Efficient Synthesis of β-CF3/SCF3-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols.

Abstract

The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of β-CF3- and β-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well.

• Authors: Yong Li, Zhishi Ye, Tabitha M Bellman, Teng Chi, Mingji Dai
• Journal: Organic letters (Org Lett) Vol. 17 Issue 9 Pg. 2186-9 (May 01 2015) ISSN: 1523-7052 [Electronic] United States
• PMID: 25885795 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkenes
• Biphenyl Compounds
• Ethers, Cyclic
• Hydrocarbons, Fluorinated
• Iodides
• Receptors, Glucagon
• cyclopropanol
• adomeglivant
• Copper
• cuprous iodide

Topics

• Alkenes (chemistry)
• Biphenyl Compounds (chemical synthesis, chemistry, pharmacology)
• Catalysis
• Copper (chemistry)
• Diabetes Mellitus, Type 2 (drug therapy)
• Ethers, Cyclic (chemistry)
• Hydrocarbons, Fluorinated (chemical synthesis, chemistry, pharmacology)
• Iodides (chemistry)
• Molecular Structure
• Receptors, Glucagon (antagonists & inhibitors)
• Stereoisomerism