My PhD dissertation - Institut Fresnel

N
(S)-14
1) NBS, THF, - 75 °C
2) - 75 °C to 25 °C
16
Br
N N Br
+ Br
(S)-17, 71% 98 : 2 (S)-18
Pure bromopyrrole (17) was then submitted to bromine/lithium permutation
with butyllithium at - 75 °C and treated with 1/3 equivalent of triethyl phosphite.
1 H NMR and thin layer chromatography analysis of the crude resulting reaction mixture
showed the presence of a mixture of mono-, di-, and trisubstituted phosphines, the major
product being the ethyl bis{N-[(1S)-phenylethyl]pyrrol-2-yl} phosphinite (19) which
could hardly be separated from the other phosphine and phosphinite. In view to this
result, a second attempt was tried and aimed at preparing the phosphinite (19)
selectively. Thus, the transient lithiated pyrrole generated with butyllithium in toluene at
0 °C was added to 1/2 equivalent of triethyl phosphite at - 75°C in order to prepare the
dipyrrolyl phosphinite (19) exclusively. This last reaction still gave a mixture of the
different substitution pattern products, but in much smaller proportions and allowed a
column chromatography isolation of phosphinite (19) in 47% yield. Although
characterization of the desired product was effected by 1 H, 13 C and 31P NMR, all
attempts of further purifications to provide analytically pure material for elemental
analysis failed. Further attempts to convert phosphinite (19) into a crystalline derivative
by means of phenyllithium resulted in no reaction, probably due to steric hindrance
around the phosphorus atom.
Br
N
(S)-17
1) LiC 4H 9, Toluene, 0 °C
2) P(OC 2H 5) 3 (0.5 équiv.)
O P
N
(S,S)-19, 47%
As in the case of binaphthyl phosphinite (5), the phosphinite (19) obtained was
believed to be an interesting phosphorylating reagent for preparing chiral ligands and
would be an alternative to chiral phosphine where the phosphorus atom is bearing the
chiral information [72, 73] . As a more efficient and convenient access to phosphinite (19)
was sought, the more robust and easily purified 2-chloro-N-(1-phenylethyl)pyrrole (20)
was prepared in an almost quantitative way by reproducing the previously described
selective mono-halogenation conditions with N-chlorosuccinimide (NCS). Chlorination
of the pyrrole (14) in tetrahydrofuran at - 75 °C was much slower than its bromination
2