Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)‐Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: Feb. 27, 2024

Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries asymmetric synthesis. Herein, by using siloxypropadienes the precursors allyl copper(I) species, copper(I)-catalyzed diastereoselective enantioselective reductive allylation ketones was achieved, providing syn-diols anti-diols good to excellent enantioselectivity. DFT calculations show that cis-γ-siloxy-allyl copper species generated favorably with either 1-TBSO-propadiene or 1-TIPSO-propadiene. Moreover, steric difference TBS group TIPS distinguishes face selectivity acetophenone, leading syn-selectivity for anti-selectivity Easy transformations were performed, demonstrating synthetic utility present method. one diol prepared above used suitable organocatalyst catalytic self-coupling aldimines situ B

Language: Английский

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Copper-Catalyzed Diastereo-, Enantio-, and (Z)-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20270 - 20278

Published: July 16, 2024

We introduce a method for the (Z)-selective aminoallylation of range ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo- and enantioselectivity. Copper-catalyzed reductive couplings 2-azatrienes aryl/alkyl dialkyl proceed Ph-BPE as supporting ligand, generating anti-amino >98% (Z)-selectivity under mild conditions. The utility products is highlighted through several transformations, including those that leverage (Z)-allylic amine moiety diastereoselective reactions alkene. Calculations illustrate Curtin–Hammett control in product formation over other possible isomers origin (Z)-selectivity.

Language: Английский

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Enantioselective Synthesis of α‐Hydroxy Allyl Ketones via BINAP‐CuH‐Catalyzed Hydroacylation

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Catalytic hydrocupration of unsaturated carbon‐carbon bonds to generate organometallic nucleophiles has recently become an attractive alternative conventional stoichiometric reagents in the stereoselective synthesis. Herein, we have developed efficient and economical method synthesize enantiopure α ‐hydroxy allyl ketones via a copper hydride (CuH)‐catalyzed hydroacylation alkoxyallenes, significant advancement given scarcity reports on such scaffolds literature. DFT calculations reveal that this reaction proceeds through nucleophilic attack kinetically favourable Z ‐selective allyl‐copper intermediate acid anhydrides six‐membered chair‐like transition state, stabilized by strongly non‐covalent interactions ultimately leads high level enantioselectivities using simple BINAP ligand. This successfully overcomes challenges over‐reduction carbonyl functionality presence CuH‐complex, olefin isomerization highly enolizable ‐stereocenter, which can lead erosion enantioselectivities, making our strategy desirable. The exhibits wide range substrate scope including symmetrical as well carbonic with both aromatic, aliphatic substitutions. In addition, ‐substituted provide exclusive syn α,α′ ‐disubstituted excellent enantiomeric ratios, where allylation occurs one carbonyls containing matched α‐ stereocenter, confirmed mechanistic studies.

Language: Английский

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Enantioselective Synthesis of α‐Hydroxy Allyl Ketones via BINAP‐CuH‐Catalyzed Hydroacylation

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Catalytic hydrocupration of unsaturated carbon‐carbon bonds to generate organometallic nucleophiles has recently become an attractive alternative conventional stoichiometric reagents in the stereoselective synthesis. Herein, we have developed efficient and economical method synthesize enantiopure α ‐hydroxy allyl ketones via a copper hydride (CuH)‐catalyzed hydroacylation alkoxyallenes, significant advancement given scarcity reports on such scaffolds literature. DFT calculations reveal that this reaction proceeds through nucleophilic attack kinetically favourable Z ‐selective allyl‐copper intermediate acid anhydrides six‐membered chair‐like transition state, stabilized by strongly non‐covalent interactions ultimately leads high level enantioselectivities using simple BINAP ligand. This successfully overcomes challenges over‐reduction carbonyl functionality presence CuH‐complex, olefin isomerization highly enolizable ‐stereocenter, which can lead erosion enantioselectivities, making our strategy desirable. The exhibits wide range substrate scope including symmetrical as well carbonic with both aromatic, aliphatic substitutions. In addition, ‐substituted provide exclusive syn α,α′ ‐disubstituted excellent enantiomeric ratios, where allylation occurs one carbonyls containing matched α‐ stereocenter, confirmed mechanistic studies.

Language: Английский

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Research Progress on Transition Metal Catalyzed Hydrocarbonation Reactions of N-Allenamines

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(1), P. 151 - 151

Published: Jan. 1, 2025

Language: Английский

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Development of regiodivergent asymmetric reductive coupling reactions of allenamides to access heteroatom-rich organic compounds

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(67), P. 10087 - 10100

Published: Jan. 1, 2023

This feature article describes the application of N -substituted allenes in regiodivergent reductive coupling strategies context new methods for synthesis heteroatom-rich organic compounds.

Language: Английский

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Asymmetric Access to Boryl-Substituted Vicinal Aminoalcohols through Cu-Catalyzed Reductive Coupling

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4644 - 4649

Published: June 20, 2023

Herein, we report the development of a Cu-catalyzed enantioselective borylative aminoallylation aldehydes using N-substituted allene to access boryl-substituted 1,2-aminoalcohol synthons for diversification chiral heteroatom-rich organic compounds. The reported reaction provides several different substitution patterns products from same readily available starting materials with high diastereo- and enantioselectivity.

Language: Английский

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Aminoalcohol Synthesis through Nonprecious Metal Catalysis: Enantioselective Cu-Catalyzed Reductive Coupling of Aldehydes and Allenamides

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4730 - 4734

Published: June 22, 2023

Herein, we report the development of a Cu-catalyzed aminoallylation aldehyde electrophiles through reductive coupling by circumventing problematic competitive reduction electrophile CuH catalyst. This leads to highly diastereo- and enantioselective process for synthesis chiral 1,2-aminoalcohols containing secondary alcohol substitution. Cleavage N substituents on reaction products was performed, allowing access other diastereomer aminoalcohol, which investigated in context eligulstat.

Language: Английский

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Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)‐Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(21)

Published: Feb. 27, 2024

Abstract Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries asymmetric synthesis. Herein, by using siloxypropadienes the precursors allyl copper(I) species, copper(I)‐catalyzed diastereoselective enantioselective reductive allylation ketones was achieved, providing syn ‐diols anti good to excellent enantioselectivity. DFT calculations show that cis ‐γ‐siloxy‐allyl copper species generated favorably with either 1‐TBSO‐propadiene or 1‐TIPSO‐propadiene. Moreover, steric difference TBS group TIPS distinguishes face selectivity acetophenone, leading ‐selectivity for Easy transformations were performed, demonstrating synthetic utility present method. one diol prepared above used suitable organocatalyst catalytic self‐coupling aldimines situ B 2 (neo) .

Language: Английский

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Reductive Metal-Catalyzed Coupling as an Alternative to the Use of Stoichiometric Organometallic Reagents in Carbonyl and Imine Additions

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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