Samarium(II) iodide promoted methods: Radical and anionic processes

In little more than twenty-five years, samarium(II) iodide (SmI 2) has become a benchmark reducing agent in organic chemistry. This powerful reductant possesses adjustable reactivity and continues to be a useful reagent in a wide array of organic reactions. SmI2 is a one-electron reducing agent that promotes both radical and anionic processes. Three fundamental transformations can be achieved using SmI2: functional group reduction, reductive coupling of halides with π-bonds, and reductive couplings of two π-bonds. The focus of this work elaborates on the latter two processes. I. Ketyl-allene cyclizations promoted by samarium(II) iodide . Carbon radicals are reliable and efficient intermediates for the construction of carbon-carbon bonds. Samarium(II) iodide has proven to be an effective reagent for intramolecular reductive coupling reactions. Earlier investigations of intramolecular ketyl-olefin coupling reactions provided carbocycles in excellent yield and good diastereoselectivity. This method has been extended to ketyl cyclizations with allenes. Allenyl substrates, which lead to both carbocycles and heterocycles in a selective manner are explored.* II. Nucleophilic acyl transfer/cyclization for the formation of lactams. It has previously been observed that a phenyl ketone containing a carbamate moiety underwent a SmI2-promoted nucleophilic acyl transfer reaction for the formation of γ-lactams. In contrast to the typical acyl substitution reaction, the carbonyl, rather than an alkyl halide, reacts with another acyl group. Additionally, the acyl group transfer occurs with a carbamate, which is uncommon. This novel SmI2-mediated nucleophilic acyl transfer/substitution is further explored.* III. Sequential intramolecular Barbier/Grob fragmentation: An anionic process. The Molander group has utilized SmI2 for entry to medium-sized carbocycles via sequential reactions. Efforts were directed toward a two-electron process, wherein an appropriately designed substrate would undergo an intramolecular Barbier reaction to afford a fused bicyclic alkoxide. With proper orbital alignment, the intermediate alkoxide is poised to undergo a Grob fragmentation to furnish both medium- and large-membered rings. Using epoxides or aziridines as leaving groups, the Grob fragmentation provides a handle for further elaboration.* *Please refer to dissertation for diagrams