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Synthesis of pyrroloindolines through formal [3 + 2]-cycloaddition of indoles with chiral N-2-acetamidoacrylyl oxazolidinones

Isaac T. Smith, Jared B. Neeley, Tanner D. Brinley, Peter R. Fullmer, Merritt B. Andrus
Tetrahedron letters 2020 v.61 no.23 pp. 151947
Lewis acids, catalysts, chemical structure, chlorides, cycloaddition reactions, enamines, indoles, methylene chloride, oxazolidinones, protonation, tautomerization, tin
Chiral N-2-acetamidoacrylyl oxazolidinones were produced and reacted with indoles under Lewis acid conditions to generate hexahydropyrrolo[2,3-b]indole products in a formal [3 + 2] cycloaddition process. Optimal conditions included the use of tin(IV) chloride in methylene chloride at 0 °C. Pyrroloindoline products were obtained from various indoles with shorter reaction times (12 hr) up to 91% yield with high, >20:1 exo selectivity. A mechanism involving reversible conjugate addition followed by an enamine lone-pair-iminium capture, tautomerization, and tin-enolate protonation accounts for the selectivity. The method enables selective applications to pyrroloindoline targets and further refinement with chiral catalysts.