Synthesis of Azepines via a [6 + 1] Annulation of Ynenitriles with Reformatsky Reagents.
A protocol for the direct synthesis of azepines using a hafnium(III)-catalyzed [6 + 1] annulation of N-tethered ynenitriles with Reformatsky reagents is reported. A broad range of 3-amino-2,7-dihydro-1H-azepine-4-carboxylates 4aa-4he were obtained in high yields and with excellent functional group tolerance. The copper-mediated reactions of isolable Blaise intermediates (enamino esters 3), uniquely underwent 5-endo cyclization to afford the β-2,5-dihydropyrrolyl α,β-unsaturated esters 5aa-5fc, which exhibit anticancer activity.
Mitsuhiro
M
Yoshimatsu
Miki
M
Tanaka
Yu
Y
Fujimura
Yukiteru
Y
Ito
Yusuke
Y
Goto
Yuka
Y
Kobayashi
Hiroaki
H
Wasada
School of Pharmaceutical Sciences, Health Sciences University of Hokkaido , Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Noriyuki
N
Hatae
Faculty of Pharmacy, Kinki University , 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Genzoh
G
Tanabe
Faculty of Pharmacy, Kinki University , 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Osamu
O
Muraoka