A valuable synthetic route to spiro-cyclopropane derivatives containing multiple stereogenic centers

The unusual, functionalized spiro-cyclopropane derivatives containing four stereogenic centers 8a-8f were obtained in good yields with d.e. greater than or equal to 98% via tandem double Michael addition/internal nucleophilic substitution of the novel chiral synthon, 5-l-menthyloxy-3-bromo-2(5H)-furanone 5a, with various oxygen nucleophiles under mild conditions. (S)-(-)-Ethyl lactate also reacted under the same conditions to afford the corresponding spiro-cyclopropane derivative 8g. Interestingly, reaction of 5a with ethyl bromo- and chloroacetate, in the usual manner, gave the spiro-cyclopropane 8h rather than the expected C-linked derivative. The absolute configuration of the interesting spiro-cyclopropanes 8 was established by X-ray crystallography. These results provide a valuable synthetic route to some complex molecules containing the spiro-cyclopropane skeleton with multiple stereogenic centers. (C) 1999 Elsevier Science Ltd. All rights reserved.