- Enantioselective, palladium-catalyzed α-arylation of N-Boc-pyrrolidine
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This communication discloses the first instance of the enantioselective Pd-catalyzed α-arylation of N-Boc-pyrrolidine. The methodology relies on Beak's sparteine-mediated, enantioselective deprotonation of N-Boc-pyrrolidine to form the 2-pyrrolidinolithium specices in high enantiomeric ratio (er). Transmetalation of this intermediate with zinc chloride generates the stereochemically rigid, 2-pyrrolidinozinc reagent, which was readily coupled to a variety of functionalized aryl halides at room temperature using a catalyst generated from Pd(OAc)2 and PtBu3-HBF4. A diverse array of 2-aryl-N-Boc-pyrrolidines was synthesized using this methodology, providing adducts consistently in a 96:4 er. A survey of the stoichiometry revealed that as little as 0.3 equiv of zinc could be used in the coupling reaction, and the 2-pyrrolidinozinc reagent was found to exhibit stereochemical stability up to 60 °C. The method allows for the most convergent and reliable preparation of a broad range of functionalized 2-aryl-N-Boc-pyrrolidines in high enantioselectivity, which is highlighted in this report by the enantioselective synthesis of (R)-nicotine. Copyright
- Campos, Kevin R.,Klapars, Artis,Waldman, Jacob H.,Dormer, Peter G.,Chen, Cheng-Yi
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- TANK-BINDING KINASE INHIBITOR COMPOUNDS
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Compounds having the following formula (I) and methods of their use and preparation are disclosed:
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Paragraph 1936
(2016/05/02)
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- Diamine-free lithiation-trapping of N-Boc heterocycles using s-BuLi in THF
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A diamine-free protocol for the s-BuLi-mediated lithiation-trapping of N-Boc heterocycles has been developed. In the optimized procedure, lithiation is accomplished using s-BuLi in THF at -30 °C for only 5 or 10 min. Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered a range of functionalized pyrrolidines, imidazolidines, and piperazines in 43-83% yield.
- Barker, Graeme,Obrien, Peter,Campos, Kevin R.
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supporting information; experimental part
p. 4176 - 4179
(2010/11/16)
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