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Base-free Enantioselective C(1)-Ammonium Enolate Catalysis Exploiting Aryloxides: A Synthetic and Mechanistic Study
Calum McLaughlin1, Alexandra M Z Slawin1, Andrew D Smith1
1EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, Fife, Scotland, KY16 9ST, UK.
Angewandte Chemie (International Ed. in English)
|August 23, 2019
Summary
A new isothiourea catalyst enables enantioselective Michael additions of aryl esters to vinyl bis-sulfones. This base-free method efficiently creates complex molecules with high stereoselectivity.
Area of Science:
- Organic Chemistry
- Asymmetric Catalysis
Background:
- Michael addition reactions are fundamental in organic synthesis.
- Developing enantioselective methods for creating stereogenic centers is crucial.
Purpose of the Study:
- To develop an enantioselective Michael addition of aryl esters to vinyl bis-sulfones.
- To achieve base-free functionalization of aryl esters.
Main Methods:
- Isothiourea catalysis
- Enantioselective Michael addition
- Variable time normalization analysis (VTNA)
- Isotopologue competition experiments
Main Results:
- High yields and excellent stereoselectivity (≥99:1 er) were achieved.
- A multifunctional aryloxide was identified as key to the catalytic cycle.
- Mechanistic studies elucidated reaction orders, rate-limiting steps, and catalyst behavior.
Conclusions:
- The developed method provides an efficient route to α-functionalized products with two contiguous tertiary stereogenic centers.
- The catalyst's multifunctional role and mechanistic insights are critical for optimizing the reaction.
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