Positional and Facial Selectivity in Diels‐Alder Reactions of (−)‐(a<i>S</i>,7<i>S</i>)‐Colchicine: Synthesis of Novel Analogues of the Alkaloid

Abstract

Abstract Positional and facial selectivity in Diels‐Alder reactions of several hetero‐ and carbodienophiles with (−)‐(a S ,7 S )‐colchicine ( 1 ) has been examined. In all cases, cycloaddition occurred with high positional selectivity at the 8,12‐positions of the alkaloid and preferentially from the diene face syn to the allylic substituent at the stereogenic center C‐7. The observed high π‐facial diastereoselectivity is independent of the polarity of the solvent used and is therefore probably a consequence of steric factors. The structures of the Diels Alder‐adducts of 1 with singlet oxygen, N ‐phenyl‐1,2,4‐triazolinedione (PTAD) and trans ‐cyclooctene, 4,5 , and 15 , respectively, were assigned on the basis of spectral data and verified by X‐ray crystallography.