A concise palladium-catalyzed carboamination route to (+/-)-tylophorine.
A total synthesis of the racemic natural product tylophorine [(+/-)-1] has been demonstrated using the palladium-catalyzed carboamination method developed by Wolfe and co-workers. In this case, an electron-rich aryl bromide 18 was prepared in four steps and subjected to palladium-catalyzed Wolfe carboamination conditions with olefinic carbamate 7 to provide the racemic 2-(arylmethyl)pyrrolidine (+/-)-19 in good yield and was further elaborated to racemic tylophorine. This application of the Wolfe carboamination protocol as a key step to construct a natural product provides further evidence of the utility of the method.
Rossiter
Lana M
LM
Medicinal Chemistry Department, Albany Molecular Research, Inc. (AMRI), P.O. Box 15098, 26 Corporate Circle, Albany, New York 12212-5098, USA.
Slater
Meagan L
ML
Giessert
Rachel E
RE
Sakwa
Samuel A
SA
Herr
R Jason
RJ
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000586:Amination; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D006842:Hydrocarbons, Brominated / Q000737:chemistry; D006844:Hydrocarbons, Cyclic / Q000737:chemistry; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D010165:Palladium / Q000737:chemistry*; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D000475:Alkenes; D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D006842:Hydrocarbons, Brominated; D006844:Hydrocarbons, Cyclic; D007212:Indolizines; D010616:Phenanthrenes; D011759:Pyrrolidines; D010165:Palladium; C004218:tylophorine