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Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines
Published on: January 3, 2018
Phthalides by rhodium-catalyzed ketone hydroacylation
Diem H T Phan1, Byoungmoo Kim, Vy M Dong
1Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Journal of the American Chemical Society
|October 10, 2009
Summary
Researchers developed a new atom-economical method for synthesizing phthalides using enantioselective ketone hydroacylation. This approach yields phthalide products with high enantioselectivity, offering a significant advancement in organic synthesis.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
- Catalysis
Background:
- Phthalides are five-membered lactones with significant biological relevance, found naturally in various plant sources.
- Existing synthetic methods for phthalides may lack atom economy or efficient enantioselective control.
Purpose of the Study:
- To introduce the first atom-economical method for phthalide synthesis.
- To achieve high enantioselectivity in phthalide production via intramolecular ketone hydroacylation.
- To investigate the influence of counterions on catalytic performance.
Main Methods:
- Employed enantioselective intramolecular ketone hydroacylation using a rhodium catalyst with a Duanphos ligand.
- Utilized various 2-ketobenzaldehydes as substrates.
- Investigated different counterions (NO3, OTf, OMs) for the rhodium complex.
Main Results:
- Achieved good yields of phthalide products.
- Demonstrated high enantioselectivities, ranging from 92% to 98% ee.
- Identified the crucial role of counterions in modulating reactivity and enantioselectivity.
- Successfully performed a concise asymmetric total synthesis of (S)-(-)-3-n-butylphthalide.
Conclusions:
- The developed enantioselective ketone hydroacylation is an efficient and atom-economical route to phthalides.
- Counterion selection is critical for optimizing the catalytic process.
- This methodology provides a valuable tool for accessing enantiomerically enriched phthalides, including natural products.
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