Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran

Yi Han Chao; Paru Jamwal; Gunda Ananda Rao; Ramani Gurubrahamam; Kwunmin Chen

doi:10.1021/acs.orglett.4c01458

Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran

Yi Han Chao, Paru Jamwal, Gunda Ananda Rao, Ramani Gurubrahamam^*, Kwunmin Chen^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an in situ generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers aza-Friedel-Crafts products. The synthetic utility of γ-butenolide is shown toward obtaining piperidone skeleton via a lactone-lactam rearrangement.

Original language	English
Pages (from-to)	4938-4944
Number of pages	7
Journal	Organic Letters
Volume	26
Issue number	23
DOIs	https://doi.org/10.1021/acs.orglett.4c01458
Publication status	Published - 2024 Jun 14

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.4c01458

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title = "Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran",

abstract = "The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an in situ generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers aza-Friedel-Crafts products. The synthetic utility of γ-butenolide is shown toward obtaining piperidone skeleton via a lactone-lactam rearrangement.",

author = "Chao, {Yi Han} and Paru Jamwal and {Ananda Rao}, Gunda and Ramani Gurubrahamam and Kwunmin Chen",

note = "Publisher Copyright: {\textcopyright} 2024 American Chemical Society.",

year = "2024",

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day = "14",

doi = "10.1021/acs.orglett.4c01458",

language = "English",

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T1 - Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran

AU - Chao, Yi Han

AU - Jamwal, Paru

AU - Ananda Rao, Gunda

AU - Gurubrahamam, Ramani

AU - Chen, Kwunmin

PY - 2024/6/14

Y1 - 2024/6/14

N2 - The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an in situ generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers aza-Friedel-Crafts products. The synthetic utility of γ-butenolide is shown toward obtaining piperidone skeleton via a lactone-lactam rearrangement.

AB - The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an in situ generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers aza-Friedel-Crafts products. The synthetic utility of γ-butenolide is shown toward obtaining piperidone skeleton via a lactone-lactam rearrangement.

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Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran

Abstract

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CCDC 2297399: Experimental Crystal Structure Determination

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Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and aza-Friedel-Crafts Reactions of 2-Methoxyfuran

Abstract

ASJC Scopus subject areas

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Datasets

CCDC 2297399: Experimental Crystal Structure Determination

Cite this