My PhD dissertation - Institut Fresnel

50
At first, bis(phenol ether) 7 was subjected to a double halogen/metal permutation
followed by addition chlorodiphenylphosphine to form the well characterized
MeO-BIPHEP 42 [16] in 64% yield. Since rotatory power obtained and those reported by
R. Schmid et al. for enantiopure MeO-BIPHEP (ee > 99%) happened to be the same, no
racemization must have occurred upon lithiation of the optically pure dibromobiphenyl 35.
Furthermore, this result permitted the deduction of the enantiomeric excess of the resolved
biphenol 31 (ee > 99%). On the other hand, the ease and rapidity to obtain ligand 42 in
enantiopure form with good overall yield showed the efficiency of the method developed.
Br
Br
O
O
(P)-(-)-35
LiC 4H 9 (2.0 eq.)
Tol./DEE (9:1)
- 75 °C to - 40 °C, 1 h
Li
Li
O
O
ClPPh 2 (2.0 eq.)
Tol., - 75 °C
Ph2P Ph2P O
O
(P)-(+)-MeO-BIPHEP 42, 64%
Another "BIPHEP-type" bisphosphine was prepared starting from diethoxyphenol
ether 36. This substrate was consecutively treated with four equivalents of tert-butyllithium in
tetrahydrofuran at -75 °C, and two equivalents of chlorodiphenylphosphine to afford (6,6’-
diethoxybiphenyl-2,2’-diyl)bis(diphenylphosphine) ("EtO-BIPHEP"; 43) in high yield (85%).
The enantiomeric excess of bisphosphine 43 thus produced was then determined by chiral
High Pressure Liquid Chromatography (HPLC). Thus each pure atropisomer was compared
with the racemic mixture under the same conditions, and ee was determined to be above 99%.
Br
Br
O
O
(P)-(-)-36
LiC(CH 3) 3 (2.0 eq.)
THF, - 75 °C, 30 min
Li
Li
O
O
ClPPh 2 (2.0 eq.)
Tol., - 75 °C
Ph2P Ph2P O
O
(P)-(+)-43, 85%
A single-crystal X-ray analysis has been carried out for (M)-(-)-43 (Figure 4)
The dihedral angle θ (C8-C7-C6-C1) was determined to be of 73.9 ° which is slightly larger
that the value found for its MeO-BIPHEP congener (70.3 °). X. Zhang [172] showed, for the
asymmetric hydrogenation of β-ketoesters, that a change of only 3 ° in the biphenyl torsion
angle could increase the enantioselectivities (ee) from 86% to 96% depending on the
[ ] 197 .