Synthetic studies toward longeracemine: a SmI₂-mediated spirocyclization and rearrangement cascade to construct the 2-azabicyclo[2.2.1]heptane framework

Abstract

Longeracemine, a member of the Daphniphyllum family of alkaloids contains a novel carbon framework featuring a highly functionalized 2-azabicyclo[2.2.1]heptane core as part of an overall 5/6/5/5/6/5 skeleton. A synthetic intermediate...

A Stereoselective Synthesis of Fused Carbocycles with a <i>cis</i>-1,2-Diol Moiety by Desymmetrization: SmI₂-Mediated Pinacol Coupling of <i>meso</i>-Cyclic 1,3-Diones

“…General Procedure for 2: Fresh SmI 2 reagent (0.1 M in THF) was prepared using the following procedure. 35) To a freshly shaved samarium (406 mg, 2.70 mmol) was added 1,2-diiodoethane (423 mg, 1.50 mmol), and the flask was immediately covered with aluminum foil due to the light sensitivity of the reagent. Then degassed THF (15 mL) was added with stirring, and the reaction mixture was heated to 55 °C, in the dark, for 4 h. At which point the reaction mixture was allowed to cool to 23 °C and settle for at least 10 min prior to use.…”

Samarium(ii) iodide-mediated reactions applied to natural product total synthesis

“…In 2020, Wood and coworkers 122 reported the total synthesis of the 2-azabicyclo[2.2.1]heptane core of longeracemine 280. The key steps contained a stereoselective SmI 2 -mediated cascade reaction to synthesize the 2-azabicyclo[2.2.1]heptene from azabicyclo[2.2.1]heptadiene.…”

Five-membered carbocycle construction in the synthesis of Daphniphyllum alkaloids: recent strategic and methodological advances

“…Spirocyclization and rearrangement cascade (Wood 2020) 39 Longeracemine was isolated by Hao, Di and their co-workers in 2013, which possesses a synthetically challenging 2-azabicyclo[2.2.1]heptane core. 38 Seven years later, Wood reported an efficient cascade reaction that fabricated this core structure (Scheme 10).…”

“…38 Seven years later, Wood reported an efficient cascade reaction that fabricated this core structure (Scheme 10). 39 An intermolecular Diels–Alder reaction between compounds 62 and 63 produced bicycles 64 and 65 (1 : 5). Further modification yielded compound 66 , which was further converted to aldehyde 67 .…”