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. 2025 Apr 23;10(17):18017-18028.
doi: 10.1021/acsomega.5c01416. eCollection 2025 May 6.

Synthesis of Δ1-Pyrrolines via Formal (3 + 2)-Cycloaddition of 2 H-Azirines with Enones Promoted by Visible Light under Continuous Flow

Lorena S R Martelli  1 , Lucas G Furniel  1 , Pedro H O Santiago  2 , Javier Ellena  2 , Arlene G Corrêa  1
Affiliations

Synthesis of Δ1-Pyrrolines via Formal (3 + 2)-Cycloaddition of 2 H-Azirines with Enones Promoted by Visible Light under Continuous Flow

Lorena S R Martelli et al. ACS Omega. .

Abstract

This work reports the first synthesis of Δ1-pyrrolines promoted by visible light under continuous flow, achieved through the formal (3 + 2)-cycloaddition of 2H-azirines to enones. A total of 22 examples of trisubstituted Δ1-pyrrolines were prepared in only 30 min of residence time, with 41-93% yield and diastereomeric ratios up to 7:3. Furthermore, continuous flow conditions were also effective when chalcones were used as starting materials, leading to the formation of 7 tetrasubstituted pyrroles with an overall yield ranging from 12 to 47%, via a photocatalyzed cycloaddition-oxidation sequence.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Examples of natural and synthetic Δ1-pyrrolines.
Scheme 1
Scheme 1. Different Approaches to Achieve Δ1-Pyrrolines via Photocatalysis
Scheme 2
Scheme 2. Scope and Limitations of the Photocatalyzed Cycloaddition between 2H-Azirines and Acrylophenones or Acrylates
Conditions: 1a (0.15 mmol), 2a (0.225 mmol), photocatalyst (7 mol %) in 1,2-DCE (1.5 mL) under 440 nm (40 W) blue LED irradiation. *40 min of residence time. d.r. is represented by the trans/cis ratio.
Figure 2
Figure 2
Crystal structures of trans- and cis-3c, cis-3g, and trans-3p.
Scheme 3
Scheme 3. Scope and Limitations of the Photocatalyzed Cycloaddition between 2H-Azirines and Chalcones Followed by Aromatization
Conditions: 4 (0.18 mmol), 2a (0.27 mmol), photocatalyst (7 mol %) in 1,2-DCE (1.5 mL) under 440 nm (40 W) blue LED irradiation. Then, DDQ (0.3 mmol), 2 mL of toluene, sealed tube, reflux.
Scheme 4
Scheme 4. Proposed Reaction Mechanism for the Photocatalytic Formal (3 + 2)-Cycloaddition of 2H-Azirines with Enones
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