Stereoselective Construction of Acyclic β,β-Disubstituted Enesulfinamides via Conjugate Addition of Organocuprates to α-Substituted α,β-Unsaturated N-Sulfinyl Ketimines

Organic Letters, Год журнала: 2023, Номер 25(29), С. 5536 - 5541

Опубликована: Июль 17, 2023

In the presence of boron trifluoride, conjugate addition organocuprates to α-substituted α,β-unsaturated N-tert-butanesulfinyl ketimines provides facile access acyclic β,β-disubstituted enesulfinamides with high ratios geometric isomers. Diverse and challenging synthesize, multisubstituted aza-enolates bearing two electronically sterically similar β-substituents, which are important precursors for asymmetric construction less accessible quaternary or tetrasubstituted stereocenters at α-position ketimines, can be efficiently prepared in good yields stereocontrol.

Язык: Английский

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Scope and Mechanistic Probe into Asymmetric Synthesis of α-Trisubstituted-α-Tertiary Amines by Rhodium Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(36), С. 19642 - 19654

Опубликована: Авг. 31, 2023

Asymmetric reactions that convert racemic mixtures into enantioenriched amines are of significant importance due to the prevalence in pharmaceuticals, with about 60% drug candidates containing tertiary amines. Although transition-metal catalyzed allylic substitution processes have been developed provide access α-disubstituted amines, enantioselective synthesis sterically demanding α-tertiary a tetrasubstituted carbon stereocenter remains major challenge. Herein, we report chiral diene-ligated rhodium-catalyzed asymmetric trichloroacetimidates aliphatic secondary afford α-trisubstituted-α-tertiary Mechanistic investigation is conducted using synergistic experimental and computational studies. Density functional theory calculations show rhodium promotes ionization substrates form both anti syn π-allyl intermediates. The pathway proceeds through higher energy than pathway. rate conversion less reactive intermediate more isomer via π–σ–π interconversion was faster nucleophilic attack onto intermediate. These data imply Curtin–Hammett conditions met amination reaction, leading dynamic kinetic transformation. Computational studies also hydrogen bonding interactions between β-oxygen substrate amine-NH greatly assist delivery amine nucleophile hindered internal synthetic utility current methodology showcased by efficient preparation featuring pharmaceutically relevant cores good yields excellent selectivities (branched–linear >99:1, up 99% enantiomeric excess).

Язык: Английский

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Stereoselective Construction of Less-Accessible Acyclic α,α-Disubstituted β-Ketiminonitriles via Electrophilic Cyanation of β,β-Disubstituted Enesulfinamides

Organic Letters, Год журнала: 2024, Номер 26(20), С. 4371 - 4376

Опубликована: Май 16, 2024

The metalloenamines, formed by NH-deprotonation of β,β-disubstituted enesulfinamides, can undergo reactions with commercially available electrophilic cyanating reagents such as tosyl cyanide (TsCN) or 3-oxo-1,2-benziodoxole-1(3

Язык: Английский

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Asymmetric Formal Synthesis of (−)-Cephalotaxine via Palladium-Catalyzed Enantioselective Tsuji Allylation

Organic Letters, Год журнала: 2018, Номер 20(4), С. 1050 - 1053

Опубликована: Фев. 5, 2018

Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor prepared from Hanaoka's ketone intermediate, which formed by a novel formic acid promoted ring-expansion reaction.

Язык: Английский

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Palladium-catalyzed enantioselective decarboxylative allylic alkylation of fully substituted N-acyl indole-derived enol carbonates

Chemical Science, Год журнала: 2019, Номер 10(23), С. 5996 - 6000

Опубликована: Янв. 1, 2019

The first enantioselective palladium-catalyzed decarboxylative allylic alkylation of fully substituted N-acyl indole-derived enol carbonates forming acyclic all-carbon quaternary stereocenters is reported. Excellent yields up to 99% and enantioselectivities 98% ee are obtained through the use a new electron-deficient phosphinoxazoline (PHOX) ligand. Control substrate enolate geometry crucial for high selectivity. α-quaternary indoles formal ester equivalents, represent useful handle further synthetic transformations.

Язык: Английский

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