1 Nucleophilic Substitution by Grignard Reagents on Sulfur Mustards Antonella Converso, Pierre-Loïc Saaidi, 1 M.G. Finn,* and K. Barry Sharpless* Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037 mgfinn@scripps.edu; sharples@scripps.edu RECEIVED DATE (to be automatically inserted) Abstract. With proper activation of the leaving group, sulfur mustards react with Grignard reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean reactivity with organomagnesium nucleophiles on a topologically constrained scaffold. The chemistry of 2,6-dichloro-9-thiabicyclo[3.3.1]nonane, 1, provides a good illustration of the power of anchimeric assistance in organic chemistry. 2,3 The behavior of this compound is dominated by the central heteroatom, which engages the β-chlorinated centers to facilitate nucleophilic substitution via a highly reactive episulfonium ion (Scheme 1). The double inversion process preserves stereochemistry in substitution reactions with a broad range of heteroatom nucleophiles. Scheme 1 S Cl Cl S Cl Cl Nuc S Nuc Cl Nuc S Nuc Nuc 1 2