title: Asymmetric lithiation trapping of N-Boc heterocycles at temperatures above -78 °C.
abstract: The asymmetric lithiation trapping of N-Boc heterocycles using s-BuLi/chiral diamines at temperatures up to -20 °C is reported. Depending on the N-Boc heterocycle, lithiation is accomplished using s-BuLi and (-)-sparteine or the (+)-sparteine surrogate in the temperature range -50 to -20 °C for short reaction times (2-20 min). Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered functionalized N-Boc heterocycles in 47-95% yield and 77:23-93:7 er. With N-Boc pyrrolidine, trapped products can be generated in ∼90:10 er even at -20 °C.
authors.affiliation: Department of Chemistry, University of York , Heslington, York YO10 5DD, U. K., and Neusentis Chemistry, Pfizer Worldwide Research and Development , The Portway Building, Granta Park, Cambridge CB21 6GS, U. K.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gelardi
authors.forename: Graeme
authors.initials: G
authors.lastname: Barker
authors.forename: Peter
authors.initials: P
authors.lastname: O'Brien
authors.forename: David C
authors.initials: DC
authors.lastname: Blakemore
mesh_terms: D003959:Diamines / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry*; D013034:Sparteine / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D003959:Diamines; C531441:N-Boc-pyrrolidine; D011759:Pyrrolidines; D013034:Sparteine; D008094:Lithium