Published January 1, 2022
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A Short and Versatile Approach for the Synthesis of Pyrrolizidinones
Creators
- 1. Syngenta Crop Protect AG, Res Chem, Crop Protect Res, Schaffhauserstr 101, CH-4332 Stein, Switzerland
- 2. Bogazici Univ, Dept Chem, TR-34342 Istanbul, Turkey
Description
Herein we describe a novel 3-step synthesis of pyrrolizidinone derivatives with good overall yield. This sequence relies on first a [2+2] cycloaddition between a keteniminium salt intermediate, bearing an alkyl chloride side chain, and an alkene partner furnishing the corresponding cyclobutanone after hydrolysis of the resulting cyclobutaniminium. Then ring expansion towards the gamma-lactam using a Beckmann-type rearrangement followed by intramolecular S(N)2 reaction in the presence of a base triggers the second ring formation of the process. This approach, which is particularly straightforward, allows a broad diversification of pyrrolizidinones by changing the nature of the substituents on the starting alkene and on the keteniminium precursor. Additionally, a computational study was conducted to assess the activation barrier of the S(N)2 step on different intermediates as well as the nitrogen pyramidalization of the resulting pyrrolizidinones adducts.
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