Wieland-Miescher ketone absolute configuration

The amplitude (A) of the exciton Cotton effect is inversely proportional to the square of the interchromophoric distance. Thus, weak exciton split Cotton effects are expected for remote dibenzoates. Nevertheless, exciton Cotton effects were used for the assignment of the configuration of dibenzoates in a steroidal skeleton separated by as many as seven or eight C—C bonds158. In one application, the absolute configuration of Wieland-Miescher ketone (—)-2 was established by the use of the dibenzoate chirality rule for the 4-bromobenzoylated derivatives of the epimeric 1,5-diols 3 and 4, obtained by reduction of (-)-2159. 

The absolute configuration of Wieland-Miescher ketone analogues bearing an angular protected hydroxymethyl group was unambiguously determined after regio- and stereoselective reduction of the saturated ketone function to cis -alcohols and application of the exciton chirality method to bicyclic enone-benzoate chromophoric systems 155-158352. 

The optically active Wieland-Miescher ketone 33 has been widely employed as an important key compound as discussed above. However, it was surprising that irrespective of such a significance of compound 33, its absolute configuration has never been directly determined by the X-ray crystallographic method. The abso-... 

In the case of the total synthesis of halenaquinol (12b5)-(+)-2 and halenaquinone (12b5)-(+)-l, we started from the Wieland-Miescher ketone (8a/ )-(-)-33, as discussed above. Therefore, it is evident that the synthetic sample of halenaquinol dimethyl ether (+)-17 has the (12b5) absolute configuration. 19 if the theoretical determination of the absolute stereochemistry of the halenaquinol family is correct, the chiroptical data of [ ]d and CD spectra of the synthetic sample should be identical with those of the authentic sample of (+)-17 derived from... 

We have succeeded in the first total synthesis of (+)-halenaquinone 1, and (+)-halenaquinol 2, (+)-xestoquinone 4, and xestoquinol 62 by starting from the (8a/ )-(-)-Wieland-Miescher ketone 33 and also have experimentally determined their absolute configurations to be 12b5. The conclusions on the absolute configuration are in agreement with those derived from the theoretical calculation of CD spectrum. So, these first total syntheses of (+)-halenaquinol, (+)-halena-... 

In the laboratory of K. Mori the task of determining the absolute configuration of the phytocassane group of phytoalexins was undertaken. To this end, the naturally occurring (-)-phytocassane D was synthesized from (R)-Wieland-Miescher ketone. During the synthesis, a tricyclic ketone intermediate was subjected to the Shapiro olefination reaction to give the desired cyclic alkene in good yield. 

---