Trisubstituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analogue of fucose

A telescoped sequence based on metallated enol acetal chemistry allowed the efficient delivery of a ring-closing metathesis (RCM) precursor, which was used to form a cyclooctenone product with a trisubstituted alkenyl group in moderate yield, though a high loading of second generation Grubbs' pre-catalyst was required. A relay RCM (RRCM) precursor was synthesised to deliver the key alkylidene at a higher rate; the catalyst loading required was high, and increasing the reaction temperature simply resulted in the loss of the cyclising alkylidene by a non-productive cross-metathesis pathway. We were forced to use high dilution conditions to suppress the unwanted CM and secure the cyclooctenone product. The cyclooctenone product could be progressed to analogues of fucose and 6-deoxyidose by UpJohn dihydroxylation.