Synthesis of spiro-cyclopropane derivatives containing multiple chiral centers

Abstract

Tandem asymmetric double Michael addition/internal nucleophilic substitution of the novel chiral source, 5-(l-menthyloxy)-3-bromo-2 (5H)-furanone with nucleophilic alcohol compounds has been investigated. The tandem asymmetric reaction can afford four new stereogenic centers with one reaction and give optically pure spiro-cyclopropane derivatives 5a–5d which are difficult to obtain by routine methods. The synthetic method for 5a–5d was studied in de-tail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]20, IR,1H NMR,13C NMR, MS and elementary analysis. The absolute configuration of the sprio [5-l-menthyloxy-3-bromobutyrolactocyclopropane-3”, 3’ (4’-methyloxy-5’-menthyloxybutyrolactone) ] (5a) was established by X-ray crystallography. The work can provide important synthetic strategy in synthesis of some new optically active spiro-cyclopropane analogues and some biologically active molecules with complex structure.