title: An experimental and computational investigation of the enantioselective deprotonation of Boc-piperidine.
abstract: The asymmetric deprotonation of N-Boc-piperidine (3) by the 1:1 complex of a sec-alkyllithium and (-)-sparteine has been investigated both experimentally and computationally. The lithiation of 3 with sec-BuL-(-)-sparteine at -78 degrees C, which is a much slower process than is the analogous deprotonation of N-Boc-pyrrolidine (1) and a minor reaction relative to the competing addition of sec-BuLi to the carbamate, proceeds with a moderate degree of selectivity (er = 87:13) for removal of the pro-S hydrogen of 3. The related deprotonation of N-Boc-4-tosyloxypiperidine (6) with two molar equiv of sec-BuL-(-)-sparteine also involves preferential transfer of the pro-S hydrogen. The computational study of the deprotonation of (3) by i-PrL-(-)-sparteine found that the proton that is preferentially transferred within three-component intermediate complex is the thermodynamically least acidic alpha-hydrogen of 3. The asymmetric deprotonation of 3 is calculated to proceed with poor enantioselectivity and to have an activation energy considerably higher than that calculated for deprotonation of N-Boc-pyrrolidine (1). The experimental and computational results are in good agreement.
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Bailey
authors.forename: Peter
authors.initials: P
authors.lastname: Beak
authors.forename: Shawn T
authors.initials: ST
authors.lastname: Kerrick
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Ma
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Wiberg
mesh_terms: D008094:Lithium / Q000737:chemistry; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry*; D011522:Protons; D013034:Sparteine / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: C454939:N-(tert-butoxycarbonyl)piperidine; D009942:Organometallic Compounds; D010880:Piperidines; D011522:Protons; D013034:Sparteine; D008094:Lithium