Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.
[reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13.
Sakai
Takashi
T
Department of Applied Chemistry, Faculty of Engineering, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan. tsakai@cc.okayama-u.ac.jp
Liu
Yu
Y
Ohta
Hiroshi
H
Korenaga
Toshinobu
T
Ema
Tadashi
T
D001388:Aziridines / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D008049:Lipase / Q000378:metabolism*; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D013696:Temperature; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
C500281:3-methyl-3-phenyl-2-aziridinemethanol; D001388:Aziridines; D011725:Pyridines; D013844:Thiazoles; C500282:dimethyl sulfomycinamate; D008049:Lipase; D000432:Methanol