Synthesis of γ‐Lactones from Cycloocta‐1,5‐diene − Starting Materials for Natural‐Product Synthesis

Abstract

AbstractThe bislactones rac‐tetrahydro‐2,2′‐bifuranyl‐5,5′‐dione (rac‐12) and its diastereomer meso‐25 were prepared from endo‐5‐hydroxy‐9‐oxabicyclo[4.2.1]nonan‐2‐one (endo‐10) and endo‐6‐hydroxy‐9‐oxabicyclo[3.3.1]nonan‐2‐one (endo‐11) or exo‐5‐hydroxy‐9‐oxabicyclo[4.2.1]nonan‐2‐one (exo‐23), respectively, under the conditions of a Baeyer−Villiger oxidation with trifluoroperacetic acid. The latter compounds were obtained by O‐heterocylization of cis,cis‐cycloocta‐1,5‐diene (1) by either reaction with peracids followed by hydrolysis and Jones oxidation or ruthenium tetraoxide oxidation, respectively. The optically active bislactone (R,R)‐(−)‐12 was prepared in a similar manner from (1S,5R,6R)‐(+)‐10 and (1R,5R,6R)‐(+)‐11, which, in turn, were obtained by lipase‐catalyzed asymmetric acetylation of the corresponding diols meso‐2 and rac‐3 and subsequent Jones oxidation of the formed hydroxy esters (1S,2S,5R,6R)‐(+)‐4 and (1R,2R,5R,6R)‐(+)‐5. Since the regioisomeric hydroxy‐9‐oxabicyclo[4.2.1]‐ and ‐[3.3.1]nonan‐2‐ones (1S,5R,6R)‐(+)‐10 and (1R,5R,6R)‐(+)‐11 yielded the same bislactone [(R,R)‐(−)‐12] it is presumed that the sequence proceeds via open‐chain intermediates. Applying this strategy to the enantiopure acetoxy ketones (1S,5R,6R)‐(+)‐8 and (1R,5R,6R)‐(+)‐9, followed by Kolbe electrolysis of the formed (R,R)‐5‐acetoxy‐7‐carboxyheptan‐4‐olide [(R,R)‐27], (R,R)‐5‐acetoxydecan‐4‐olide [(R,R)‐29] was accessible in a five‐step synthesis. The absolute configuration of (+)‐8 was determined by X‐ray analysis of the dithiepane derivative 14. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)