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. 2020 Mar 6;22(5):1813-1817.
doi: 10.1021/acs.orglett.0c00138. Epub 2020 Feb 17.

Asymmetric Synthesis of [2.2.2]-Bicyclic Lactones via All-Carbon Inverse-Electron-Demand Diels-Alder Reaction

Maciej Saktura  1 , Paulina Grzelak  1 , Joanna Dybowska  1 , Łukasz Albrecht  1
Affiliations

Asymmetric Synthesis of [2.2.2]-Bicyclic Lactones via All-Carbon Inverse-Electron-Demand Diels-Alder Reaction

Maciej Saktura et al. Org Lett. .

Abstract

In this paper, a new cycloaddition between α,β-unsaturated aldehydes and coumalates realized under dienamine activation has been described. The reaction proceeds regioselectively with the distal double bond of the dienamine system acting as electron-rich dienophile. It leads to the formation of biologically relevant [2.2.2]-bicyclic lactones. Their functionalization potential has been confirmed in selected, diastereoselective transformations.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Importance of [2.2.2]-bicyclic lactones
Scheme 1
Scheme 1. Importance of Coumalates and Dienamine Activation and the Synthetic Objectives of Our Study
Scheme 2
Scheme 2. Asymmetric Synthesis of [2.2.2]-Bicyclic Lactones 6: Pyrone 1 Scope
All reactions were performed in a 0.1 mmol scale using 1a (1.5 equiv) and 2 (1.0 equiv) in 0.4 mL of diethyl ether (for details, see the Supporting Information). Isolated yields are given. In parentheses, isolated yields of the major diastereoisomer are given; dr was determined by 1H NMR of the crude reaction mixture; er was determined by chiral HPLC analysis for 6. Reaction performed for 48 h reaction time. Reaction performed for 72 h.
Scheme 3
Scheme 3. Diastereoselective Transformations of [2.2.2]-Bicyclic Lactone 4 or 6
Scheme 4
Scheme 4. Asymmetric Synthesis of [2.2.2]-Bicyclic Lactones 4: Mechanistic Considerations
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