Synthesis of 7a-substituted Hajos-Wiechert ketone analogues.

A general and efficient route to 2-substituted 1,3-cyclopentadiones 3 has been developed. This operationally simple, two-step procedure is amenable to multigram scale preparations of these useful synthetic intermediates. These compounds are then transformed to previously unknown, higher analogues of the Hajos-Parrish-Eder-Sauer-Wiechert ketone (enone 1, R = Me) following an enantioselective Robinson annulation.

From solution-phase to solid-phase enyne metathesis: crossover in the relative performance of two commonly used ruthenium pre-catalysts.

A crossover in the ability of two distinct ruthenium-based metathesis pre-catalysts to effect the synthesis of dialkenylboronic esters in solution and on the solid-phase was observed. Specifically, while the Grubbs 2nd generation pre-catalyst 3 affords a greater degree of conversion to product than the Hoveyda-Grubbs pre-catalyst 2 in a solution-phase enyne-metathesis reaction, this trend is reversed in the solid-phase variant. Systematic investigation showed this trend to be general, regardless of variations in the homoallylic alcohol and alkynylboronic ester components of the reaction, as well as in the type of solid support employed. Experiments to determine a mechanistic hypothesis for this trend highlighted the significance of the ruthenium remaining bound to the substrate after metathetic rearrangement and found the presence of phosphine ligand to be detrimental to the success of the solid-phase reaction. Therefore, these results suggest an expanded role for phosphine-free pre-catalysts, such as 2, in challenging solid-phase metathesis reactions.