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. 2024 Jan 8;136(2):e202315345.
doi: 10.1002/ange.202315345. Epub 2023 Dec 11.

Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates

Lukas S Vogl  1 , Peter Mayer  2 , Raphaël Robiette  3 , Mario Waser  1
Affiliations

Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates

Lukas S Vogl et al. Angew Chem Weinheim Bergstr Ger. .

Abstract
in English, German

Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the first example of allenoate activation by using chiral isochalcogenoureas (IChU) for formal (4+2) cycloaddition reactions. Compared to established phosphine and amine catalysis, the use of these easily available Lewis bases enables new stereoselective reaction pathways proceeding with high enantioselectivities, diastereoselectivities, and in good yields. In addition, the factors governing enantioselectivity and the origin of the observed differences compared to other commonly used Lewis bases are explained.

Chiral isochalcogenoureas (IChU) were successfully established as powerful organocatalysts for the activation and control of allenoates. This unprecedented strategy allows for unique reactivities and high levels of stereocontrol, facilitating reaction pathways that are not possible with the existing methods.

Keywords: Allenoates; Cycloadditions; DFT Calculations; Lewis Bases; Organocatalysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
General activation of allenoates with Lewis bases (A); orthogonal reactivities of allenoates 1 with enones 2 using different Lewis bases (B); established applications of isochalcogenoureas (IChU) (C); and the herein reported novel activation of allenoates with isochalcogenoureas (D).
Scheme 2
Scheme 2
Asymmetric application scope of the (4+2) cycloaddition (isolated yields; [a] er after recrystallization; [b] er of the minor diastereoisomers). Molecular structure of 3 p determined by single‐crystal X‐ray structure analysis.
Scheme 3
Scheme 3
Further functionalizations of compounds 3.
Figure 1
Figure 1
Computed free energy profile (kcal/mol relative to reactants) for the formation of 3 b and 5 b (see Supporting Information for additional data and full details).
Scheme 4
Scheme 4
Origin of the high Z selectivity of the exocyclic double bond formed in the IChU‐catalysed (4+2) cycloaddition (relative free energy to reactants in kcal/mol).
Scheme 5
Scheme 5
Origin of enantioselectivity in the chiral IChU catalysed (4+2) cycloaddition (relative free energy to reactants in kcal/mol).
Figure 2
Figure 2
Computed free energy profile (kcal/mol relative to reactants) for the complementary cycloadditions catalysed by DABCO (A) and PPh3 (B) (see Supporting Information for additional data and full details).
Scheme 6
Scheme 6
Rationale for the orthogonal reactivities ((4+2) vs (3+2)) between amine‐ (IChU or DABCO) and phosphine‐catalysed cycloadditions.
See this image and copyright information in PMC

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