2-Substituted pyrrolidin-3-ol moiety is present in many biologically active natural products and pharmaceutical interest compounds. Most strategies for synthesis of 2-substituted pyrrolidin-3-ols involve pyrrolidine ring closing from open chain precursors. However, the direct functionalization of the α-C–H of pyrrolidines is a more concise way to synthesis α-substituted pyrrolidines. Among various elegant methods, redox-neutral C–H functionalization offers special redox and atom economy. We here found a redox-neutral α-C-H functionalization of pyrrolidin-3-ol. The commercial available pyrrolidin-3-ol underwent a redox-neutral α-C-H oxidation to facilitate an iminium intermediate, which further reacted in situ with various organoboron nucleophiles to produce a series of cis-2-substituted pyrrolidin-3-ol. With this strategy, the indolizidine alkaloid 8-epi-(-)-lentiginosine was synthesized from (3R,4R)-pyrrolidine-3,4-diol.

Redox-triggered α-C-H functionalizations of pyrrolidin-3-ol

255th National Meeting (2018)

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