Synthesis of 2,4-methanoproline analogues via an addition-intramolecular substitution sequence.
A new two-step synthetic approach toward 3-(chloromethyl)cyclobutanone is described and used in the synthesis of 2,4-methanoproline analogues. The key step consists of a reversible addition of hydrogen cyanide onto the imines 12 in 50-74% yield under conditions that allow ring closure. 2-Alkyl-2-azabicyclo[2.1.1]hexane-1-carbonitriles 19, synthesized in four steps, can also be converted to the corresponding amines.
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Coupure links 653, B-9000 Gent, Belgium.
Thomas
T
Rammeloo
Christian V
CV
Stevens
Norbert
N
De Kimpe
D000588:Amines / Q000138:chemical synthesis*; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D006856:Hydrogen Cyanide / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism
C450189:2,4-methanoproline; D000588:Amines; D007097:Imines; D006856:Hydrogen Cyanide; D011392:Proline