Inter‐ and intramolecular hetero Diels‐Alder reactions, 28. Synthesis of (±)‐secologanin aglucone <i>O</i>‐ethyl ether and derivatives by tandem Knoevenagel hetero Diels‐Alder reaction

Abstract

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.