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Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
Iridium-catalyzed enantioselective allylic alkynylation
James Y Hamilton1, David Sarlah, Erick M Carreira
1ETH Zürich, HCI H335, 8093 Zürich, Switzerland.
Angewandte Chemie (International Ed. in English)
|May 29, 2013
Summary
This study introduces a new method for enantioselective allylic alkynylation using an iridium catalyst and potassium alkynyltrifluoroborates. This efficient process avoids the need for leaving groups and simplifies synthesis, including for the GPR40 receptor agonist AMG 837.
Area of Science:
- Organometallic Chemistry
- Asymmetric Catalysis
- Synthetic Organic Chemistry
Background:
- Direct functionalization of allylic alcohols is a key transformation in organic synthesis.
- Developing catalytic systems that avoid traditional leaving groups is crucial for atom economy and step efficiency.
- Enantioselective synthesis of complex molecules requires robust and selective catalytic methods.
Purpose of the Study:
- To develop a novel method for the direct enantioselective allylic alkynylation of secondary allylic alcohols.
- To utilize potassium alkynyltrifluoroborates as efficient alkynylating reagents.
- To demonstrate the applicability of the developed protocol in the synthesis of a pharmaceutically relevant compound.
Main Methods:
- Catalysis using an iridium complex with phosphine-olefin ligands (Ir(P,olefin)).
- Direct reaction between secondary allylic alcohols and potassium alkynyltrifluoroborates.
- Optimization of reaction conditions to achieve high yield and enantioselectivity.
Main Results:
- Successful direct enantioselective allylic alkynylation of secondary allylic alcohols was achieved.
- High yields and excellent levels of enantioselectivity were obtained.
- The protocol was effectively applied to the synthesis of the GPR40 receptor agonist AMG 837.
Conclusions:
- A novel, operationally simple, and robust catalytic system for allylic alkynylation has been established.
- The method offers a significant advancement in asymmetric synthesis, eliminating the need for leaving groups.
- This protocol provides a valuable tool for the efficient synthesis of complex organic molecules and drug candidates.
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