MICROBIAL OXIDATION OF CHLOROAROMATICS IN THE ENANTIODIVERGENT SYNTHESIS OF PYRROLIZIDINE ALKALOIDS - TRIHYDROXYHELIOTRIDANES

Both enantiomers of the pyrrolizidine alkaloid trihydroxyheliotridane 1 have been prepared in an efficient and stereocontrolled fashion in 10 steps. Key steps involve the microbial oxidation of chlorobenzene with Pseudomonas putida to afford chiral cyclohexadienediol 4 with high enantiomeric excess and its conversion to lactone 7, from which either enantiomer of azide 18 can be prepared. The azides are converted to the title compounds via a [4 + 1] pyrroline annulation based on an intramolecular azide—diene cycloaddition/thermal rearrangement. © 1990, American Chemical Society. All rights reserved.