Platinum-catalyzed asymmetric alkylation of bis(isitylphosphino)ethane: Stereoselectivity reversal in successive formation of two P-C bonds

Article abstract of DOI:10.1021/om900800z

Alkylation of the bis(secoridary) phosphine IsHP(CH₂) ₂PHIs (1; Is = isityl = 2,4,6-(i-Pr)₃C₆H ₂) with 2-(bromomethyl)naphthalene using 10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl) and the base NaOSiMe₃ selectively yielded weio-IsP(CH₂Ar)(CH₂) ₂P(CH2Ar)(Is) (2; Ar = 2-naphthyl; dr = meso/rac ratio = 3.4:1). Half-alkylated IsP(CH₂Ar)(CH₂)₂PH(Is) (3), an intermediate in this reaction, was prepared from 1 by deprotonation (s-BuLi) and alkylation with 2-(chloromethyl)naphthalene. Analysis of the observed diastereo- and enantioselectivity in the Pt-catalyzed alkylations of 1 and 3 yielded quantitative information on the stereoselectivity of both P-C bond-forming steps. The first alkylation (1 -3) resulted in diastereoselective formation of a tertiary phosphine stereocenter (~2:1 ratio). In the second alkylation (3 -2), however, both (Rp)-3 and (Sp)-3 (the label refers to the configuration of the tertiary phosphine) selectively formed meso-2, instead of (R,R)-2 or (S,S)-2, respectively (the ratios were ca. 3:1 and 7:1). Thus, the tertiary phosphine in 3 favored alternation of stereochemistry in the alkylation of the secondary phosphine (substrate control with negative cooperativity). Platinum-catalyzed alkylation of IsPH(CH₂)₂OSi(iPr) ₃ (6) gave IsP(CH₂Ar)(CH₂)₂OSi(i-Pr) ₃ (9) in a 1.5:1 enantiomeric ratio (er). A related reaction of IsPH(CH₂)₂OSiMe₃ (4) gave a mixture of IsP(CH₂Ar)(CH₂)₂OR (R = SiMe₃ (7); R = H (8)), while alkylation of IsPH(CH₂)₂OH (5) gave 8 in about 2:1 er. Thus, the nature, and even the absolute configuration, of the pendant group X three bonds from the reactive phosphorus center in the substrates IsHP(CH₂)₂X (X = PHIs (1), P(CH ₂Ar)(Is) (3), OSiMe₃ (4), OH (5), OSi(i-Pr)₃ (6)) had a strong influence on the selectivity of Pt-catalyzed phosphorus alkylation. Possible mechanistic explanations for this substrate control are discussed.

Full text of DOI:10.1021/om900800z

378 Organometallics 2010, 29, 378–388
DOI: 10.1021/om900800z
Platinum-Catalyzed Asymmetric Alkylation of
Bis(isitylphosphino)ethane: Stereoselectivity Reversal in Successive
Formation of Two P-C Bonds
Timothy W. Chapp,† David S. Glueck,*,† James A. Golen,‡ Curtis E. Moore,‡ and
Arnold L. Rheingold‡
†6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755
and ‡Department of Chemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla,
California 92093
Received September 14, 2009
Alkylation of the bis(secondary) phosphine IsHP(CH2)2PHIs (1; Is = isityl = 2,4,6-(i-Pr)3C6H2)
with 2-(bromomethyl)naphthalene using 10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)-
(Ph)(Cl) and the base NaOSiMe3 selectively yielded meso-IsP(CH2Ar)(CH2)2P(CH2Ar)(Is) (2; Ar =
2-naphthyl; dr = meso/rac ratio = 3.4:1). Half-alkylated IsP(CH2Ar)(CH2)2PH(Is) (3), an inter-
mediate in this reaction, was prepared from 1 by deprotonation (s-BuLi) and alkylation with
2-(chloromethyl)naphthalene. Analysis of the observed diastereo- and enantioselectivity in the
Pt-catalyzed alkylations of 1 and 3 yielded quantitative information on the stereoselectivity of both
P-C bond-forming steps. The first alkylation (1 f 3) resulted in diastereoselective formation of a
tertiary phosphine stereocenter (∼2:1 ratio). In the second alkylation (3 f 2), however, both (RP)-3
and (SP)-3 (the label refers to the configuration of the tertiary phosphine) selectively formed meso-2,
instead of (R,R)-2 or (S,S)-2, respectively (the ratios were ca. 3:1 and 7:1). Thus, the tertiary
phosphine in 3 favored alternation of stereochemistry in the alkylation of the secondary phosphine
(substrate control with negative cooperativity). Platinum-catalyzed alkylation of IsPH(CH2)2OSi(i-
Pr)3 (6) gave IsP(CH2Ar)(CH2)2OSi(i-Pr)3 (9) in a 1.5:1 enantiomeric ratio (er). A related reaction of
IsPH(CH2)2OSiMe3 (4) gave a mixture of IsP(CH2Ar)(CH2)2OR (R = SiMe3 (7); R = H (8)), while
alkylation of IsPH(CH2)2OH (5) gave 8 in about 2:1 er. Thus, the nature, and even the absolute
configuration, of the pendant group X three bonds from the reactive phosphorus center in the
substrates IsHP(CH2)2X (X = PHIs (1), P(CH2Ar)(Is) (3), OSiMe3 (4), OH (5), OSi(i-Pr)3 (6)) had a
strong influence on the selectivity of Pt-catalyzed phosphorus alkylation. Possible mechanistic
explanations for this substrate control are discussed.
Introduction
be the same (catalyst control) or different (substrate con-
trol).1 Catalyst control may result in asymmetric amplifica-
tion and high enantiomeric ratio (er) for the rac product.
Substrate control may reinforce the selectivity of the catalyst
(positive cooperativity) or compete with it (negative coop-
erativity).2 These effects depend on the length of the linker
between the reactive sites, as shown spectacularly in Ru-
(Binap)-catalyzed hydrogenation of diketones (Scheme 1).
Catalyst control in reduction of A led to high diastereoselec-
tivity, and the favored rac product was formed in high ee.
While hydrogenation of B also gave the rac diol enantio-
selectively, the major product was meso, presumably as a
result of substrate control.3
Bifunctional symmetrical substrates with two equivalent
reactive sites present special problems and opportunities in
asymmetric catalysis. After the catalyst mediates formation
of one chiral center, the selectivity of the second reaction may
*To whom correspondence should be addressed. E-mail: Glueck@
Dartmouth.Edu.
(1) Lagasse, F.; Tsukamoto, M.; Welch, C. J.; Kagan, H. B. J. Am.
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H. B. Bull. Soc. Chim. Fr. 1994, 131, 525–533. (c) Rautenstrauch, V. Bull.
Soc. Chim. Fr. 1994, 131, 515–524. (d) Tai, A.; Ito, K.; Harada, T. Bull.
Chem. Soc. Jpn. 1981, 54, 223–227. (e) Muramatsu, H.; Kawano, H.; Ishii,
Y.; Saburi, M.; Uchida, Y. J. Chem. Soc., Chem. Commun. 1989, 769–770.
(f) Aggarwal, V. K.; Evans, G.; Moya, E.; Dowden, J. J. Org. Chem. 1992,
57, 6390–6391. (g) Hoye, T. R.; Mayer, M. J.; Vos, T. J.; Ye, Z. J. Org. Chem.
1998, 63, 8554–8557. (h) Kuwano, R.; Sawamura, M.; Shirai, J.; Takahashi,
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Understanding the structural basis for such effects is poten-
tially useful in designing substrates for asymmetric catalysis.4
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H.; Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J. Am. Chem. Soc.
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2008, 252, 2171–2179. (d) Glueck, D. S. Synlett 2007, 2627–2634.
r
pubs.acs.org/Organometallics
Published on Web 12/28/2009
2009 American Chemical Society

Article
Organometallics, Vol. 29, No. 2, 2010 379
Scheme 1. Catalyst vs Substrate Control in
Ru(Binap)-Catalyzed Asymmetric Reduction
of Diketones3 (dr = rac/meso Ratio)
Figure 1. ORTEP diagram of meso-1. Of all the hydrogen
atoms, only the P-H hydrogen atom, which was located and
refined, is shown.
Scheme 2
Chart 1. Bis(secondary) phosphines C and 1 and Alkylation
Product D
Scheme 3. meso-Selective Pt-Catalyzed Alkylation of 1 with
2-(Bromomethyl)naphthalene
With this goal in mind, we recently reported studies of Pt-
catalyzed asymmetric alkylation of bis(secondary) phos-
phines, including synthesis, from C, of the enantiomerically
pure DiPAMP analogue D (Chart 1).5 Here we report meso-
selective Pt-catalyzed alkylation of the related bulky bis-
(secondary) phosphine 1 (Chart 1), along with quantitative
information on the stereoselectivity of both P-C bond-
forming steps.
Alkylation8 of 1 with 2-(bromomethyl)naphthalene using
10 mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)-
(Ph)(Cl) and the base NaOSiMe3 gave ca. a 3.5:1 ratio of
diastereomeric products 2, according to 31P NMR monitor-
ing of the crude reaction mixture (Scheme 3).5 After protec-
tion of 2 with BH3(SMe2), the major diastereomer of
bis(phosphine) borane 2-BH3 was isolated by recrystalliza-
tion in 44% yield. The crystal structures of meso-2 and rac-2-
BH3 (see Figures 2 and 3, Table 1, and the Supporting
Information) as well as HPLC and NMR analyses (see
below) showed that the Pt-catalyzed reaction was meso-
selective.
The bis(phosphine) oxide 2-O (Chart 2; see Figure 4 for
the crystal structure of the meso diastereomer) was prepared
in high yield from 2 and hydrogen peroxide; such oxidations
are known to proceed with retention of configuration at
phosphorus.9 Complementary HPLC and NMR assays of
the diastereomeric ratio (dr) and the enantiomeric ratio (er)
of 2-O provided information on the selectivity of the cataly-
tic alkylation which formed 2.
Results and Discussion
The diphosphine IsPH(CH2)2PHIs (1; Is = isityl =
2,4,6-(i-Pr)3C6H2) was synthesized from Cl2P(CH2)2PCl2
(Scheme 2) by selective arylation6 followed by LiAlH4
reduction and then protected as a borane adduct to sim-
plify purification. Removing the borane using a polymer-
supported amine gave a mixture of rac and meso diastereo-
mers of 1.7
The crystal structure of meso-1 is shown in Figure 1. See
Table 1 for crystallographic data and the Supporting In-
formation for additional details.
(5) Anderson, B. J.; Glueck, D. S.; DiPasquale, A. G.; Rheingold,
A. L. Organometallics 2008, 27, 4992-5001; 2009, 28, 386 (addition/
correction).
(6) Chandrasekhar, V.; Sasikumar, P.; Boomishankar, R.; Anantha-
The three diastereomers of 2-O could be separated by
HPLC on a ChiralPak AD-H column. Integration of the
peaks in the chromatogram gave the meso/rac ratio (dr) and
the er of the rac diastereomers. Unusually, isomer separation
improved when the column was heated to slightly above
raman, G. Inorg. Chem. 2006, 45, 3344–3351.
(7) Sayalero, S.; Pericas, M. A. Synlett 2006, 2585–2588.
(8) (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; 2007, 26, 5124 (addition/
correction). (c) Anderson, B. J.; Guino-o, M. A.; Glueck, D. S.; Golen,
J. A.; DiPasquale, A. G.; Liable-Sands, L. M.; Rheingold, A. L. Org. Lett.
2008, 10, 4425–4428. (d) Chan, V. S.; Stewart, I. C.; Bergman, R. G.; Toste,
F. D. J. Am. Chem. Soc. 2006, 128, 2786–2787. (e) Chan, V. S.; Chiu, M.;
Bergman, R. G.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 6021–6032.
(9) Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley-
Interscience: New York, 2000, pp 300-303.

380 Organometallics, Vol. 29, No. 2, 2010
Table 1. Crystallographic Data for meso-1, meso-2, rac-2-BH3, meso-2-O, and 5
Chapp et al.
meso-1
meso-2
rac-2-BH3
meso-2-O
5
formula
formula wt
space group
C
498.68
C2/c
34.140(5)
5.9658(9)
16.029(2)
90
107.001(2)
90
3122.0(8)
4
1.061
0.156
208(2)
5.10
14.07
P
32H52P2
C54H68P2
779.02
P1
C54H74B2P2
804.68
Pbcn
30.6779(6)
18.9288(3)
16.8358(3)
90
90
90
9776.5(3)
8
1.093
C54H68O2P2•C3H8O
871.12
C2/c
22.621(5)
11.064(3)
21.618(5)
90
111.474(5)
90
5035(2)
4
1.149
C17H29OP
280.37
P42/n
23.7985(14)
23.7985(14)
5.9808(3)
90
90
90
3387.3(3)
8
1.100
˚
a, A
9.5176(8)
10.9546(9)
12.5468(11)
64.4770(10)
80.3910(10)
73.5900(10)
1130.86(17)
1
1.144
0.131
100(2)
3.41
˚
b, A
˚
c, A
R, deg
β, deg
γ, deg
3
˚
V, A
Z
D(calcd), g/cm3
μ(Mo KR), mm-1
temp, K
1.043
0.129
0.155
100(2)
7.81
20.69
P
100(2)
6.79
18.42
150(2)
4.12
9.76
R(F), %a
Rw(F2), %a
8.88
P
P
a Quantity minimized: Rw(F2) = [w(Fo2 - Fc2)2]/ [(wFo2)2]1/2; R = Δ/ (Fo), Δ = |(Fo - Fc)|, w = 1/[σ2(Fo2) þ (aP)2 þ bP], P = [2Fc
þ
2
Max(Fo2,0)]/3. A Bruker CCD diffractometer was used in all cases.
Figure 4. ORTEP diagram of meso-2-O.
Figure 2. ORTEP diagram of meso-2.
Chart 2. Phosphine Oxide 2-O, Used for HPLC and NMR
Measurements of dr and er, and the Shift Reagent
Fmoc-Trp(Boc)-OH11
Although overlap in the NMR spectra and broad HPLC peaks
in the chromatograms increased the error in these measure-
ments, they showed that the dr (meso/rac ratio) in Pt-catalyzed
alkylation of 1 to form 2 (10% catalyst loading) was 3.4(2),
which was consistent with the original NMR observations
from crude reaction mixtures, while the er was 3.9(3).12
During Pt-catalyzed alkylation of 1 to give 2, the half-alky-
lated intermediate IsHP(CH2)2P(Is)(CH2Ar) (3; Ar=2-
naphthyl) was observed by 31P NMR spectroscopy in the re-
action mixture along with 1and 2. Selective monodeprotonation
Figure 3. ORTEP diagram of rac-2-BH3. One naphthyl ring
was disordered over two positions, only one of which is shown.
The naphthyl groups were constrained to idealized rigid bodies.
ambient temperature (see the Supporting Information for
details and chromatograms).10
Similarly, treatment of 2-O with the chiral shift reagent11
Fmoc-Trp(Boc)-OH (Chart 2) and integration of the 31P
NMR spectra of these mixtures enabled measurement of dr
and er of samples of diphosphine 2. The two methods gave
consistent results (see the Supporting Information).
(11) Li, Y.; Raushel, F. M. Tetrahedron: Asymmetry 2007, 18, 1391–
1397.
(12) Reported errors are standard deviations from several duplicate
(10) (a) Meyer, V. R. Pitfalls and Errors of HPLC in Pictures, 2nd ed.;
Wiley-VCH: Weinheim, Germany, 2006. (b) Vecchi, M.; Englert, G.; Maurer,
R.; Meduna, V. Helv. Chim. Acta 1981, 64, 2746–2758.
runs. See the Supporting Information for additional details.

Article
Organometallics, Vol. 29, No. 2, 2010 381
Scheme 4. Synthesis and Pt-Catalyzed Alkylation of Secondary/
Tertiary Bis(phosphine) 3a
The values of x, a, and b may be determined from the
observed product ratios in separate Pt-catalyzed alkylations
of 1 and 3, using eqs 1 and 2 (dr = meso/rac ratio for 2).2 For
alkylation of 3, its 1:1 dr means that x = 0.5.
ðxÞð1 -aÞ þ ð1 -xÞð1 -bÞ
dr ¼
ð1Þ
ð2Þ
xa þ ð1 -xÞðbÞ
xa
er ¼
ð1 -xÞðbÞ
These equations hold only if the reaction is clean, forming
no byproducts, and if all the products are formed by the
catalyst, not in a background reaction or in a process
mediated by products of catalyst decomposition. Monitor-
ing the reactions by 31P NMR spectroscopy showed com-
plete conversion of 1 (or 3) to the diastereomers of 2; no other
organophosphorus products were observed. Once reactions
were complete, the catalyst precursor was converted to
Pt((R,R)-Me-DuPhos)(Ph)(Br), as observed previously in
alkylation of PHMe(Is).8a,b
a Legend: Ar = 2-naphthyl, [Pt] = Pt((R,R)-Me-DuPhos).
Scheme 5. Stereoselectivity of Pt-Catalyzed Alkylation of 1
(To Yield 3) and of 3 (To Yield 2), Defined by the Mole Fractions
x, a, and b
Control experiments showed that the catalytic alkylations
of 1 and 3 were faster than the Pt-free background process.
Thus, conversion of 1 to 2 catalyzed by 10 mol % Pt was
complete in 9 h, at which point the background reaction
resulted in formation of 21% of intermediate 3 and a trace of
product 2. Similarly, Pt-catalyzed alkylation of 3 yielded 2 in
3 h, when the background conversion over this time was 7%.
In the catalytic alkylation, contributions from the back-
ground reaction should be reduced from these values, since
the concentrations of the substrates, and hence the back-
ground reaction rate, will be reduced. Corrections for the
background reactions changed the values of x, a, and b
negligibly, within experimental error (see the Supporting
Information for details). Further, the dr of 2 in Pt-catalyzed
alkylation of 1 was the same, within experimental error, at
5 and 10 mol % catalyst loading, suggesting that the back-
ground reaction is insignificant.13 For these reasons, we have
neglected corrections due to the background alkylation and
used eqs 1 and 2 directly. Scheme 6 shows the resulting values
of x, a, and b.14
Although the error in quantitative determination of these
parameters was relatively large, the qualitative conclusion is
clear: the absolute configuration of the tertiary phosphine in
3 had a striking effect on the selectivity of Pt-catalyzed
alkylation of the secondary phosphine. This substrate con-
trol resulted in alternation of stereochemistry ((RP)-3 f (R,
S)-2; (SP)-3 f (S,R)-2) by margins of about 3:1 and 7:1. This
meso selectivity appears to result from negative cooperati-
vity, in which the first-formed tertiary phosphine favors
alkylation of the second, originally identical P stereocenter
with opposite configuration.
of 1 and treatment of the resulting anion with 2-(chloro-
methyl)naphthalene gave 3as the major component of a mixture
which included the under- and overalkylation products 1 and 2
(Scheme 4). After chromatographic separation, Pt-catalyzed
alkylation of a 1:1 mixture of diastereomers of 3 gave 2. As
for 1, thisreactionwasmeso-selective, with dr = 4.8(6) and er =
2.1(5) for 10 mol % catalyst loading.12
Origin of meso Selectivity. These observations enabled
quantitative analysis of the selectivity of both Pt-catalyzed
alkylations (1 f 3; 3 f 2), which provided information on
catalyst vs substrate control and on the origin of the meso
selectivity (Scheme 5).
To describe the selectivity in conversion of 1 to 3, we define
the mole fractions x for the diastereomers of the R-tertiary
phosphine ((R,R)-3 plus (R,S)-3; the labels refer to the tertiary
and secondary phosphine stereocenters, respectively) and 1 - x
for the S-tertiary phosphine ((S,R)-3 plus (S,S)-3). Conversion
of 3 to 2 then occurs in two parallel channels, which differ only
in the configuration of the tertiary phosphine in substrate 3.
(We assume that alkylation of PHMe(Is) via the diastereo-
meric intermediates Pt((R,R)-Me-DuPhos)(Ph)(PMeIs), which
interconvert by P inversion, is a good model for the analogous
reactions of 1.8a,b Then, the selectivities of alkylation of the
diastereomers ((R,R)-3 and (R,S)-3) are expected to be identi-
cal, since both will form the same mixture of Pt-phosphido
intermediates.) Therefore, R-tertiary phosphines (R,R)-3 and
(R,S)-3 yield a mixture of (R,R)-2 and meso-2 with mole
fractions a and 1 - a. Similarly, (S,S)-3 and (S,R)-3 yield
(S,S)-2 and meso-2 with mole fractions b and 1 - b. The
absolute configuration of rac-2 is unknown; therefore, the
major isomer was assigned as R,R by analogy to the favored R
configuration of PMeIs(CH2Ph) formed by alkylation of
PHMe(Is) using the same precatalyst.8a,b
Because of the likely epimerization of secondary phos-
phines under the reaction conditions,15 deconvoluting the
(13) (a) Balsells, J.; Walsh, P. J. J. Am. Chem. Soc. 2000, 122, 1802–
1803. (b) The er values of 2 were similar at the two different catalyst loadings.
(14) Values of x, a, and b are not independent, which affects the
reported values and makes the error bars reported for b artificially low.
See the Supporting Information for more details.
(15) (a) Albert, J.; Magali Cadena, J.; Granell, J.; Muller, G.;
~
Panyella, D.; Sanudo, C. Eur. J. Inorg. Chem. 2000, 1183–1186. (b)
Bader, A.; Pabel, M.; Willis, A. C.; Wild, S. B. Inorg. Chem. 1996, 35, 3874–
3877. (c) Bader, A.; Nullmeyers, T.; Pabel, M.; Salem, G.; Willis, A. C.; Wild,
S. B. Inorg. Chem. 1995, 34, 384–389. (d) Bader, A.; Pabel, M.; Wild, S. B.
J. Chem. Soc., Chem. Commun. 1994, 1405–1406. (e) Bader, A.; Salem, G.;
Willis, A. C.; Wild, S. B. Tetrahedron: Asymmetry 1992, 3, 1227–1230.

382 Organometallics, Vol. 29, No. 2, 2010
Chapp et al.
Scheme 6. Stereoselectivity in Pt-Catalyzed Alkylation of 1
(To Yield 3) and of 3 (To Yield 2)
Figure 5. ORTEP diagram of PHIs(CH2CH2OH) (7). Hydro-
gen atoms are not shown, except for the P-H, which was located
and refined, and the O-H, which was placed in a calculated
position.
Scheme 7. Synthesis and Pt-Catalyzed Asymmetric Alkylation
of Secondary Phosphines 4-6a
Scheme 8. Pt-Catalyzed Alkylation of Isityl(methyl)phosphinea
a Legend: [Pt] = Pt((R,R)-Me-DuPhos), Ar = 2-naphthyl.
Table 2. Selectivity of Pt-Catalyzed Alkylation of PH(Is)-
(CH2)2X
aLegend: [Pt] = Pt((R,R)-Me-DuPhos), Ar = 2-naphthyl. Alkylation
of 4 gave 7 and 8, while 5 gave 8 and 6 gave 9.
observed ca. 2:1 selectivity in formation of intermediate 3 is
more complicated; we cannot tell if selectivity of the first
alkylation of 1 depends on the absolute configuration of
the pendant PHIs group, as it does for the PIs(CH2Ar) group
in 3.
X (compd no.)
RP selectivity (mole fraction)
RP-P(Is)(CH2Ar) ((RP)-3)
SP-P(Is)(CH2Ar) ((SP)-3)
PH(Is) (1)
0.27
0.87
0.65
0.66
0.60
0.84
To investigate these effects in more detail, the secondary
phosphines IsHP(CH2)2OR (R = SiMe3 (4), R = H (5), R =
Si(i-Pr)3 (6)) were prepared (Scheme 7). Treatment of LiPHIs
with Cl(CH2)2OSiMe3 gave 4, which on acid hydrolysis
yielded the alcohol 5, whose crystal structure is shown in
Figure 5. Silylation of 5 with Si(i-Pr)3Cl/imidazole gave 6.
Pt-catalyzed alkylation of the triisopropylsilyl substrate 6
yielded 9 with an er value of 1.5:1 (Scheme 7). Pt-catalyzed
alkylation of alcohol 5 gave 8 in about 2:1 er, but an
unidentified byproduct (ca. 10%) also formed. A related
reaction with trimethylsilyl ether 4 was slower than that of 5
and 6 and was also complicated by OSiMe3 hydrolysis, both
during the reaction and the workup. Both silyl ether 7
(minor) and alcohol 8 (major) were formed with similar er
values of 1.8:1. We cannot tell if Pt-catalyzed alkylation of 4
proceeded mostly via the original trimethylsilyl ether sub-
strate or from alcohol 5, but the results for alkylation of pure
5 suggested that the selectivities were similar.
In contrast to the results for these functionalized β-ethyl-
phosphines, Pt-catalyzed alkylation of the methylphosphine
PHMe(Is) with 2-bromomethylnaphthalene (Scheme 8) was
both faster (complete in ca. 2 h; compare to 9 h for alcohol 5
and silyl ether 6) and more selective (er = 5.2).
Substituent effects on selectivity of Pt-catalyzed P-alkyla-
tion of isitylphosphines are summarized in Table 2, using
mole fractions for ease of comparison.
OH (5)
OSi(i-Pr)3 (6)
PHMe(Is)a
a The substrate was PHMe(Is) (see Scheme 8).
Conclusion
Pt-catalyzed alkylation of the bis(secondary) phosphine 1
was meso-selective because the two diastereomers of IsHP-
(CH2)2PIs(CH22-naphthyl) (3), differing only in the absolute
configuration of a pendant phosphine group three bonds
away from the reactive site, were alkylated with reversed
stereoselectivity. The R or S tertiary phosphine stereocenter
in 3 favored alkylation of the secondary phosphine with
opposite configuration (negative cooperativity). The selec-
tivities of alkylation of the related substrates IsHP(CH2)2X
(X = PHIs (1), OH (5), OSi(i-Pr)3 (6)) were similar, perhaps
as a result of catalyst control; it is possible that only the very
bulky β-ethyl substituents in 3 result in substrate control.
What is the origin of this substrate control? The X group
might affect the speciation and relative reactivity of the
presumed Pt-phosphido intermediates in several ways. Ter-
tiary phosphines are good ligands for platinum, so that
chelation in five-coordinate 11 or formation of dinuclear

Article
Organometallics, Vol. 29, No. 2, 2010 383
Chart 3. Possible Role of X in Pt-Catalyzed Alkylation of
IsHP(CH2)2Xa
otherwise noted, reagents were from commercial suppliers.
Pt((R,R)-Me-Duphos)(Ph)(Cl),19 PH2Is,20 PHMe(Is),21 and
(S)-{Pd[NMe2CH(Me)C6H4](μ-Cl)}222 were made by literature
methods.
PH(Is)(BH3)(CH2)2PH(Is)(BH3) (1-BH3). Under nitrogen, a
Schlenk flask was loaded with Mg (Aldrich, 50 mesh powder,
730 mg, 30 mmol, 2 equiv), which was then slurried in THF
(75 mL). To this was added dropwise a solution of 2-bromo-
1,3,5-triisopropylbenzene (8.50 g, 30 mmol, 2 equiv) in THF
(25 mL) via cannula with stirring. Two drops of 1,2-dibromo-
ethane were added to initiate the reaction. The mixture was
gently refluxed for 1 h and then stirred for 14 h. The resulting
dark gray solution was transferred via cannula to a cooled
(-40 °C) solution of Cl2P(CH2)2PCl2 (3.48 g, 15 mmol, 1 equiv)
in THF (100 mL). A solution of anhydrous ZnCl2 (8.17 g,
60 mmol, 4 equiv) in THF (100 mL) was then added via cannula;
a white solid precipitated.6 The solution was stirred at -40 °C
for 5 h and then warmed to room temperature.
a Legend: [Pt] = Pt((R,R)-Me-DuPhos), R = H, CH2Ar, Ar =
2-naphthyl, X = PHIs, P(CH2Ar)(Is), OR0 (R0 = SiMe3, Si(i-Pr)3, H).
The mixture was transferred via wide-bore cannula to a filter
frit with a Celite bed (3 cm high ꢀ 6 cm wide) and filtered under
N2. The solid was washed with two 150 mL portions of Et2O,
and the solvent was removed from the filtrate under reduced
pressure to leave an oily off-white solid. The residue was
redissolved in 250 mL of Et2O, and the solution with some
white precipitate was transferred via filter cannula to a slurry of
LiAlH4 (600 mg, 15 mmol, 1 equiv) in Et2O (20 mL) at 0 °C. The
resulting mixture was stirred for 1 h, and then triethanolamine
(2.0 mL, 15 mmol, 1 equiv)23 was injected via wide-bore syringe
at 0 °C, producing some effervescence. The solution was
warmed to room temperature and was stirred vigorously for
2 h, causing the residual gray solid to become very finely divided.
To this was added degassed H2O (40 mL), generating minimal
effervescence. The mixture was transferred via wide-bore can-
nula to a filter frit with a Celite bed (3 cm high ꢀ 6 cm wide) and
filtered under N2. The gray solid was washed with two 100 mL
portions of Et2O, and the organic layer was separated from the
aqueous layer via cannula and dried over MgSO4. After cannula
filtration, the solvent was removed under reduced pressure to
give 5.60 g (75% yield) of white solid. The solid was redissolved
in petroleum ether (100 mL) and cooled to 0 °C, and BH3(SMe2)
(20 mL, 2.0 M in THF, 40 mmol, 2.66 equiv) was added via
cannula with stirring. Upon warming to room temperature, a
white solid precipitated and the solvent was removed under
reduced pressure. The solid was recrystallized from THF/
petroleum ether at -28 °C to give 4.59 g of fine white solid
(58% overall yield).
intermediates, such as 12, is possible (Chart 3). The pendant
group might simply affect the conformations of the phos-
phinoethyl group and control Keq in the equilibrium of 13, as
well as the relative reactivity of these diastereomers. Alter-
natively, developing positive charge at the phosphido P during
nucleophilic attack on a benzyl bromide might be stabilized by
donation from the pendant phosphine (14); such anchimeric
assistance has been proposed in related systems.16
In future work, we will examine these possibilities with
related bis(secondary) phosphines having varied linker
lengths, to determine the structural requirements for sub-
strate vs catalyst control and to investigate potential positive
cooperativity via substrate control.17
Experimental Section
General Experimental Details. Unless otherwise noted, all
reactions and manipulations were performed in dry glassware
under a nitrogen atmosphere at ambient temperature in a dry-
box 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.18 NMR
spectra were recorded by using a Varian 300 or 500 MHz
1
spectrometer. H or 13C NMR chemical shifts are reported vs
1
Me4Si and were determined by reference to the residual H or
Anal. Calcd for C32H58P2B2: C, 73.02; H, 11.11. Found: C,
72.65; H, 11.19. HRMS (FAB) for C32H52P2B2 (M - 6H)þ:
calcd m/z 520.3730, found m/z 520.3797.24 IR (KBr): 2964, 2927,
2867, 2433, 2399, 2367, 2344, 2250. 31P{1H} NMR (CDCl3): δ
-21.2 (broad). 1H NMR (CDCl3): δ 7.07 (d, J = 3, 4H, Is), 5.82
(d of m, JPH = 371, 2H, P-H), 3.26 (apparent quint, J = 7, 4H,
i-Pr CH), 2.89 (sep, J = 7, 2H, i-Pr CH), 2.32 (m, 2H, P-CH2),
2.02 (m, 2H, P-CH2), 1.28 (d, J = 7, 6H, i-Pr CH3), 1.25 (d, J =
7, 6H, CH3, i-Pr), 1.20 (d, J = 7, 6H, CH3, i-Pr). The BH3 signals
13C solvent peaks. 31P NMR chemical shifts are reported vs
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. IR spectra
were recorded on KBr disks and are reported in cm-1. Quanti-
tative Technologies Incorporated provided elemental analyses.
Mass spectrometry was performed at the University of Illinois.
Chiral HPLC was done on an Agilent Technologies 1200 series
HPLC instrument using a ChiralPak AD-H column (4.6 mm
inner diameter, 250 mm length, flow rate 1-1.2 mL/min)
contained within a thermostated column compartment. Unless
(19) 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.
(20) van der Winkel, Y.; Bastiaans, H. M. M.; Bickelhaupt, F.
J. Organomet. Chem. 1991, 405, 183–194.
(21) Brauer, D. J.; Bitterer, F.; Dorrenbach, F.; Hessler, G.; Stelzer,
O.; Kruger, C.; Lutz, F. Z. Naturforsch., B 1996, 51, 1183–1196.
(22) Tani, K.; Brown, L. D.; Ahmed, J.; Ibers, J. A.; Nakamura, A.;
Otsuka, S.; Yokota, M. J. Am. Chem. Soc. 1977, 99, 7876–7886.
(23) Powell, J.; James, N.; Smith, S. J. Synthesis 1986, 338–340.
(24) We have observed similar mass spectrometric behavior in other
primary and secondary phosphine-boranes: (a) Brunker, T. J.; Ander-
son, B. J.; Blank, N. F.; Glueck, D. S.; Rheingold, A. L. Org. Lett. 2007,
9, 1109–1112. (b) Blank, N. F.; McBroom, K. C.; Glueck, D. S.; Kassel,
W. S.; Rheingold, A. L. Organometallics 2006, 25, 1742–1748.
(16) (a) Sriramurthy, V.; Barcan, G. A.; Kwon, O. J. Am. Chem. Soc.
2007, 129, 12928–12929. (b) Cairns, S. M.; McEwen, W. E. Phosphorus,
Sulfur Silicon 1990, 48, 77–95. (c) McEwen, W. E.; Smith, J. H.; Woo, E. J.
J. Am. Chem. Soc. 1980, 102, 2746–2751. (d) McEwen, W. E.; Janes, A. B.;
Knapczyk, J. W.; Kyllingstad, V. L.; Shiau, W.-I.; Shore, S.; Smith,
J. H. J. Am. Chem. Soc. 1978, 100, 7304–7311. (e) Keldsen, G. L.; McEwen,
W. E. J. Am. Chem. Soc. 1978, 100, 7312–7317. (f) McEwen, W. E.;
Fountaine, J. E.; Schulz, D. N.; Shau, W. J. Org. Chem. 1976, 10, 1684–
1690.
(17) Walsh, P. J.; Kozlowski, M. C. Fundamentals of Asymmetric
Catalysis; University Science Books: Sausalito, CA, 2009.
(18) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518–1520.

384 Organometallics, Vol. 29, No. 2, 2010
Chapp et al.
were not observed. 13C{1H} NMR (CDCl3): δ 152.7 (quat o and
p, Ar), 122.7 (CH, Ar), 117.9 (d, J = 53, quat, P-C), 34.3 (CH, i-
Pr), 32.4 (CH, i-Pr), 24.5 (CH3, i-Pr), 24.3 (br, CH3, i-Pr), 23.6
(d, J = 6, CH3, i-Pr), 20.8 (d, J = 26, P-CH2).
IsHP(CH2)2PH(Is) (1). Piperazinomethyl polystyrene (5.6 g,
2.7 mmol/g, 15 mmol, 4 equiv) and 1-BH3 (1.99 g, 3.75 mmol,
1 equiv) were slurried in toluene (200 mL) under N2.7 The
mixture was stirred at 50 °C for 24 h, after which 31P NMR
spectroscopy showed complete deprotection (δ -87.2, -88.6).
The solution was transferred under N2 via filter cannula to a
round-bottom Schlenk flask equipped with a stir bar. The
remaining resin was washed with three 20 mL portions of
toluene, and the extracts were combined with the filtrate. The
toluene was removed under reduced pressure to leave 1.79 g of
white solid (96% yield).
Anal. Calcd. for C32H52P2: C, 77.07; H, 10.51. Found: C,
76.93; H, 10.65. HRMS (ESþ) for C32H53P2 (MHþ): calcd m/z
499.3623, found m/z 499.3609. 31P{1H} NMR (C6D6): δ -87.2,
-88.6 (mixture of rac and meso, ∼1:1). 1H NMR (C6D6): δ 7.07
(4H, Ar), 4.43 (br d, JPH = 212, 2H, P-H), 3.71 (broad, 4H,
CH, i-Pr), 2.74 (apparent quint, J = 7, 2H, CH, i-Pr), 1.89
(broad, 2H, P-CH2), 1.78 (broad, 2H, P-CH2), 1.20 (d, J = 7,
24H, CH3, i-Pr), 1.12 (broad, 12H, CH3, i-Pr). 13C{1H} NMR
(C6D6): δ 153.2 (broad, quat, Ar), 149.7 (quat, Ar), 128.1 (d, J =
48, quat, Ar P-C), 121.6 (CH, Ar), 34.7 (CH, i-Pr), 32.9 (m, CH,
i-Pr), 24.9 (CH3, i-Pr), 24.4 (broad, CH3, i-Pr), 24.1 (CH3, i-Pr),
23.1 (broad, P-CH2).
(BH3)(Is)(CH2-2-naphthyl)P(CH2)2P(CH2-2-naphthyl)(Is)(BH3)
(2-BH3). In a flask under nitrogen, bis(isitylphosphino)ethane
(1; 499 mg, 1.0 mmol), NaOSiMe3 (224 mg, 2.0 mmol, 2 equiv),
and Pt((R,R)-Me-Duphos)(Ph)(Cl) (61 mg, 0.1 mmol, 10 mol %)
were dissolved in THF (150 mL) to give a yellow solution. To
this was added a solution of 2-(bromomethyl)naphthalene
(442 mg, 2.0 mmol, 2 equiv) in THF (20 mL). The mixture
was stirred for 14 h, over which time a white solid precipitated.
In situ 31P NMR spectroscopy showed two peaks (δ -23.3,
-22.6) in a 3.6:1 ratio, indicating that the reaction was complete.
The solvent was removed under reduced pressure to leave a
yellow residue that was partially redissolved in 9:1 petroleum
ether-THF (30 mL) and eluted over a silica plug (5.0 cm wide ꢀ
3.5 cm high) with two 20 mL portions of 9:1 petroleum
ether-THF and then two 50 mL portions of petroleum ether.
The catalyst and the NaBr did not elute. The solvent was
removed from the eluent under reduced pressure to leave
710 mg of white solid (91% yield). The solid was dissolved in
30 mL of a 1:1 THF-petroleum ether mixture, and BH3(SMe2)
(2.0 mL, 2.0 M solution in THF, 4.0 mmol, 4 equiv) was added to
the solution via cannula at 0 °C. The solution was warmed to
room temperature and was stirred for 14 h. In situ 31P NMR
spectroscopy in THF showed complete protection of the bis-
(tertiary) phosphine (δ 13.1). The solvent was removed under
reduced pressure to give a white solid that was recrystallized
under N2 from THF (3 mL) layered with petroleum ether
(12 mL) at -28 °C to give 323 mg (44% yield) of the meso
diastereomer as a white crystalline solid. A second and third
recrystallization gave an additional 57 and 53 mg of white solid.
Slow evaporation of a toluene solution of a sample from the
third crop gave crystals of rac-2-BH3 suitable for X-ray crystallo-
graphic analysis.
JPH = 5, 6, 2H, P-CH2), 3.37 (AB, JHH = 14, JPH = 5, 2H,
P-CH2), 2.92 (sep, J = 7, 2H, CH, i-Pr), 2.65-2.61 (m, 2H,
P-CH2), 2.02-1.96 (m, 2H, P-CH2), 1.30 (dd, J = 7, 2, 12H,
CH3, i-Pr), 1.18 (d, J = 7, 12H, i-Pr-CH3), 1.05 (d, J = 7, 12H,
CH3, i-Pr). The BH3 signals were not observed. 13C{1H} NMR
(CDCl3): δ 155.8 (t, J = 5, quat Ar), 152.5 (quat, Ar), 133.1
(quat, Ar), 132.2 (quat, Ar), 130.6 (t, J = 2, quat, Ar), 128.7 (t,
J = 3, CH, Ar), 128.2 (t, J = 2, CH, Ar), 127.6 (CH, Ar), 127.5
(CH, Ar), 127.4 (CH, Ar), 125.9 (CH, Ar), 125.6 (CH, Ar), 123.6
(t, J = 4, CH, Ar), 118.8 (d, J = 43, quat, Ar), 35.7 (filled-in
doublet,25 J = 17, P-CH2), 34.0 (CH, i-Pr), 30.6 (t, J = 3, CH,
i-Pr), 25.2 (CH3, i-Pr), 25.2 (CH3, i-Pr), 23.6 (d, J = 3, CH3,
i-Pr), 23.3 (filled-in doublet,25 J = 17, P-CH2).
(Is)(CH2-2-naphthyl)P(CH2)2P(CH2-2-naphthyl)(Is) (2). Pipe-
razinomethyl polystyrene (1.2 g, 2.7 mmol/g, 3.2 mmol, 9.7 equiv)
and meso-2-BH3 (264 mg, 0.33 mmol, 1 equiv) were slurried in
toluene (20 mL) under N2.7 The mixture was stirred at room
temperature for 13 days, after which 31P NMR spectroscopy
showed almost complete deprotection (δ -23.0) with a trace
of partially deprotected (Is)(2-naphthylCH2)P(CH2)2P(CH22-
naphthyl)(Is)(BH3) (δ -22.4, -22.6). The broad peak for the
starting material was not observed. (In a similar experiment but
on a smaller scale (ca. 150 mg, 0.19 mmol of 2-BH3), heating to
60 °C resulted in much faster deprotection that went to comple-
tion in less than 1 day.) The solution was transferred under N2 via
filter cannula to a round-bottom Schlenk flask equipped with a
stir bar. The remaining resin was washed with two 15 mL portions
of toluene, and the extracts were combined with the filtrate. The
toluene was removed under reduced pressure to leave 256 mg of
oily white solid. The solid was washed with two 1 mL portions of
petroleum ether to remove the trace impurities, giving 220 mg
(86% yield) of meso-2. In a similar deprotection, crystals suitable
for X-ray analysis were obtained after dissolving the sample in
petroleum ether, eluting through a silica pipet filter (0.5 cm wideꢀ
3.0 cm high), and allowing the petroleum ether to slowly evapo-
rate.
Elemental analysis of the air-sensitive phosphine was consis-
tent with oxidation. Anal. Calcd for C54H68O2P2: C, 79.97; H,
8.45. Found: C, 80.38; H, 8.52. HRMS (ESþ) for C54H69P2
(MHþ): calcd m/z 779.4875, found m/z 779.4843. 31P{1H} NMR
(CDCl3): δ -22.7 (meso; the rac peak appears at δ -22.1). 1H
NMR (CDCl3): δ 7.76-7.74 (m, 2H, Ar), 7.65 (d, J = 8, 2H,
Ar), 7.63-7.61 (m, 2H, Ar), 7.44 (2H, Ar), 7.41-7.36 (m, 4H,
Ar), 7.23 (dd, J = 9, 2, 2H, Ar), 6.97 (4H, Ar), 3.81 (broad, 4H,
CH, i-Pr), 3.41 (AB pattern, J = 14, 2H, P-CH2), 3.32 (AB
pattern, J = 14, 2H, P-CH2), 2.87 (sep, J = 7, 2H, CH, i-Pr),
2.12-2.07 (m, 2H, P-CH2), 1.99-1.94 (m, 2H, P-CH2), 1.27
(d, J = 7, 12H, CH3, i-Pr), 1.20 (d, J = 7, 12H, CH3, i-Pr), 1.00
(d, J = 7, 12H, CH3, i-Pr). 13C{1H} NMR (CDCl3): δ 155.4
(broad, Ar), 150.2 (Ar), 137.3 (t, J = 6, Ar), 133.5 (Ar), 131.8
(Ar), 127.9 (m, Ar), 127.5 (Ar), 127.3 (Ar), 126.8 (t, J = 4, Ar),
125.7 (Ar), 125.0 (Ar), 122.0 (Ar), 109.7 (Ar), 35.8-35.6 (m,
P-CH2), 34.1 (CH, i-Pr), 31.4 (t, J = 11, CH, i-Pr), 26.0 (d, J =
5, P-CH2), 24.8 (CH3, i-Pr), 24.7 (CH3, i-Pr), 23.8 (CH3, i-Pr).
Is(CH2-2-naphthyl)P(CH2)2PHIs (3). Under N2, a solution of
IsHP(CH2)2PHIs (1; 124 mg, 0.25 mmol) in 5 mL of THF was
cooled to -78 °C. To this was added s-BuLi (250 μL, 1.05 M in
hexane, 0.26 mmol, 1.05 equiv) via microliter syringe, and the
solution turned yellow. The solution was stirred for 1 h and then
transferred dropwise via cannula over 15 min to a -78 °C
solution of 2-(chloromethyl)naphthalene (46 mg, 0.26 mmol,
1.05 equiv, technical grade, 90% purity from Matrix Scientific)
in 5 mL of THF. The solution was stirred for 1 h more and then
warmed to room temperature to give a pale yellow solution. The
solvent was removed under reduced pressure, and the white
residue was partially redissolved in Et2O (15 mL) to give a
cloudy white solution. To this was added 4 mL of a degassed
Anal. Calcd for C54H74B2P2: C, 80.40; H, 9.25. Found: C,
79.35; H, 8.95. These unsatisfactory results may be due to
oxidation of the air-sensitive diphosphine (Anal. Calcd for
C54H68O2P2: C, 79.97, H, 8.45) after loss of the labile borane
(observed on workup with water or aqueous acid, suggesting
sensitivity to moisture, and by mass spectrometry (see below)).
HRMS (ESþ) for C54H69O2P2 (MO2Hþ): calcd m/z 811.4773,
found m/z 811.4766. 31P{1H} NMR (CDCl3): δ 12.1 (broad). 1H
NMR (CDCl3): δ 7.72-7.70 (m, 2H, Ar), 7.60-7.56 (m, 4H,
Ar), 7.41-7.37 (m, 6H, Ar), 7.15 (dd, J = 10, 2, 2H, Ar), 7.07
(4H, Ar), 3.84 (sep, J = 7, 4H, CH, i-Pr), 3.70 (AB, JHH = 14,
(25) Redfield, D. A.; Cary, L. W.; Nelson, J. H. Inorg. Chem. 1975, 14,
50–59.

Article
Organometallics, Vol. 29, No. 2, 2010 385
saturated solution of NH4Cl in distilled H2O, and the solution
turned colorless. The organic layer was removed via cannula,
and the aqueous layer was extracted with two 15 mL portions of
ether and dried over MgSO4. The solvent was removed under
reduced pressure, and the white residue was brought into the
drybox for column chromatography. The sample was dissolved
in 1 mL of 98:2 petroleum ether-THF and loaded onto a silica
column (14.0 cm high, 1.3 cm wide). The column was eluted with
the same solvent mixture and 20 5 mL fractions were collected.
The desired product was collected over fractions 2-4 (the most
was in fraction 3) to give 54 mg (34% yield) of a white solid as a
1:1 mixture of diastereomers that also contained 2% of IsHP-
(CH2)2PHIs (1) and 1% of Is(CH2-2-naphthyl)P(CH2)2P(CH2-
2-naphthyl)Is (2) as determined by 31P NMR spectroscopy. In a
subsequent preparation of a different sample, all impurities were
removed through purification by column chromatography, as
ascertained by 31P NMR spectroscopy.
The mass spectrum was consistent with oxidation at both P
centers. HRMS (ESþ) for C43H61O2P2 (MO2Hþ): calcd m/z
671.4147, found m/z 671.4137. 31P{1H} NMR (C6D6): δ -23.6
(d, J = 30), -23.9 (d, J = 30), -88.6 (d, J = 30), -89.6 (d, J =
30). 1H NMR (C6D6): δ 7.59-7.53 (m, 4H, Ar), 7.38-7.34 (m,
1H, Ar), 7.25-7.18 (m, 2H, Ar), 7.10 (apparent t, J = 3, 2H, Is),
7.05 (d, J = 2, 2H, Is), 4.44 (dt, JPH = 211, JHH = 7, 0.5 H, 1
diastereomer), 4.40 (dt, JPH = 212, JHH = 7, 0.5H, 1 dia-
stereomer), 4.11 (broad, 2H, CH, i-Pr), 3.74-3.65 (m, 2H, CH, i-
Pr), 3.42 (AB pattern, JHH = 13, JPH = 12, 1H, 1 diastereomer),
3.41 (AB pattern, JHH = 13, JPH = 20, 1H, 1 diastereomer),
2.76-2.69 (m, 2H, CH, i-Pr), 2.35-2.25 (m, 1H, P-CH2), 2.21-
2.12 (m, 1H, P-CH2), 2.05-1.98 (m, 0.5H, P-CH2), 1.92-
1.86 (m, 0.5H, P-CH2), 1.82-1.68 (m, 1H, P-CH2), 1.31 (d,
J = 7, 3H, CH3, i-Pr), 1.30 (d, J = 7, 3H, CH3, i-Pr), 1.23 (d, J =
7, 3H, CH3, i-Pr), 1.20-1.17 (m, 15H, CH3, i-Pr), 1.15-1.12
(m, 9H, CH3, i-Pr), 1.08 (d, J = 7, 3H, CH3, i-Pr). 13C{1H}
NMR (C6D6): δ 156.2 (broad, quat, Ar), 156.1 (broad, quat,
Ar), 153.3 (d, J = 11, quat, Ar), 153.2 (d, J = 11, quat, Ar),
150.8 (quat, Ar), 150.7 (quat, Ar), 149.8 (quat, Ar), 149.7 (quat,
Ar), 137.6 (d, J = 4, quat, Ar), 137.5 (d, J = 4, quat, Ar), 134.21
(quat, Ar), 134.20 (quat, Ar), 132.5 (quat, Ar), 129.3 (d, J =
8, quat, Ar), 129.2 (d, J = 8, quat, Ar), 128.4-128.3 (m, CH,
Ar), 128.3 (CH, Ar), 127.9 (CH, Ar), 127.7 (CH, Ar), 127.42 (d,
J = 2, CH, Ar), 127.36 (d, J = 2, CH, Ar), 126.2 (CH, Ar), 126.1
(CH, Ar), 125.4 (CH, Ar), 122.3 (d, J = 3, CH, Ar), 121.6 (d, J =
3, CH, Ar), 36.3 (d, J = 20, P-CH2-Nap), 34.7 (CH), 34.6 (CH),
32.91 (d, J = 14, CH), 32.89 (d, J = 14, CH), 31.9 (CH), 31.7
(CH), 26.9-26.4 (m, P-CH2), 25.2 (CH3), 25.0 (CH3), 24.9 (CH3),
24.5 (CH3), 24.4 (CH3), 24.1-24.0 (m, CH3), 23.1-22.6 (m,
P-CH2). One set of quaternary aryl carbons was not found. The
number of H atoms reported is for one compound. A signal for one
isomer is 0.5 H.
altered. It was redissolved in 5 mL of THF and oxidized in the air
using excess H2O2 (0.2 mL, 30% in H2O). After the mixture was
stirred for 1 h, the solvent was removed under reduced pressure
and the residue was dried in a vacuum desiccator for 12 h to yield
a white solid with typical yields ranging from 90 to 96%.
Evaporation of a solution in hexanes/isopropyl alcohol gave
X-ray-quality crystals.
HRMS (ESþ) for C54H69O2P2 (MHþ): calcd m/z 811.4773,
found m/z 811.4767. 31P{1H} NMR (CD2Cl2): δ 47.6. 31P{1H}
NMR (CDCl3): δ 44.6 (meso), 44.1 (rac). 1H NMR (CD2Cl2): δ
7.79-7.76 (m, 2H, Ar), 7.71-7.69 (m, 4H, Ar), 7.58 (2H, Ar),
7.46-7.42 (m, 4H, Ar), 7.27 (d, J = 8, 2H, Ar), 7.06 (t, J = 2,
2H, Is), 3.71-3.56 (m, 8H, CH, i-Pr, P-CH2-Nap), 2.86 (sep,
J = 7, CH, i-Pr), 2.46-2.39 (broad m, 4H, P-CH2), 1.23 (d, J =
7, 6H, CH3, i-Pr), 1.22 (d, J = 7, 6H, CH3, i-Pr), 1.18 (d, J = 7,
12H, CH3, i-Pr), 0.84 (d, J = 7, 12H, CH3, i-Pr). 13C{1H} NMR
(CD2Cl2): δ 154.6 (broad, Ar), 153.3 (Ar), 133.7 (Ar), 132.7 (Ar),
129.4 (t, J = 4, Ar), 129.1 (t, J = 3, Ar), 128.4 (Ar), 128.3 (Ar),
127.84 (Ar), 127.82 (Ar), 126.5 (Ar), 126.1 (Ar), 123.6 (t, J = 6,
Ar), 120.8 (m, Ar), 40.7 (m, P-CH2), 34.5 (CH, i-Pr), 30.4 (CH,
i-Pr), 26.0 (m, P-CH2), 25.2 (CH3, i-Pr), 24.5 (CH3, i-Pr), 23.6
(d, J = 8, CH3, i-Pr).
To provide a reference sample of 2-O for the assays below, an
enriched sample of diphosphine 2, prepared on the same scale,
was heated to epimerize the P stereocenters and then oxidized.
Solid 2 was heated under N2 in an oil bath for 3 days at 165 °C. A
31P NMR spectrum of this material in THF revealed an approxi-
mate 1.2:1 rac:meso ratio, confirming that the sample had been
epimerized. It also contained some of the phosphine oxide 2-O.
The residue was oxidized completely with H2O2 (0.2 mL, 30% in
H2O). The residual H2O2 was removed under reduced pressure,
and the sample was dried for 12 h in a vacuum desiccator to yield
36 mg (89% yield) of white solid, which contained a trace of an
unidentified impurity (31P NMR (THF): δ 40.7).
31P NMR Analysis of 2-O. This general procedure was used
for measuring the dr and er of 2-O by 31P NMR spectroscopy
following catalytic alkylation, subsequent oxidation, and treat-
ment with the shift reagent L-FmocTrp(Boc)-OH (Novabio-
chem).11 The NMR solvents C6D6, CD2Cl2, and CDCl3 were
tested, but CDCl3 gave the best chemical shift dispersion for
accurate integration. A sample of 2-O (10 mg, 0.01 mmol) was
dissolved in 1 mL of CDCl3. To this was added FmocTrp(Boc)-
OH (13 mg, 0.025 mmol, 2.5 equiv). Integration of the peaks in
the 31P NMR spectrum (Figure S4, Supporting Information)
gave the er and dr of the diphosphine oxide. 31P{1H} NMR
(CDCl3): δ 47.6 (rac, minor), 47.5 (rac, major), 47.3 (AB pattern,
J = 50, meso) for a sample prepared with Pt((R,R)-Me-
DuPhos)(Ph)(Cl).
HPLC Analysis of 2-O. A sample of 2-O (4 mg, 0.005 mmol)
was dissolved in 0.4 mL of HPLC grade isopropyl alcohol. An
additional 0.6 mL of HPLC grade hexanes was added, and the
sample was loaded into the autosampler. The column (Daicel
Chiralpak AD-H, 4.6 mm inner diameter, 250 mm length) was
equilibrated for 30 min at 36 °C with 98:2 hexanes-isopropyl
alcohol. The sample was injected using the autosampler. The
meso isomer eluted at 18 min, and the rac isomers eluted at
27 and 34 min, respectively (1.0-1.2 mL/min, 36 °C). The peaks
were identified by isolation of the pure meso compound and also
by changing the hand of the catalyst to observe the change in the
rac product ratios. Each enantiomer’s peak was well-resolved
from the others, but the peak widths were large and resulted in a
broad elution window for each isomer.
Preparation of (Is)(2-naphthylCH2)P(O)(CH2)2P(O)(CH22-
naphthyl)(Is) (2-O) for er and dr Analysis. This general procedure
was used to prepare 2-O from either IsHP(CH2)2PHIs (1) or
Is(CH2-2-naphthyl)P(CH2)2PHIs (3) using either enantiomer of
the Pt catalyst. Reactions were run on the same scale relative to
the starting diphosphine. One or two equiv of NaOSiMe3 and 2-
bromomethylnaphthalene was used, depending on how many P
centers were alkylated. IsHP(CH2)2PHIs (1; 25 mg, 0.05 mmol)
was dissolved in 7 mL of THF, and the solution was transferred
to a vial containing NaOSiMe3 (12 mg, 0.1 mmol, 2 equiv). The
resulting solution was transferred to another vial containing
Pt((R,R)-Me-Duphos)(Ph)(Cl) (3 mg, 0.005 mmol, 10 mol %) to
give a yellow solution. To this was added 2-bromomethyl-
naphthalene (22 mg, 0.1 mmol, 2 equiv) and the solution was
stirred for 12 h, over which time a white solid precipitated. The
solvent was removed under reduced pressure, and the product
was extracted and eluted over a silica pipet filter (0.5 cm wide ꢀ
3.0 cm high) with three 2 mL portions of 9:1 petroleum
ether-THF. The product was checked by 31P NMR spectro-
scopy before and after oxidation to ensure that the dr was not
IsHP(CH2)2OSiMe3 (4). To a solution of PH2Is (390 mg,
73% purity, 26% 1,3,5-triisopropylbenzene according to 1H
NMR integration, 1.34 mmol of PH2Is) in 5 mL of THF at
-78 °C was added s-BuLi (1260 μL, 1.1 M in cyclohexane,
1.4 mmol, 1.05 equiv), and the solution turned yellow. The
solution was stirred at -78 °C for 1 h, and then a solution of
Cl(CH2)2OSiMe3 (229 mg, 1.5 mmol, 1.1 equiv) was added
dropwise via cannula. The solution was stirred an additional

386 Organometallics, Vol. 29, No. 2, 2010
Chapp et al.
1 h at -78 °C and then warmed to room temperature. The
solvent was removed under reduced pressure, and the residue
was dissolved in 15 mL of Et2O to give a cloudy white solution.
To this was added 5 mL of a degassed saturated aqueous
solution of NaHCO3. The aqueous layer was extracted with
three 15 mL portions of Et2O, dried over MgSO4, and filtered,
and the solvent was removed under reduced pressure to leave a
clear oil (466 mg, 76% purity, containing 24% 1,3,5-triisopropyl-
benzene according to 1H NMR spectroscopy). Note that a similar
workup at this point using degassed distilled H2O instead of
NaHCO3 resulted in hydrolysis of the OSiMe3 group to give 5.
The oil was dissolved in 1 mL of petroleum ether and loaded onto
a silica plug (2.5 cm wide ꢀ 4.0 cm high). The plug was eluted with
15 mL of petroleum ether and then two 15 mL portions of 9:1
petroleum ether-THF. The second of the mixed solvent fractions
contained 224 mg (47% yield based on PH2Is) of the desired
phosphine as an oil free from 1,3,5-triisopropylbenzene, as deter-
mined by 1H NMR spectroscopy.
thin pale yellow layer on top of the DMF. The reaction was
monitored by 31P NMR spectroscopy and was complete within
1.5 h on the basis of the disappearance of IsHP(CH2)2OH (δ
-100.3) and formation of 6 (δ -102.1). Upon completion of the
reaction there were still two layers but the cloudiness had
disappeared. The mixture was added to 12 mL of petroleum
ether in a Schlenk flask. The solution was washed with three
3 mL portions of degassed distilled water. The organic layer was
dried over MgSO4 and then filtered, and the solvent was
removed under reduced pressure to give a clear oil. The oil
was dissolved in 1 mL of 9:1 petroleum ether-Et2O and eluted
over a silica pipet filter (0.5 cm wide ꢀ 3.0 cm high) with three
1 mL portions of the same solvent mixture to give the desired
product as a clear oil (77 mg, 77% yield, ∼97% purity). An
unidentified trace impurity (δ -93.8 (<1%)), PH2Is (<1%),
and P(CH2)2(Is) (<1%) were observed by 31P NMR spectro-
scopy.
HRMS (ESþ) for C26H50OPSi (MHþ): calcd m/z 437.3369,
found m/z 437.3365. 31P{1H} NMR (CDCl3): δ -106.9. 1H
NMR (CDCl3): δ 7.05 (d, J = 2, 2H, Is), 4.41 (dt, JPH = 220,
JHH = 8, 1H, P-H), 3.92-3.85 (m, 1H, CH2), 3.83-3.78 (m,
1H, CH2), 3.73-3.67 (m, 2H, CH, i-Pr), 2.90 (sep, J = 7, 1H,
CH, i-Pr), 2.17-2.09 (m, 1H, CH2), 1.92-1.84 (m, 1H, CH2),
1.33 (d, J = 7, 6H, CH3, i-Pr), 1.28 (d, J = 7, 6H, CH3, i-Pr),
1.25 (d, J = 7, 6H, CH3, i-Pr), 1.11-1.06 (m, 21H, Si(CH-
(CH3)2)3, Si(CH(CH3)2)3). 13C{1H} NMR (CDCl3): δ 152.7 (d,
J = 11, quat, Ar), 149.3 (quat, Ar), 127.6 (d, J = 14, quat, Ar),
121.3 (d, J = 3, CH, Ar), 62.1 (d, J = 13, CH2), 34.3 (CH, i-Pr),
32.5 (d, J = 14, CH, i-Pr), 28.0 (d, J = 13, CH2), 24.9 (CH3,
i-Pr), 24.2 (CH3, i-Pr), 23.9 (d, J = 5, CH3, i-Pr), 18.0 (Si(CH-
(CH3)2)3), 12.0 (Si(CH(CH3)2)3).
(Is)(CH2-2-naphthyl)P(CH2)2OH (8). This phosphine was
prepared indirectly by Pt-catalyzed alkylation of trimethylsilyl
ether 4 (hydrolysis of the OSiMe3 group occurred during reac-
tion and workup) or by Pt-catalyzed alkylation of alcohol 5.
(a) From Silyl Ether 4. A solution of PH(Is)(CH2)2OSiMe3 (4;
26 mg, 0.07 mmol) in 6 mL of THF was added to Pt((R,R)-Me-
DuPhos)(Ph)(Cl) (2 mg, 0.004 mmol, 5 mol %). This solution
was transferred to solid NaOSiMe3 (8 mg, 0.07 mmol), and
the solution turned yellow. To this solution was added 2-
(bromomethyl)naphthalene (16 mg, 0.07 mmol). The reaction
was monitored by 31P NMR spectroscopy, which showed the
formation of two products: presumably the silyl ether 7 and the
alcohol 8, respectively (δ -34.4 (minor), -34.9 (major), 3.6:1
ratio). The solvent was removed under reduced pressure to leave
a white residue. Extraction with two 3 mL portions of 9:1
petroleum ether-THF and filtration through Celite gave a
quantitative yield of oil containing (Is)(CH2-2-naphthyl)P-
(CH2)2OSiMe3 (7; δ -35.5, minor, CDCl3) and (Is)(CH2-2-
naphthyl)P(CH2)2OH (8; δ -37.9, major, CDCl3) in a 4.5:1
ratio. The enantioselectivity of the alkylation (er = 1.8 for both
7 and 8) was determined after oxidation of this mixture to 7-O
and 8-O (see below).
In a duplicate experiment, the solution was stirred for 16 h,
over which time a white precipitate developed. The solvent was
removed under reduced pressure, and the white residue was
taken up in 9:1 petroleum ether-THF. The white slurry was
eluted over a silica pipet column (0.5 cm wide ꢀ 3.0 cm high)
with two 2 mL portions of 9:1 petroleum ether-THF. The
solvent was removed under reduced pressure to leave 15 mg of
white residue, which contained a mixture of 7, 8, and impurities.
Passing three additional portions of 9:1 petroleum ether-THF
over the silica pipet column gave 11 mg (36% yield) of the
alcohol 8 with only trace impurities.
(b) From Alcohol 5. A solution of IsHP(CH2)2OH (5; 38 mg,
0.13 mmol) in 6 mL of THF was added to solid Pt((R,R)-Me-
DuPhos)(Ph)(Cl) (4 mg, 0.006 mmol, 5 mol %). This solution
was transferred to solid NaOSiMe3 (16 mg, 0.05 mmol) to give
a yellow solution, to which was added 2-(bromomethyl)-
naphthalene (31 mg, 0.14 mmol). As the reaction progressed, a
Anal. Calcd for C20H37OPSi: C, 68.13; H, 10.58. Found: C,
68.60; H, 10.30. The mass spectrum was consistent with hydrþo-
lysis of the silyl ether. HRMS (ESþ) for C17H30OP (MH2
-
SiMe3): calcd m/z 281.2034, found m/z 281.2028. 31P{1H} NMR
(CDCl3): δ -106.1. 1H NMR (CDCl3): δ 7.03 (d, J = 3, 2H, Is),
4.32 (dt, JPH = 218, JHH = 7, 1H, P-H), 3.77-3.69 (m, 2H,
CH2), 3.69-3.61 (m, 2H, CH, i-Pr), 2.88 (sep, J = 7, 1H, CH, i-
Pr), 2.12-2.05 (m, 1H, CH2), 1.89-1.81 (m, 1H, CH2), 1.30 (d,
J = 7, 6H, CH3, i-Pr), 1.26 (d, J = 7, 6H, CH3, i-Pr), 1.23 (d, J =
7, 6H, CH3, i-Pr), 0.11 (9H, OSi(CH3)3). 13C{1H} NMR
(CDCl3): δ 152.7 (d, J = 11, quat, Ar), 149.4 (quat, Ar), 127.3
(d, J = 14, quat, Ar), 121.3 (d, J = 4, CH, Ar), 61.4 (d, J = 14,
CH2), 34.2 (CH, i-Pr), 32.6 (d, J = 14, CH, i-Pr), 27.5 (d, J = 14,
CH2), 24.9 (CH3, i-Pr), 24.2 (CH3, i-Pr), 23.8 (d, J = 4, CH3,
i-Pr), -0.5 (OSi(CH3)3).
IsHP(CH2)2OH (5). IsHP(CH2)2OSiMe3 (4; 95 mg, 0.11
mmol) was dissolved in 5 mL of degassed 5% v/v concentrated
HCl in MeOH, and the mixture was stirred for 1 h. The solvent
was removed under reduced pressure, and the oily residue was
redissolved in Et2O. Residual HCl was neutralized with the
addition of 5 mL of saturated aqueous NaHCO3. The organic
layer was removed via cannula, and the aqueous layer was
extracted with two additional 15 mL portions of Et2O. The
combined extracts were dried over MgSO4 and filtered. The
solvent was removed under reduced pressure, and the remaining
oil was eluted over a silica pipet filter (0.5 cm wide ꢀ 3.0 high)
with 5 mL of Et2O. The solvent was removed under reduced
pressure to give a cloudy white oil that solidified and became a
waxy white solid upon standing (69 mg, 92% yield). This
material was ∼97% pure by 31P NMR spectroscopy (CDCl3);
it contained an unidentified trace impurity (δ -94.2, 1.5%),
PH2Is (δ -157.0, <1%), and P(CH2)2(Is) (δ -241.9, <1%).26
HRMS (ESþ) for C17H30OP (MHþ): calcd m/z 281.2034,
found m/z 281.2021. 31P{1H} NMR (CDCl3): δ -105.8. 1H
NMR (CDCl3): δ 7.05 (d, J = 3, 2H, Is), 4.37 (dt, JPH = 219,
JHH = 7, 1H, P-H), 3.82-3.75 (m, 2H, P-CH2), 3.69-3.61 (m,
2H, CH, i-Pr), 2.89 (sep, J = 7, 1H, CH, i-Pr), 2.19-2.12 (m, 1H,
CH2), 1.93-1.85 (m, 1H, CH2), 1.49 (t, J = 5, 1H, OH, also
observed at δ 1.70 (broad) in a separate sample), 1.31 (d, J = 7,
6H, CH3, i-Pr), 1.27 (d, J = 7, 6H, CH3, i-Pr), 1.25 (d, J = 7, 6H,
CH3, i-Pr). 13C{1H} NMR (CDCl3): δ 152.7 (d, J = 11, quat,
Ar), 149.6 (quat, Ar), 126.7 (d, J = 13, quat, Ar), 121.4 (d, J = 3,
CH, Ar), 61.8 (d, J = 13, CH2), 34.2 (CH, i-Pr), 32.7 (d, J = 14,
CH, i-Pr), 27.4 (d, J = 13, CH2), 24.9 (CH3, i-Pr), 24.2 (CH3,
i-Pr), 23.8 (d, J = 4, CH3, i-Pr).
IsHP(CH2)2OSi(i-Pr)3 (6). IsHP(CH2)2OH (5; 64 mg, 0.23
mmol) was dissolved in 1 mL of DMF and transferred first to
Si(i-Pr)3Cl (44 mg, 0.23 mmol), and this solution was transferred
to solid imidazole (39 mg, 0.58 mmol, 2.5 equiv). Within 10 min
the solution turned cloudy white and developed an additional
(26) Synthesis of this phosphirane will be described separately.

Article
Organometallics, Vol. 29, No. 2, 2010 387
white precipitate developed. The solvent was removed under
reduced pressure, and the white residue was taken up in 9:1
petroleum ether-THF. The white slurry was eluted over a silica
pipet column (0.5 cm wide ꢀ 3.0 cm high) with 9 mL of 9:1
petroleum ether-THF and then 4 mL of 3:1 petroleum
ether-THF. The solvent was removed under reduced pressure
to leave 52 mg (91%) of a white residue of 8. This material
contained 12% of an unidentified impurity (31P NMR: δ 40.2
(CDCl3)). After oxidation to 8-O, the er was found to be 2.0 (see
below).
The background reaction of alcohol 5 with NaOSiMe3 and
2-(bromomethyl)naphthalene was much slower than the Pt-
catalyzed one, which was complete after 9 h; the background
reaction had proceeded to only 4% conversion to 8. Similarly,
only 5% conversion of trimethylsilyl ether 4 to 7 occurred after
30 h, although the accompanying catalytic reaction was not yet
complete.
CH3, i-Pr), 1.18 (d, J = 7, 6H, CH3, i-Pr), 0.95-0.93 (m, 21H,
Si(CH(CH3)2)3, Si(CH(CH3)2)3). 13C{1H} NMR (CDCl3): δ
155.2 (d, J = 14, quat, Ar), 150.3 (d, J = 1, quat, Ar), 137.0
(d, J = 11, quat, Ar), 133.6 (d, J = 2, quat, Ar), 131.9 (d, J = 2,
quat, Ar), 129.5 (d, J = 22, quat, Ar), 128.0 (d, J = 1, CH, Ar),
127.8 (d, J = 6, CH, Ar), 127.5 (d, J = 1, CH, Ar), 127.3 (CH,
Ar), 126.9 (d, J = 7, CH, Ar), 125.8 (CH, Ar), 125.0 (CH, Ar),
122.0 (broad, CH, Ar), 63.3 (d, J = 47, CH2), 36.0 (d, J = 17,
CH2), 34.2 (CH, i-Pr), 31.8 (d, J = 17, CH2), 31.6 (d, J = 20,
CH, i-Pr), 24.9 (CH3, i-Pr), 24.7 (CH3, i-Pr), 23.8 (d, J = 1, CH3,
i-Pr), 17.9 (d, J = 1, Si(CH(CH3)2)3), 11.8 (Si(CH(CH3)2)3).
(Is)(CH2-2-naphthyl)P(O)(CH2)2OH (8-O). To a solution of
(Is)(CH2-2-naphthyl)P(CH2)2OH (8; prepared from 5 (see
above), 28 mg, ca. 88% purity, 0.067 mmol) in 2 mL of THF
was added excess H2O2 (0.2 mL, 30% in H2O). The solution was
stirred for 2 h, and the solvent was removed under reduced
pressure. The residue was further dried for 5 h under vacuum to
give 20 mg (70% yield) of the desired product as an oil. The
impurity observed in the starting phosphine by 31P NMR
spectroscopy (∼12%, δ 40.2 (CDCl3)) remained unchanged.
The er of this sample was measured using 31P NMR spectro-
scopy by dissolving the oil (19 mg, ca. 0.04 mmol) in CDCl3 with
Fmoc(Trp)Boc-OH (34 mg, 0.07 mmol). The er was 2.0:1 (δ
48.8, minor, 48.5 major). The signal at δ 40.2 shifted to δ 44.4
but did not separate into two signals.
A second preparation of 8-O used a 4.5:1 mixture of (Is)(CH2-
2-naphthyl)P(CH2)2OH (8) and (Is)(CH2-2-naphthyl)P(CH2)2-
OSiMe3 (7), prepared by Pt-catalyzed alkylation of PH(Is)-
(CH2)2OSiMe3 (4), which was oxidized by the same procedure.
The final product contained alcohol 8-O (δ 48.4, CDCl3) and the
silyl ether (Is)(CH2-2-naphthyl)P(O)(CH2)2OSiMe3 (7-O, δ
41.5, CDCl3) in a 9.2:1 ratio. The er of this sample was measured
using 31P NMR spectroscopy by dissolving the oil (22 mg, ca.
0.05 mmol) in CDCl3 with Fmoc(Trp)Boc-OH (32 mg, 0.06
mmol). The er for both 8-O (δ 48.8, minor, 48.5 major) and 7-O
(δ 45.94, major, 45.89 minor) was 1.8:1, although overlap of the
peaks for the silyl ether adduct made that measurement less
reliable.
HRMS (ESþ) for C28H38OP (MHþ): calcd m/z 421.2660,
found m/z 421.2645. 31P{1H} NMR (CDCl3): δ -37.9. 1H NMR
(CDCl3): δ 7.80-7.72 (m, 3H, Ar), 7.58 (1H, Ar), 7.46-7.39 (m,
2H, Ar), 7.36 (d, J = 8, 1H, Ar), 7.04 (d, J = 3, Ar), 3.96-3.88
(m, 2H, CH, i-Pr), 3.62-3.56 (m, 2H, P-CH2), 3.46 (AB
pattern, J = 14, 2H, P-CH2), 2.89 (sep, J = 7, 1H, CH, i-Pr),
2.38-2.33 (m, 1H, PCH2CH2), 2.31-2.25 (m, 1H,
P-CH2CH2), 1.57 (td, J = 2, 6, 1H, OH), 1.31 (d, J = 7, 6H,
CH3, i-Pr), 1.28 (d, J = 7, 6H, CH3, i-Pr), 1.19 (d, J = 7, 6H,
CH3, i-Pr). 13C{1H} NMR (CDCl3): δ 155.3 (d, J = 13, quat,
Ar), 150.6 (quat, Ar), 136.7 (d, J = 11, quat, Ar), 133.6 (quat,
Ar), 132.0 (quat, Ar), 128.7 (d, J = 21, quat, Ar), 128.1 (d, J = 1,
CH, Ar), 127.7 (d, J = 6, CH, Ar), 127.6 (d, J = 1, CH, Ar),
127.4 (CH, Ar), 126.9 (d, J = 7, CH, Ar), 125.9 (CH, Ar), 125.2
(CH, Ar), 122.2 (d, J = 4, CH, Ar), 61.9 (d, J = 34, CH2), 35.9
(d, J = 17, CH2), 34.2 (CH, i-Pr), 31.8 (d, J = 18, CH2), 31.7 (d,
J = 20, CH, i-Pr), 24.9 (CH3, i-Pr), 24.8 (CH3, i-Pr), 23.8 (d,
J = 1, CH3, i-Pr).
(Is)(CH2-2-naphthyl)P(CH2)2OSi(i-Pr)3 (9). IsHP(CH2)2OSi-
(i-Pr)3 (6; 23 mg, 0.05 mmol) was dissolved in 1 mL of toluene
and transferred first to Pt((R,R)-Me-DuPhos)(Ph)(Cl) (2 mg,
0.003 mmol, 5 mol %) and then to solid NaOSiMe3 (6 mg,
0.05 mmol) to give a yellow solution, which was transferred to
solid 2-(bromomethyl)naphthalene (12 mg, 0.05 mmol); the
reaction was monitored by 31P NMR spectroscopy. After 3 h
the solution had become cloudy with a white precipitate. The
reaction was complete after 21 h. The solvent was removed
under reduced pressure, and the residue was taken up in 9:1
petroleum ether-Et2O. The solution was eluted over a silica
pipet filter (0.5 cm wide ꢀ 3.0 cm high) with four 1 mL portions
of the same solvent mixture. The catalyst and the NaBr did not
elute. The solvent was removed under reduced pressure to leave
30 mg (97% yield) of clear oil. Impurities derived from the
starting material were observed by 31P NMR spectroscopy but
totaled less than 4% (δ -20.2 (<1%), -27.0 (<2%), -241.9
(<1%)). The er of the catalytic alkylation (1.5) was determined
after oxidation of the phosphine to 9-O (see below). Note: in a
similar experiment, the Pt-catalyzed and background reactions
were monitored in THF. After 9 h, when the catalytic reaction
was complete (er =1.4), the background reaction had pro-
ceeded to about 20% conversion of 6 to form 9 plus some
unidentified byproducts (δ -83.0). Assuming that the contribu-
tion of the background to formation of 9 during catalysis is
reduced, no attempts were made to correct the observed en-
antioselectivity.
HRMS (ESþ) for C28H38O2P (MHþ): calcd m/z 437.2609,
found m/z 437.2622. 31P{1H} NMR (CDCl3): δ 48.4. 1H NMR
(CDCl3): δ 7.82-7.75 (m, 3H, Ar), 7.66 (1H, Ar), 7.48-7.44 (m,
2H, Ar), 7.40-7.38 (m, 1H, Ar), 7.12 (d, J = 4, 2H, Ar), 4.33
(broad, 1H, OH), 3.85-3.75 (m, 4H, CH, i-Pr, CH2), 3.72-3.63
(m, 2H, CH2), 2.91 (sep, J = 7, 1H, CH, i-Pr), 2.41-2.27 (m, 2H,
CH2), 1.31 (d, J = 7, 6H, CH3, i-Pr), 1.27 (d, J = 7, 6H, CH3,
i-Pr), 1.11 (d, J = 7, 6H, CH3, i-Pr). 13C{1H} NMR (CDCl3): δ
153.8 (d, J = 13, quat, Ar), 152.6 (d, J = 3, quat, Ar), 133.4 (d,
J = 3, quat, Ar), 132.4 (d, J = 3, quat, Ar), 129.4 (d, J = 8, quat,
Ar), 128.5 (d, J = 6, CH, Ar), 128.3 (d, J = 2, CH, Ar), 127.9 (d,
J = 4, CH, Ar), 127.6 (CH, Ar), 127.5 (CH, Ar), 126.2 (d, J = 1,
CH, Ar), 125.8 (d, J = 1, Ar), 123.1 (d, J = 11, CH, Ar), 123.0
(d, J = 89, quat, Ar), 58.4 (d, J = 7, CH2), 42.4 (d, J = 60, CH2),
34.8 (d, J = 68, CH2), 34.1 (CH, i-Pr), 30.0 (d, J = 4, CH, i-Pr),
25.2 (CH3, i-Pr), 24.6 (CH3, i-Pr), 23.6 (CH3, i-Pr).
(Is)(CH2-2-naphthyl)P(O)(CH2)2OSi(i-Pr)3 (9-O). (Is)(CH2-
2-naphthyl)P(CH2)2OSi(i-Pr)3 (9; 28 mg, 0.049 mmol) was dis-
solved in 2 mL of THF, and excess H2O2 (0.2 mL, 30% in H2O)
was added. The solution was stirred for 2 h, and the solvent was
removed under reduced pressure. The oil was further dried for
15 h in a vacuum desiccator to give 27 mg (93% yield) of the
desired product as a thick oil.
The er of this sample was measured using 31P NMR spec-
troscopy by dissolving the oil (25 mg, 0.04 mmol) in CDCl3 with
Fmoc(Trp)Boc-OH (33 mg, 0.06 mmol, 1.5 equiv). The er was
1.5:1 (δ 46.2, major, 46.0, minor). HRMS (ESþ) for C37H58O2P-
Si (MHþ): calcd m/z 593.3944, found m/z 593.3943. 31P{1H}
NMR (CDCl3): δ 41.6. 1H NMR (CDCl3): δ 7.80-7.73 (m, 3H,
Ar), 7.67 (1H, Ar), 7.45-7.42 (m, 2H, Ar), 7.41-7.38 (m, 1H,
Ar), 7.10 (d, J = 3, 2H, Ar), 4.01-3.72 (m, 4H, CH, i-Pr, CH2),
3.73-3.63 (m, 2H, CH2), 2.89 (sep, J = 7, 1H, CH, i-Pr),
HRMS (ESþ) for C37H58OPSi (MHþ): calcd m/z 577.3995,
found m/z 577.3986. 31P{1H} NMR (CDCl3): δ -35.7. 1H NMR
(CDCl3): δ 7.79-7.71 (m, 3H, Ar), 7.57 (1H, Ar), 7.45-7.39 (m,
2H, Ar), 7.37-7.27 (m, 1H, Ar), 7.03 (d, J = 3, 2H, Ar),
4.00-3.88 (broad m, 2H, CH, i-Pr), 3.69-3.64 (m, 1H, CH2),
3.58-3.52 (m, 1H, CH2), 3.51-3.42 (m, 2H, CH2), 2.89 (sep,
J = 7, 1H, CH, i-Pr), 2.43-2.37 (m, 1H, CH2), 2.25-2.19 (m,
1H, CH2), 1.31 (d, J = 7, 6H, CH3, i-Pr), 1.28 (d, J = 7, 6H,

388 Organometallics, Vol. 29, No. 2, 2010
Chapp et al.
2.43-2.36 (m, 1H, CH2), 2.34-2.27 (m, 1H, CH2), 1.30 (d, J =
7, 6H, CH3, i-Pr), 1.26 (d, J = 7, 6H, CH3, i-Pr), 1.11 (d, J = 7,
6H, CH3, i-Pr), 0.96-0.91 (m, 21H, Si(CH(CH3)2)3, Si(CH-
(CH3)2)3). 13C{1H} NMR (CDCl3): δ 153.8 (d, J = 11, quat,
Ar), 152.0 (d, J = 3, quat, Ar), 133.4 (d, J = 3, quat, Ar), 132.3
(d, J = 2, quat, Ar), 130.3 (d, J = 9, quat, Ar), 128.4 (d, J = 7,
CH, Ar), 128.2 (d, J = 4, CH, Ar), 128.0 (d, J = 2, CH, Ar),
127.6 (d, J = 1, CH, Ar), 127.5 (d, J = 1, CH, Ar), 125.9 (d, J =
1, CH, Ar), 125.5 (CH, Ar), 123.6 (d, J = 89, quat, Ar), 122.9 (d,
J = 11, CH, Ar), 57.9 (broad d, J = 2, CH2), 42.1 (d, J = 60,
CH2), 36.6 (d, J = 66, CH2), 34.1 (d, J = 1, CH, i-Pr), 29.8 (d,
J = 4, CH, i-Pr), 25.1 (CH3, i-Pr), 24.8 (CH3, i-Pr), 23.6 (d,
J = 1, CH3, i-Pr), 17.8 (d, J = 1, Si(CH(CH3)2)3), 11.7 (Si(CH-
(CH3)2)3).
PMeIs(CH2(2-naphthyl)) (10). PHMe(Is) (18 mg, 0.07 mmol)
was dissolved in 0.5 mL of THF. The resulting solution was
added to Pt((R,R)-Me-DuPhos)(Ph)(Cl) (2 mg, 0.0035 mmol,
5 mol %) and then transferred to NaOSiMe3 (8 mg, 0.07 mmol),
and the solution turned yellow. A solution of 2-naphthylCH2Br
(16 mg, 0.07 mmol) in 250 μL of THF was added; within a few
minutes, a white precipitate formed. The reaction was moni-
tored by 31P NMR spectroscopy and was complete after <2.5 h.
(Note: 4% conversion to 10 was observed in the background
reaction over this time.) The solvent was removed under reduced
pressure to leave an oily orange-yellow residue, which was eluted
over a silica column (0.6 cm width ꢀ 5.0 cm height) with 3 ꢀ
1.5 mL portions of 9:1 petroleum ether-THF. The catalyst and
the NaBr did not elute. The eluted solvent was removed under
reduced pressure to leave a clear oily residue (25 mg, 92% yield),
which was dissolved in C6D6 for spectroscopic characterization.
The ee of 10 (17 mg, 0.04 mmol) was determined by binding it to
(S)-{Pd[NMe2CH(Me)C6H4](μ-Cl)}2 (15 mg, 0.025 mmol) and
integrating the 31P NMR signals (31P{1H} NMR (C6D6): δ
15.7 minor, 14.9 major) of the diastereomers, giving an ee of
68% (er = 5.2).
HRMS (ESþ) for C27H36P (MHþ): calcd m/z 391.2555,
found m/z 391.2572. 31P{1H} NMR (C6D6): δ -40.6. 1H
NMR (C6D6): δ 7.56 (broad, 4H, Ar), 7.35 (broad, 1H, Ar),
7.24-7.18 (broad m, 2H, Ar), 7.12 (d, J = 2, 2H, CH, Is), 4.18-
4.10 (broad m, 2H, CH, i-Pr), 3.42-3.38 (m, 1H, CH2Nap),
3.35-3.31 (m, 1H, CH2Nap), 2.78-2.70 (m, 1H, CH, i-Pr),
1.43-1.39 (m, 3H, P-CH3), 1.34-1.30 (m, 6H, CH3, i-Pr),
1.21-1.16 (m, 12H, CH3, i-Pr). 13C{1H} NMR (C6D6): δ
156.9 (d, J = 13, quat), 150.7 (quat), 137.6 (d, J = 12, Ar),
134.2 (Ar), 132.5 (Ar), 130.8 (d, J = 25, Ar), 128.4 (Ar), 128.3
(Ar), 127.8 (Ar), 127.3 (d, J = 7, Ar), 126.1 (Ar), 125.4 (Ar), 122.3
(d, J = 4, CH, Is), 37.1 (d, J = 18, P-CH2), 34.6 (CH, i-Pr), 31.5
(d, J = 21, CH, i-Pr), 25.1 (CH3, i-Pr), 24.9 (CH3, i-Pr), 24.0 (CH3,
i-Pr), 11.5 (d, J = 21, P-CH3). One Ar peak was not found.
Acknowledgment. We thank the National Science
Foundation for support, the Department of Education
for a GAANN fellowship for T.W.C., and Jimmy Wu for
assistance with HPLC.
Supporting Information Available: Text, tables, figures, and
CIF files giving details of the X-ray crystallographic studies,
HPLC chromatograms, 31P NMR spectra, determination of er,
dr, and mole fractions x, a, and b, and additional NMR spectra.
This material is available free of charge via the Internet at http://
pubs.acs.org.