Enantioselective, palladium-catalyzed alpha-arylation of N-Boc-pyrrolidine

Journal of the American Chemical Society
Kevin R CamposCheng-yi Chen

Abstract

This communication discloses the first instance of the enantioselective Pd-catalyzed alpha-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 degrees 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.

References

Oct 8, 2004·Journal of the American Chemical Society·Jacqueline E Milne, Stephen L Buchwald
May 27, 2005·Organic & Biomolecular Chemistry·Kristin M Brinner, Jonathan A Ellman
Oct 14, 2005·Journal of the American Chemical Society·Takuo HamaJohn F Hartwig

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Citations

Oct 15, 2013·Chemical Reviews·Jacques RoudenJérôme Baudoux
Apr 8, 2010·Journal of the American Chemical Society·Robert R KnowlesEric N Jacobsen
Aug 14, 2012·Journal of the American Chemical Society·Timothy K BengRobert E Gawley
May 16, 2008·Journal of the American Chemical Society·Sarah E ReismanEric N Jacobsen
Feb 12, 2011·Organic Letters·Matthew BrichacekJon T Njardarson
Jun 20, 2007·Chemical Society Reviews·Kevin R Campos
Aug 22, 2015·Journal of the American Chemical Society·Josep LlaveriaVarinder K Aggarwal
Sep 1, 2015·Journal of the American Chemical Society·Jillian E SpanglerJin-Quan Yu
Jun 3, 2017·The Journal of Organic Chemistry·James D FirthLeigh Ferris
Dec 22, 2016·Angewandte Chemie·Kaitlyn M Logan, M Kevin Brown
Aug 4, 2015·Chemical Science·Christopher K Prier, David W C MacMillan
Jan 7, 2017·Chemical Science·Derek T Ahneman, Abigail G Doyle
Jun 28, 2017·Advanced Synthesis & Catalysis·Jacqueline JiménezPatrick J Walsh
Feb 23, 2010·Chemistry : a European Journal·Iain ColdhamNadeem S Sheikh
Feb 8, 2014·Angewandte Chemie·Anthony MilletOlivier Baudoin
Jul 18, 2018·Angewandte Chemie·Qun CaoDuncan L Browne
Aug 30, 2018·Chemical Communications : Chem Comm·Yuko IkedaEiji Shirakawa
Jun 23, 2006·Organic & Biomolecular Chemistry·Syed Raziullah Hussaini, Mark G Moloney
Oct 19, 2006·Organic & Biomolecular Chemistry·Mark G MoloneyRichard Pike
Mar 12, 2008·Angewandte Chemie·Peter O'Brien, Julia L Bilke
Jan 20, 2019·Angewandte Chemie·Xi-Jie DaiStephen L Buchwald
Jan 24, 2018·Nature Chemistry·Weijie ChenDaniel Seidel
Sep 12, 2019·Angewandte Chemie·Yueyue MaJinxing Ye

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