chelation with metal which could hinder the product
eliminination process during the catalytic cycle. However,
some efforts have been made toward catalytic synthesis of
chiral diphosphines. Toste et al. reported a Ru-catalyzed
enantioselective synthesis of P-stereogenic phosphine-bor-
anes via alkylation which included one example of a PCP
diphosphine with a chiral center at phosphorus.10 Duan et
al. reported a one-pot synthesis of a chiral PCP palladium
pincer complex.9e Glueck et al. reported Pt-catalyzed
asymmetric alkylation of bis(secondary phosphines) with
aryl halides.11 Considering the importance of chiral dipho-
sphines and their scarcity of catalytic synthetic methods, it
is of great significance to develop efficient catalysts and
methodologies for direct and stereoselective preparation of
chiral tertiary diphosphines.
Initially, we employed it as a catalyst for the hydropho-
sphination but found out that it could not efficiently
catalyze the reaction. We then generated the phosphapal-
ladacycle complex (R)-1 by treatment of (R)-2 with Ag-
ClO4 in the presence of acetonitrile in high yields (Scheme 1).
The structure was confirmed by single crystal X-ray
diffraction analysis.14
Scheme 1. Formation of the Phosphapalladacycle Catalyst (R)-1
In preceding contributions, our group has reported the
asymmetric synthesis of chiral diphosphines promoted by
stoichiometric amounts of palladium complexes.12 Herein,
we report a highly efficient asymmetric hydrophosphination
reaction between dienones and Ph2PH catalyzed by (R)-1
involving formation of two C*ÀP bonds (eq 1), for the direct
preparation of chiral tertiary PCP diphosphines (avoiding
any protection and deprotection process). Broad functional
group tolerance is exhibited, and a wide range of substrates
can be efficiently converted into the desired products in high
yields with excellent diastereo- and enantioselectivities.
To our delight, (R)-1 showed high reactivity and excel-
lent stereoselectivity when it was employed as a catalyst
instead of (R)-2 for the same reaction at À80 °C. The
reaction was conveniently monitored by 31P{1H}NMR
spectroscopy. The diastereomeric ratio (dr = rac/meso)
was determined from the 31P{1H} NMR spectrum of the
crude product, and the enantiomeric excess (ee) was
determined from the 31P{1H} NMR spectrum of the
derivatives which resultedfrom treatment of the phosphine
product with an enantiopure palladacycle containing a
chiral naphthylamine auxiliary (R)-3.9h,i X-ray crystal dif-
fraction analysis of one such derivative (R1 = H, R2 = Ph)
revealed that the absolute configurations of chiral carbon
centers of the major product were S (Figure 1).14
Our group had previously reported the synthesis of
the chiral dimeric phosphapalladacycle complex (R)-2.13
Various reactionconditions weresubsequently screened,
and the results are given in Table 1. The results revealed
that toluene is the best solvent for the reaction with 99:1 dr
and >99% ee (entry 4). Good selectivity was also achieved
in THF, acetone, and benzene. We further surveyed the
temperature effect. It was found that the ee value decreased
to 98% at À40 °C and 93% at 20 °C (entries 6 to 7). Yield
also decreased when the temperature was raised due to
formation of unidentified side products. Base also plays an
important role in the reaction. In the absence of base, only
trace conversion was observed under the same conditions.
Theresults from the screeningofvariousbases showedthat
Et3N is the best one for the reaction due to its appropriate
basicity level and its easy removal under vacuum which
contributes to obtaining clean products. As expected,
when the equally accessible (S)-1 is employed as the
catalyst for the reaction, the same enantioselectivity was
achieved with reversal in configuration at the chiral center
(entry 5). The amount of catalyst loading has little effect on
the selectivity but affects the rate of the reaction. A longer
reaction time is required to complete the reaction with
decreasing catalyst loading.
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With the optimal conditions established, a range of
aromatic dienones were screened for the asymmetric hydro-
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(14) For more details see Supporting Information.
Org. Lett., Vol. 13, No. 21, 2011
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