Gold(I)-catalyzed tandem reactions initiated by hydroamination of alkynyl carbamates: application to the synthesis of nitidine.
As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.
Enomoto
Taro
T
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Girard
Anne-Lise
AL
Yasui
Yoshizumi
Y
Takemoto
Yoshiji
Y
D000480:Alkynes / Q000737:chemistry; D000586:Amination; D053119:Benzophenanthridines / Q000138:chemical synthesis*; D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D006046:Gold / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis*
D000480:Alkynes; D053119:Benzophenanthridines; D002219:Carbamates; C109853:G 1617; D007546:Isoquinolines; D006046:Gold; C013615:nitidine