Synthesis of 1-alkyl-2-(trifluoromethyl)azetidines and their regiospecific ring opening toward diverse α-(trifluoromethyl)amines via intermediate azetidinium salts.
A convenient approach toward nonactivated 1-alkyl-2-(trifluoromethyl)azetidines as a new class of constrained azaheterocycles was developed starting from ethyl 4,4,4-trifluoroacetoacetate via imination, hydride reduction, chlorination, and base-induced ring closure. Furthermore, the reactivity profile of these 2-CF(3)-azetidines was assessed by means of quaternization and subsequent regiospecific ring opening at C4 of the azetidinium intermediates by oxygen, nitrogen, carbon, sulfur, and halogen nucleophiles, pointing to a clear difference in reactivity compared to azetidines bearing other types of electron-withdrawing groups at C2.
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Sara
S
Kenis
Matthias
M
D'hooghe
Guido
G
Verniest
Tuyet Anh
TA
Dang Thi
Chinh
C
Pham The
Tuyen
T
Van Nguyen
Norbert
N
De Kimpe
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D012492:Salts / Q000737:chemistry; D013237:Stereoisomerism
D000588:Amines; D001384:Azetidines; D012492:Salts