Rhodium catalyzed hydroformylation of kaurane derivatives: a route to new diterpenes with potential bioactivity

Abstract

Kaurenic and grandiflorenic acids are naturally occurring diterpenes whose biological activity has beedescribed. Both acids contain an exocyclic methylenic double bond that allows further functionalization on their structure. In an attempt to expand the number of derivatives of these two natural products, we have undertaken a study on the hydroformylation of the methyl esters of the two acids and the trimethylsilyl ether of kaurenol. These substrates have been hydroformylated by using unmodified Rh catalysts, as well as Rh/PPh3 and Rh/tris-(o-t-butylphenyl)phosphite catalytic systems at 100 8C and Keywords: 20 bar of CO/H2 (1:1). For the three substrates, the two Rh catalysts modified with P-donor ligands, Diterpenes produced high conversions and chemo- and regioselectivities in the diastereoisomeric pair of linear Kauranes aldehydes. In all cases, the stereoselectivity observed is strongly dependent of the system used, being the Hydroformylation most diastereoselective the least hindered unmodified Rh/CO catalyst. A correlation between the higher Rhodium diastereoselectivity and the faster b-elimination of the metal-alkyl intermediate observed in the Phosphite unmodified system is discussed. Phosphine