Highly diastereoselective cyanation of methyl ketimines obtained from (R)-glyceraldehyde.
[reaction: see text] Addition of trimethylsilyl cyanide to ketimines derived from (R)-2,2-dimethyl-1,3-dioxolan-4-yl methyl ketone to generate a quaternary stereocenter has been achieved with high yields and excellent diastereoselectivity. The stereoselectivity was found to be temperature and solvent dependent. The beta-hydroxy-alpha-amino nitrile of syn configuration was the major compound in kinetically controlled reactions, whereas the anti stereoisomer was obtained in excess in thermodynamically controlled reactions. Double stereodifferentiation under kinetic control conditions was successful, and the cyanation reaction occurred with complete syn diastereoselectivity using the matched pair. The versatility of the resulting amino nitrile as a synthetic intermediate was tested by performing the synthesis of orthogonally protected (R)-(2-aminomethyl)alanine.
Badorrey
Ramón
R
Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, E-50009 Zaragoza, Spain.
Cativiela
Carlos
C
Díaz-de-Villegas
María D
MD
Díez
Roberto
R
Galbiati
Fabrizio
F
Gálvez
José A
JA
D003486:Cyanides / Q000737:chemistry*; D005985:Glyceraldehyde / Q000737:chemistry*; D007097:Imines / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D003486:Cyanides; D007097:Imines; D005985:Glyceraldehyde