Substrate and catalyst screening in platinum-catalyzed asymmetric alkylation of bis(secondary) phosphines. Synthesis of an enantiomerically-pure C2-symmetric diphosphine

Article abstract of DOI:10.1021/om800534k

Platinum-catalyzed asymmetric alkylation of bis(secondary) phosphines was investigated. The modular design of the catalyst precursor Pt(diphos*) (R′)(Cl) and the substrates, a bis(secondary) phosphine HRP-PHR and a benzyl halide, along with an efficient ³¹P NMR screening method, enabled rapid evaluation of the rate and diastereoselectivity of these reactions. These experiments identified a selective catalyst, Pt(DuPhos)(Ph)(Cl), and showed that the alkylation of PhHP(CH₂) ₃PHPh (2) was faster and more selective than that of PhHP(CH ₂)₂PHPh (1), MesHP(CH₂)₃PHMes (3), or 1,1′-(C₅H₄PHPh)₂Fe (4). Alkylation of 1 with o-CF₃C₆H₄CH₂Br using the base NaOSiMe₃ and the catalyst precursor Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl), or the analogous Me-DuPhos complex, gave the diphosphine Ph(CH ₂o-CF₃C₆H₄)P(CH₂) ₂P(CH₂o-CF₃C₆H₄)Ph (7), which was prepared on a multigram scale and isolated as a borane adduct (6). The rac and meso diastereomers of 6 were separated by recrystallization, and enantiomerically pure 6 was isolated. Both (R,R)- and (S,S)-6, prepared separately in high ee using appropriate catalyst precursors, were characterized by X-ray crystallography, as was meso-7. Separate treatment of (S,S)-1 and meso-7 with Pt(COD)(Ph)(Cl) gave the complexes Pt((S,S)-7)(Ph)(Cl) ((S,S)-8) and Pt(meso-7)(Ph)(Cl) (meso-8). Both diastereomers of 8 were catalyst precursors for synthesis of 7 by alkylation of 1 with o-CF₃C₆H ₄CH₂Br, but these reactions were unselective, because ligand 7 was rapidly displaced from its complex, 8.

Full text of DOI:10.1021/om800534k

4992
Organometallics 2008, 27, 4992–5001
Substrate and Catalyst Screening in Platinum-Catalyzed
Asymmetric Alkylation of Bis(secondary) Phosphines. Synthesis of
an Enantiomerically Pure C2-Symmetric Diphosphine
Brian J. Anderson,† David S. Glueck,*,† Antonio G. DiPasquale,‡ and Arnold L. Rheingold‡
Department of Chemistry, 6128 Burke Laboratory, Dartmouth College, HanoVer, New Hampshire 03755,
and Department of Chemistry, UniVersity of California, San Diego, 9500 Gilman DriVe,
La Jolla, California 92093
ReceiVed June 9, 2008
Platinum-catalyzed asymmetric alkylation of bis(secondary) phosphines was investigated. The modular
design of the catalyst precursor Pt(diphos*)(R′)(Cl) and the substrates, a bis(secondary) phosphine
HRP∼PHR and a benzyl halide, along with an efficient 31P NMR screening method, enabled rapid
evaluation of the rate and diastereoselectivity of these reactions. These experiments identified a selective
catalyst, Pt(DuPhos)(Ph)(Cl), and showed that the alkylation of PhHP(CH2)3PHPh (2) was faster and
more selective than that of PhHP(CH2)2PHPh (1), MesHP(CH2)3PHMes (3), or 1,1′-(C5H4PHPh)2Fe (4).
Alkylation of 1 with o-CF3C6H4CH2Br using the base NaOSiMe3 and the catalyst precursor Pt((R,R)-i-
Pr-DuPhos)(Ph)(Cl), or the analogous Me-DuPhos complex, gave the diphosphine Ph(CH2o-
CF3C6H4)P(CH2)2P(CH2o-CF3C6H4)Ph (7), which was prepared on a multigram scale and isolated as a
borane adduct (6). The rac and meso diastereomers of 6 were separated by recrystallization, and
enantiomerically pure 6 was isolated. Both (R,R)- and (S,S)-6, prepared separately in high ee using
appropriate catalyst precursors, were characterized by X-ray crystallography, as was meso-7. Separate
treatment of (S,S)-7 and meso-7 with Pt(COD)(Ph)(Cl) gave the complexes Pt((S,S)-7)(Ph)(Cl) ((S,S)-8)
and Pt(meso-7)(Ph)(Cl) (meso-8). Both diastereomers of 8 were catalyst precursors for synthesis of 7 by
alkylation of 1 with o-CF3C6H4CH2Br, but these reactions were unselective, because ligand 7 was rapidly
displaced from its complex, 8.
Scheme 1.a Pt-Catalyzed Asymmetric Alkylation of Bis-
Introduction
(secondary) Phosphines2,3
We recently reported a new approach to catalytic asymmetric
synthesis of chiral phosphines1 via Pt-catalyzed asymmetric
alkylation of racemic secondary phosphines with benzyl halides
in the presence of base.2 Alkylation of bis(secondary) phosphine
substrates 1 and 2 gave significantly enantioenriched C2-
symmetric (rac) products, although diastereoselectivity was
modest (rac/meso ratio (dr) ∼3-4:1, Scheme 1).2,3
Such reactions might be synthetically useful if it was possible
to separate the rac and meso diphosphines and to increase the
ee of the rac isomer by recrystallization.4 Analogous C2-
* Corresponding author. E-mail: glueck@dartmouth.edu.
† Dartmouth College.
a
The catalyst precursor was Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl) (for 1)
‡ University of California, San Diego.
or Pt((R,R)-Me-DuPhos)(Ph)(Cl) (for 2); reactions were done at room
temperature in THF with 10 mol % catalyst precursor per diphosphine
(5 mol % in terms of the P-H bonds). Diastereomeric (rac/meso) ratio
) dr; enantiomeric ratio ) er. The absolute configurations of the
products, which have not been determined, are drawn arbitrarily.
(1) (a) Glueck, D. S. Synlett 2007, 2627–2634. (b) Glueck, D. S. Coord.
Chem. ReV. 2008, in press (doi:10.1016/j.ccr.2007.12.023). (a) Glueck, D. S.
Chem.-Eur. J. 2008, 14, 7108–7117. (d) Glueck, D. S. Dalton Trans.
2008, in press (doi:10.1039/b806138f).
(2) (a) Scriban, C.; Glueck, D. S. J. Am. Chem. Soc. 2006, 128, 2788–
2789. (b) Scriban, C.; Glueck, D. S.; Golen, J. A.; Rheingold, A. L.
Organometallics 2007, 26, 1788–1800 (Addition/Correction: Organome-
tallics 2007, 26, 5124). For analogous Ru-catalyzed reactions, see: (c) Chan,
V. S.; Stewart, I. C.; Bergman, R. G.; Toste, F. D. J. Am. Chem. Soc. 2006,
128, 2786–2787.
(3) The dr and er in the Pt-catalyzed alkylation of 2 with benzyl bromide
were originally reported to be 3.9 and 26 (93% ee), respectively.2a
Subsequent duplicate experiments showed that the average diastereoselec-
tivity (dr ) 4.2 ( 0.3) was reproducibly similar to the first report, while
the enantioselectivity (er ) 68 ( 12 (∼97% ee)) was even higher (Anderson,
B. J. Ph.D. Thesis, Dartmouth College, 2008; manuscript in preparation).
(4) Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.;
Tsuruta, H.; Matsukawa, S.; Yamaguchi, K. J. Am. Chem. Soc. 1998, 120,
1635–1636.
symmetric P-stereogenic diphosphines, such as DiPAMP,5 are
important ligands in asymmetric catalysis.6 Pt-catalyzed asym-
metric alkylation is also attractive as a potential route to libraries
of chiral diphosphines, taking advantage of the modular nature
(5) Knowles, W. S. Angew. Chem., Int. Ed. 2002, 41, 1998–2007.
(6) (a) Blaser, H.-U., Schmidt, E., Eds. Asymmetric Catalysis on
Industrial Scale. Challenges, Approaches, and Solutions; Wiley-VCH:
Weinheim, Germany, 2004. For recent reviews of P-stereogenic phosphines,
see: (b) Grabulosa, A.; Granell, J.; Muller, G. Coord. Chem. ReV. 2007,
251, 25–90. (c) Phosphorus Ligands in Asymmetric Catalysis. Synthesis
and Applications; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008.
10.1021/om800534k CCC: $40.75
2008 American Chemical Society
Publication on Web 09/04/2008

Pt-Catalyzed Asymmetric Alkylation of Phosphines
Organometallics, Vol. 27, No. 19, 2008 4993
Scheme 2. Diversity Elements in Pt-Catalyzed Asymmetric
Alkylation of Bis(secondary) Phosphines
Chart 1. Chiral Diphosphines Screened in Pt-Catalyzed
Alkylation of 1 with Benzyl Bromide
of the substrates.7 Thus, bis(secondary) phosphine substrates
can be modified by changing either the phosphorus substituent
or the linker, while many sterically and electronically varied
benzyl halides are commercially available. Finally, a family of
Pt catalyst precursors may be prepared readily by changing either
the chiral diphosphine ligand or the ancillary Pt-R′ group
(Scheme 2).8
Scheme 3. Pt-Catalyzed Asymmetric Alkylation of 1 Using
Precursors Pt(diphos*)(R′)(Cl) Prepared in situa
Results and Discussion
Because it is difficult to rationally predict what combination
of bis(secondary) phosphine, benzyl halide, and catalyst will
lead to highly enantioenriched products, we developed a simple
screening process. Stock solutions of the phosphine, NaOSiMe3
base, and catalyst precursor were prepared and combined in
NMR tubes. After addition of benzyl halides, reactions were
monitored by 31P NMR spectroscopy and the dr was determined
by integration; in most cases, 31P NMR signals due to the rac
and meso diastereomers of the diphosphine products were well
separated. This approach enabled the screening of about 20
catalytic reactions per day and provided information on both
the rate and the diastereoselectivity of reaction. Synthetically
valuable processes would have a high dr (rac/meso ratio), which
may be associated with high er of the rac isomers, as in Scheme
1.9 In principle, er values could also be measured for each
substrate, or at least for those with high dr. However, we avoided
this extra step, which would make the screening process much
slower.
The first screens sought to find the best catalyst, which could
be prepared in situ from a variety of chiral diphosphine ligands
(Chart 1) and Pt(COD)(R′)(Cl) (R′ ) Ph, Me).10 The catalysts
generated were screened in the alkylation of 1,2-bis(phenylphos-
phino)ethane (1), using NaOSiMe3 and benzyl bromide (Scheme
3). As shown in Table 1, DuPhos ligands gave the highest dr
values; we also observed that Pt-Ph catalyst precursors mediated
faster and more selective reactions than those with a Pt-Me
substituent. The major products were always the desired
bis(tertiary) phosphines, but in several cases byproducts were
also observed, typically for the less diastereoselective catalysts.
Qualitatively, these results showed that the original catalyst
precursors, Pt(DuPhos)(Ph)(Cl), were the best for the alkylation
of 1 with benzyl bromide. Although the reactions were done
under similar conditions, the dr value in the screening process
a[Pt] ) Pt(diphos*); see Chart 1 for structures of the chiral diphosphines.
R′ ) Ph or Me, COD ) cyclooctadiene.
Table 1. Diastereomer Product Ratios in Pt-Catalyzed Asymmetric
Alkylation of 1 with Benzyl Bromide Using Catalysts Generated in
Situ from Pt(COD)(R′)(Cl) (R′ ) Ph, Me) and a Chiral Diphosphine
(diphos*)a
diphos*
dr (R′ ) Ph)
dr (R′ ) Me)
(R,R)-Me-DuPhos
(R,R)-Et-DuPhos
(R,R)-i-Pr-DuPhos
(R,S)-CyPF-t-Bu
(R,S)-PPF-t-Bu
(S)-BoPhoz
(S,S)-Et-FerroTANE
(S,S)-Chiraphos
(S)-Tol-BINAP
(R)-BINAP
2
1.2b
1.2
1.2
2.1
1.9
1.2
0.9b
1b
1.1
1.1b
1.1b
1.1b
1.1
1b
0.9b
0.9b
0.9b
0.9b
0.9b
1.1
(S,S)-DIOP
1.1b
a Time for complete conversion of the bis(secondary) phosphine
substrate (typically ca. 1-2 h) and the dr (rac/meso product ratio) were
determined by 31P NMR spectroscopy. b Additional products also
formed.
using (R,R)-i-Pr-DuPhos (1.9, Table 1) was somewhat less than
that using isolated Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl) (2.8, Scheme
1). These differences may result from catalyst generation in situ
or the use, in the screening experiments, of 1.0 M NaOSiMe3
in THF instead of solid sodium silanolate. Finally, the dr value
in Table 1 was measured on the crude reaction mixture, while
that in Scheme 1 was obtained after workup and purification of
the product. Despite the quantitative disagreement, the screening
results confirmed that this combination of catalyst precursor and
substrateyieldeddiastereoselectivityworthyoffurtherinvestigation.
To investigate the generality of this process, Pt((R,R)-Me-
DuPhos)(Ph)(Cl) was used as a catalyst precursor in alkylation
of four different bis(secondary) phosphines (Scheme 4) with
18 commercially available benzyl halides; see the Experimental
Section and the Supporting Information for details. Integration
(7) (a) Lennon, I. C.; Pilkington, C. J. Synthesis 2003, 11, 1639–1642.
(b) de Vries, J. G.; Lefort, L. Chem.-Eur. J. 2006, 12, 4722–4734. (c)
Dolhem, F.; Johansson, M. J.; Antonsson, T.; Kann, N. J. Comb. Chem.
2007, 9, 477–486. (d) Landis, C. R.; Clark, T. P. Proc. Nat. Acad. Sci.
2004, 101, 5428–5432.
(8) Some of the results in this article were reported in preliminary form
in a patent application: Scriban, C.; Glueck, D. S. WO2007016264, 2007.
(9) (a) Fleming, I.; Ghosh, S. K. J. Chem. Soc., Chem. Commun. 1994,
99–100. (b) Muci, A. R.; Campos, K. R.; Evans, D. A. J. Am. Chem. Soc.
1995, 117, 9075–9076. (c) Negishi, E. Dalton Trans. 2005, 827–848.
(10) Clark, H. C.; Manzer, L. E. J. Organomet. Chem. 1973, 59, 411–
428.

4994 Organometallics, Vol. 27, No. 19, 2008
Anderson et al.
Scheme 4. Screening Benzyl Halides in Pt-Catalyzed Asymmetric Alkylation of Bis(secondary) Phosphinesa
a
([Pt] ) Pt((R,R)-Me-DuPhos), Mes ) 2,4,6-Me3C6H2).
of 31P NMR spectra of the crude reaction mixtures gave the
slower than those of the bromides, especially with the bulkier
diphosphines 3 and 4 (see the Supporting Information for
details).
diastereomer ratios in Table 2, although selectivity was difficult
to measure reliably in some cases, where reaction was incom-
plete, byproducts were formed, or P-F coupling produced broad
31P NMR multiplet signals. We hoped that these dr values
reflected preference for the rac isomer, as in the selective
alkylation of 1 and 2 with benzyl bromide, but note that false
positives (high dr associated with a meso-selective catalyst) are
possible.
How reliable are the results in Table 2? The dr values for
alkylation of 1 with benzyl bromide using isolated Pt((R,R)-
Me-DuPhos)(Ph)(Cl) (Table 2, entry 1a, dr ) 1.6) and a catalyst
precursor generated in situ (Table 1, row 1, dr ) 2) were
qualitatively similar, despite the differences in preparation of
the catalyst. The reproducibility of the dr in alkylation of 2 with
benzyl bromide was investigated in more detail. The dr value
from the reaction mixture in the screening process (4.3, Table
2) was similar to that determined after workup and purification
(4.2, Scheme 1).3
Analysis of the data in Table 2 revealed some structure/
reactivity/selectivity relationships for the catalytic alkylations.
Reactions of propane-bridged bis(phenylphosphine) 2 occurred
fastest and with the highest diastereoselectivity. The qualitative
order of reaction rates was 2 > 1 > 3 ∼ 4, while diastereose-
lectivity varied in the order 2 > 1 ∼ 3 > 4. Among the benzyl
halides, no direct structure/selectivity relationship was apparent.
However, most reactions of benzyl chloride substrates were
The anomalously high diastereoselectivity observed in alkyl-
ation of 1 with 9-chloromethylanthracene (Table 2, entry 1m,
dr ) 75) was investigated by scaling up this reaction (Scheme
5). A single diastereomer of 5 was readily isolated, but in only
30% yield and 70% ee. As described in more detail in the
Experimental Section, it appears that meso-5 was much less
soluble than the rac isomer; its precipitation led to the apparent
high dr and the low yield. This is consistent with observations
from the original screening experiment, in which the dr was
5.7 at incomplete conversion, but much higher at the end of
the reaction. This demonstrated a drawback of the screening
process, which requires solubility of all the products to ensure
a reliable assay.
The alkylation of 1 with o-trifluorobenzyl bromide (Table 2,
entry 1b) was also examined in detail. We originally thought
that this reaction was highly diastereoselective, because a 19F
NMR signal due to an impurity was mistakenly assigned to
meso-7; this illustrates a liability of screening crude reaction
mixtures.8 In fact, the dr of 7 was relatively low (1.4).
Conveniently, however, the diastereomers of phosphine-borane
6 could be separated by recrystallization. Unusually for this class
of compounds, the racemic diastereomer was less soluble than
the meso one.4,9b A series of recrystallizations, which were
monitored by 19F and 1H NMR spectroscopy, gave rac-6 in pure

Pt-Catalyzed Asymmetric Alkylation of Phosphines
Organometallics, Vol. 27, No. 19, 2008 4995
Table 2. Diastereomeric Product Ratios in Pt-Catalyzed Asymmetric
Alkylation of Bis(secondary) Phosphines with Benzyl Halidesa
Scheme 6. Pt-Catalyzed Asymmetric Alkylation of 1 and
Synthesis of Diphosphine 7
diphosphine
benzyl halide
1
2
3
4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
1.6
4.3
1.7
2.2
1.3
b
b
1.4
1.1
1.1
1.5
1.3
1.1
2.1
2.2
1.7
2.0
1.7
75d
4.4
1.5
1.4
b
1.5
1.6
c
b
1.9
1.4
1.3
2.3
1.4
1.8
1.2
2.3
1.1
1.1
1.4
3
4.0
b
1.6
b
2.6
2.3
2.9
2.2
1.4
1.5
1.6
1.6
2.4
1.8
1.4
1.4
1
b
b
b
b
b
b
b
b
b
b
b
b
b
Table 3. Effect of Reaction Conditions on Selectivity in
Pt-Catalyzed Asymmetric Synthesis of Diphosphine 7a
1.8
2.2
1.9
entry
temp (°C)
time
yield (%)b
dr
er
a Reactions were carried out at room temperature in THF with 10
mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl) (5 mol %
per P-H bond). The product diastereomer ratio (dr) was determined by
integration of 31P NMR spectra of crude reaction mixtures. See the
Experimental Section and the Supporting Information for details. b The
dr was not readily determined when reaction was incomplete, byproducts
were formed or P-F coupling produced broad 31P NMR multiplet signals.
See the Supporting Information for details on individual reactions. c Not
performed. d The meso diastereomer precipitated during catalysis; the
actual dr was significantly lower (see discussion in the text).
1
2
3
4
5
6
-20
0
rt
40
rtc
rte
4 days
<12 h
<12 h
2 h
12 h
4 h
80 (∼2.2 g)
1.7
2.2
1.8
1.2
1.7
2.2
11
14
12
88 (∼1.8 g)
6
d
8.4
a Reactions were performed with 5 mol % catalyst precursor in THF.
For entries 1-4, the precursor was Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl). The
reported temperatures are those of the cooling/heating bath; rt ) room
temperature. b Isolated yields of phosphine-borane 6. c Pt((R,R)-Me-
DuPhos)(Ph)(Cl) was used as catalyst precursor. d The er was not
determined. e Pt((R,R)-Me-DuPhos)(9-phenanthryl)(Br) was used as
catalyst precursor.
Scheme 5. Pt-Catalyzed Asymmetric Alkylation of 1 with
9-Chloromethylanthracenea
a
Pt catalyst precursor ) Pt((R,R)-Me-Duphos)(Ph)(Cl).
form; deprotection using either an amine or HBF4 gave 7
(Scheme 6).11
Under optimized conditions (Table 3), using the catalyst
precursor Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl) in THF at 0 °C,
diphosphine 7 was prepared on a large scale, then converted to
6. Recrystallization gave 1.24 g (32%) of (S,S)-6 (>99% ee;
see the Experimental Section for ee determination), along with
0.55 g (14%) of meso-6 and 0.91 g of a mixture of rac- and
meso-6 (total 2.7 g, 70% yield). Similarly, (R,R)-6 was isolated
using the catalyst precursor Pt((R,R)-(Me-DuPhos)(Ph)(Cl).12
The crystal structures of both enantiomers of rac-6 (deter-
mined separately) and of meso-7 are shown in Figures 1 and 2.
Table 4 summarizes the crystallographic data; see the Supporting
Information for more details.
Figure 1. ORTEP diagrams of (S,S)-6 (left) and (R,R)-6 (right).
6. Experimental and simulated spectra are shown in Figure 3
for rac-7 (AA′X3X3′ spin system).13 The coupling constants JPP
and JPF were 31 and 15 Hz, respectively, as in similar
phosphines (Chart 2).14-16 The spectra for meso-7 were es-
sentially identical.17
The 31P and 19F NMR spectra of 7 were complicated by long-
range coupling, which was not observed in the borane adduct
The enantiomeric purity of diphosphine 7 was determined
by 31P NMR spectroscopy after binding it to a chiral Pd reporter
complex (see the Experimental Section and Table 4 for
details).1b,18 Because signals due to the diastereomeric Pd
(11) (a) Brunel, J. M.; Faure, B.; Maffei, M. Coord. Chem. ReV. 1998,
178–180, 665-698. (b) McKinstry, L.; Livinghouse, T. Tetrahedron Lett.
1994, 35, 9319–9322.
(12) As described elsewhere,1,2a as a result of the conventions for
assigning absolute configuration, (R,R)-Me-DuPhos and (R,R)-i-Pr-DuPhos
have opposite configurations. See: Burk, M. J.; Feaster, J. E.; Nugent, W. A.;
Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125–10138.
(13) Budzelaar, P. gNMR v3.6.5; Cherwell Scientific, 1992-1996.
(14) NMR data for dppe: Hersh, W. H. J. Chem. Educ. 1997, 74, 1485–
1488.

4996 Organometallics, Vol. 27, No. 19, 2008
Anderson et al.
Figure 2. ORTEP diagram of meso-7.
Table 4. Crystallographic Data for Phosphine-Boranes (S,S)-6 and
(R,R)-6, and the Phosphine meso-7
(S,S)-6
(R,R)-6
meso-7
formula
fw
C30H32B2F6P2
590.12
C30H32B2F6P2
590.12
C30H26F6P2
562.45
space group
a, Å
b, Å
P2(1)2(1)2(1) P2(1)2(1)2(1) C2/c
10.3800(16)
13.920(2)
20.209(3)
90
10.3469(7)
13.8409(9)
20.1361(13)
90
14.5330(18)
15.6300(19)
11.6520(14)
90
c, Å
R, deg
ꢀ, deg
90
90
90
90
94.356(2)
90
γ, deg
Figure 3. Experimental (in C6D6, above) and simulated (below)
31P (top) and 19F (bottom) NMR spectra of rac-7. Coupling
constants (in Hz) used in the simulation: JPP ) 30.8, JPF ) 15.0,
-0.4, JFF ) -3.3.
V, Å3
2920.0(8)
4
2883.7(3)
4
2639.1(6)
4
Z
D(calc), g/cm3
µ(Mo KR), mm-1
temp, K
R(F), %a
R(wF2), %a
1.342
0.206
208(2)
5.64
1.345
0.209
100(2)
4.44
1.416
0.226
100(2)
3.42
Chart 2. NMR Coupling Constants in Phosphines Related
to 7
11.73
12.10
9.14
absolute struct param 0.12(12)
-0.01(9)
2
2 2
a Quantity minimized: Rw(F2) ) ∑[w(Fo - Fc ) ]/∑[(wFo2)2]1/2; R )
∑∆/∑(Fo), ∆ ) |(Fo - Fc)|, w ) 1/[σ2(Fo2) + (aP)2 + bP], P ) [2Fc
2
+ Max(Fo2,0)]/3. A Bruker CCD diffractometer was used in all cases.
complexes of (R,R)-7 and (S,S)-7 could be distinguished readily,
these spectra showed that 7 was highly enantioenriched. The
13C satellite peaks19 in the 19F NMR spectrum of (S,S)-7-Pd
enabled quantification of the enantiomeric purity. Under condi-
tions where these satellite signals (2% of the intensity of the
central peak) were observed, the 19F NMR signal of (R,R)-7-
Pd was not, suggesting that the enantiomeric purity was
>99%.20
Scheme 7. Synthesis of Pt Complexes 8
Attempted Chirality Breeding. The availability of enantio-
merically pure 7 suggested the possibility of using it in “chirality
breeding”21 as a ligand in a Pt complex that could catalyze
(15) NMR data for Me2PCH2CH2P(CF3)2: Field, L. D.; Wilkinson, M. P.
Tetrahedron Lett. 1997, 38, 2779–2782.
(16) NMR data for 1-CF3,2,6(CH2P(t-Bu)2)2C6H3: van der Boom, M. E.;
Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 1999, 121, 6652–6656.
(17) In the diphosphine oxides and sulfides PhHP(E)CH2CH2PHPh(E)
(E ) O or S, Grossmann, G.; Walther, B.; Gastrock-Mey, U. Phosphorus
Sulfur 1981, 11, 259–272. ) JPP values for the rac and meso diastereomers
were the same, and the JPC values for these diastereomers were also very
similar.
(18) (a) Kyba, E. P.; Rines, S. P. J. Org. Chem. 1982, 47, 4800–4801.
(b) Wild, S. B. Coord. Chem. ReV. 1997, 166, 291–311.
(19) Dukat, W.; Naumann, D. J. Chem. Soc., Dalton Trans. 1989, 739,
744.
asymmetric alkylation of 1 with o-CF3C6H4CH2Br to yield 7.22
Separate reactions of (S,S)-7 and meso-7 with Pt(COD)(Ph)(Cl)
gave the rac and meso diastereomers of Pt(7)(Ph)(Cl) (8, Sch-
eme 7).
The diastereomers of 8 were then used separately as catalyst
precursors in alkylation of 1 with o-trifluorobenzyl bromide.
(22) For chirality breeding in Pd-catalyzed asymmetric phosphination,
and for references to additional examples of this phenomenon, see: Blank,
N. F.; McBroom, K. C.; Glueck, D. S.; Kassel, W. S.; Rheingold, A. L.
Organometallics 2006, 25, 1742–1748.
(20) Vedejs, E.; Donde, Y. J. Am. Chem. Soc. 1997, 119, 9293–9294.
(21) Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1978, 100, 5491–
5494.

Pt-Catalyzed Asymmetric Alkylation of Phosphines
Organometallics, Vol. 27, No. 19, 2008 4997
Scheme 8. Attempted Chirality Breeding: Pt-Catalyzed
Synthesis of 7 using Precursors 8, which Contain (S,S)-7 or
meso-7
Conclusions
A rapid process for screening rate and diastereoselectivity in
the Pt-catalyzed asymmetric alkylation of bis(secondary) phos-
phines with benzyl halides has been developed. Using this
approach, the alkylation of 1 with o-CF3C6H4CH2Br was scaled
up and enantiopure diphosphine 7 was prepared on a multigram
scale. We expect that related diphosphines can be prepared in
a similar way. The diphosphine (S,S)-7 was used as a ligand in
a platinum complex to breed itself, but without any selectivity,
because it was displaced rapidly. This approach may be more
successful with more tightly binding diphosphines, and we are
currently examining this possibility.
Table 5. Synthesis of 7 from 1 Using the Catalyst Precursors (S,S)-8
and meso-8
Experimental Section
entry catalyst precursor dr of 7 er of 7 time (h) yield (%)
1
2
3
4
5
6
(S,S)-8
(S,S)-8
(S,S)-8
meso-8
meso-8
meso-8
1.1
1.3
1.4
0.9
0.7
0.6
1.5
1.4
1.9
1.06
1.10
1.13
<1
<1
<4
<4
<4
<4
86
General Experimental Details. Unless otherwise noted, all
reactions and manipulations were performed in dry glassware under
a nitrogen atmosphere at 20 °C in a drybox or using standard
Schlenk techniques. Petroleum ether (bp 38-53 °C), CH2Cl2, ether,
THF, and toluene were dried over alumina columns similar to those
described by Grubbs.23 NMR spectra were recorded using Varian
84
a
80
78
b
a Approximately 50% conversion to 7 with 10% oxide formation (δ
24.7 (d, J ) 42), 24.2 (d, J ) 43), -10.3 to -10.7 (m)), and 29%
monoalkylated P(Ph)(o-CF3C6H4CH2)(CH2)2PHPh (δ (THF) -12.1 to
-12.4 (m), -12.8 to -12.9 (m), -44.2, -45.9). b Approximately 60%
conversion to 7 with 15% oxide formation and 24% monoalkylated
P(Ph)(o-CF3C6H4CH2)(CH2)2PHPh.
1
300 or 500 MHz spectrometers. H or 13C NMR chemical shifts
are reported versus Me4Si and were determined by reference to
the residual 1H or 13C solvent peaks. 31P NMR chemical shifts are
reported versus H3PO4 (85%) used as an external reference.
Coupling constants are reported in Hz as absolute values unless
noted otherwise. Unless indicated, peaks in NMR spectra are
singlets. Instead of the expected quartet resonances11a in the 31P
NMR spectra of the phosphine-boranes, poorly resolved multiplets
were often observed; in some cases the signal was an apparent
doublet. Elemental analyses were provided by Schwarzkopf Mi-
croanalytical Laboratory or Quantitative Technologies Inc. Mass
spectrawererecordedattheUniversityofIllinois,Urbana-Champaign
(http://www.scs.uiuc.edu/∼msweb).
Table 6. 31P and 19F NMR Data for Diastereomeric Complexes of
the Diphosphine PhP(CH2o-C6H4CF3)CH2CH2PPh(CH2o-C6H4CF3)
a
(7) with (S)-(Pd(NMe2CH(Me)C10H6)(µ-Cl))2
monodentate
complex
RR
SS
meso
δ (31P) (C6D6)
δ (31P) (CD2Cl2)
δ (19F) (C6D6)
δ (19F) (CD2Cl2)
38.6
38.2
38.7
37.8
39.2, 38.0b
38.5, 36.4c
-57.9d
-58.5f
-58.5e
-59.0g
-57.5, -59.3
-58.1, -59.7
Reagents were from commercial suppliers, except for these
compounds, which were made by the literature procedures: Pt(CO-
D)(R)Cl) (COD ) cyclooctadiene, R ) Me or Ph),10 Pt((R,R)-Me-
DuPhos)(Ph)(Cl),24 Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl),2a,b (S)-(Pd(Me2-
NCH(Me)C6H4)(µ-Cl))2,25 (S)-(Pd(Me2NCH(Me)C10H6)(µ-Cl))2,26
MesPH(CH2)3PHMes.27 The complex Pt((R,R)-Me-DuPhos)(9-
phenanthryl)(Br) (see Table 3) was prepared from Pt((R,R)(Me-
DuPhos)Cl2 and (9-phenanthryl)MgBr; details will be reported
separately.
PhPH(CH2)2PHPh (1) via PhP(O)(O-i-Pr)(CH2)2PPh(O)(O-
i-Pr). In a modification of the literature method,28 PhP(O-i-Pr)2
(10 g, 0.04 mmol, bp 112-114 °C) and 1,2-dibromoethane (1.9
mL, 0.022 mmol, bp 131 °C) were combined under N2 in a
Kugelrohr apparatus and heated under vacuum at 140 °C for 3 h,
although this temperature was higher than the boiling points of both
reactants. About 5 mL of distillate was collected, leaving behind a
white solid. Cyclohexane (40 mL) was added to the solid, and the
resulting slurry was heated to a boil for 5 min. The slurry was
allowed to cool to room temperature and filtered to give a white
solid, which was again boiled with 40 mL of cyclohexane. Filtration
after cooling to room temperature gave 5.65 g (65% yield) of a
mixture of two diastereomers; an impurity (31P NMR: δ 23.4)
remained in the filtrate. Boiling this mixture with 30 mL of
chelate complex
δ (31P) (CD2Cl2)
RR
65.4, 35.5h
SS
65.0, 37.2i
mesoj
66.2, 39.2k 65.0, 37.4l
δ (19F) (CD2Cl2) -58.1, -59.1 -58.1, -59.1 -57.9, -58.2k -58.0,
-58.3
a Chemical shifts are in ppm, coupling constants in Hz. b AB pattern;
both peaks are doublets with J ) 52. c AB pattern; both peaks are
doublets with J ) 51. d The 13C satellite peak was observed at δ -58.0
(d, J ) 274). e The 13C satellite peak was observed at δ -58.7 (d, J )
274). f The 13C satellite peak was observed at δ -58.0 (d, J ) 274).
g The 13C satellite peak was observed at δ -59.1 (d, J ) 274). h Broad
doublets, J ) 22. i Doublets, J ) 24. j Two diastereomers of the meso
chelate complex were observed. k Broad peaks. l doublets, J ) 23.
With (S,S)-8, the product was enriched in the diphosphine (S,S)-7
(dr ) 1.2, er ) 1.4). In contrast, 7 formed using catalyst
precursor meso-8, was meso-enriched (dr ) 0.8, Scheme 8).
These results are consistent with displacement of the original
diphosphine ligand, which was present from the 10 mol %
catalyst loading. Addition of 10 mol % of (S,S)-7 to a 1:1
racemic/meso mixture of 7 formed by an unselective catalyst
would give a dr of 1.2 and an er of 1.4, as observed. Similarly,
adding 10 mol % of meso-7 to a 1:1 mixture yields a dr of 0.8.
Consistent with these results, treatment of either (S,S)-8 or
meso-8 with 1,2-bis(phenylphosphino)ethane and NaOSiMe3
caused rapid displacement of 7, as observed by 31P NMR
spectroscopy.
(24) Brunker, T. J.; Blank, N. F.; Moncarz, J. R.; Scriban, C.; Anderson,
B. J.; Glueck, D. S.; Zakharov, L. N.; Golen, J. A.; Sommer, R. D.; Incarvito,
C. D.; Rheingold, A. L. Organometallics 2005, 24, 2730–2746.
(25) Roberts, N. K.; Wild, S. B. J. Am. Chem. Soc. 1979, 101, 6254–
6260.
(26) Otsuka, S.; Nakamura, A.; Kano, T.; Tani, K. J. Am. Chem. Soc.
1971, 93, 4301–4303.
(27) Naumov, R. N.; Karasik, A. A.; Sinyashin, O. G.; Loennecke, P.;
Hey-Hawkins, E. Dalton Trans. 2004, 357–358.
(28) Mastalerz, P. Rocznicki Chem. 1965, 39, 33–38.
(23) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518–1520.

4998 Organometallics, Vol. 27, No. 19, 2008
Anderson et al.
cyclohexane, then filtering the hot slurry, gave one diastereomer
as a white solid; the filtrate was enriched in the other diastereomer.
The product is a known compound,28 for which we report additional
characterization data.
THF, 0.1 mmol) was added via syringe and a white precipitate
formed. NaOSiMe3 (200 µL of a 1.0 M solution in THF (Aldrich),
0.2 mmol) was added; the precipitate dissolved and the solution
turned yellow. The benzyl halide (0.2 mmol) was added (neat, for
liquids, or as a solution in the minimum amount of dry THF, about
100 µL) and a white precipitate formed. The reaction was monitored
by 31P NMR spectroscopy. See Table 2 for diastereomeric product
ratios and the Supporting Information for additional data. Analogous
screening experiments with diphosphines 2, 3, and 4 were carried
out similarly (see the Supporting Information for details).
Anal. Calcd for C20H28O4P2: C, 60.91; H, 7.16. Found: C, 60.75;
H, 7.21. HRMS: m/z calcd for C20H28O4P2 m/z 394.1463, found
m/z 394.1468. 31P{1H} NMR (CDCl3): δ 43.02 (a), 43.00 (b), 1:1
ratio of diastereomers. For pure diastereomer a, 1H NMR (CDCl3):
δ 7.80-7.75 (m, 4H, Ar), 7.57 (t, J ) 7, 2H, Ar), 7.49 (t, J ) 7,
4H, Ar), 4.50-4.47 (m, 2H, O-CH), 2.06-2.05 (m, 4H, CH2), 1.32
(d, J ) 6, 6H, CH3), 1.12 (d, J ) 6, 6H, CH3). 13C{1H} NMR
(CDCl3): δ 132.6 (Ar), 132.0 (t, J ) 5, Ar), 128.9 (t, J ) 6, Ar),
Pt-Catalyzed Asymmetric Synthesis of 1,2-Bis((anthracen-9-
methyl)(phenyl)phosphino)ethane (5). A solution of 1,2-bis(phe-
nylphosphino)ethane (1, 197 mg, 0.8 mmol) in 2 mL of THF was
treated with NaOSiMe3 (1.6 mL of a 1.0 M solution in THF, 1.6
mmol) and Pt((R,R)-Me-Duphos)(Ph)(Cl) (49 mg, 0.10 mmol, 12
mol %); the solution turned yellow. A solution of 9-(chloromethyl)-
anthracene (363 mg, 1.6 mmol) in 2 mL of THF was added. The
solution immediately turned orange, and a white precipitate formed
within 5 min. The mixture was stirred overnight, then filtered
through Celite to remove the salt, washing with THF. However,
the Celite remained yellow even after washing. The solvent was
removed from the filtrate in Vacuo to give approximately 300 mg
of an orange solid, which was dissolved in a 1:1 mixture of
petroleum ether/THF and passed through a 35 mm wide frit filled
25 mm high with silica gel. The pale yellow filtrate was concen-
trated under vacuum, and the resulting solid was recrystallized from
THF/petroleum ether at -40 °C. The pale yellow supernatant was
decanted to give 130 mg of yellow solid. The silica plug was washed
with 20 mL (each) of THF, petroleum ether, toluene, CH2Cl2, and
ether to give, after removal of the solvent, 20 mg more yellow
solid (total yield 150 mg, 30%, of a single diastereomer). However,
the silica plug remained yellow even after the sequential washings,
suggesting that some product may remain insoluble, explaining the
low yield.
70.2, 24.7, 24.1 (t, J ) 3), 22.7 (5-line pattern, JPP ) 67, JPC
)
104, -6).29 One of the expected aryl carbon signals was not
observed. For the mixture of diastereomers a and b, 1H NMR
(CDCl3): δ 7.78-7.69 (m, 4H a, 4H b, Ar), 7.58-7.42 (m, 6H a,
6H b, Ar), 4.54-4.44 (m, 2H a, 2H b, O-CH), 2.21-2.13 (m, 2H,
b), 2.05-2.04 (m, 4H a, CH2), 1.94-1.86 (m, 2H b), 1.36 (d, J )
6, 6H b, CH3), 1.31 (d, J ) 6, 6H a, CH3), 1.14 (d, J ) 6, 6H b,
CH3), 1.11 (d, J ) 6, 6H a, CH3). 13C{1H} NMR (CDCl3): δ 132.63
(a, Ar), 132.59 (b, Ar), 132.0-131.9 (m, a, b), 128.9-128.8 (m, a,
b), 70.2 (m, a, b), 24.8-24.7 (m, a, b), 24.1 (m, a, b), 22.7 (m,
overlapping five-line patterns, a, b).29
Synthesis of 1 by reduction of this Arbuzov product with LiAlH4
was reported earlier.30 However, we found the procedure with
LiAlH4/Me3SiCl to be more convenient.31 A slurry of LiAlH4 (1.39
g, 36.7 mmol) in 50 mL of dry THF was cooled to -78 °C, and
Me3SiCl (4.70 mL, 36.7 mmol) was added via a syringe. The gray
slurry was slowly allowed to warm to room temperature and stirred
for an additional 2 h. The resulting mixture was cooled to -40 °C,
and a solution of the Arbuzov product above (2.14 g, 6.1 mmol),
in 100 mL of anhydrous THF under N2, was added via cannula.
The mixture was stirred at room temperature overnight. In the
morning, degassed water (100 mL, added dropwise until the fizzing
ceased) and ether (100 mL) were added and the organic layer was
separated. The aqueous layer was extracted with 2 × 50 mL of
ether, and the organic layers were combined and dried with MgSO4.
The ether was then removed in Vacuo, yielding a pale yellow oil,
which was stored under N2 at -40 °C overnight to give 1.01 g
(67% yield) of a white solid.
Screening Chiral Diphosphine Ligands with in Situ Precata-
lyst Formation in the Catalytic Reaction of Benzyl Bromide
with 1. To a solution of diphosphine 1 (0.2 mL of 0.05 M THF
solution, 0.01 mmol) was added Pt(COD)(R)(Cl) (100 µL of a 0.1
M solution in THF, 0.01 mmol, R ) Me or Ph). After 15 min,
1,2-bis(phenylphosphino)ethane (1, 50 µL of 2.0 M solution in THF,
0.1 mmol) was added and the solution became cloudy. NaOSiMe3
(0.2 mL of 1.0 M solution in THF, 0.2 mmol) was added and the
solution became yellow. The reaction mixture was transferred to
an NMR tube. Benzyl bromide (24 µL, 34 mg, 0.2 mmol) was
added via microliter syringe, and a white precipitate immediately
formed. The reaction mixture was monitored by 31P NMR
spectroscopy, which enabled determination of the extent of conver-
sion and the rac/meso ratio of the product diphosphine (Table 1).
31P NMR data (THF) for 1,2-bis(benzylphenylphosphino)ethane:
δ -13.1 (meso), -13.6 (rac).
The mass spectrum of the air-sensitive diphosphine was consis-
tent with oxidation at both P centers. HRMS: m/z calcd for
C44H37O2P2 (MO2H)+ 659.2269, found m/z 659.2274. 31P{1H}
1
NMR (C6D6): δ -11.1. H NMR (CDCl3): δ 8.28 (2H, Ar), 8.03
(d, J ) 8, 4H, Ar), 7.94 (d, J ) 7, 4H, Ar), 7.42-7.32 (m, 14H,
Ar), 7.29-7.26 (m, 4H, Ar), 3.99 (d, J ) 14, 2H, benzyl H), 3.77
(d, J ) 14, 2H, benzyl H), 1.89-1.84 (m, 2H, CH2), 1.59-1.54
1
(m, 2H, CH2). H{31P} NMR (C6D6): δ 8.04 (2H, Ar), 8.00 (m,
4H, Ar), 7.75 (m, 4H, Ar), 7.21 (m, 8H, Ar), 7.14 (d, J ) 8, 4H,
Ar), 7.01 (m, 2H, Ar), 6.91 (t, J ) 8, 4H, Ar), 3.72 (d, J ) 14,
2H), 3.53 (d, J ) 14, 2H), 1.91-1.86 (m, 2H), 1.65-1.58 (m, 2H).
13C{1H} NMR (C6D6): δ 138.5 (m, Ar), 133.0 (m, Ar), 132.0 (Ar),
130.8 (m, Ar), 130.4 (m, Ar), 129.3 (Ar), 129.1 (Ar), 128.5 (t, J )
3, Ar), 126.3 (Ar), 125.5 (Ar), 125.2 (Ar), 125.0 (Ar), 29.8 (m,
benzyl C), 24.2 (apparent t, J ) 34, CH2). For ee determination,
the product (30 mg, 0.048 mmol) was dissolved in 1 mL of CH2Cl2
andasolutionofthereportercomplex(S)-(Pd(NMe2CH(Me)C10H6)(µ-
Cl))2 (35 mg, 0.053 mmol) in 1 mL of CH2Cl2 was added.
Integration of the 31P{1H} NMR spectrum showed the ee to be
70%: δ 38.6 (major), 34.6 (minor).
Effect of Reaction Conditions on the Selectivity of Forma-
tion of 7 (Sample Procedure, Table 3). A solution of 1,2-
bis(phenylphosphino)ethane (1.2 g, 4.7 mmol) in 10 mL of THF
was treated with a solution of NaOSiMe3 (1.0 g, 9.3 mmol) in 10
mL of THF and a solution of Pt((R,R)-i-Pr-Duphos)(Ph)(Cl) (169
mg, 0.23 mmol, 5 mol %) in 10 mL of THF, and the bright yellow
solution was stirred at -20 °C. A solution of 1-(bromomethyl)-2-
(trifluoromethyl)benzene (2.2 g, 9.3 mmol) in 5 mL of THF was
added to the mixture, and within 5 min, the solution turned a darker
yellow-orange and a white precipitate was observed. The progress
of the reaction was monitored by removing an aliquot (0.5 mL)
for 31P NMR spectroscopy. Once the reaction was complete, the
sample from the NMR tube was filtered through silica, eluting with
Screening Benzyl Halides in Pt-Catalyzed Asymmetric Alkyl-
ation of 1. A 50 µL (0.01 mmol) amount of a stock solution of 0.2
M Pt((R,R)-Me-Duphos)(Ph)(Cl) in THF was charged to an NMR
tube. The disecondary phosphine (50 µL of a 2.0 M solution in
(29) This signal was similar to that reported for analogous AXX′ spin
systems; see: Redfield, D. A.; Nelson, J. H.; Cary, L. W. Inorg. Nucl. Chem.
Lett. 1974, 10, 727–733. The coupling constants were obtained from
simulations using gNMR.
(30) Issleib, K.; Weichmann, H. Chem. Ber. 1968, 101, 2197–2202.
(31) Kyba, E. P.; Liu, S.-T.; Harris, R. L. Organometallics 1983, 2,
1877–1879.

Pt-Catalyzed Asymmetric Alkylation of Phosphines
Organometallics, Vol. 27, No. 19, 2008 4999
10% THF/petroleum ether. The solvent was removed under vacuum
to give ∼30 mg of a colorless oil. The selectivity was determined
by treatment of the diphosphine with (S)-(Pd(NMe2CH(Me)C10H6)(µ-
Cl))2 (1.1 equiv) in CD2Cl2 and integration of the 31P NMR
spectrum (see below).
was observed.11b The mixture was stirred for 12 h, and then 10
mL of degassed aqueous NaHCO3 was added and the mixture was
stirred for another 12 h. The mixture was extracted with ether (2
× 30 mL) and dried with MgSO4, and the solvent was removed in
Vacuo to give a white solid. The solid was eluted over silica with
50/50 THF/petroleum ether, and the solvent was removed in Vacuo
to give 103 mg (76% yield) of 7 as a white solid. A similar
procedure, or deprotection with DABCO (see below), was used to
isolate meso-7.
Data for rac-7. Mass spectroscopic results were consistent with
oxidation at both P centers. HRMS: m/z calcd for C30H27F6O2P2
(MO2H)+ 595.1391, found 595.1387. Alternatively, a solution of
crude 7 (430 mg, 0.76 mmol, dr ) 1.8) in 10 mL of THF was
treated with sulfur (78 mg, 2.4 mmol, 3.2 equiv). The bright yellow
slurry was stirred for 1 h, then filtered through Celite, eluting with
CH2Cl2. The solvent was removed under vacuum to give a yellow
solid, which was dissolved in ether and filtered through Celite again.
The ether was removed under vacuum to give the product as a
yellow solid. The dr remained unchanged and was easily measured
from integration of the 31P{1H} NMR spectrum (CDCl3). HRMS:
m/z calcd for C30H27S2F6P2 (MH)+ 627.0934, found 627.0927.
31P{1H} NMR (CDCl3): δ 49.3 (minor), 49.0 (major). 19F{1H}
NMR (CDCl3): δ -58.5 (major), -58.6 (minor).
Pt-Catalyzed Asymmetric Synthesis of 1,2-Bis((o-trifluo-
robenzyl)(phenyl)phosphino)ethane (7) and Separation of rac
and meso Diphosphine-Borane 6. A solution of 1,2-bis(phe-
nylphosphino)ethane (1.64 g, 6.6 mmol) in 50 mL of THF was
treated with a solution of NaOSiMe3 (1.49 g, 13.3 mmol) in 50
mL of THF and a solution of Pt((R,R)-i-Pr-Duphos)(Ph)(Cl) (240
mg, 0.33 mmol, 5 mol %) in 50 mL of THF, and the bright yellow
solution was stirred at 0 °C. A solution of 1-(bromomethyl)-2-
(trifluoromethyl)benzene (3.2 g, 13.3 mmol) in 20 mL of THF was
added to the mixture, and within 5 min, the solution turned a darker
yellow-orange and a white precipitate was observed. After 4 h the
reaction was complete as determined by 31P NMR spectroscopy.
While still at 0 °C, BH3(SMe2) (7.3 mL of a 2.0 M solution in
THF, 14.5 mmol) was added and the mixture was stirred overnight,
then filtered through Celite to remove insoluble salts. The solvent
was removed in Vacuo to yield a yellow oil. The crude product dr
was 1.6 (23% de), according to 19F NMR spectroscopy in C6D6 (δ
-58.4 (rac, major), -58.5 (meso, minor)). The two diastereomers
were separated by a series of recrystallizations from CH2Cl2 layered
with petroleum ether at 0 °C for 12 h, giving the rac diastereomer
as white solid. After one recrystallization the dr was improved to
6:1 (70% de). Repeated recrystallization gave steady enrichment
of the rac diastereomer, which was isolated after four recrystalli-
zations. The solutions from these recrystallizations were concen-
trated and then recrystallized in a similar manner to give more
isolated rac compound. A total of 1.24 g of the rac diastereomer
was isolated (32% yield, > 99% ee, (S,S)-6), as well as 550 mg
(14%) of the meso diastereomer, plus an additional 910 mg of rac/
meso mixtures (total yield 2.7 g, 70%). A similar experiment using
Pt((R,R)-Me-DuPhos)(Ph)(Cl) gave enrichment of (R,R)-6.
31P{1H} NMR (C6D6): δ -11.6 to -12.0 (m, JPP ) 30.8, JPF
15.0, -0.4, JFF ) -3.3). 31P{19F} NMR (C6D6): δ -11.8. 19F{1H}
NMR (C6D6): δ -59.0 (m, JPP ) 30.8, JPF ) 15.0, -0.4, JFF
)
)
-3.3), -59.1 (d of m, JCF ) 275, 13C satellites). 1H NMR (C6D6):
δ 7.38-7.31 (m, 6H, Ar), 7.09-7.04 (m, 6H, Ar), 6.94-6.83 (m,
4H, Ar), 6.73 (q, J ) 7, 2H, Ar), 3.11 (d, AB pattern, J ) 14,
CH2, 2H), 2.95 (d, AB pattern, J ) 14, CH2, 2H), 1.87-1.83 (m,
2H), 1.75-1.73 (m, CH2, 4H). 13C{1H} NMR (C6D6): δ 137.7-137.5
(m, Ar), 133.4-133.2 (m, Ar), 131.8-131.7 (m, Ar), 131.5 (Ar),
129.6 (Ar), 128.73-128.68 (m, Ar), 128.3 (overlapping with solvent
peaks, Ar), 126.3 (q, J ) 6, Ar), 126.0 (Ar), 125.2 (q, J ) 274,
CF3), 33.9 (filled-in d,32 J ) 19, CH2), 24.1 (br, CH2).
meso-7. A solution of meso-6 (190 mg, 0.32 mmol) was stirred
in 5 mL of THF, and a solution of DABCO (109 mg, 0.97 mmol)
in 5 mL of THF was added. The mixture was stirred for 48 h and
monitored by 31P NMR spectroscopy; deprotection was not
complete after 24 h. The THF was removed in Vacuo, and the
resulting oil was dissolved in petroleum ether and filtered through
a silica column (15 by 1 mm) eluting with 7 × 15 mL fractions of
petroleum ether to remove excess amine. Then the phosphine was
eluted with 3 × 15 mL fractions of CH2Cl2. The solvent was
removed in Vacuo to give 150 mg (83% yield) of a white solid.
Crystals of meso-7 were obtained by slow evaporation of petroleum
ether.
31P{1H} NMR (C6D6): δ -11.8 to -11.9 (m). 31P{19F} NMR
(C6D6): δ -11.8 (br). 19F{31P} NMR (C6D6): δ -59.0, -59.1 (d,
J ) 273, 13C satellite). 1H NMR (C6D6): δ 7.38-7.34 (m, 6H,
Ar), 7.08-7.03 (m, 6H, Ar), 6.93 (d, J ) 7, 2H, Ar), 6.84 (t, J )
7, 2H, Ar), 6.72 (t, J ) 7, 2H, Ar), 3.14 (d, AB pattern, J ) 14,
2H, CH2), 3.00 (d, AB pattern, J ) 14, 2H, CH2), 1.88-1.83 (m,
2H, CH2), 1.74-1.69 (m, 2H, CH2). 13C{1H} NMR (C6D6): δ
137.8-137.6 (m, Ar), 133.3-133.1 (m, Ar), 131.8-131.7 (m, Ar),
131.5 (Ar), 129.5 (Ar), 128.8-128.7 (m, Ar), 126.3 (quintet, J )
6, Ar), 126.0 (Ar), 125.2 (q, J ) 274, CF3), 33.5 (filled-in d,32 J )
18, CH2), 24.1 (m, CH2).
Anal. Calcd for C30H32B2F6P2: C, 61.06; H, 5.47. Found: C,
60.86; H, 5.64. HRMS: m/z calcd for C30H32B2F6P2 (M+) 590.2070,
found 590.2053. 31P{1H} NMR (C6D6): δ 22.8 (br). 19F{1H} NMR
(CDCl3): δ -58.6, -58.8 (d, JCF ) 274, 13C satellite); minor
(impurity) peaks were observed in some samples at δ -58.68,
-58.71, and -59.1. 1H NMR (CDCl3): δ 7.57 (d, J ) 8, 2H, Ar),
7.52-7.46 (m, 8H, Ar), 7.39 (t, J ) 7, 6H, Ar), 7.35 (t, J ) 8, 2H,
Ar), 3.51-3.46 (m, 2H, benzyl CH2), 3.40-3.35 (m, 2H, benzyl
CH2), 1.97-1.92 (m, 2H, CH2), 1.88-1.85 (m, 2H, CH2) 1.1-0.4
(br, 6H, BH3). 13C{1H} NMR (C6D6): δ 132.7 (t, J ) 2, Ar), 132.5
(t, J ) 5, Ar), 131.8 (Ar), 131.7 (Ar), 131.4 (Ar), 129.0 (t, J ) 5,
Ar), 128.3 (Ar), 127.5 (d, J ) 51, Ar), 127.2 (Ar), 126.4 (q, J )
6), 124.7 (q, J ) 274, CF3), 30.8 (filled-in d,32 J ) 29, benzyl C),
18.7 (filled-in d,32 J ) 35, CH2).
Data for meso-6. HRMS: m/z calcd for C30H31B2F6P2 (M - H)+
589.1991, found 589.1995. 31P{1H} NMR (C6D6): δ 22.9 (br).
19F{1H} NMR (C6D6): δ -58.4, -58.6 (d, J ) 274, 13C satellite).
1H NMR (C6D6): δ 7.61-7.57 (m, 4H, Ar), 7.13 (d, J ) 8, 2H,
Ar), 7.09 (d, J ) 8, 2H, Ar), 6.98-6.84 (m, 8H, Ar), 6.64 (t, J )
8, 2H, Ar), 3.15-3.10 (m, 2H, benzyl CH2), 2.98-2.93 (m, 2H,
benzyl CH2), 2.50-2.46 (m, 2H, CH2), 1.67-1.65 (m, 2H, CH2),
1.8-1.2 (br m, 6H, BH3). 13C{1H} NMR (CDCl3): δ 132.6 (t, J )
5, Ar), 132.5 (m, Ar), 132.4-132.3 (m, Ar), 132.2-131.8 (m, Ar),
131.76 (Ar), 130.9 (Ar), 129.1 (t, J ) 5, Ar), 129.0 (Ar), 127.46
(Ar), 126.6-126.4 (m, Ar), 126.2 (Ar), 125.8 (Ar), 124.1 (q, J )
274, CF3), 31.3-31.1 (m, benzyl C), 18.2-17.6 (m, CH2).
Deprotection of Diphosphine-Borane 6. On addition of
HBF4(OMe2) (322 mg, 2.4 mmol, 10 equiv) to a stirred solution of
(S,S)-6 (142 mg, 0.24 mmol) in 2 mL of CH2Cl2, gas evolution
Nonselective Synthesis of 6. BH3(SMe2) (1.0 mL of a 2 M
solution in THF, 2.0 mmol) was added via a syringe to a solution
of 1 (225 mg, 0.91 mmol) in 10 mL of DMF at 0 °C. The mixture
was stirred for 1 h at 0 °C, then stirred at room temperature
overnight. The mixture was cooled to -40 °C, n-BuLi (0.91 mL
of a 2.0 M solution in cyclohexane, 1.83 mmol) was added via a
syringe, and the solution was stirred for 1 h. A solution of degassed
1-(bromomethyl)-2-(trifluoromethyl)benzene (437 mg, 1.83 mmol)
in 10 mL of dry DMF was added to the reaction mixture, which
(32) Redfield, D. A.; Cary, L. W.; Nelson, J. H. Inorg. Chem. 1975, 14,
50–59.

5000 Organometallics, Vol. 27, No. 19, 2008
Anderson et al.
was stirred for 2 h at -40 °C, then overnight at room temperature.
Water and CH2Cl2 (50 mL) were added, and the organic layer was
separated. The aqueous layer was extracted with 4 × 10 mL of
CH2Cl2. The organic layers were combined and dried with MgSO4.
The solvent was removed in Vacuo to give 500 mg of a pale yellow
oil. Column chromatography (7 in. tall, 1 in. wide silica column,
10% ethyl acetate/petroleum ether) was used to isolate the product,
Rf 0.2, as 150 mg (28%) of colorless oil.
CD2Cl2 (31P{1H} NMR: major peak δ 24.0, minor peak δ 22.5;
by 19F NMR integration the ee was 24%, major peak δ -56.8,
minor δ -56.6).
HRMS: m/z calcd for C15H15F3PO (MOH)+ m/z 299.0813, found
299.0818. 31P{1H} NMR (CDCl3): δ -24.9 (q, J ) 12). 19F{1H}
NMR (CDCl3): δ -59.0 (d, J ) 12), -59.1 (dd, J ) 274, 12, 13
C
satellites). 1H NMR (CDCl3): δ 7.67 (d, J ) 7, 1H, Ar), 7.60-7.54
(m, 2H, Ar), 7.43-7.38 (m, 4H, Ar), 7.32-7.22 (m, 2H, Ar), 3.27
1
(m, 2H), 1.38 (d, J ) 4, 3H). Selected H{31P} NMR (CDCl3): δ
31P{1H} NMR (C6D6): δ 22.9 (br). 19F{1H} NMR (C6D6): δ
-58.3 (rac), -58.4 (meso), -58.5 (d, J ) 273, 13C satellite, rac),
-58.6 (d, J ) 274, 13C satellite, meso). 1H NMR (C6D6): δ
7.61-7.57 (m, 4H, Ar, meso), 7.50-7.46 (m, 4H, Ar, rac), 7.30
(d, J ) 8, 2H, Ar, rac), 7.24 (d, J ) 8, 2H, Ar, rac), 7.13 (d, J )
8, 2H, Ar, meso), 7.09 (d, J ) 8, 2H, Ar, meso), 6.98-6.84 (m,
16H, 8H rac, 8H meso, Ar), 6.71 (t, J ) 8, 2H, rac, Ar), 6.64 (t, J
) 8, 2H, meso, Ar), 3.30-3.25 (m, 2H, rac, benzyl), 3.15-3.10
(m, 2H, meso, benzyl), 3.05-2.99 (m, 2H, rac, benzyl), 2.98-2.93
(m, 2H, meso, benzyl), 2.50-2.46 (m, 2H, CH2, meso), 2.19-2.14
(m, 2H, rac CH2), 2.07-2.01 (m, 2H, rac CH2), 1.67-1.65 (m,
2H, meso CH2), 1.8-1.2 (12H, br m, BH3). 1H{31P} NMR (C6D6):
δ 7.59 (d, J ) 8, 4H, Ar, meso), 7.48 (d, J ) 8, 4H, Ar, rac), 7.30
(d, J ) 8, 2H, Ar, rac), 7.24 (d, J ) 8, 2H, Ar, rac), 7.14 (d, J )
8, 2H, Ar, meso), 7.09 (d, J ) 8, 2H, Ar, meso), 6.98-6.84 (m,
16H, 8H rac, 8H meso, Ar), 6.71 (t, J ) 8, 2H, rac Ar), 6.64 (t, J
) 8, 2H, meso Ar), 3.28 (d, J ) 15, 2H, rac benzyl, AB pattern),
3.12 (d, J ) 15, 2H, meso benzyl, AB pattern), 3.02 (d, J ) 15,
2H, rac benzyl, AB pattern), 2.96 (d, J ) 15, 2H, meso benzyl,
AB pattern), 2.50-2.46 (m, 2H, meso CH2), 2.19-2.13 (m, 2H,
rac CH2), 2.08-2.01 (m, 2H, rac CH2), 1.68-1.64 (m, 2H, meso
CH2), 1.8-1.2 (m, 12H, BH3). 13C{1H} NMR (CDCl3): δ 132.6
(t, J ) 5, Ar, meso), 132.5 (t, J ) 2, Ar, rac, overlapping with
meso), 132.4-132.3 (m, Ar), 132.2-131.8 (m, Ar), 131.83 (rac,
Ar), 131.76 (meso, Ar), 130.9 (Ar), 129.1 (t, J ) 5, Ar), 129.0
(meso, Ar), 127.53 (rac, Ar), 127.46 (meso, Ar), 126.8 (rac, Ar),
126.6-126.4 (m, Ar), 126.2 (meso, Ar), 125.8 (meso, Ar), 124.14
(q, J ) 274, rac, CF3), 124.06 (q, J ) 274, meso, CF3), 31.3-31.1
(m, meso, benzyl C), 30.9-30.7 (m, rac, benzyl C), 18.2-17.6
(m, rac and meso overlapping, CH2).
3.30 (d, J ) 14, 1H, AB), 3.24 (dd, J ) 14, 1, 1H, AB). 13C{1H}
NMR (CDCl3): δ 139.6 (d, J ) 16, Ar), 137.2 (m, Ar), 131.9 (Ar),
131.8 (Ar), 131.7 (Ar), 131.6 (Ar), 129.1 (Ar), 128.6 (d, J ) 6,
with low-intensity shoulders (d, J ) 3)), 126.3 (q, J ) 6, Ar), 126.1
(d, J ) 2, Ar), 124.7 (q, J ) 274, CF3), 35.2 (d, J ) 21, CH2),
10.9 (d, J ) 16, Me).
Pt(meso-7)(Ph)(Cl) (meso-8). A solution of Pt(COD)(Ph)(Cl)
(70 mg, 0.17 mmol) in 1 mL of CH2Cl2 was treated with a solution
of meso-7 (95 mg, 0.17 mmol) in 1 mL of CH2Cl2. The mixture
was stirred for 20 min, and then the solvent was removed in Vacuo.
The resulting white solid was washed with petroleum ether (3 × 2
mL), and the remaining solvent was removed in Vacuo to give 135
mg (91%) of a white solid, which could be recrystallized from THF/
ether.
Anal. Calcd for C36H31ClF6P2Pt: C, 49.69; H, 3.59. Found: C,
49.91, H, 3.48. HRMS: m/z calcd for C36H31F6P2Pt (M - Cl)+
834.1453, found 834.1428. 31P{1H} NMR (CDCl3): δ 48.0 (JPt-P
) 1657), 40.8 (JPt-P ) 4230). 19F{1H} NMR (CDCl3): δ -58.1,
1
-58.2. H NMR (CDCl3): δ 8.19 (d, J ) 8, 1H), 7.94 (t, J ) 9,
2H), 7.85 (d, J ) 8, 1H), 7.72-7.69 (m, 2H), 7.66-7.59 (m, 4H),
7.47-7.22 (m, 10H), 7.12 (t, J ) 7, 2H), 6.95 (t, J ) 7, 1H), 4.10
(dd, JHH ) 14, JPH ) 10, 1H, CH2), 3.81 (apparent t, JHH ) 14, JPH
) 14, 1H, CH2), 3.66 (d, JPH ) 14, 2H, CH2), 1.85-1.70 (m, 2H,
CH2), 1.48-1.26 (m, 2H, CH2). 13C{1H} NMR (CDCl3): δ 137.2
(br m, Ar), 136.1 (Ar), 133.8 (d, J ) 5, Ar), 133.4 (d, J ) 11, Ar),
133.2 (d, J ) 12, Ar), 132.6 (br m, Ar), 132.4 (d, J ) 6, Ar),
132.3 (br m, Ar), 132.1 (br, Ar), 132.0 (d, J ) 3, Ar), 131.5 (d, J
) 2, Ar), 130.9 (d, J ) 41, Ar), 129.1 (t, J ) 10, Ar), 128.7 (br m,
Ar), 128.5 (d, J ) 7, Ar), 127.2 (d, J ) 26, Ar), 127.1 (d, J ) 26,
Ar), 126.7-126.6 (br m, Ar), 126.4-126.3 (br m, Ar), 125.5 (d, J
) 14, Ar), 123.8 (Ar), 29.4 (dm, J ) 27, CH2), 29.0 (dd, J ) 40,
21, CH2), 26.8 (d, J ) 36, CH2), 22.7 (dm, J ) 36, CH2). The CF3
signals and some aryl peaks were not observed.
Determination of the ee for 7. The ee of the diphosphine was
determined using either a slight excess of the Pd reporter complex
(S)-(Pd(NMe2CH(Me)C10H6)(µ-Cl))2 in C6D6, to ensure monoden-
tate coordination of the diphosphine, or 0.5 equiv of the Pd complex
in CD2Cl2, to favor bidentate coordination (some monodentate
coordination also occurred under these conditions). Integration of
the 31P and 19F NMR spectra gave the ee of the diphosphine (see
Table 6 for the NMR data). Using highly rac-enriched diphosphine-
borane gave material of >99% de and ee.
Pt((S,S)-7)(Ph)(Cl) ((S,S)-8). A solution of Pt(COD)(Ph)(Cl) (39
mg, 0.09 mmol) in 1 mL of CH2Cl2 was treated with a solution of
(S,S)-7 (53 mg, 0.09 mmol) in 1 mL of CH2Cl2. The mixture was
stirred for 20 min, and then the solvent was removed in Vacuo.
The resulting white solid was washed with petroleum ether (3 × 2
mL), dried under vacuum, and recrystallized from 1:1 ether/
petroleum ether to give 85 mg (67%) of a white solid.
Pt-Catalyzed Asymmetric Synthesis of PMePh(CH2C6H4-
o-CF3). A solution of methylphenylphosphine (2.1 mmol, 264 mg)
in 5 mL of THF was treated with a solution of NaOSiMe3 (2.1
mmol, 239 mg) in 2 mL of THF and a solution of Pt((R,R)-i-Pr-
DuPhos)(Ph)(Cl) (77 mg, 0.11 mmol, 5 mol %) in 3 mL of THF,
and the solution turned yellow. A solution of 1-(bromomethyl)-2-
(trifluoromethyl)benzene (509 mg, 2.1 mmol) in 10 mL of THF
was added slowly to the mixture via cannula. The mixture showed
a hint of orange before turning bright yellow followed by the
formation of a white precipitate. After 3 h, the reaction was observed
to be complete by 31P NMR spectroscopy, and the white slurry
was filtered through Celite to remove the insoluble salt. The orange
filtrate was pumped down to give an orange oil, which was loaded
onto a 5 mm wide, 50 mm high silica column with a 1:3 mixture
of THF/petroleum ether, leaving an orange precipitate behind. The
column was eluted with 30 mL of petroleum ether; the solution
was concentrated to yield the product (360 mg, 60%) as a colorless
oil. The ee was determined to be 21% by treating the phosphine
(25 mg, 0.089 mmol) with the chiral Pd reporter compound (S)-
Pd(Me2NCH(Me)C6H4)(µ-Cl))2 (31 mg, 0.053 mmol) in 1 mL of
Anal. Calcd for C36H31ClF6P2Pt: C, 49.69; H, 3.59. Found:
C, 50.14, H, 3.60. HRMS: m/z calcd for C36H31F6P2Pt (M -
Cl)+ 834.1453, found 834.1442. 31P{1H} NMR (CDCl3): δ 50.5
(JPt-P ) 1682), 43.2 (JPt-P ) 4263). 19F{1H} NMR (CDCl3): δ
1
-58.4, -58.7. H NMR (CDCl3): δ 8.73 (d, J ) 8, 1H), 8.30
(d, J ) 8, 1H), 7.98-7.94 (m, 2H), 7.73-7.68 (m, 3H), 7.64 (t,
J ) 7, 2H), 7.58 (d, J ) 8, 1H), 7.49-7.40 (m, 6H), 7.34-7.28
(m, 3H), 7.17 (t, J ) 8, 1H), 7.11 (t, J ) 7, 2H), 6.96 (t, J ) 7,
1H), 4.39-4.34 (m, 1H, CH2), 3.82 (t, J ) 14, 1H, CH2), 3.72
(t, J ) 15, 1H, CH2), 3.63 (t, J ) 14, 1H, CH2), 1.99-1.73 (m,
2H, CH2), 1.33-1.12 (m, 2H, CH2). 13C{1H} NMR (CDCl3): δ
161.2 (d, J ) 7, Ar), 160.2 (d, J ) 7, Ar), 137.2 (br m, Ar),
134.1 (d, J ) 5, Ar), 133.5 (t, J ) 11, Ar), 133.6-133.4 (br,
overlapping previous peak, Ar), 132.8 (br, Ar), 132.5 (Ar), 132.3
(Ar), 132.2-132.1 (m, Ar), 131.7 (br, Ar), 131.6 (d, J ) 2, Ar),
129.6 (d, J ) 40, Ar), 129.10 (d, J ) 10, Ar), 129.08 (d, J )
11, Ar), 128.5 (d, J ) 7, Ar), 127.9 (d, J ) 55, Ar), 127.1 (t, J
) 3, Ar), 126.3-126.2 (m, Ar), 125.6 (d, J ) 12, Ar), 123.9

Pt-Catalyzed Asymmetric Alkylation of Phosphines
Organometallics, Vol. 27, No. 19, 2008 5001
(Ar), 123.4 (d, J ) 14, Ar), 28.5 (d, J ) 23, CH2), 27.0 (dd, J
) 40, 17, CH2), 25.5 (d, J ) 37, CH2), 21.4 (br d, J ) 34,
CH2). The CF3 signals were not observed.
3 and 6, before the addition of benzyl bromide, 31P NMR
spectroscopy showed the formation of diphosphine 7; the original
Pt complex was not observed. The benzyl bromide was added
approximately 30 min later; the catalytic reactions did not go to
completion under these conditions. The workup was the same as
described above.
Attempted Chirality Breeding. The following procedure was
used for entries 1, 2, 4, and 5 in Table 5. A solution of 1 (25 mg,
0.1 mmol) in 0.5 mL of THF was treated with NaOSiMe3 (23 mg,
0.2 mmol) and either (S,S)-8 or meso-8 (8 mg, 0.01 mmol). The
resulting yellow solution was treated with 1-(bromomethyl)-2-
(trifluoromethyl)benzene (24 µL, 0.2 mmol); the solution slowly
became colorless, and a white precipitate was observed. When the
reaction was complete, as determined by 31P NMR spectroscopy,
petroleum ether was added (4 mL) and the mixture was filtered
through silica eluting with 50% THF/petroleum ether. The solvent
was removed under vacuum to give the product as a colorless oil.
The selectivity was determined by binding the diphosphine to the
Pd reporter complex (S)-[Pd(NMe2CH(Me)C10H6)(µ-Cl)]2. In entries
Acknowledgment. We thank the National Science Foun-
dation for support, and the Department of Education for a
GAANN fellowship for B.J.A.
Supporting Information Available: Additional experimental
and crystallographic data (CIF) is available free of charge via the
Internet at http://pubs.acs.org.
OM800534K