Inter- and intramolecular hetero Diels-Alder reactions, 28. Synthesis of (±)-secologanin agluconeO-ethyl ether and derivatives by tandem Knoevenagel hetero Diels-Alder reaction

✍ Scribed by Tietze, Lutz F. ;Meier, Heinrich ;Nutt, Heinrich

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 875 KB
• Volume: 1990
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199019900146

✦ Synopsis

Abstract

The tandem Knoevenagel hetero Diels‐Alder reaction of 4,4,4‐trichloro‐3‐oxobutanal (4), the malondialdehyde derivative 11a, and the enol ether 13 was followed by separation of the diastereomers and treatment with DBU in methanol. Thermolysis in xylene then gave the secologanin derivative 25a in 14% yield with the correct relative stereochemistry at all stereogenic centers. Hydrolysis of the dithiane moiety afforded secologanin aglucone O‐ethyl ether 9 in 86% yield. In a similar way, 25b and 25c were obtained in 14% and 28% yield from the malondialdehyde derivatives 11b and 11c, respectively. Reduction of 9 with sodium borohydride gave swerosid aglucone O‐ethyl ether 24 in 69% yield. The dihydrosecologanin derivative 32 was obtained in 20% yield by reaction of 5, 11c, and 26 followed by methanolysis. In this transformation the initially formed cycloadducts 27 and 28 were isolated; 33, the other type of product obtained by reaction of the second heterodiene moiety in the intermediate Knoevenagel product 18, was also found.