Super acid-induced Pummerer-type cyclization reaction: improvement in the synthesis of chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines.
Improved synthesis of four stereoisomeric chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines (1a, b, ent-1a, b) was achieved via the super acid-induced cyclization of chiral N-[1-methyl-2-(phenylsulfinyl)ethyl]-N-(1-phenylethyl)formamides (4a, b, ent-4a, b) using the Pummerer-type cyclization reaction as a key step. The cyclization leading to the isoquinoline ring proceeded in a quantitative manner when trifluoromethane sulfonic acid (TFSA) was used as the super acid, although Friedel-Crafts-type alkylation of 4-phenylsulfanyl TIQ derivatives (5) with benzene used as the solvent accompanied cyclization to yield the 4-phenyl-TIQs (7). The byproduct (7) was exclusively formed when a large excess amount of TFSA was used.
Saitoh
Toshiaki
T
Showa Pharmaceutical University, Tokyo, Japon. saitoh-t@ac.shoyaku.ac.jp
Shikiya
Kentaro
K
Horiguchi
Yoshie
Y
Sano
Takehiro
T
D003500:Cyclization; D008698:Mesylates / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013454:Sulfoxides / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry
D008698:Mesylates; D013454:Sulfoxides; D044005:Tetrahydroisoquinolines; C065331:1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; C012077:trifluoromethanesulfonic acid