title: Synthesis of P-stereogenic compounds via kinetic deprotonation and dynamic thermodynamic resolution of phosphine sulfides: opposite sense of induction using (-)-sparteine.
abstract: A systematic study of the asymmetric deprotonation of a dimethyl-substituted phosphine sulfide using organolithium bases in the presence of (-)-sparteine has been carried out. Use of nBuLi and (-)-sparteine in Et(2)O at -78 °C gave trapped adducts in ∼88:12 er via a kinetically controlled process that was successfully predicted using a computational approach at the B3LYP/6-31+G(d) level. This initial kinetic enantioselectivity could be enhanced up to 97:3 er by trapping the lithiated intermediate with a prochiral electrophile (e.g., pivaldehyde or tBuPCl(2)). In addition, it was found that the R(P) and S(P) stereoisomers of the lithiated methylphosphine sulfide could interconvert at temperatures above 0 °C. Such interconversion is unprecedented and differs from the configurational instability of organolithiums that are stereogenic at a lithiated carbon atom. The major, thermodynamically preferred diastereomeric (-)-sparteine-complexed lithated phosphine sulfide was investigated by X-ray crystallography and computational methods at the B3LYP/6-31+G(d) level. Through the interconversion of the R(P) and S(P) stereoisomers of the lithiated methylphosphine sulfide, a novel dynamic thermodynamic resolution of a racemic lithiated phosphine sulfide has been developed. Thus, the phosphine sulfide was lithiated with nBuLi, and then (-)-sparteine was added. After equilibration at 0 °C for 3 h, electrophilic trapping generated an adduct in 81:19 er with the configuration opposite to that obtained under kinetic control. Thus, the methodology provides access to P-stereogenic compounds with the opposite sense of induction using (-)-sparteine as the ligand simply by changing the reaction conditions (kinetic or thermodynamic control).
authors.affiliation: Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Gammon
authors.forename: Viktoria H
authors.initials: VH
authors.lastname: Gessner
authors.forename: Greg R
authors.initials: GR
authors.lastname: Barker
authors.forename: Johan
authors.initials: J
authors.lastname: Granander
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Whitwood
authors.forename: Carsten
authors.initials: C
authors.lastname: Strohmann
authors.forename: Peter
authors.initials: P
authors.lastname: O'Brien
authors.forename: Brian
authors.initials: B
authors.lastname: Kelly
mesh_terms: D018360:Crystallography, X-Ray; D007700:Kinetics; D008094:Lithium / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009942:Organometallic Compounds / Q000737:chemistry; D010720:Phosphines / Q000138:chemical synthesis* / Q000737:chemistry; D013034:Sparteine / Q000737:chemistry*; D013237:Stereoisomerism; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009942:Organometallic Compounds; D010720:Phosphines; D013440:Sulfides; D013034:Sparteine; D008094:Lithium