Sequential reactions and new methods in organic synthesis mediated by samarium(II) iodide

A continuing objective in organic synthesis is the construction of complex organic molecules from relatively simple precursors. In this investigation, samarium(II) iodide (SmI{dollar}sb2{dollar}) was developed as a reagent capable of performing a series of reactions in a one-pot process in high yield and with excellent diastereoselectivities. Initially, an examination of a sequential nucleophilic acyl substitution/Barbier-type cyclization reaction permitted the rapid and efficient synthesis of highly complex ring systems from readily prepared acyclic precursors. In this study, the strong reducing ability and high chemoselectivity of the reductive coupling reagent, SmI{dollar}sb2{dollar}, was exploited in a sequencial intramolecular nucleophilic acylation/Barbier-type cyclization process that facilitated access to a variety of synthetically useful bicyclic and tricyclic ring systems. This sequencial process provided a unique entry into several bicyclo (m.n.0) and tricyclic (m.n.0.0) ring systems commonly found in nature.; In a subsequent study, this powerful ring-building strategy mediated by SmI{dollar}sb2{dollar} was extended to include a sequential nucleophilic acyl substitution/ketyl-olefin coupling to gain access to a number of complex ring systems including the angular and linear triquinane ring systems found in the naturally occurring sesterterpenes. This concise transformation combined a sequential anionic and radical coupling sequence to provide a novel approach to a variety of bicyclic, tricyclic, and spirocyclic ring systems from simply prepared acyclic substrates. Both carbocycles and heterocycles were prepared employing this strategy.; Thirdly, a SmI{dollar}sb2{dollar}-mediated intramolecular cyclization of alkyl halides with unsaturated carboxylic acid derivatives was fully developed wherein 7- or 8-iodoalkyl {dollar}alpha{dollar}, {dollar}beta{dollar}-unsaturated enoates underwent intramolecular radical cyclization reactions to generate a samarium(III) enolate which could be quenched by an internal proton source. Generation of the samarium(III) enolate in these cyclization reactions lends this newly developed method to a sequential process and consequently creates a new frontier for serial processes that may be mediated by SmI{dollar}sb2{dollar}. For this reason, a brief investigation was performed to demonstrate the remarkable ability of SmI{dollar}sb2{dollar} to promote a combined intramolecular radical cyclization/nucleophilic addition reaction of these systems.; Finally, ketyl-olefin cyclization reactions of vinyl ethers were investigated and found to undergo the desired ketyl-olefin coupling reaction. However, upon organosamarium formation these systems were discovered to undergo rapid {dollar}beta{dollar}-elimination to generate the allylic diols in high yield and with excellent diastereoselectivity. Although not fully investigated, this protocol provides a novel strategy for the net addition of a vinyl moiety to a carbonyl ketone in high yields and a highly diastereoselective manner.