143008-97-3Relevant academic research and scientific papers
Application of palladium-catalyzed [3 + 2] cycloaddition technology to the elaboration of kempane diterpenes. Stereocontrolled Synthesis of (±)-3α-hydroxy-7β-kemp-8(9)-en-6-one and (±)-3β-hydroxykemp-7(8)-en-6-one
Paquette, Leo A.,Sauer, Daryl R.,Cleary, Darryl G.,Kinsella, Mary A.,Blackwell, Christopher M.,Anderson, Lawrence G.
, p. 7375 - 7387 (2007/10/02)
The total synthesis of three hydroxykempenones (8-10) has been accomplished. The retrosynthetic elements of the strategy focused on setting four key stereocenters in rings A and B, followed by annulation of ring C and ultimate cyclization to construct the seven-membered ring, D. Since the target molecule carries eight contiguous stereogenic centers, proper attention to stereocontrolled processes was mandatory. The key features of the scheme include the palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane to an activated octalone with complete control of π-facial selectivity, fully regiospecific monooxidation of a diol with ammonium molybdate uniquely at the secondary site to provide a key hydroxy ketone, hydroxyl-directed hydride reduction of the latter intermediate in order to override a contrary kinetic preference for nucleophilic attack, avoidance of Grob fragmentation in diaxial, monofunctionalized 1,3-diols, and selective deoxygenation of a 1,3-diol. The stereochemical results featured in the cycloaddition step were elucidated preliminarily in experiments designed to probe cyclopentannulation in general. The striking kinetic stability of the α,β- and β,γ-unsaturated tetracyclic end products has been analyzed by means of molecular modeling.
