Efficient Biomimetic Synthesis of Indole Alkaloids of the Vallesiachotamine Group by a Domino Knoevenagel Hetero Diels-Alder Hydrogenation Sequence

An efficient three-step biomimetic synthesis of the four diastereomeric 18,19-dihydroantirhines 4a-d starting from the tetrahydrocarboline aldehydes 5a and 5b is described. Domino reaction of the aldehydes 5a and 5b, respectively, with Meldrum's acid (6) and the enol ethers 8a and 8b in the presence of catalytic amounts of ethylenediammonium diacetate leads to the strictosidine analogues 10a-d and 11a-h, respectively, in 74-86% yield, hydrogenation of which gives mainly 15 and 16 with the skeleton of the vallesiachotamine indole alkaloids (55-86%). In addition, small amounts of 17 and 18 with the corynanthe skeleton are also formed (10-12%). Reduction of both 15 and 16 with LiAlH4 yields the diastereomeric rac-18,19-dihydroantirhines 4a-d in 78-86% yield.