Enantioselective Formal Synthesis of (+)-Dihydrocorynantheine and (−)-Dihydrocorynantheol

The enantioselective construction of the 3-ethylindolo[2,3-a]quinolizidine moiety present in numerous indole alkaloids is reported, the key steps being a stereoselective cyclocondensation of (S)-tryptophanol with an appropriate racemic δ-oxoester and a regio- and stereoselective cyclization of the resulting oxazolopiperidones on the lactam carbonyl group. A new procedure for the removal of the hydroxymethyl auxiliary group, involving oxidation to an aldehyde, dehydration of the corresponding oxime, and reductive decyanation of the resulting α-aminonitrile, has been developed. The preparation of indoloquinolizidine 27 represents a formal total synthesis of (+)-dihydrocorynantheine, (−)-dihydrocorynantheol, and other indolo[2,3-a]quinolizidine and oxindole alkaloids bearing the same substitution pattern.