Desymmetrisation of cyclic dienes. An efficient strategy for natural products synthesis

Abstract

Desymmetrisation processes allow a rapid and stereocontrolled elaboration of readily available σ-symmetric precursors. Since it is often more convenient to prepare symmetrical compounds, breaking the symmetry at a well-defined point in a synthesis may constitute a powerful manner to introduce several chiral centres with high level of diastereo- and enantiocontrol. This review is intended to provide the reader with a timely report on the novel synthetic possibilities offered by desymmetrisation of some substituted 1,3-cyclopentadienes and 1,4-cyclohexadienes. Our recent investigations in this field, mainly on silicon derived cyclopenta- and cyclohexadienes will be described along with reports by other groups working on closely related precursors. The scope and limitation of this methodology will be examined. The influence of the ring substituents on the regio- and stereochemical outcome of the desymmetrisation processes will also be discussed. For instance, we have demonstrated that a silicon group at the pseudo-symmetrical position, was crucial for the control of the diastereofacial selectivity. The discussion will also focus on the asymmetric processes which have been used to break the symmetry of the dienes on the elaboration of the adducts to construct biologically relevant targets. Sharpless asymmetric diahydroxylation and amino-hydroxylation, hydroboration and cyclopropanation are the most reliable and efficient processes, which have been used so far. Asymmetric Heck reaction has also been employed demonstrating that this methodology can be further enriched with new asymmetric processes and that numerous homochiral intermediates would be at hand in a near future. Finally, illustration of the viability of such a strategy will be provided along with the total synthesis of relevant classes of natural products such as cyclitols, sugar mimics having glycosidase inhibitory activities, alkaloids and sesquiterpenes.