Synthesis of enantiomerically pure spiro-cyclopropane derivatives containing multichiral centers

A novel chiral source, 5-(R)-[(1R,2S,5R)-(-)-menthyloxy]-3-bromo-2(5H)-fura none (5a), was obtained in 46% yield with d.e.greater than or equal to 98% from the epimeric mixture of 5-(l-menthyloxy)-3-bromo-2(5H)-furanone (5a+5b ) obtained via the bromination of an epimeric mixture of 5-(l-menthyloxy)-2 (5H)-furanone (3a+3b) followed by the elimination of hydrogen bromide. The asymmetric reaction of 5a with a nucleophilic alcohol afforded enantiomeric ally pure spiro-cyclopropane derivatives containing four stereogenic center s, 9a-9e, in 50-68% yield with d.e.greater than or equal to 98%. The enanti omerically pure compounds 9a-9e were identified on the basis of their analy tical data and spectroscopic data, such as [alpha](D)(20), UV, IR, H-1 NMR, C-13 NMR, MS and elementary analysis. The absolute configuration of the ch iral spiro-cyclopropane compound 9a was established by X-ray crystallograph y. (C) 1998 Elsevier Science Ltd. All rights reserved.