My PhD dissertation - Institut Fresnel

39
4 A Novel Access to Atropisomeric Biphenylbisphosphines
Two main strategies are currently followed to prepare pure atropisomeric
bisphosphine ligands. The first and most frequently used approach can be illustrated by the
preparation of MeO-BIPHEP [16] , where the phosphine and the methoxy substituants are
introduced at the very first steps of the synthesis, whereas the resolution is accomplished at
the end. Although very efficient and applicable to a large scale, this protocol suffers from a
lack of modularity since the structure of the targeted ligand is set since the second step of its
preparation. The whole sequence has then to be repeated for each subtle modification of the
ligand's structure. Furthermore, the racemate resolution of atropisomers occurs in the late
stages of the preparation, and implies losses of molecules with high added value. The second
strategy to produce enantiopure axially chiral bisphosphines was first introduced by
[ , ]
B.H. Lipshutz et al. 170 171 and relied on an asymmetric biaryl coupling process. Thus, by
linking two aryl units with a chiral tether such as 2,3-butanediol or 1,2-diphenyl-1,2ethanediol,
these authors could achieve copper-mediated intramolecular biaryl couplings with
asymmetric induction. This method afforded several biaryl substrates with reasonable to high
enantiomeric excesses (ee) depending on their substitution pattern. Once the optically pure
atropisomers are produced, it is possible to derivatize them and convert them into
bisphosphines by various classical methods [17] . However, since this synthetic route should
give ee close to 100% to be used for producing chiral ligands, only a limited number of
substrates were amenable to that technique.
The present work intended to propose and evaluate an alternative synthetic approach
to access pure atropisomeric biphenylbisphosphines via the key intermediate 2,2',6,6'tetrabromobiphenyl
(30). This achiral and readily available biphenyl motif was chosen as a
common pivot for the whole synthesis scheme, because of its versatility. The presence of four
heavy halogens in ortho- and ortho'- positions made it a particularly attractive candidate since
it was prone to successive and selective bromine/lithium permutations [45, 46] as previously
demonstrated by F. Leroux [54] .