A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines.
A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone.
Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
Hieu-Trinh
HT
Luu
Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
Stefan
S
Wiesler
Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
Georg
G
Frey
Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
Jan
J
Streuff
D002384:Catalysis; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D014025:Titanium / Q000737:chemistry*
C514302:3-demethoxyerythratidinone; D026121:Indole Alkaloids; D009570:Nitriles; D044005:Tetrahydroisoquinolines; D014025:Titanium