Partial Reduction of 3-Heteroatom Substituted 2-Furoic Acids: The Role of an ortho Group in Viability and Stereoselectivity.

The synthesis of 2-furoic acid derivatives containing both 3-methoxy and 3-TMS groups is described. Reductive alkylation proceeded well to give us access to a series of highly functionalised dihydrofurans with potential for further elaboration. Of the two groups tested at C-3, the TMS derivative was found to be the more useful and gave rise to high levels of stereoselectivity when attached to a furan bearing a chiral auxiliary at C-2. A modification of the reaction conditions was made which enabled the TMS group to be cleaved during the reduction reaction without loss of stereoselectivity. Finally, it was also shown that the chiral auxiliary could be removed under acidic conditions to form 2-alkyl-3-TMS substituted dihydrofurans with excellent levels of enantiomeric purity.