Transition-Metal-Free Enantioselective Reactions of Organo­magnesium Reagents Mediated by Chiral Ligands

Boussonnière, Anne; Castanet, Anne-Sophie; Guyon, Hélène

doi:10.1055/s-0037-1610135

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Zhang

¹

,

Luo

²

,

Zhang

³

et al. 2022

Angewandte Chemie

2

0

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The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long-standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W-Phos) was designed and applied in copper-catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94 % yield, 96 % ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,βunsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram-scale synthesis and modification of various densely functionalized medicinally relevant molecules.

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Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Zhang

¹

,

Luo

²

,

Zhang

³

et al. 2022

View full text Add to dashboard Cite

The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long-standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W-Phos) was designed and applied in copper-catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94 % yield, 96 % ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,βunsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram-scale synthesis and modification of various densely functionalized medicinally relevant molecules.

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Organometallic Reagents: Efficient Tools for the Synthesis of Fused Pyridinyl‐Lactones

Hammas,

Touchet,

Adach

et al. 2023

Eur J Org Chem

0

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: Herein we disclose an efficient one‐pot route to a wide range of 3‐substituted fused pyridinyl‐lactones so called aza‐phthalides. The developed strategy involves a Metal/Halogen Exchange (MHE) reaction as key step, followed by an electrophile trapping using various carbonyl derivatives and a subsequent lactonization. To promote the MHE reaction with high chemoselectivity, our investigations have particularly focused on the nature of mono‐ or bimetallic derivatives as metalation reagents including organolithiums, Grignard reagents and lithium organomagnesiate complexes, and highlighted the positive salt effect on reactional sequence. An extension to fused heteroaryl‐lactones (benzothienyl‐, benzofuranyl‐ and naphthofuranyl scaffolds) was explored.

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Transition-Metal-Free Enantioselective Reactions of Organomagnesium Reagents Mediated by Chiral Ligands

Cited by 5 publications

References 42 publications

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Organometallic Reagents: Efficient Tools for the Synthesis of Fused Pyridinyl‐Lactones

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Transition-Metal-Free Enantioselective Reactions of Organo­magnesium Reagents Mediated by Chiral Ligands

Cited by 5 publications

References 42 publications

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Synthesis of W‐Phos Ligand and Its Application in the Copper‐Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones

Organometallic Reagents: Efficient Tools for the Synthesis of Fused Pyridinyl‐Lactones

Contact Info

Product

Resources

About

Transition-Metal-Free Enantioselective Reactions of Organomagnesium Reagents Mediated by Chiral Ligands