A synthesis of heteroaromatic analogues of 1-methyl-1,2,3,4-tetrahydroisoquinoline using the Pummerer-type cyclization reaction: observation of tandem cyclization reaction.
The sulfoxides 7b and 7d carrying thiophene or benzothiophene as heteroaromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction), underwent an intramolecular alkylation in an exclusive manner to yield 4,5,6,7-tetrahydro-7-methyl-4-phenylsulfanylthieno[2,3-c]pyridine-6-carbaldehyde (10) and the corresponding benzothiophene derivative (12b) in high yields, respectively. Thus, this route provides biologically interesting nitrogen heterocycles (1b) and (2b). On the other hand, the sulfoxide (7c) carrying benzofuran as a nucleophile on reaction with TFAA yielded not only the Pummerer-type cyclization product (12a), but also the diastereoisomeric tandem cyclization products (13) and (14) having a noble 11-aza-2-oxa-7-thiatricyclo[4.3.3.0(1,5)]dodecane ring system (B). The formation of these products can be readily rationalized by the intervention of the oxonium ion intermediate (21).
Horiguchi
Yoshie
Y
Showa Pharmaceutical University, Machida, Tokyo, Japan. horiguti@ac.shoya.ac.jp
Ogawa
Keita
K
Saitoh
Toshiaki
T
Sano
Takehiro
T
D003500:Cyclization; D006868:Hydrolysis; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013454:Sulfoxides / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry
D013454:Sulfoxides; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline