Abstract
This note describes a sequence converting an oxime-substituted pyrrolidine into a trisubstituted pyrrole structure. The synthetic route is based on a double chlorination of the pyrrolidine substrate followed by the base induced formation of both an imine and a nitrile oxide functionality. The latter reacts with an immobilized thiourea to yield an isothiocyanate which upon elimination generates the final pyrrole in an unprecedented cascade of events.
Highlights
Filtration and evaporation yielded a yellow oil that was further purified by silica column chromatography (10–20% EtOAc/hexanes) to furnish pyrrole 10 as a colorless solid, which was recrystallized from DCM/toluene giving the desired product as colorless crystals (74%, 114 mg)
We describe an efficient reaction sequence converting an oxime bearing pyrrolidine into its pyrrole counterpart. This is based on dichlorination of the oxime substrate followed by treatment with excess base and an immobilized thiourea species, triggering a series of events including formation of a cyclic imine, rearrangement of the oxime into an isothiocyanate, and its subsequent elimination to render the final pyrrole product after tautomerization
The identity and connectivity of this structure was unambiguously established by single crystal X-ray diffraction experiments
Summary
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Uboptohnthterehaitgmhelyntreoafcttihvies ndiitcrihleloorxinidateeadndmtahteermiaol r(e7)stwabitleh osxiliimcae-swueprpeorted genepraytreidd,inseub(Pseyqr-uSeinOt2ly, 2l.e5aedqinugiv.t)obtohteh cthorerhesigpholnydrienagctiisvoethniiotcryilaenoaxtiedperaondductht e9.mIomrpe osrtatabnletlyo,xitmhies were generated, subsequently leading to the corresponding isothiocyanate product 9. Importantly, this procpMerdoolubcaernedk u2w0r1eo7r,wk20oe1dr7k, Meeqd9u5e1aqlulyalwlyewlleflolrfodriadsitaesrteeorepouprueresasmamplpelse,s,asaswweellllaassmmixixttuurreessooff ddiiaasstteerreeoommeerr2ssoafat4t the quatMpehorrelonbacqaneurkday2ut0ecr1rae7n,rw2ab0ro1oy7nr,kc.Maer9db51oeqnu. ally well for diastereopure samples, as well as mixtures of diastereomers at pthroecqeudautreernwaoryrkceadrbeoqnu.ally well for diastereopure samples, as well as mixtures of diastereomers at the quaternary carbon. SchSechmeem2e.2C. 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