Synthesis of Enantiopure 9‐Oxabicyclononanediol Derivatives by Lipase‐Catalyzed Transformations and Determination of Their Absolute Configuration

• Published in: European Journal of Organic Chemistry
• Main Authors: Hegemann, Klaus, Fröhlich, Roland, Haufe, Günter
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2004
• Subjects: Rugosa; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/ejoc.200300783; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.200300783; https://onlinelibrary.wiley.com/doi/full/10.1002/ejoc.200300783

Abstract Mixtures of endo , endo ‐9‐oxabicyclo[4.2.1]nonane‐2,5‐diol ( meso ‐ 2 ) and endo , endo ‐9‐oxabicyclo[3.3.1]nonane‐2,6‐diol [(±)‐ 3 ] were prepared from cycloocta‐1,5‐diene ( 1 ) upon treatment with peracids by transannular O ‐heterocyclization and subsequent saponification of the formed diol monoesters such as (±)‐ 4 and (±)‐ 5 . The corresponding diacetates, meso ‐ 6 and (±)‐ 7 , were formed by acetylation of either meso ‐ 2 and (±)‐ 3 or (±)‐ 4 and (±)‐ 5 with acetic anhydride/pyridine. These diacetates were enantioselectively hydrolyzed by microbial enzymes such as the lipases from Candida antarctica (CAL) or Candida rugosa (CRL). The corresponding enantiomers were formed by lipase‐catalyzed acetylation of the diols meso ‐ 2 and (±)‐ 3 with vinyl acetate. The skeletal isomers can also be separated in this way because the enantiopure monoacetates 4 were formed from the meso ‐compounds 2 or 6 , while one enantiomer of the racemic diacetate (±)‐ 7 [or the diol (±)‐ 3 ] was transformed into the enantiopure diol 3 (or the enantiopure diacetate 7 , respectively) via the corresponding enantiomers of the monoacetate 5 . The other enantiomer remained untouched in both cases. The lipases reacted enantioselectively to give the R isomer. Cycloocta‐1,5‐diene ( 1 ) was also used to synthesize 2‐oxa‐6‐thiatricyclo[3.3.1.1 3,7 ]decane‐4,8‐diol [(±)‐ 11 ] in a four‐step sequence. This racemic diol was also acetylated selectively ( R isomer) with vinyl acetate and CRL. Reductive desulfuration of (±)‐ 11 gave exo , exo ‐9‐oxabicyclo[3.3.1]nonane‐2,6‐diol [(±)‐ 12 ], which was acetylated selectively ( S isomer) with CRL under the same conditions. The similarity in size and particularly in shape is responsible for the observed stereoselectivity of the lipases for the racemic endo , endo compounds (±)‐ 3 and (±)‐ 7 on the one hand and the exo , exo compound (±)‐ 12 on the other hand. The absolute configuration and crystal packing of the products was determined by X‐ray structural analysis. (© Wiley‐VCH Verlag GmbH & ...