General entry to asymmetric one-pot [N + 2 + n] cyclization for the synthesis of three- to seven-membered azacycloalkanes.
Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Shingo
S
Harada
Takeo
T
Sakai
Kiyosei
K
Takasu
Ken-ichi
K
Yamada
Yasutomo
Y
Yamamoto
Kiyoshi
K
Tomioka
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003516:Cycloparaffins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D001372:Aza Compounds; D003516:Cycloparaffins