Gold-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols. A concise synthesis of (+/-)-angustureine.
An efficient synthetic route to 1,2-dihydroquinolines that relies on AuCl(3)/AgSbF(6)-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols is described herein. Uniquely, the reactions were found to only proceed rapidly at room temperature in the presence of the gold and silver catalyst combination and produce the 1,2-dihydroquinoline products in yields of 40-91%. The method was shown to be applicable to a broad range of 2-tosylaminophenylprop-1-en-3-ols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the alcohol substrate by the AuCl(3)/AgSbF(6) catalyst. This is followed by ionization of the starting material, which causes intramolecular nucleophilic addition of the sulfonamide unit to the allylic cation moiety and construction of the 1,2-dihydroquinoline. The utility of this N-heterocyclic ring forming strategy as a synthetic tool that makes use of alcohols as pro-electrophiles was exemplified by its application to the synthesis of the bioactive tetrahydroquinoline alkaloid (+/-)-angustureine.
Kothandaraman
Prasath
P
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
Foo
Shi Jia
SJ
Chan
Philip Wai Hong
PW
D000433:1-Propanol / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D000586:Amination; D002384:Catalysis; D006046:Gold / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry; D012834:Silver / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
C403008:1,4-dihydroquinone; D000470:Alkaloids; D000475:Alkenes; D011804:Quinolines; D011809:Quinones; C452941:angustureine; D012834:Silver; D006046:Gold; D000433:1-Propanol