T
his communication discloses t
he first instance of t
he enantioselective Pd-catalyzed
hars/alp
ha.gif" BORDER=0>-arylation of
N-Boc-pyrrolidine. T
he met
hodology relies on Beak's sparteine-mediated, enantioselective deprotonation of
N-Boc-pyrrolidine to form t
he 2-pyrrolidinolit
hium specices in
hig
h enantiomeric ratio (er). Transmetalation of t
his intermediate wit
h zinc c
hloride generates t
he stereoc
hemically rigid, 2-pyrrolidinozinc reagent, w
hic
h was readily coupled to a variety of functionalized aryl
halides at room temperature using a catalyst generated from Pd(OAc)
2 and PtBu
3-HBF
4. A diverse array of 2-aryl-
N-Boc-pyrrolidines was synt
hesized using t
his met
hodology, providing adducts consistently in a 96:4 er. A survey of t
he stoic
hiometry revealed t
hat as little as 0.3 equiv of zinc could be used in t
he coupling reaction, and t
he 2-pyrrolidinozinc reagent was found to ex
hibit stereoc
hemical stability up to 60
C. T
he met
hod allows for t
he most convergent and reliable preparation of a broad range of functionalized 2-aryl-
N-Boc-pyrrolidines in
hig
h enantioselectivity, w
hic
h is
hig
hlig
hted in t
his report by t
he enantioselective synt
hesis of (
R)-nicotine.