Chemistry of Tetrahydro-1, 3-oxazin-2-one : New Method for the Synthesis of Indoloquinolizidine Derivatives

Abstract

The aldol condensation of the N-Boc-tetrahydro-β-carboline-1-acetate (4) with acrolein in the presence of lithium diisopropylamide (LDA) gave an allyl alcohol (6), which was then treated with methanesulfonyl chloride and triethylamine to give a mixture of the mesylate (8) (55%) and the indolopyrido-3, 5-oxyazin-4-one (10) (14%). When 8 was treated with 1, 8-diazabicyclo[5.4.0.]-7-undecene (DBU) in dimethylsulfoxide (DMSO) at room temperature, the azetopyridoindoles (12 and 13) were obtained unexpectedly. Alternative preparation of the indolopyrido-3, 5-oxazin-4-ones (15 and 16), which are stereoisomers of 10, from 6 followed by heating with DBU in DMSO gave several indoloquinolizidines (18, 19 and 20), which are key intermediates for the synthesis of the indole alkaloids vindolosine and vindoline.