Synthetic approaches towards the taxane group of natural products
In a series of synthetic studies towards the taxane group of natural products, we have developed a synthesis of 2-lithio-1, 3-butadiene from 3-buten-2-one-2',4',6'-tri-iso-propylbenzenesulphonyl hydrazone using the Shapiro reaction. The reaction of 2-lithio-1,3-butadiene with a series of aldehydes and other electrophiles was then studied. In contrast to the corresponding Grignard, the major isolated products from the reaction of 2-lithio-1,3-butadiene with aliphatic aldehydes were 2-substituted dienyl alcohols, whilst with aromatic and some a,b-unsaturated aldehydes varying amounts of the regioisomeric allenic alcohols were also formed. Two of the dienyl alcohols were shown to undergo the amide acetal Claisen rearrangement. 2-Lithio-1,3- butadiene was then used in an attempt to synthesise a taxane model compound. In an alternative approach to a different taxane model compound, we developed a stereocontrolled route to a trisubstituted cyclohexane derivative. The cyclohexane was then converted into a Diels-Alder substrate using a stepwise diene synthesis which employed silicon as a control element. Lewis acid catalysed cyclisation of the Diels-Alder substrate gave stereospecifically a tricyclo [9. 3.1.03,8] pentadecane taxane model compound, which had the same relative configuration about its chiral centres as the taxane natural products. Attempts were then made to extend the synthesis to incorporate the C-14-gem-dimethyl groups.