title: Enantioselective, palladium-catalyzed α-arylation of N-Boc pyrrolidine: in situ react IR spectroscopic monitoring, scope, and synthetic applications.
abstract: A comprehensive study of the enantioselective Pd-catalyzed α-arylation of N-Boc pyrrolidine has been carried out. The protocol involves deprotonation of N-Boc pyrrolidine using s-BuLi/(-)-sparteine in TBME or Et(2)O at -78 °C, transmetalation with ZnCl(2) and Negishi coupling using Pd(OAc)(2), t-Bu(3)P-HBF(4) and the aryl bromide. This paper reports several new features including in situ React IR spectroscopic monitoring of the process; use of (-)-sparteine and the (+)-sparteine surrogate to access products with opposite configuration; development of a catalytic asymmetric lithiation-Negishi coupling reaction; extension to a wide range of heteroaromatic bromides; total synthesis of (R)-crispine A, (S)-nicotine and (S)-SIB-1508Y via short synthetic routes; and examples of α-vinylation of N-Boc pyrrolidine using vinyl bromides exemplified by the total synthesis of naturally occurring (+)-maackiamine (thus establishing its configuration as (R)). In this way, the full scope and limitations of the methodology are delineated.
authors.affiliation: Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Barker
authors.forename: Julia L
authors.initials: JL
authors.lastname: McGrath
authors.forename: Artis
authors.initials: A
authors.lastname: Klapars
authors.forename: Darren
authors.initials: D
authors.lastname: Stead
authors.forename: George
authors.initials: G
authors.lastname: Zhou
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Campos
authors.forename: Peter
authors.initials: P
authors.lastname: O'Brien
mesh_terms: D002384:Catalysis; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013034:Sparteine / Q000737:chemistry; D013057:Spectrum Analysis; D013237:Stereoisomerism
chemical_list: D007546:Isoquinolines; C531441:N-Boc-pyrrolidine; D011725:Pyridines; D011759:Pyrrolidines; C523713:crispine A; D013034:Sparteine; D010165:Palladium; C100989:altinicline maleate