Regiodivergent Synthesis Utilizing Alkyl Hex-5-en-2-ynoates and 3-Homoacyl Coumarins: Phenol-Mediated Controllable Phosphine-Catalyzed Michael and 1,7-Umpolung Addition

We disclose a first example of regiodivergent addition between alkyl hex-5-en-2-ynoates and 3-homoacyl coumarins under phosphine catalysis, in which phenol serves as a decisive additive. This study demonstrates a phenol-mediated switchable pathway between Michael addition and 1,7-umpolung addition, expanding the scope of alkynoate reactivity with biologically relevant pronucleophiles. The reaction proceeds under mild conditions with high regioselectivity, broad substrate scope, and good functional group tolerance, and its utility was validated through scale-up and product derivatization. Mechanistic studies reveal that solvent-modulated phenol acidity directs regioselectivity and drives the control of kinetic Michael adducts and thermodynamically favored 1,7-adducts.

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Publication Details

Journal
Organic Letters
Published
2025-10-27
DOI
https://doi.org/10.1021/acs.orglett.5c04035
Primary Topic
Asymmetric Synthesis and Catalysis
Type
article
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Regiodivergent Synthesis Utilizing Alkyl Hex-5-en-2-ynoates and 3-Homoacyl Coumarins: Phenol-Mediated Controllable Phosphine-Catalyzed Michael and 1,7-Umpolung Addition

Yadav Kacharu Nagare, Ching‐Wen Hsu, Wenwei Lin, Yi‐Ru Chen et al.
Organic Letters
Asymmetric Synthesis and Catalysis
article

Regiodivergent Synthesis Utilizing Alkyl Hex-5-en-2-ynoates and 3-Homoacyl Coumarins: Phenol-Mediated Controllable Phosphine-Catalyzed Michael and 1,7-Umpolung Addition

Yadav Kacharu Nagare, Ching‐Wen Hsu, Wenwei Lin, Yi‐Ru Chen, Chunhong Shi, Gangababu Marri, Tzuting Lin, Teh Fu Yen, X. HUANG, Yi‐Jen Chen
article en

Abstract

We disclose a first example of regiodivergent addition between alkyl hex-5-en-2-ynoates and 3-homoacyl coumarins under phosphine catalysis, in which phenol serves as a decisive additive. This study demonstrates a phenol-mediated switchable pathway between Michael addition and 1,7-umpolung addition, expanding the scope of alkynoate reactivity with biologically relevant pronucleophiles. The reaction proceeds under mild conditions with high regioselectivity, broad substrate scope, and good functional group tolerance, and its utility was validated through scale-up and product derivatization. Mechanistic studies reveal that solvent-modulated phenol acidity directs regioselectivity and drives the control of kinetic Michael adducts and thermodynamically favored 1,7-adducts.

Organic LettersVol. 27(44)
National Taiwan Normal University (TW), Chung Yuan Christian University (TW)
Openalex Percentile: Top 76%
Asymmetric Synthesis and Catalysis
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