Enantioselective ring construction: synthesis of halogenated marine natural spiro[5.5]undecane sesquiterpenes

Abstract

The primary objective in this investigation was to develop a general method to achieve a significant amount of asymmetric induction in the bromonium initiated intramolecular carbocyclization reaction. This goal has been achieved by generation of exocyclic alkylidienes containing two stereogenic atoms located on the cyclohexene ring. The stereochemistry of the process has been investigated in some detail, and the total synthesis of (-)-(2R,6S,8S,9S)-2,8-dibromo-9-hydroxy-a-chamigrene (9), (-)-(2R,6S,8S,95)-2,8-dibromo-9-hydroxy-β-chamigrene (10), (-)-(2R,6S)2-bromo-β-chamigrene (5), (-)-β-chamigrene (6), and their corresponding (+)-11, -12, -7, and -8 enantiomers is described for the first time. These compounds were prepared from (8S,9S)-8-bromo-9-hydroxy-(E)-γ-bisabolene, (-)-33, and (8R,9R)-8-bromo-9-hydroxy-(E)-γ-bisabolene, (+)-33, as the basic building blocks. This asymmetric methodology represents a general strategy for the enantioselective construction of spiro[5.5]undecane systems containing a chiral quaternary center. This approach should be generally useful for the preparation of a wide variety of six-membered spirocycle-containing natural compounds. © 1986, American Chemical Society. All rights reserved.