An anion-induced regio- and chemoselective acylation and its application to the synthesis of an anticancer agent.
[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.
Poirier
M
M
Chemical Process Research and Development, Schering-Plough Research Institute, 1011 Morris Avenue, Union, New Jersey 07083, USA.
Chen
F
F
Bernard
C
C
Wong
Y S
YS
Wu
G G
GG
D000215:Acylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D003500:Cyclization; D007202:Indicators and Reagents; D007659:Ketones / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis*; D003986:Dibenzocycloheptenes
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007659:Ketones; D010880:Piperidines; D011725:Pyridines; C115354:lonafarnib; D003986:Dibenzocycloheptenes