyclic Quaternary Carbon Stereocenters

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(5), С. 2087 - 2096

Опубликована: Янв. 25, 2019

Iridium complexes modified by the chiral phosphine ligand PhanePhos catalyze 2-propanol-mediated reductive coupling of diverse 1,1-disubstituted allenes 1a–1u with fluoral hydrate 2a to form CF3-substituted secondary alcohols 3a–3u that incorporate acyclic quaternary carbon-containing stereodiads. By exploiting concentration-dependent stereoselectivity effects related interconversion kinetic (Z)- and thermodynamic (E)-σ-allyliridium isomers, adducts are formed complete levels branched regioselectivity high anti-diastereo- enantioselectivity. The utility this method for construction CF3-oxetanes CF3-azetidines is illustrated formation 4a 6a, respectively. Studies reaction mechanism aimed at illuminating singular effectiveness as a supporting in transformations have led identification chromatographically stable cyclometalated iridium–(R)-PhanePhos complex, Ir-PP-I, catalytically competent allene–fluoral previously reported transfer hydrogenative C–C couplings dienes or CF3-allenes methanol. Deuterium labeling studies, progress analysis (RPKA) computational studies corroborate catalytic involving rapid allene hydrometalation followed turnover-limiting carbonyl addition. A computationally determined stereochemical model shows ortho-CH2 group iridium–PhanePhos complex plays key role directing diastereo- collective data provide insights into structural–interactional features allyliridium required enforce nucleophilic character, which should inform design catalysts umpoled allylation.

Язык: Английский

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Enantioselective Ni/N-Heterocyclic Carbene-Catalyzed Redox-Economical Coupling of Aldehydes, Alkynes, and Enones for Rapid Construction of Acyclic All-Carbon Quaternary Stereocenters

Journal of the American Chemical Society, Год журнала: 2021, Номер 144(1), С. 130 - 136

Опубликована: Дек. 23, 2021

Acyclic quaternary carbon stereocenters exist widely in natural products and bioactive molecules, but their enantioselective construction remains a prominent challenge. In particular, multicomponent couplings of simple precursors to acyclic all-carbon are very rare. We describe herein an N-heterocyclic carbene (NHC)-Ni catalyzed redox-economical three-component reaction aldehydes, alkynes, enones that proceeds highly chemo-, regio-, manner. A wide variety valuable α-quaternary chiral ketones were synthesized single step with 100% atom economy. This through the formation transient cyclic enolate followed by aldol reaction/ring-opening sequence. The strategy is expected inspire new efficient approaches generate other stereocenters.

Язык: Английский

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Asymmetric Three-Component Reaction to Assemble the Acyclic All-Carbon Quaternary Stereocenter via Visible Light and Phosphoric Acid Catalysis

ACS Catalysis, Год журнала: 2022, Номер 12(21), С. 13282 - 13291

Опубликована: Окт. 17, 2022

Chiral acyclic all-carbon quaternary stereocenters are widely present in natural products and pharmaceuticals. However, their introduction remains a challenging topic the synthetic research community. Here, we report an efficient metal-free method for construction of chiral centers sited at α-position aldehyde or ketone moiety. This is achieved via well-designed reaction cascade involving arylalkynes, benzoquinones, electron-rich (hetero)arenes use visible light phosphoric acid catalysis. Notably, asymmetric catalytic visible-light-induced Paternò–Büchi cycloaddition/electrocyclic ring-opening/α-selective arylation α,β-unsaturated carbonyl compound cascades achieved. Moreover, works well broad range these three components (>70 examples). Furthermore, rich chemistry embedded provides variety synthetically useful building blocks that otherwise difficult to access. Lastly, origin enantioselectivity was investigated by density functional theory, revealing CH/π interactions play crucial role stereocontrol reaction.

Язык: Английский

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Enantioselective Copper-Catalyzed Borylative Amidation of Allenes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(50), С. 22850 - 22857

Опубликована: Дек. 6, 2022

An approach for the copper-catalyzed synthesis of enantioenriched amides bearing an α-stereogenic center is disclosed. This method involves addition allyl copper species to isocyanate and allows access α-substituted chiral in high yields high-to-excellent enantioselectivities. The utility α-vinyl β-boryl highlighted by diversification products afford highly useful scaffolds. DFT calculations reveal that catalyst preferentially coordinates oxygen isocyanate. Enantiocontrol arises from steric repulsion between boryl group stereodirecting phenyl ligand.

Язык: Английский

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