Short stereocontrolled synthesis of trans and cis-tetrahydro-pyrazinoisoquinolinediones

✍ Scribed by Juan Francisco González; Elena de la Cuesta; Carmen Avendaño

• Book ID: 104253642
• Publisher: Elsevier Science
• Year: 2003
• Tongue: French
• Weight: 115 KB
• Volume: 44
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(03)00897-9

✦ Synopsis

Addition of aldehyde dimethyl acetals (here acetaldehyde) to unisolated O-trimethylsilyl derivatives of 1-acetyl-3-arylmethylpiperazine-2,5-diones (here 2,5-dimethoxyphenyl), in the presence of TMSOTf as the catalyst, gave nearly quantitatively the corresponding N-methoxyalkyl derivatives which, under acidic treatment, gave in very good yield through a Pictet-Spengler-type reaction involving N-acyliminium cations (6S*,11aR*)-2-acetyl-6-alkyl-3,6,11,11a-tetrahydro-2H-pyrazino[1,2-b]isoquinoline-1,4diones. Epimerization of the 11a-stereocentre was accomplished by radical bromination, spontaneous hydrobromide elimination and catalytic hydrogenation, to give the (6S*,11aS*)-isomers. We propose these compounds as precursors of tetrahydroisoquinoline antitumour antibiotics.