A convenient synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines via Pictet-Spengler reaction using titanium(IV) isopropoxide and acetic-formic anhydride.
A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.
Horiguchi
Yoshie
Y
Showa Pharmaceutical University, Machida, Tokyo, Japan. horiguti@ac.shoyaku.ac.jp
Kodama
Hirokazu
H
Nakamura
Masayoshi
M
Yoshimura
Tsuyoshi
T
Hanezi
Kaori
K
Hamada
Hiroko
H
Saitoh
Toshiaki
T
Sano
Takehiro
T
D000812:Anhydrides; D007546:Isoquinolines / Q000138:chemical synthesis*; D009942:Organometallic Compounds; D014025:Titanium
D000812:Anhydrides; D007546:Isoquinolines; D009942:Organometallic Compounds; C102815:titanium isopropoxide; D014025:Titanium