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P OP Ligands
FULL PAPER
quadrant, far from the steric congestion of BINOL, and as a
result this is the most favored manifold. For manifold S(B),
the steric congestion increases the energy by 2.17 kcalmolÀ1.
The difference in distances between olefin and naphthyl
fects of BINOL, whereas one of the left-hand quadrants is
blocked by the steric effects of BINOL. The sterically
blocked quadrant depends on the stereochemistry of
BINOL, which in this way decides the selectivity in the
product. The quadrant diagram in Figure 4 smoothly inte-
grates our current results on a C1 diphosphine with well-es-
tablished concepts for C2 diphosphines (Figure 1), and
points to a behavior that can be general for efficient C1 li-
gands.
The computed results are in qualitative (and within
10% ee of quantitative) agreement with experimental re-
sults, but do not quite match the relative magnitudes of the
observed enantioselection in each ligand, as we predict
ligand 8b (95% ee of S product) to be more effective than
8a (90% ee of R product) and the experiment shows the op-
posite trend (88% ee of S vs. 99% ee of R). There is some
kind of communication between the left and right quadrants
of the system (matched vs. mismatched effect) that our
model is unable to capture properly. However, the discrimi-
nation between 90 and 95% ee would require sub-kcalmolÀ1
accuracies that should not be expected from our DFT
method, especially taking into account that a balance be-
tween electronic and steric effects seems to be present in
this case. At any rate, the current results provide a solid
base for the explanation of the observed selectivities and
provide a simple interpretation for the behavior of catalysts
with phosphine–phosphite ligands.
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atoms is clear in both cases. The shortest H H and H C dis-
tances for sterically congested S(B) are 2.247 and 2.526 ꢆ,
respectively, whereas none of these distances are below 5 ꢆ
for the most stable R(A) transition state. The comparison
for the electronically disfavored pair of manifolds R(B) and
S(A) is also straightforward. The highest energy (by
2.08 kcalmolÀ1) corresponds to the R(B) manifold because
of the presence of the backbone phenyl, P-phenyl groups,
and the a-ester substituent in the same quadrant.
In the discussion above, we have shown that enantioselec-
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tion in the P OP catalysts is a fine balance of electronic and
steric effects. Primarily, the strong electronic effect of the
phosphite donor results in almost complete blocking of
product formation through the two manifolds with the
olefin trans to phosphite (namely, R(B) and S(A)). The
phenyl group in the backbone provides additional steric
blocking to the R(B) manifold. The principal steric director
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in our P OP catalysts is clearly the BINOL, which directly
affects the favorability of the R(A) and S(B) manifolds.
We note finally that the mechanism follows anti lock-and-
key behavior in this system. The most stable adduct (see the
Supporting Information) is in the S(B) manifold, but prod-
uct formation proceeds by means of the R(A) manifold.
Origin of enantioselectivity in the hydrogenation with (Ra)-
BINOL-derived ligand 8b: We followed the same procedure
for ligand 8b as in 8a, with the lowest-energy structures for
the OATS structures and selected geometrical parameters
presented in the Supporting Information. As for 8a, we in-
cluded all possible conformations of all four manifolds for a
more accurate result of the enantiomeric excess, by which
we obtained an ee value of 95% (S) (cf. 88% (S) experi-
mentally).
Conclusion
Chiral phosphine–phosphite ligands 6, 7a–h, and 8a,b, easily
derived from Sharpless epoxy ethers, have proven to be
highly efficient ligands in the Rh-catalyzed reduction of a
wide variety of functionalized alkenes (26 examples). In par-
ticular, the “lead” ligand of the series (8a) has been shown
to have outstanding catalytic properties in this transforma-
tion and is able to tolerate a broad range of carbamate-type
amino-protecting groups (Boc, Cbz, and Fmoc). The pres-
ence of the BINOL-derived phosphite group has thus a dual
effect on the behavior of these C1 ligands. On one hand, the
electronic properties of phosphite hinder binding of the sub-
strate in two out of the four possible manifolds, whereas on
the other hand, its steric effects allow for the discrimination
between the two remaining manifolds, thereby explaining
the high efficiency of these catalysts.
The strategy described in this paper to discover new
chiral catalysts—the tuning of the performance of the cata-
lyst by modifying the steric and electronic properties of the
molecular fragments or modules—is based on a correct hy-
pothesis. The results described show that the different parts
of a given chiral catalyst can be optimized separately, so
that it is possible to achieve high levels of enantioselectivity
even when starting from an initially mediocre ligand. Future
work is in progress, applying these ligands towards new
asymmetric reactions, such as allylic substitutions or in hy-
The qualitative picture closely follows the lines discussed
above for 8a. Manifolds R(B) and S(A) are disfavored by
the electronic effects of the phosphorus donors, reflected in
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the different Rh PO and Rh PC distances. Manifold R(B)
is further disfavored due to extreme steric crowding in the
upper-right quadrant. Comparing the R(A) and S(B) mani-
folds, there is very little difference in the key metal geome-
try and metal–ligand parameters. Between these two fa-
vored manifolds, the difference is in the steric interactions.
There is a repulsion present between the a-ester substituent
and BINOL in the R(A) OATS, which is absent in the S(B)
OATS and thus the reaction proceeds to product through
S(B).
Again, the mechanism follows anti lock-and-key behavior,
in which the major product forms by means of the S(B)
adduct, and not the favored R(A) adduct (see the Support-
ing Information for details on the adducts). The results for
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the P OP systems with the 8a and 8b ligands are summar-
ized in the quadrant diagram in Figure 4. The two right-
hand quadrants are always disfavored by the electronic ef-
Chem. Eur. J. 2010, 16, 6495 – 6508
ꢅ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6505
Fernandez-Perez, Hector
