Base-induced sequential cyclization-rearrangement of enantioenriched 3-aminoalkanoates to five- and seven-membered lactams.
By treatment with tBuLi, linear 3-aminoalkanoates (4) were converted stereoselectively into five- and seven-membered lactams (trans-5 and cis-6). Initial cyclization to azetidin-2-one with subsequent aza-[1,2] and [2,3] rearrangement is the probable mechanistic pathway from 4 to 5 and 6. Although enantioenriched 4 was converted into nearly racemic 5 and 6, a linear 3-amino-2-methylalkanoate (17) with 90 % ee bearing chirality at the ester alpha-position afforded an all-cis seven-membered lactam (18) bearing three asymmetric centers with 85 % ee.
Sakai
Takeo
T
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Japan.
Yamada
Ken-Ichi
K
Tomioka
Kiyoshi
K
D000473:Alkanes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D003500:Cyclization; D007769:Lactams / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000473:Alkanes; D000588:Amines; D007769:Lactams; D008024:Ligands