An approach to the synthesis of phomactins using a Wittig rearrangement

Anna Marsden,Eric J Thomas,Christian V Stevens

doi:10.3998/ark.5550190.0003.909

Abstract

Preliminary studies to evaluate the feasability of an approach to the synthesis of the phomactin diterpenes are outlined. The key step is the 2,3-Wittig rearrangement of the propargylic ether 32 which gives a mixture of the diastereoisomeric alcohols 33. Oxidation to the ketones 34 and 35 followed by conjugate addition of lithium dimethylcuprate and deprotection gives the unsaturated diketone 37 so providing a strategy for the synthesis of the cyclohexenyl core of the phomactins.

Highlights

The phomactins are a group of diterpenes some of which are of interest as platelet activating factor antagonists.[1]
Wittig rearrangements of unsymmetrical bis-allylic ethers tend to involve deprotonation of the less alkylated, presumably more acidic and accessible, allylic system,[9] and so initial studies were carried out to establish the regioselectivity of rearrangement of ethers analogous to 7
The mixture of ketones and was reacted with lithium dimethylcuprate to give the dienyl ketone which on treatment with pyridinium toluene p-sulfonate in acetone-water was converted into the 2-(3-methylbut-2-enoyl)cyclohex-2-enone. During this hydrolysis of the ketal, the exocyclic alkene had migrated inside the ring and so the ketone 37 was formed as a single stereoisomer having lost both of the stereogenic centres introduced during the Wittig rearrangment. This synthesis of the ketone 37 shows that the 2,3-Wittig rearrangement of cyclohexenylmethyl propargyl ethers is regioselective and provides access to intermediates which may be useful for a synthesis of the phomactins