A general carbometalation, three component coupling strategy for the synthesis of α,β-unsaturated γ-sultines including thio-rofecoxib, a selective COX-2 inhibitor

Magnesium mediated carbometalation (Grignard addition) to appropriate propargyl alcohols to synthesize a cross-section of variably substituted α,β-unsaturated γ-sultines is described. Thio-rofecoxib, a selective COX-2 inhibitor (12), is synthesized by this method and its IC50, μM COX-1 and COX-2 inhibition, and whole blood stability values reported.