Effects of linker length on the rate and selectivity of platinum-catalyzed asymmetric alkylation of the bis(isitylphosphino)alkanes IsHP(CH 2)nPHIs (Is = 2,4,6-(i -Pr)3C6H 2, n = 1-5)

Article abstract of DOI:10.1021/om100174c

Catalytic asymmetric alkylation of the bis(secondary phosphines) IsHP(CH₂)_nPHIs (1a-e, n = 1-5, Is = isityl = 2,4,6-(i-Pr)₃C₆H₂) with benzyl bromide using the base NaOSiMe₃ and the catalyst

Full text of DOI:10.1021/om100174c

Organometallics 2010, 29, 2465–2473 2465
DOI: 10.1021/om100174c
Effects of Linker Length on the Rate and Selectivity of Platinum-
Catalyzed Asymmetric Alkylation of the Bis(isitylphosphino)alkanes
IsHP(CH2)nPHIs (Is = 2,4,6-(i-Pr)3C6H2, n = 1-5)
Timothy W. Chapp, Adam J. Schoenfeld, and David S. Glueck*
6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755
Received March 3, 2010
Catalytic asymmetric alkylation of the bis(secondary phosphines) IsHP(CH2)nPHIs (1a-e, n = 1-5,
Is = isityl = 2,4,6-(i-Pr)3C6H2) with benzyl bromide using the base NaOSiMe3 and the catalyst precursor
Pt((R,R)-Me-DuPhos)(Ph)(Cl) gave the bis(tertiary phosphines) Is(PhCH2)P(CH2)nP(CH2Ph)Is (2a-e,
n = 1-5) via the intermediates Is(PhCH2)P(CH2)nPHIs (4a-e, n = 1-5). The rates of these reactions
depended strongly on n, in the order 1a < 1b < 1c ≈ 1d ≈ 1e. The bulkier bis(secondary phosphine)
Mes*HP(CH2)2PHMes* (5, Mes* = 2,4,6-(t-Bu)3C6H2) did not undergo catalytic alkylation under these
conditions. The alkylation selectivity also depended on n. Alkylation of 1b was meso-selective, while
alkylation of 1a,c-e was rac-selective, occurring with similar diastereoselectivity and enantioselectivity
for the longer linkers (1c-e). The product ratios suggested that the catalyst controlled the selectivity for
1d,e, while substrate control operated for ethano-bridged 1b, with negative cooperativity. Substrate
control also likely occurred for 1a, for which competition from the background alkylation was significant.
Analysis of the observed diastereo- and enantioselectivity for Pt-catalyzed alkylation of 1c and the mixed
secondary/tertiary phosphine IsHP(CH2)3P(CH2Ph)Is (4c) yielded quantitative information on the
selectivity of both P-C bond-forming steps, which was consistent with predominant catalyst control,
altered slightly by the influence of the substrate.
Introduction
of this class of compounds by Pt-catalyzed asymmetric alkyla-
tion of bis(secondary phosphines).3 With these symmetrical
bifunctional substrates, after formation of one chiral center,
the selectivity of the second alkylation may be the same (catalyst
control) or different (substrate control).4 Catalyst control may
lead to asymmetric amplification and increased enantiomeric
ratio (er) for the rac product; this process is presumably impor-
tant in the alkylation of PhHP(CH2)2PHPh (A), which enabled
isolation of enantiomerically pure B (Scheme 1).5
P-stereogenic bidentate diphosphines such as Knowles’
DiPAMP1 are important ligands in catalytic asymmetric
reactions.2 We recently developed a new method for synthesis
*To whom correspondence should be addressed. E-mail: glueck@
dartmouth.edu.
(1) Knowles, W. S. Angew. Chem., Int. Ed. 2002, 41, 1998–2007.
(2) (a) Phosphorus Ligands in Asymmetric Catalysis. Synthesis and
Substrate control may occur with positive or negative co-
operativity. We recently characterized the latter in the Pt-
catalyzed alkylation of IsHP(CH2)2PHIs (1b; Is=isityl=2,4,-
6-(i-Pr)3C6H2) with 2-(bromomethyl)naphthalene, which was
meso-selective. Although the catalyst controlled the selectivity of
the first alkylation (1b f C), its preference was overridden in the
second alkylation (C f D) by substrate control. In particular,
the absolute configuration of the tertiary phosphine in inter-
mediate Ccontrolled the selectivity of the second alkylation with
alternation of stereochemistry ((RP)-C f (R,S)-D; (SP)-C f
(S,R)-D), selectively yielding meso-D (Scheme 1).6
This negative cooperativity (formation of meso-D instead of
one enantiomer of rac-D) presumably occurred because one P
stereocenter in 1b and C was close enough to the other to
influence its reactivity. Such effects are expected to depend on
the linker connecting the two reactive centers in bifunctional
€
Applications; Borner, A., Ed.; Wiley-VCH: Weinheim, Germany, 2008.
(b) Asymmetric Catalysis on Industrial Scale. Challenges, Approaches,
and Solutions; Blaser, H.-U., Schmidt, E., Eds.; Wiley-VCH: Weinheim,
Germany, 2004.
(3) (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, 5124 (addition/correction). For
related syntheses using secondary phosphines and bifunctional alkyl
halides, see: (c) Chan, V. S.; Chiu, M.; Bergman, R. G.; Toste, F. D.
J. Am. Chem. Soc. 2009, 131, 6021–6032.
(4) (a) Takahata, H.; Takahashi, S.; Kouno, S.; Momose, T. J. Org.
Chem. 1998, 63, 2224–2231. (b) El Baba, S.; Sartor, K.; Poulin, J.-C.; Kagan,
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, M.;
Ito, Y. Tetrahedron Lett. 1995, 36, 5239–5242. (i) Hayashi, T.; Hayashizaki, K.;
Ito, Y. Tetrahedron Lett. 1989, 30, 215–218. (j) Kalck, P.; Urrutigoïty, M.
Coord. Chem. Rev. 2004, 248, 2193–2200. (k) Masamune, S.; Choy, W.;
Petersen, J. S.;Sita, L. R. Angew. Chem., Int. Ed. 1985, 24, 1–30. (l) Lagasse, F.;
Tsukamoto, M.; Welch, C. J.; Kagan, H. B. J. Am. Chem. Soc. 2003, 125, 7490–
7491. (m) Kitamura, M.; Ohkuma, T.; Inoue, S.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J. Am. Chem. Soc. 1988, 110,
629–631.
(5) Anderson, B. J.; Glueck, D. S.; DiPasquale, A. G.; Rheingold,
A. L. Organometallics 2008, 27, 4992-5001; 2009, 28, 386 (addition/
correction).
(6) Chapp, T. W.; Glueck, D. S.; Golen, J. A.; Moore, C. E.;
Rheingold, A. L. Organometallics 2010, 29, 378–388.
r
2010 American Chemical Society
Published on Web 05/11/2010
pubs.acs.org/Organometallics

2466 Organometallics, Vol. 29, No. 11, 2010
Chapp et al.
Scheme 2. Synthesis of Bis(secondary phosphines) 1d,e
Scheme 1. Pt-Catalyzed Asymmetric Alkylation of
Bis(secondary phosphines)
Scheme 3. Pt-Catalyzed Asymmetric Alkylation of
Bis(secondary isitylphosphines) 1a-e
Scheme 4. Synthesis and Pt-Catalyzed Alkylation of 4c
substrates; they should vanish at sufficiently long separa-
tions (catalyst control). Understanding these structure/reac-
tivity/selectivity relationships is potentially useful for develo-
ping improved catalytic processes for the synthesis of chiral
ligands. With this goal in mind, we report here studies of the
effects of the linker in the bis(secondary phosphines) IsHP-
(CH2)nPHIs (1a-e, n=1-5) on rate and selectivity in their
Pt-catalyzed asymmetric alkylation with benzyl bromide.
The mixed secondary/tertiary phosphines Is(PhCH2)P(CH2)n-
PHIs (4a-e, n = 1-5) were intermediates in these reactions;
their 31P NMR data are reported in the Experimental Section
(Table 4). Control experiments showed that the background
reactions (Pt-free alkylation of 1a-e) were much slower than the
catalytic processes for substrates 1b-e but about as fast as the
catalytic reaction of 1a (see the Supporting Information for
details).
Results and Discussion
Deprotonation/alkylation of 1c with 1 equiv of s-BuLi/
PhCH2Cl gave the mixed tertiary/secondary bis(phosphine)
4c as the major component of an inseparable mixture
containing unreacted 1c and overalkylated 2c (Scheme 4).
However, adding additional s-BuLi and monitoring the
deprotonation of 1c by 31P NMR spectroscopy enabled
isolation of a 63/37 mixture of 4c (1/1 mixture of dia-
stereomers) and 2c (0.65/1 rac/meso ratio). Pt-catalyzed
alkylation of this mixture converted 4c to 2c, which was
not further alkylated under these conditions (Scheme 4).
The observed times for completion of the Pt-catalyzed
double alkylations (Scheme 3) suggested that their rates
depended strongly on n, in the order 1a < 1b < 1c ≈ 1d ≈ 1e.
(We did not measure the reaction rates, but catalyst decom-
position was not observed; therefore, we assume that the
reaction times correlate with rates.) These observations can
be explained most simply by steric effects, in which the
presence of another bulky isitylphosphino group near the
reactive center slows alkylation or another step in the
catalytic cycle. A similar trend occurred in substrates which
differed only in the P substituent; the rate of catalytic
alkylation of the bis(secondary phosphines) ArHP(CH2)n-
PHAr depended on the aryl group (for n = 3, Ph > Mes ≈ Is;
for n = 2, Ph > Is).5 For comparison, we prepared the even
bulkier bis(secondary phosphine) Mes*HP(CH2)2PHMes*
(5; Mes*=2,4,6-(t-Bu)3C6H2; see the Experimental Section),
Preparation of Bis(secondary phosphines). The bis(secondary
phosphines) IsHP(CH2)nPHIs (1a,b; n=1-2) are known,7 and
we prepared the longer chain substrates by alkylation of PH2Is
with dibromoalkanes in the superbasic medium8 KOH/DMSO
(Scheme 2), as we recently reported for 1c.9,7c Under these
conditions, 1c was formed more slowly than the less hindered
MesHP(CH2)3PHMes9 (Mes = 2,4,6-Me3C6H2).7c The rates of
formation of 1d,e were similar to that of 1c; these compounds
were relatively insoluble in DMSO, which simplified their
purification.
Catalytic Alkylation. Catalytic alkylation of bis(secondary)
phosphines 1a-e with benzyl bromide and NaOSiMe3 using 10
mol % of the catalyst precursor Pt((R,R)-Me-DuPhos)(Ph)(Cl)
(see Scheme 1) gave bis(tertiary phosphines) 2a-e (Scheme 3).
(7) n = 1: (a) Bitterer, F.; Kucken, S.; Langhans, K. P.; Stelzer, O. Z.
Naturforsch., B 1994, 49, 1223–1238. Bitterer, F.; Brauer, D. J.; Dorrenbach,
F.; Fischer, J.; Stelzer, O. Z. Naturforsch., B 1992, 47, 1529–1540. n = 2:
(b) Reference 6. n = 3: (c) Lane, E. M.; Chapp, T. W.; Hughes, R. P.; Glueck,
D. S.; Feland, B. C.; Bernard, G. M.; Wasylishen, R. E.; Rheingold, A. L.
Inorg. Chem. 2010, 49, 3950–3957.
(8) (a) Tsvetkov, E. N.; Bondarenko, N. A.; Malakhova, I. G.;
Kabachnik, M. I. Synthesis 1986, 198–208. (b) Terekhova, M. I.;
Bondarenko, N. A.; Malakhova, I. G.; Tsvetkov, E. N.; Petrov, E. S.;
Shatenshtein, A. I. J. Gen. Chem. U.S.S.R. 1982, 52, 452–455.
(9) Karasik, A. A.; Naumov, R. N.; Spiridonova, Y. S.; Sinyashin,
O. G.; Lonnecke, P.; Hey-Hawkins, E. Z. Anorg. Allg. Chem. 2007, 633,
205–210.

Article
Organometallics, Vol. 29, No. 11, 2010 2467
Table 1. 31P NMR Data for Diphosphines 2a-e and Their Derivatives, with Product Ratios from Schemes 3 and 4a
n (No.)
δ (diphosphine 2)b
δ (oxide 3)b
δ (3/6 adduct)c
drd
ere
1 (a)
2 (b)
3 (c)
4 (d)
5 (e)
3 (c)g
-30.9, -33.9
-22.0, -22.1
-26.9, -27.0
-26.0, -25.9
-25.9f
40.4, 38.4
43.8, 44.3
43.7, 43.5
43.6, 43.4
44.6, 44.3
41.9, 41.8, 40.2 (AB, J = 14)
47.9, 47.8, 47.6 (AB, J = 53)
48.1, 47.9, 47.5, 47.4
47.7, 47.6, 47.5, 47.4
49.2, 49.1, 48.8, 48.7
1.4(3)
0.33(1)
1.8(1)
1.4(1)
1.3(1)
1.5(1)
1.2(1)
3.9(1)
4.6(3)
4.7(4)
4.8(5)
2.1(1)
a The external standard for 31P NMR chemical shifts was 85% H3PO4. Coupling constants are reported in Hz. Solvents: CDCl3 for 2a,c-e, 3a-e, and
adducts of 3b,c; C6D6 for 2b and the adduct of 3e; CD2Cl2 for adducts of 3a,d. b The chemical shift of the rac diastereomer (which was the major one for all
but b) is listed first, followed by that for the meso isomer. c Chemical shifts are reported in the order minor rac, major rac, meso, for products formed using
the Pt((R,R)-Me-DuPhos)(Ph)(Cl) catalyst precursor. d dr = diastereomer ratio, rac/meso. e er = enantiomer ratio. The dr and er values reported are the
average of two or more separate experiments, with the standard deviation reported as the error (see the Supporting Information). f Only one peak was
observed g Data for alkylation of 4c (Scheme 4), corrected for the presence of 2c in the starting material
Scheme 5. Formation of 3a-e by Oxidation of 2a-e and Struc-
ture of the Shift Reagent 6
Scheme 6. Stereoselectivity of Pt-Catalyzed Alkylation of 1
(To Yield 4) and of 4 (To Yield 2), Defined by the Mole Fractions
x, a, and ba
which did not undergo catalytic alkylation under these
conditions.
The selectivity of alkylation of 1a-e also depended on
linker length n. In most cases (n = 1-4; 2a-d), the diastereo-
selectivity could be ascertained directly from 31P NMR
spectra, since the rac and meso isomers had distinct chemical
shifts.5 Bis(tertiary phosphines) 2a-e were then treated with
H2O2 to yield phosphine oxides 3a-ein high yields (Scheme 5);
such oxidations proceed with retention of configuration at
phosphorus.10 The improved 31P NMR chemical shift dis-
persion in 3a-e provided another opportunity to measure
the diastereomeric ratio (dr).11 Treatment of 3a-e with the
chiral amino acid shift reagent Fmoc-Trp(Boc)-OH (6) gave
diastereomeric mixtures of hydrogen-bonded adducts with
distinct singlet 31P NMR chemical shifts for the R,R and S,S
diphosphine oxides, while the meso R,S isomers gave rise to
two peaks, for which AB patterns with P-P couplings were
observed for shorter chain lengths (n = 1, 2).12 Integration of
these spectra provided the product ratios shown in Table 1,
which also contains results for the Pt-catalyzed alkylation of
4c (Scheme 4, corrected for the presence of 2c in the starting
material; see the Supporting Information for details). Con-
sistent dr values were obtained from spectra of 2a-e, 3a-e,
and the adducts with 6 (see the Supporting Information). We
have previously validated this approach by comparing 31P
NMR and chiral HPLC assays of product ratios for closely
related diphosphine oxides.6
a The mole fraction x is defined by the relative amounts of inter-
mediates 4; x = [R]/([R] þ [S]).
similar for substrates 1c-e, with linkers of three to five
methylenes, while 1a,b gave anomalous results.
The simplest hypothesis to explain the observed selectivity
is that alkylation of the short-linker substrates 1a,b was
under substrate control, while catalyst control prevailed
for longer linkers in 1c-e. As described previously, alkyla-
tion selectivity may be described quantitatively using para-
meters shown in Scheme 6 and eqs 1-4.6
xa þ ð1 - xÞðbÞ
substrate control : dr ¼
ð1Þ
ð2Þ
ðxÞð1 - aÞ þ ð1 - xÞð1 - bÞ
xa
er ¼
ð1 - xÞðbÞ
2
x2 þ ð1 - xÞ
catalyst control : dr ¼
ð3Þ
ð4Þ
2xð1 - xÞ
Selectivity of Catalytic Alkylation. These data showed that
the linker length had a strong influence on the selectivity of the
double alkylation (Scheme 3). Most strikingly, formation of
ethano-bridged 2b was meso-selective, as observed previously
with the same substrate (1b) and 2-(bromomethyl)naphthalene
(Scheme 1).6 Diastereoselectivity and enantioselectivity were
x2
er ¼
2
ð1 - xÞ
Considering the two alkylations of 1separately, the mole frac-
tions x and 1 - x define the amounts of diastereomeric inter-
mediates 4 (for example, RP-4 refers to (R,R)-4 plus (R,S)-4; the
labels are for the tertiary and secondary phosphine stereocen-
ters, respectively). Note that the absolute configuration of the
diphosphines has not been established; therefore, we have
arbitrarily assigned the major rac diastereomers of 2 to be R,R,
(10) Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley-
Interscience: New York, 2000; pp 300-303.
(11) Gawley, R. E. J. Org. Chem. 2006, 71, 2411–2416.
(12) Li, Y.; Raushel, F. M. Tetrahedron: Asymmetry 2007, 18, 1391–
1397.

2468 Organometallics, Vol. 29, No. 11, 2010
Chapp et al.
Table 3. Experimental and Calculated Product Ratios in
Pt-Catalyzed Formation of 2c from 1c and from 4c under
Table 2. Predicted and Experimental Selectivities for
Pt-Catalyzed Alkylation of 1c-e
Substrate Control (SC) or Catalyst Control (CC)a
entry
n (no.)
x
dr
dr (calcd)
er
er (calcd)
(R,R)-2c meso-2c (S,S)-2c
dr
er
1
2
3
4
5
3 (c)
3 (c)
3 (c)
4 (d)
5 (e)
0.77
0.73
0.68
0.69
0.68
1.8(1)
1.82
1.54
1.30
1.34
1.30
4.6(3)
11
7.3
4.5
4.9
4.5
from 1c (exptl)
0.525b
0.53
0.49
0.41
0.39
0.35
0.36
0.35
0.42
0.40
0.43
0.50
0.115b
0.11
0.09
0.19
0.18
0.15
1.8(1) 4.6(3)
1.8
1.4
1.5(1) 2.1(2)
1.3
1.0
from 1c (calcd (SC))c
from 1c (calcd (CC))
from 4c (exptl)
4.8
5.4
1.4(1)
1.3(1)
4.7(4)
4.8(5)
from 4c (calcd (SC))
from 4c (calcd (CC))
2.2
2.3
Scheme 7. Stereoselectivity in Pt-Catalyzed Alkylation of 1c
(To Yield 4c) and of 4c (To Yield 2c)
a The major enantiomer of 2c was arbitrarily assumed to have an R,R
configuration. For SC, x = 0.69, a = 0.77, b = 0.37 (1 - b = 0.63). For
CC, x = a = 1 - b = 0.70. b The third digit is included to avoid rounding
errors. c These product ratios do not sum to 1.0 because of rounding
errors.
Table 4. 31P NMR Data for the Intermediates IsHP(CH2)n-
P(CH2Ph)(Is) (4a-e)a
n (no.)
1 (a)
δ(PH)
δ(PCH2Ph)
J
-97.2
-97.1
-90.6
-89.3
-95.9
-95.8
-94.9
-95.0
-94.90
-94.91
-28.0
-28.6
-22.8
-23.1
-27.8
-27.7
-26.7
-26.8
-26.75
-26.77
119
125
31
2 (b)
3 (c)
4 (d)
5 (e)b
30
by analogy to the (RP)-PMe(Is)(CH2Ph) formed in Pt-catalyzed
alkylation of PHMe(Is) with the same catalyst precursor.3b,13
Conversion of 4 to 2 then occurs in two parallel channels, which
differ only in the configuration of the tertiary phosphine in
substrate 46,14 and are defined by the mole fractions a and b. If
the selectivities of alkylation of the two phosphorus sites in
substrates 1 differ (x ¼ a ¼ 1 - b), then the product ratios are
given by eqs 1 and 2 (substrate control). If they are the same (x=
a=1- b), eqs 3 and 4 give dr and er values (catalyst control).6,15
If catalyst control is operative in a given reaction, there
must be an x value which yields product ratios from eqs 3
and 4 that match the experimental observations. For exam-
ple, approximately the same x predicts dr and er values for
alkylation of 1d,e in reasonable agreement with the experi-
mental data (Table 2, entries 4 and 5; results are included for
two different values of x to show how sensitive the predic-
tions are to small changes in this parameter). In contrast to
this catalyst control, the selectivity of the two alkylation
steps for 1b must be different (substrate control), as char-
acterized quantitatively with a different benzyl bromide
(Scheme 1).6 Because the background reaction competes
with the Pt-catalyzed alkylation of 1a, we did not attempt
such analyses for this substrate, but the observed product
distribution is most consistent with substrate control. Sub-
strate 1c is an intermediate case, where a choice of x to match
the experimental dr (entry 1) predicts too large an er, but
reducing x to fit the experimental enantioselectivity (entry 3)
leads to a too-small dr, and an intermediate value (entry 2)
gets them both wrong. These observations suggested a low
degree of substrate control, which was investigated in more
detail.
a 31P NMR chemical shift standard: 85% H3PO4. Coupling constants
are reported in Hz. Solvent: THF. Intermediates 4 were generated during
Pt-catalyzed conversion of bis(secondary phosphines) 1a-e to bis-
(tertiary phosphines) 2a-e. In most cases, the ratio of diastereomers
of 4 was close to 1/1; data for the major isomers are given first.
b Overlapping signals.
Values of x, a, and b (Scheme 6), and hence quantitative
characterization of catalyst vs substrate control, may be
obtained by comparing the product ratios in separate Pt-
catalyzed alkylations of substrate 1c and intermediate 4c.6
Substituting these data from Table 1 (rows 3 and 6) into eqs 1
and 2 gave x = 0.69(4), a = 0.77(5), and b = 0.37(3) (1 - b =
0.63(3)), as shown in Scheme 7.16 As anticipated from the
discussion of the data in Table 2, these values are close to, but
not identical with, those required for catalyst control (x = a =
1 - b). The predicted product ratios are in good agreement
with experimental dr and er values for Pt-catalyzed formation
of 2c from either 1c or 4c (Table 3) and significantly better than
the catalyst-control predictions made by using an average
value, x = a = 1 - b = 0.70 (see Tables 2 and 3).16
Therefore, alkylation of 1c appears to be mainly catalyst-
controlled, with a minor contribution from substrate con-
trol; the selectivities of alkylation of RP-4c, SP-4c, and 1c are
slightly different.17 Note that the value x = 0.69 is similar to
those deduced for catalyst-controlled alkylation of the longer-
chain substrates 1d,e, suggesting that the selectivity of the
first alkylation of 1c may be unaffected by the pendant
(13) It is plausible that the major rac diastereomer has the same
configuration in each case; this would be consistent with the 31P NMR
chemical shift trends for adducts of 3a-e with 6, in which the major rac
signal appears upfield of the minor one, but there is no direct evidence
for this assumption.
(14) As described in ref 6 (see Scheme 5 and accompanying dis-
cussion), the selectivity of alkylation of the diastereomers in a given
channel (such as (R,R)-4 and (R,S)-4) is expected to be identical, since
both will form the same mixture of Pt-phosphido intermediates.
(15) Fleming, I.; Ghosh, S. K. J. Chem. Soc., Chem. Commun. 1994,
99–100.
(16) See the Supporting Information for estimates of the errors in
determination of the parameters x, a, and b; note that they are not
independent. Rounding errors in calculations of product ratios and dr
and er values in Table 3 also affect those numbers; see the Supporting
Information for more discussion.
(17) It is plausible that the selectivity of alkylation of RP-1c also
differs from that of SP-1c, but as discussed previously,6 we cannot
determine these parameters independently.

Article
Organometallics, Vol. 29, No. 11, 2010 2469
(CH2)3PHIs group, and only in the second alkylation does
the larger (CH2)3P(CH2Ph)(Is) moiety affect the selectivity.
as reported in ref 8a, were no faster than those in its absence.)
The solution was stirred for 1 h, and then 1,4-dibromobutane
(253 μL, 2.12 mmol, 1 equiv) was injected via microliter syringe.
The solution turned clear and then cloudy. The mixture was
stirred for 62 h, over which time a white solid precipitated. The
reaction was quenched with 30 mL of degassed H2O, and then
the mixture was extracted with three 30 mL portions of petro-
leum ether. The 31P NMR spectrum of the crude reaction
mixture showed mainly the desired bis(phosphine) (δ -101.3,
-101.4), the starting material PH2Is (δ -166.6), an unidentified
peak (δ -39.0), and some phosphine oxide (δ 59.0). The
petroleum ether solution was dried over MgSO4 and filtered,
and the solvent was removed to leave an oily white residue.
PH2Is was removed from the crude product by Kugelrohr
distillation. The residue melted completely at 100-110 °C, and
PH2Is was distilled away from the product at 151 °C under
vacuum. Upon cooling, the solid bis(phosphine) was further
purified to remove the phosphine oxide by eluting over a silica
column (0.5 cm wide ꢀ 3.5 cm high) with 15 mL of petroleum
ether and then washing the solid with three 10 mL portions of
DMSO to leave 383 mg (34% yield) of white solid.
The mass spectrum was consistent with oxidation of the air-
sensitive phosphine: calcd HRMS (ESþ) for C34H57O2P2
(MO2Hþ) m/z 559.3834, found m/z 559.3829. 31P{1H} NMR
(CDCl3): δ -94.28, -94.29 (overlapping, ∼1:1); plus traces of
unidentified impurities:, δ -32.6, -112.2, -116.6. 1H NMR
(CDCl3): δ 7.03 (d, J = 2, 4H, Ar), 4.25 (dm, JPH = 215, 2H,
P-H), 3.67-3.60 (m, 4H, i-Pr CH), 2.88 (sep, J = 7, 2H, i-Pr
CH), 1.82 (broad, 2H, P-CH2), 1.58 (broad m, 6H, CH2), 1.30
(d, J = 7, 12H, i-Pr CH3), 1.27 (d, J = 7, 12H, i-Pr CH3), 1.23 (d,
J = 7, 12H, i-Pr CH3). 13C{1H} NMR (CDCl3): δ 152.7 (d, J =
11, quat, Ar), 149.3 (quat, Ar), 128.1 (d, J = 14, quat, Ar), 121.3
(d, J = 3, CH, Ar), 34.2 (i-Pr CH), 32.6 (d, J = 14, i-Pr CH), 29.8
(t, J = 11, P-CH2), 24.9 (i-Pr CH3), 24.3 (i-Pr CH3), 23.8 (d,
J = 2, i-Pr CH3), 23.7 (d, J = 11, CH2).
IsHP(CH2)5PHIs (1e). To a mixture of PH2Is (1.03 g, 79%
purity by 1H NMR spectroscopy, containing 21% 1,3,5-triiso-
propylbenzene, 3.67 mmol, 2 equiv) and anhydrous K2CO3 (553
mg, 4 mmol, 2.2 equiv) in DMSO (ca. 40 mL) under N2, was
added freshly ground KOH (216 mg, 3.85 mmol, 2 equiv) to
produce a yellow solution. The solution was stirred for 1 h, and
then 1,5-dibromobutane (251 μL, 1.83 mmol, 1 equiv) was
injected via microliter syringe. The solution turned clear and
then cloudy. The mixture was stirred for 62 h, over which time a
white solid precipitated. The mixture was quenched with 25 mL
of degassed H2O and then extracted with three 30 mL portions
of ether. The 31P NMR spectrum of the crude reaction mixture
showed mainly the desired bis(phosphine) (δ -100.9), the start-
ing material PH2Is (δ -166.4), and an unidentified peak (δ
-51.0). The ether solution was dried over MgSO4 and filtered,
and the solvent was removed to leave an oily white residue.
PH2Is was removed from the crude product by Kugelrohr
distillation under vacuum at 140 °C. When the distillation pot
was cooled, a white solid was recovered, which was further
purified by washing with three 10 mL portions of DMSO to give
514 mg (52% yield) of the desired product.
Anal. Calcd for C35H58P2: C, 77.73; H, 10.81. Anal. Calcd for
C35H58O2P2: C, 73.39; H, 10.21. Found: C, 71.16; H, 9.88. The
mass spectrum was consistent with oxidation of the air-sensitive
phosphine: calcd HRMS (ESþ) for C35H59O2P2 (MO2Hþ) m/z
573.3990, found m/z 573.3976. 31P{1H} NMR (CDCl3): δ
-94.06, -94.07 (∼1:1 mixture of diastereomers). 1H NMR
(CDCl3): δ 7.02 (d, J = 2, 4H, Ar), 4.23 (d of apparent t,
JPH = 215, J = 8, 2H, P-H), 3.70-3.61 (m, 4H, i-Pr CH), 2.88
(sep, J = 7, 2H, i-Pr CH), 1.84-1.76 (broad m, 2H, P-CH2),
1.61-1.44 (broad m, 8H, CH2), 1.29 (d, J = 7, 12H, i-Pr CH3),
1.26 (d, J = 7, 12H, i-Pr CH3), 1.22 (d, J = 7, 12H,
i-Pr CH3). 13C{1H} NMR (CDCl3): δ 152.7 (d, J = 11, quat, Ar),
149.3 (quat, Ar), 128.2 (d, J = 15, quat, Ar), 121.3 (d, J = 4, CH,
Ar), 34.2 (i-Pr CH), 32.6 (d, J = 14, i-Pr CH), 32.4 (t, J = 10,
Conclusion
In catalytic asymmetric reactions of symmetrical bifunc-
tional substrates, the selectivity of a transformation at one
site may affect the selectivity of the same transformation at
the nominally identical second site (substrate control). This
effect should depend on the separation between the reactive
centers, vanishing at sufficiently long distances (catalyst
control). In Pt-catalyzed alkylation of the bis(secondary
phosphine) substrates 1a-e, four or five methylene groups
provided a long enough linker to insulate the two P-nucleo-
philes and ensure catalyst-controlled rac-selective alkylation
for 1d,e. In contrast, a two-carbon linker in 1b resulted in
substrate control with negative cooperativity (meso-selective
alkylation), and substrate control also appeared to be opera-
tive for 1a. The three-carbon linker in 1c resulted in inter-
mediate behavior, where the catalyst control was only
slightly affected by the substrate.
The linker also affected the rate of catalysis, which was
slower for 1a,b, presumably due to steric effects of the large
isityl groups, which is also the likely origin of the substrate-
controlled selectivity.6 Logical future steps in establishing
such structure/reactivity/selectivity relationships include vary-
ing the size of the P substituent and using more rigid linkers;
both are currently under investigation.
Experimental Section
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.18 NMR spectra
were recorded using Varian 300 or 500 MHz spectrometers. 1H
or 13C NMR chemical shifts are reported vs Me4Si and were
determined by reference to the residual 1H or 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. Elemental analyses were provided
by Quantitative Technologies Inc. Mass spectra were recorded
at the University of Illinois, Urbana-Champaign (http://www.
scs.uiuc.edu/∼msweb).
Reagents were from commercial suppliers, except for these
compounds, which were made by the literature procedures: Pt-
((R,R)-Me-DuPhos)(Ph)(Cl),19 PH2Is,20 Mes*Br,21 IsHP(CH2)-
PHIs (1a),7a IsHP(CH2)2PHIs (1b),7b and IsHP(CH2)3PHIs (1c).7c
IsHP(CH2)4PHIs (1d). To a mixture of PH2Is (1.18 g, 79%
purity by 1H NMR spectroscopy, containing 21% 1,3,5-triiso-
propylbenzene, 4.23 mmol, 2 equiv) and anhydrous K2CO3 (691
mg, 5 mmol, 2.4 equiv) in DMSO (ca. 40 mL) under N2 was
added freshly ground KOH (238 mg, 4.23 mmol, 2 equiv) to
produce a yellow solution. (Note: reactions with added K2CO3,
(18) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518–1520.
(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) Cowley, A. H.; Norman, N. C.; Pakulski, M. Inorg. Synth. 1990,
27, 235–240.

2470 Organometallics, Vol. 29, No. 11, 2010
Chapp et al.
P-CH2), 28.1 (d, J = 12, CH2), 24.9 (i-Pr CH3), 24.3 (i-Pr CH3),
23.86 (d, J = 2, i-Pr CH3), 23.8 (d, J = 11, CH2).
J = 8, 12, CH2Ph, rac), 35.8 (dd, J = 8, 12, CH2Ph, meso), 34.6
(CH, i-Pr, meso), 34.5 (CH, i-Pr, rac), 31.7 (apparent t, J = 10,
CH, i-Pr, rac/meso), 26.8 (d, J = 6, P-CH2, rac/meso), 25.1 (i-Pr
CH3, rac/meso), 25.0 (i-Pr CH3, meso), 24.8 (i-Pr CH3, rac), 24.0
(i-Pr CH3, meso), 23.9 (i-Pr CH3, rac). One quaternary carbon
signal was not found.
Pt-Catalyzed Alkylation of 1a-e. General Procedure for
Synthesis of Is(PhCH2)P(CH2)nP(CH2Ph)Is (2a-e). A solution
of Pt((R,R)-Me-DuPhos)(Ph)(Cl) (3 mg, 0.005 mmol, 10 mol %)
in 1 mL of THF was added to the bis(secondary phosphine)
(0.05 mmol; for example, 25 mg of 1b) followed by NaOSiMe3
(12 mg, 0.1 mmol, 2 equiv), and the solution turned yellow. The
mixture was transferred to an NMR tube, and benzyl bromide
(12 μL, 0.1 mmol, 2 equiv) was added neat via syringe. Once the
reaction was complete, as monitored by 31P NMR spectroscopy,
the solvent was removed under reduced pressure to leave an
oily white residue, which was eluted over a silica column (0.6 cm
width ꢀ 3.0 cm height) with three 1 mL portions of 9/1 petro-
leum ether/THF. The catalyst and the NaBr did not elute. The
eluted solvent was removed under reduced pressure to leave an
oily residue of 2a-e. See the individual compounds for the
amounts of 1a-e, reaction times, and yields of 2a-e.
Is(PhCH2)PCH2P(CH2Ph)Is (2a). A 24 mg amount of 1a was
used; 4 days, 66% yield (22 mg of 2a). The time for completion of
this slow reaction varied in duplicate experiments from ca. 2-4
days. Despite standard precautions to exclude oxygen, an addi-
tional product tentatively assigned as Is(CH2Ph)P(O)CH2P-
(CH2Ph)Is (2a-O, 31P{1H} NMR (THF) δ 40.7 (d, J = 83),
40.2 (d, J = 68), -39.3 (d, J = 68), -42.4 (d, J = 83); dr ranged
from 1.6/1 to 1.3/1) was also observed in varying amounts (from
ca. 10 to 20%). Oxidation of a sample of 2a containing this
material with H2O2 (see below) gave the bis(phosphine oxide)
3a, consistent with the proposed structure of 2a-O. The er of 2a
did not depend on the amount of this impurity, but the dr of 2a
was higher in samples which contained more of it. See the
Supporting Information for more details and information on
the Pt-free background alkylation, which occurred at a similar
rate.
Is(PhCH2)P(CH2)3P(CH2Ph)Is (2c). A 25 mg amount of 1c
was used; 1 h, 84% yield (29 mg of 2c). HRMS (ESþ): calcd for
C47H67P2 (MHþ) m/z 693.4718, found m/z 693.4713. 31P{1H}
NMR (C6D6): δ -27.3 (rac), -27.4 (meso), ∼1.8/1 (rac/meso).
1H NMR (C6D6): δ 7.13-7.11 (m, 4H, Ar, rac/meso), 7.10 (d,
J = 2, 4H, Ar, rac), 7.09 (d, J = 2, 4H, Ar, meso), 7.07-7.03 (m,
4H, Ar, rac/meso), 6.99-6.96 (m, 2H, Ar, rac/meso), 4.04
(broad, 4H, i-Pr CH, rac/meso), 3.19 (AB pattern, J = 14, 4H,
CH2Ph, rac), 3.18 (AB pattern, J = 13, 4H, CH2Ph, meso),
2.76-2.70 (m, 2H, i-Pr CH, rac/meso), 2.08-1.98 (m, 4H,
P-CH2, rac/meso), 1.65-1.56 (m, 2H, P-CH2, rac/meso),
1.28 (d, J = 7, 12H, i-Pr CH3, meso), 1.27 (d, J = 7, 12H, i-Pr
CH3, rac), 1.19-1.16 (m, 24H, i-Pr CH3, rac/meso). 13C{1H}
NMR (C6D6): δ 156.0 (broad, quat, Ar, meso), 155.9 (broad,
quat, Ar, rac), 150.5 (quat, Ar, rac/meso), 140.19 (d, J = 12,
quat, Ar, meso), 140.17 (d, J = 12, quat, Ar, rac), 130.0 (d, J =
26, quat, Ar, rac), 129.9 (d, J = 26, quat, Ar, meso), 129.41 (d,
J = 7, CH, Ar, rac), 129.40 (d, J = 7, CH, Ar, meso), 128.54 (m,
CH, Ar), 125.9 (d, J = 3, CH, Ar, rac/meso), 122.3 (broad, CH,
Ar, rac/meso), 36.1 (d, J = 19, CH2, rac/meso), 34.57 (i-Pr CH,
rac), 34.56 (i-Pr CH, meso), 31.8 (i-Pr CH, meso), 31.6 (i-Pr CH,
rac), 29.7-29.4 (m, CH2, rac/meso), 27.8 (apparent t, J = 27,
P-CH2CH2, rac), 27.7 (apparent t, J = 27, P-CH2CH2, meso),
25.1 (i-Pr CH3, rac), 25.03 (i-Pr CH3, meso), 25.00 (i-Pr CH3,
rac/meso), 24.0 (i-Pr CH3, rac/meso).
Is(PhCH2)P(CH2)4P(CH2Ph)Is (2d). A 26 mg amount of 1d
was used; 2 h, 97% yield of 2d (34 mg). HRMS (ESþ): calcd for
C48H69P2 (MHþ) m/z 707.4875, found m/z 707.4881. 31P{1H}
NMR (C6D6): δ -26.30 (meso), -26.33 (rac), ∼1.3/1 (rac/meso,
overlapping signals). 1H NMR (C6D6): δ 7.15-7.13 (m, 4H, Ar,
rac/meso), 7.11-7.09 (m, 4H, Ar, rac/meso), 7.07-7.02 (m, 4H,
Ar, rac/meso), 6.99-6.95 (m, 2H, Ar, rac), 4.05 (broad, 4H, i-Pr
CH, rac/meso), 3.17 (overlapping AB patterns, J = 14, 4H,
P-CH2Ph, rac/meso), 2.78-2.68 (m, 2H, i-Pr CH, rac/meso),
1.90-1.84 (m, 2H, CH2, rac/meso), 1.82-1.76 (m, 2H, CH2, rac/
meso), 1.42-1.38 (broad m, 4H, CH2, rac/meso), 1.31 (d, J = 7,
12H, i-Pr CH3, meso), 1.30 (d, J = 7, 12H, i-Pr CH3, rac),
1.18-1.15 (m, 24H, i-Pr CH3, rac/meso). 13C{1H} NMR (C6D6):
δ 156.0 (broad, quat, Ar, meso), overlapping 155.9 (broad, quat,
Ar, rac), 150.5 (quat, Ar, rac/meso), 140.2 (d, J = 12, quat, Ar,
rac/meso), 129.9 (d, J = 27, quat, Ar, meso), 129.8 (d, J = 27,
quat, Ar, rac), 129.4-129.3 (m, CH, Ar, rac/meso), 128.55 (CH,
Ar, rac), 128.54 (CH, Ar, meso), 125.9-125.8 (m, CH, Ar, rac/
meso), 122.3 (broad, CH, Ar, rac/meso), 36.1 (d, J = 19, CH2Ph,
meso), 36.0 (d, J = 20, PCH2Ph, rac), 34.6 (i-Pr CH, rac/meso),
31.63 (d, J = 21, i-Pr CH, meso), 31.60 (d, J = 21, i-Pr CH, rac),
30.5-29.9 (m, CH2, rac/meso), 27.9 (d, J = 18, CH2, meso), 27.8
(d, J = 18, CH2, rac), 25.1 (i-Pr CH3, overlapping rac/meso),
25.0 (i-Pr CH3, overlapping rac/meso), 24.02 (i-Pr CH3, rac),
24.00 (i-Pr CH3, meso).
HRMS (ESþ): calcd for C45H63P2 (MHþ) m/z 665.4405, found
m/z 665.4399. 31P{1H} NMR (C6D6): δ -31.6 (rac), -34.1 (meso),
∼1.4/1 (rac/meso). 1H NMR (C6D6): δ 7.18-7.13 (m, 4H, Ar, rac/
meso), 7.10 (2H, Ar, rac/meso), 7.05-6.92 (m, 8H, Ar, rac/meso),
3.98 (broad, 4H, i-Pr CH, rac/meso), 3.47 (AB pattern, J = 13, 4H,
CH2Ph, rac), 3.30 (AB pattern, J=13, 4H, CH2Ph, meso), 2.80-
2.73 (m, 2H, CH2, rac/meso), 2.72-2.60 (m, 2H, i-Pr CH, rac/
meso), 1.30 (d, J = 7, 12H, i-Pr CH3, rac), 1.20 (d, J = 7, 12H, i-Pr
CH3, meso), 1.17-1.04 (m, 24H, i-Pr CH3, rac/meso). 13C{1H}
NMR (C6D6): δ 150.9 (quat, Ar, rac/meso), 150.6 (quat, Ar, rac/
meso), 139.9-139.7 (m, quat, Ar, rac/meso), 129.6-129.5 (m, CH,
Ar, rac/meso), 128.53 (CH, Ar, meso), 128.49 (CH, Ar, rac), 128.3-
127.7 (m, Ar, rac/meso, overlapping C6D6 peaks), 125.9 (CH, Ar,
rac/meso), 122.3-122.2 (m, CH, Ar, rac/meso), 36.3 (t, J = 6, CH2,
meso), 35.88 (t, J = 7, CH2, rac), 34.6 (i-Pr CH, rac), 34.5 (i-Pr CH,
meso), 31.8-31.5 (m, P-CH2-P, rac/meso), 25.2 (broad, i-Pr CH,
rac/meso), 24.84 (i-Pr CH3, meso), 24.80 (i-Pr CH3, rac), 23.99 (i-Pr
CH3, rac), 23.97 (i-Pr CH3, meso).
Is(PhCH2)P(CH2)2P(CH2Ph)Is (2b). A 25 mg amount of 1b
was used; 10 h, 85% yield (29 mg). HRMS (ESþ): calcd for
C46H65P2 (MHþ) m/z 679.4562, found m/z 679.4580. 31P{1H}
NMR (C6D6): δ -22.0 (rac), -22.1 (meso), ∼2.9/1 meso/rac
1
(overlapping peaks). H NMR (C6D6): δ 7.16-6.91 (m, 14H,
Is(PhCH2)P(CH2)5P(CH2Ph)Is (2e). A 27 mg amount of 1e
was used; 2 h, 97% yield of 2e (35 mg). HRMS (ESþ): calcd for
C49H71P2 (MHþ) m/z 721.5031, found m/z 721.5022. 31P{1H}
NMR (C6D6): δ -26.3 (meso), -26.4 (rac), ∼1.2/1 (overlapping,
rac/meso). 1H NMR (C6D6): δ 7.17-7.13 (m, 4H, Ar, rac/meso),
7.12-7.10 (m, 4H, Ar, rac/meso), 7.08-7.03 (m, 4H, Ar, rac/
meso), 6.99-6.96 (m, 2H, Ar, rac/meso), 4.09 (broad, 4H, i-Pr
CH, rac/meso), 3.29-3.24 (m, 2H, CH2Ph, rac/meso), 3.16-3.11
(m, 2H, CH2Ph, rac/meso), 2.73 (sep, 2H, i-Pr CH, rac/meso),
1.92-1.87 (m, 2H, P-CH2, rac/meso), 1.84-1.79 (m, 2H,
P-CH2, rac/meso), 1.32 (d, J = 7, 12H, i-Pr CH3, meso), 1.31
(d, J = 7, 12H, i-Pr CH3, rac), 1.29 (broad, 6H, CH2, rac/meso),
1.20 (d, J = 7, 12H, i-Pr CH3, meso), 1.19 (d, J = 7, 12H, i-Pr
CH3, rac), 1.18 (d, J = 7, 12H, i-Pr CH3, rac), 1.17 (d, J = 7,
Ar), 4.04 (broad, 4H, i-Pr CH), 3.22 (AB pattern, J=13, 2H,
CH2Ph, meso), 3.21 (AB pattern, J=13, 2H, CH2Ph, rac), 3.14
(AB pattern, J = 13, 2H, CH2Ph, rac), 3.06 (AB pattern, J = 13,
2H, CH2Ph, meso), 2.70 (m, 2H, i-Pr CH, overlapping rac/
meso), 2.26 (broad m, 1.5H, P-CH2, overlapping rac/meso),
2.09 (broad m, 2.5H, P-CH2, overlapping rac/meso), 1.28 (d,
J = 7, 12H, i-Pr CH3, meso), 1.27 (d, J = 7, 12H, i-Pr CH3, rac),
1.18-1.13 (m, 24H, i-Pr CH3, meso, m, 12H, i-Pr CH3, rac), 1.03
(d, J = 7, 12H, i-Pr CH3, rac). 13C{1H} NMR (C6D6): δ 156.1
(broad, quat, Is), 150.6 (quat, Is, meso), 150.5 (quat Is, rac),
140.2 (t, J = 6, Ar, rac), 140.0 (t, J = 6, Ar, meso), 129.4 (m, Ar,
rac/meso), 128.6 (m, Ar, rac), 128.5 (Ar, meso), 125.9 (Ar, rac),
125.8 (Ar, meso), 122.3 (CH, Is, overlapping rac/meso), 36.0 (dd,

Article
Organometallics, Vol. 29, No. 11, 2010 2471
12H, i-Pr CH3, meso). 13C{1H} NMR (C6D6): δ 156.1 (broad,
quat, Ar, meso), 155.9 (broad, quat, Ar, rac), 150.52 (quat, Ar,
meso), 150.51 (quat, Ar, rac), 140.26 (d, J = 12, quat, Ar, rac),
140.25 (d, J = 12, quat, Ar, meso), 130.1 (d, J = 26, quat, Ar,
rac), 130.0 (d, J = 26, quat, Ar, meso), 129.4 (d, J = 7, CH, Ar,
rac/meso), 128.57-128.56 (m, CH, Ar, rac/meso), 125.91-
125.88 (m, CH, Ar, rac/meso), 122.3 (broad, CH, Ar, rac/meso),
36.11 (d, J = 19, CH2, meso), 36.08 (d, J = 19, CH2, rac), 34.6
(i-Pr CH, rac/meso), 32.9 (t, J = 14, CH2, rac), 32.8 (t, J = 14,
CH2, meso), 31.66 (d, J = 21, i-Pr CH, meso), 31.65 (d, J = 21,
i-Pr CH, rac), 28.40 (d, J = 26, CH2, meso), 28.37 (d, J = 25,
CH2, rac), 28.05 (d, J = 18, CH2, meso), 28.01 (d, J = 18, CH2,
rac), 25.12 (i-Pr CH3, meso), 25.11 (i-Pr CH3, rac), 25.03 (i-Pr
CH3, rac/meso), 24.0 (d, J = 3, i-Pr CH3, rac/meso).
Is(PhCH2)P(CH2)3PHIs (4c). To a solution of IsHP(CH2)3-
PHIs (1c; 100 mg, 0.20 mmol, 1 equiv) in 5 mL of THF at -78 °C
was added s-BuLi (210 μL, 0.21 mmol, 1 equiv, 1.0 M in
cyclohexane) dropwise with stirring, and the solution turned
yellow. The solution was stirred at -78 °C for 10 min, at which
point the 31P NMR spectrum showed a mixture of the starting
IsHP(CH2)3PHIs (δ -99.4, -99.5, 28%), the desired IsLiP-
(CH2)3PHIs (-98.0 (broad), -98.4, 64%), and IsLiP(CH2)3-
PLiIs (-108, very broad, 8%). Additional s-BuLi was added in
small portions (155 μL added, 365 μL (1.9 equiv) total) until the
mixture contained 2% of the starting IsHP(CH2)3PHIs, 58% of
the desired IsLiP(CH2)3PHIs, and 40% of IsLiP(CH2)3PLiIs.
To this solution was added dry degassed benzyl chloride (54 μL,
0.39 mmol, 1.9 equiv) via microliter syringe, and the solution
turned pale yellow and slightly cloudy. The solution was stirred
an additional 1 h at -78 °C and was then warmed to room
temperature and stirred overnight. The THF was removed
under reduced pressure, and the residue was redissolved in 20
mL of Et2O. To this solution was added 10 mL of a degassed
saturated aqueous NH4Cl solution, and the two layers were
stirred vigorously until both layers were clear. The organic layer
was removed via cannula, and the aqueous layer was extracted
with two additional 20 mL portions of Et2O. The combined
extracts were dried over MgSO4, the solid was filtered off, and
the solvent was removed under reduced pressure. The oily white
residue was eluted over a silica pipet column (0.5 cm wide by 3.0
cm high) with four 1 mL fractions of 9/1 petroleum ether/THF.
The solvent was removed under reduced pressure to yield 125
mg of a white residue containing 62% of the desired (Is)(CH2-
Ph)P(CH2)3PHIs (4c; δ -27.29, -27.30, -95.05, -95.36 (CD-
Cl3), ∼1/1 mixture of diastereomers), 37% (Is)(CH2Ph)P(CH2)3-
P(CH2Ph)(Is) (2c; δ -26.9, -27.0 (CDCl3), ∼0.65/1 rac/meso), and
1% unidentified impurities (δ -30.1) by 31P NMR spectroscopy in
CDCl3. This is a quantitative yield based on the starting bis-
(secondary phosphine) 1c (theoretical yield of 4c 120 mg).
Pt-Catalyzed Alkylation of 4c To Yield 2c. A solution of Pt((R,
R)-Me-DuPhos)(Ph)(Cl) (3 mg, 0.005 mmol, 10 mol %) in 1 mL
of THF was added to Is(CH2Ph)P(CH2)3PHIs (4c; 0.05 mmol
total, containing 0.031 mmol of 4c and 0.019 mmol of 2c, 32 mg
total) followed by NaOSiMe3 (4 mg, 0.03 mmol), and the
solution turned yellow. The mixture was transferred to an
NMR tube, and benzyl bromide (4 μL, 0.03 mmol) was added
neat via syringe. The reaction was complete in <30 min by 31
P
NMR spectroscopy. The solvent was removed under reduced
pressure to leave an oily white residue, which was eluted over a
silica column (0.5 cm width ꢀ 3.0 cm height) with three 1 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 27 mg (79% yield) of an oily residue.
The product ratios were determined after oxidation, as de-
scribed below.
General Procedure for Oxidation of 2a-e: Synthesis of Is-
(PhCH2)P(O)(CH2)nP(O)(CH2Ph)Is (3a-e) and Assay of Alky-
lation Selectivity Using Fmoc(Trp)Boc-OH (6). To a solution
of Is(PhCH2)P(CH2)nP(CH2Ph)Is (2a-e; 0.03-0.05 mmol) in
1 mL of THF was added excess H2O2 (0.1 mL of a 30% solution
in H2O). The solution was stirred for 1 h, and the solvent was
removed under reduced pressure. Drying in a vacuum desiccator
gave a quantitative yield of the desired phosphine oxide. See
below for the amounts of 2a-e used. The er and dr were
measured using 31P NMR spectroscopy by dissolving either all
or a portion of phosphine oxides 3a-e in 1 mL of a deuterated
solvent with Fmoc(Trp)Boc-OH (6; 2.5 equiv). See below for the
amounts of 3a-e and 6 used and the solvents, Table 2 for 31P
NMR data, and the Supporting Information for a table of data
from multiple er and dr determinations.
Is(PhCH2)(O)PCH2P(O)(CH2Ph)Is (3a). Amounts: 22 mg
(0.03 mmol) of 2a; all of 3a was used in the assay with 39 mg
(0.075 mmol, 2.5 equiv) of 6 in CD2Cl2. HRMS (ESþ): calcd for
C45H63O2P2 (MHþ) m/z 697.4303, found m/z 697.4297. 31P{1H}
1
NMR (C6D6): δ 40.8 (rac), 38.7 (meso), ∼1.7/1 rac/meso. H
NMR (C6D6): δ 7.20-7.13 (m, 8H, Ar, rac/meso), 7.10-7.06
(m, 6H, Ar, rac/meso), 4.27-4.20 (m, part of an ABXX0 pattern,
2H, P-CH2Ph, rac), 3.92-3.82 (broad m, 4H, i-Pr CH, rac/
meso), 3.81-3.68 (m, 4H, P-CH2Ph, rac/meso), 3.68-3.52 (m,
part of an ABXX0 pattern, 2H, P-CH2Ph, meso), 3.29 (filled-in
d,22 J = 13, 2H, P-CH2-P, rac), 3.00-2.93 (m, 2H, P-CH2-
P, meso), 2.88 (sep, J = 7, i-Pr CH, rac/meso), 1.26-1.22 (m,
24H, i-Pr CH3), 0.97-0.94 (m, 12H, i-Pr CH3). 13C{1H} NMR
(C6D6): δ 153.8 (broad, quat, Ar, rac/meso), 152.4 (quat, Ar,
rac/meso), 132.0-131.9 (m, quat, Ar, rac/meso), 130.6 (t, J = 3,
CH, Ar, rac), 130.3 (t, J = 3, CH, Ar, meso), 128.4 (CH, Ar,
meso), 128.2 (CH, Ar, rac), 126.8 (quat, Ar, meso), 126.3 (quat,
Ar, rac), 123.3-123.1 (m, CH, Ar, rac/meso), 42.8 (d, J = 66,
P-CH2Ph, rac), 41.7 (d, J = 62, P-CH2Ph, meso), 40.1 (t, J =
53, P-CH2-P, rac), 38.5 (t, J = 53, P-CH2-P, meso), 34.0
(i-Pr CH, rac/meso), 29.8 (i-Pr CH, rac), 29.5 (i-Pr CH, meso),
25.0 (i-Pr CH3, rac/meso), 24.7 (i-Pr CH3, rac), 24.6 (i-Pr CH3,
meso), 23.6 (i-Pr CH3, rac), 23.5 (i-Pr CH3, meso).
HRMS (ESþ): calcd for C40H61P2 (MHþ) m/z 603.4249,
found m/z 603.4252. 31P{1H} NMR (CDCl3): δ -27.29, -27.30,
-95.05, -95.36 (∼1/1). 1H NMR (CDCl3): δ 7.23-7.19 (m, 2H,
Ar), 7.13-7.11 (m, 3H, Ar), 6.98 (d, J = 2, 2H, Ar), 6.97 (d, J = 2,
2H, Ar), 4.16 (dq, JPH = 216, JHH = 7, 1H, Ar), 3.87 (broad,
2H, i-Pr CH), 3.57-3.50 (m, 2H, i-Pr CH), 3.26-3.15 (m, 2H,
PCH2Ph), 2.91-2.82 (m, 2H, i-Pr CH), 2.08-1.94 (broad m,
2H, CH2), 1.81-1.75 (broad m, 1H, CH2), 1.61-1.53 (broad m,
1H, P-CH2), 1.53-1.42 (broad m, 2H, CH2), 1.29-1.21 (m,
24H, i-Pr CH3), 1.15 (overlapping d, J = 7, 6H, i-Pr CH3), 1.11
(d, J = 7, 6H, i-Pr CH3). 13C{1H} NMR (CDCl3): δ 155.4 (quat,
Ar), 155.3 (quat, Ar), 152.7 (quat, Ar), 152.5 (d, J = 4, quat, Ar),
150.1 (quat, Ar), 149.3 (d, J = 16, quat, Ar), 139.6 (quat, Ar),
128.9 (d, J = 7, CH, Ar), 128.3 (d, J = 2, CH, Ar), 128.1-127.8
(m, overlapping quat, Ar), 125.6 (CH, Ar), 122.0 (quat, Ar),
121.3 (d, J = 4, CH, Ar), 121.2 (d, J = 4, CH, Ar), 35.6 (d, J =
18, PCH2Ph), 34.2 (i-Pr CH), 34.1 (i-Pr CH), 32.7-32.5 (m, i-Pr
CH), 31.5 (i-Pr CH), 31.3 (i-Pr CH), 29.3-29.1 (m, CH2), 27.1
(m, CH2), 25.6-25.4 (m, CH2), 24.8-24.7 (m, i-Pr CH3),
23.9-23.8 (m, i-Pr CH3), 24.3-24.2 (m, i-Pr CH3).
Is(PhCH2)(O)P(CH2)2P(O)(CH2Ph)Is (3b). Amounts: 29 mg
(0.04 mmol) of 2b; 21 mg (0.03 mmol) of 3b, 39 mg (0.075 mmol,
2.5 equiv) of 6 in CDCl3. HRMS (ESþ): calcd for C46H65O2P2
(MHþ) m/z 711.4460, found m/z 711.4441. 31P{1H} NMR
1
(CDCl3): δ 44.3 (meso), 43.8 (rac), ∼3.1/1 meso/rac. H NMR
(CDCl3): δ 7.27-7.21 (m, 2H, Ar, rac/meso), 7.16-7.08 (m, 8H,
Ar, rac/meso), 7.07 (t, J = 2, 4H, Is, meso), 7.01 (t, J = 2, 4H, Is,
rac), 3.81-3.76 (m, 4H, i-Pr CH, rac/meso), 3.43-3.34 (m, 4H,
CH2Ph, rac/meso), 2.93-2.80 (m, 2H, i-Pr CH, overlapping rac/
meso), 2.32-2.26 (m, 2H, P-CH2, rac/meso), 2.16-2.10 (m, 2H,
P-CH2, rac), 2.06-2.00 (m, 2H, overlapping rac/meso), 1.27 (d,
J = 7, 12H, i-Pr CH3, meso), 1.21 (d, J = 7, 12H, i-Pr CH3, rac/
meso), 1.18 (d, J = 7, 12H, i-Pr CH3, rac), 1.06 (d, J = 7, 12H,
(22) Redfield, D. A.; Cary, L. W.; Nelson, J. H. Inorg. Chem. 1975, 14,
50–59.
31P NMR data for 4a-e are given in Table 4.

2472 Organometallics, Vol. 29, No. 11, 2010
Chapp et al.
i-Pr CH3, meso), 0.92 (d, J = 7, 12H, i-Pr CH3, rac). 13C{1H}
NMR (CDCl3): δ 154.1 (broad, quat, Ar), 152.2 (quat, Ar),
132.0 (t, J = 4, Ar), 130.0 (t, J = 2, Ar, rac), 129.8 (t, J = 2, Ar,
meso), 128.44 (Ar, rac), 128.38 (Ar, meso), 126.75 (Ar, rac),
126.66 (Ar, meso), 123.0 (t, J = 6, CH, Is), 122.6-121.3 (m,
quat, Ar), 41.8-40.9 (m, CH2Ph), 34.1 (i-Pr CH, meso), 34.0
(i-Pr CH, rac), 29.8 (i-Pr CH, meso), 29.7 (i-Pr CH, rac), 25.8-
25.5 (m, P-CH2, rac), 25.2 (i-Pr CH3, meso), 25.09 (i-Pr CH3,
rac), 25.3-24.8 (m, P-CH2, meso), 24.7 (i-Pr CH3, meso), 24.6
(i-Pr CH3, rac), 23.6 (d, J = 1, i-Pr CH3, meso), 23.5 (d, J = 5,
i-Pr CH3, rac).
2.88 (sep, J = 7, 2H, i-Pr CH, rac/meso), 1.87-1.78 (broad m,
4H, CH2, rac/meso), 1.58-1.42 (broad m, 2H, CH2, rac/meso),
1.40-1.24 (broad m, 4H, CH2, rac/meso), 1.27-1.23 (m, 24H,
i-Pr CH3, rac/meso), 1.10 (d, J = 7, 12H, i-Pr CH3, meso), 1.08
(d, J = 7, 12H, i-Pr CH3, rac). 13C{1H} NMR (CDCl3): δ 153.95
(d, J = 12, quat, Ar, rac), 153.92 (d, J = 11, quat, Ar, meso),
151.9 (apparent t, J = 2, quat, Ar, rac/meso), 132.5 (d, J = 8, Ar,
rac/meso), 129.8 (apparent t, J = 6, CH, Ar, rac/meso), 128.43
(CH, Ar, meso), 128.42 (CH, Ar, rac), 126.7 (d, J = 3, Ar, rac/
meso), 122.9 (d, J = 3, CH, Ar, meso), 122.8 (d, J = 3, CH, Ar,
rac), 122.3 (d, J = 27, quat, Ar, rac/meso), 41.5 (d, J = 60,
P-CH2Ph, rac/meso), 34.05 (i-Pr CH, meso), 34.03 (i-Pr CH,
rac), 32.6 (d, J = 14, CH2, rac/meso), 32.1 (apparent t, J = 13,
CH2, meso), 32.0 (apparent t, J = 13, CH2, rac), 29.74-29.67
(m, i-Pr CH, rac/meso), 25.08 (i-Pr CH3, meso), 25.05 (i-Pr CH3,
rac), 24.8 (i-Pr CH3, rac/meso), 23.6 (i-Pr CH3, rac/meso), 21.71
(d, J = 15, CH2, rac/meso), 21.69 (d, J = 14, CH2, rac/meso).
Mes*HP(CH2)2PHMes* (5). A solution of Mes*Br (3.13 g,
9.6 mmol) in 20 mL of THF was cooled to -78 °C, and then n-
BuLi (4.8 mL of a 2.0 M solution in cyclohexane, 9.6 mmol) was
added dropwise via cannula over 2 h to give a yellow solution,
which was added via cannula to a solution of Cl2P(CH2)2PCl2
(1.1 g, 4.8 mmol, 0.5 equiv) in 20 mL of THF, and this mixture
was cooled to -78 °C. After 2 h at -78 °C, the 31P{1H} NMR
spectrum of a sample of the reaction mixture (CDCl3) showed
that the reaction was incomplete, with signals assigned to
Mes*ClP(CH2)2PClMes* (δ 80.0, 77.5), Cl2P(CH2)2PCl2 (δ
191.0), and Mes*ClP(CH2)2PCl2 (δ 191.2 (d, J = 23), 75.9 (d,
J = 23)), in a 6/1/3 ratio. Another 1 equiv (9.6 mmol) of n-BuLi/
Mes*Br was added as above, and the mixture was stirred over-
night, which improved the ratio to 8/1/1. The reaction mixture
was then added to a solution of LiAlH4 (368 mg, 9.7 mmol) in 20
mL of THF at -78 °C. The mixture was warmed to room
temperature and then stirred overnight to give a gray slurry.
Triethanolamine (1.3 mL, 9.7 mmol) was added via syringe to
give a white solid and a clear solution.23 Bubbling was observed.
The mixture was stirred for 2 h, and then 10 mL of distilled H2O
was added dropwise over 1 h. H2 evolution was observed. The
clear solution was filtered and washed with 50 mL of ether. The
solution was extracted with H2O (3 ꢀ 75 mL); the organic layer
was separated, dried over MgSO4, and then filtered. The solvent
was removed from the filtrate to give a white solid, whose
31P{1H} NMR spectrum in CDCl3 revealed a 3/2 mixture of
the desired product, Mes*HP(CH2)2PHMes* (5: δ -67.8,
-68.2; 1/1 ratio) and Mes*HP(CH2)2PH2 (δ -69.1 (d, J =
12), -127.4 (d, J = 12)).24 This mixture was dissolved in warm
isopropyl alcohol (50 mL). Cooling this solution to -15 °C
overnight gave a white solid, which was one diastereomer of 5
(31P{1H} NMR (CDCl3) δ -68; 330 mg, 12% yield), which
could be washed with Et2O to remove impurities, which were
observed in some cases by 31P{1H} NMR in CDCl3 (δ 25.7, 25.4,
2.8). When the material was purified by filtration through silica,
with 40/60 CH2Cl2/petroleum ether as eluent, 5 appeared to
isomerize to yield a 1/1 mixture of diastereomers (31P{1H} NMR
(CDCl3) δ -67.7, -68.3).
Is(PhCH2)(O)P(CH2)3P(O)(CH2Ph)Is (3c). Amounts: 29 mg
(0.05 mmol) of 2c; 21 mg (0.03 mmol) of 3c, 39 mg (0.075 mmol,
2.5 equiv) of 6 in CDCl3. HRMS (ESþ): calcd for C47H67O2P2
(MO2Hþ) m/z 725.4616, found m/z 725.4623. 31P{1H} NMR
1
(CDCl3): δ 43.7 (rac), 43.5 (meso), ∼1.8/1 rac/meso. H NMR
(CDCl3): δ 7.24-7.13 (m, 10H, Ar, rac/meso), 7.05-7.04 (m,
4H, Ar, rac/meso), 3.82-3.75 (m, 4H, i-Pr CH, rac/meso),
3.40-3.30 (m, 4H, CH2Ph, rac/meso), 2.86 (sep, J = 7, 2H, i-
Pr CH, rac/meso), 2.11-2.04 (m, 2H, CH2, rac/meso), 2.01-1.94
(m, 2H, CH2, rac/meso), 1.91-1.84 (m, 2H, CH2, rac/meso),
1.244 (d, J = 7, 12H, i-Pr CH3, rac), 1.238 (d, J = 7, 12H, i-Pr
CH3, meso), 1.20 (d, J = 7, 12H, i-Pr CH3, meso), 1.17 (d, J = 7,
12H, i-Pr CH3, rac), 1.04 (d, J = 7, 12H, i-Pr CH3, rac), 1.03
(d, J = 7, 12H, i-Pr CH3, meso). 13C{1H} NMR (CDCl3): δ
154.0 (broad, quat, Ar, rac), 153.9 (broad, quat, Ar, rac), 152.0
(quat, Ar, rac/meso), 132.3-132.2 (m, quat, Ar, rac/meso),
129.94-129.91 (m, CH, Ar, rac/meso), 128.4 (CH, Ar, rac/
meso), 126.7 (CH, Ar, rac/meso), 123.0-122.9 (m, CH, Ar,
rac/meso), 122.2 (quat, Ar, rac/meso), 41.3 (d, J = 60, P-
CH2Ph, rac/meso), 34.0 (i-Pr CH, rac/meso), 33.6 (dd, J = 67,
12, P-CH2CH2, rac/meso), 29.7 (i-Pr CH, rac/meso), 25.0 (i-Pr
CH3, rac/meso), 24.8 (i-Pr CH3, meso), 24.7 (i-Pr CH3, rac),
23.6-23.5 (i-Pr CH3, rac/meso), 16.04-16.01 (m, PCH2CH2,
rac/meso).
Is(PhCH2)(O)P(CH2)4P(O)(CH2Ph)Is (3d). Amounts: 34 mg
(0.05 mmol) of 2d; 21 mg (0.03 mmol) of 3d, 39 mg (0.075 mmol,
2.5 equiv) of 6 in CDCl3. HRMS (ESþ): calcd for C48H69O2P2
(MHþ) m/z 739.4773, found m/z 739.4755. 31P{1H} NMR
(CDCl3): δ 43.6 (rac), 43.4 (meso), ∼1.4/1 (rac/meso). 1H
NMR (CDCl3): δ 7.26-7.16 (m, 10H, Ar, rac/meso), 7.08 (d,
J = 4, 4H, Ar, meso), 7.06 (d, J = 4, 4H, Ar, rac), 3.86 (sep, J =
7, 4H, i-Pr CH, rac/meso), 3.47-3.30 (m, 4H, CH2Ph, rac/meso),
2.90-2.82 (m, 2H, i-Pr CH, rac/meso), 1.87-1.81 (broad m, 4H,
CH2, rac/meso), 1.58-1.49 (m, 2H, CH2, rac/meso), 1.48-1.40
(m, 2H, CH2, rac/meso), 1.26 (d, J = 7, 12H, i-Pr CH3, meso),
1.24 (d, J = 7, 12H, i-Pr CH3, rac/meso), 1.22 (d, J = 7, 12H,
i-Pr CH3, rac), 1.09 (d, J = 7, 12H, i-Pr CH3, meso), 1.07 (d, J = 7,
12H, i-Pr CH3, rac). 13C{1H} NMR (CDCl3): δ 154.2 (d, J = 11,
quat, Ar, rac/meso), 152.26-152.20 (m, quat, Ar, rac/meso),
132.8 (d, J = 6, quat, Ar, rac/meso), 130.15-130.09 (m, CH, Ar,
rac/meso), 128.73-128.70 (apparent t, J = 3, CH, Ar, rac/
meso), 127.00-126.96 (apparent t, J = 3, CH, Ar, rac/meso),
123.27 (d, J = 88, quat, Ar, meso), 123.21 (d, J = 11, CH, Ar,
meso), 123.18 (d, J = 11, CH, Ar, rac), 123.12 (d, J = 88, quat,
Ar, rac), 41.76 (d, J = 61, PCH2Ph, meso), 41.73 (d, J = 61,
P-CH2Ph, rac), 34.3 (i-Pr CH, rac/meso), 32.50 (d, J = 69,
P-CH2, meso), 32.47 (d, J = 68, P-CH2, rac), 30.10-30.01 (m,
i-Pr CH, rac/meso), 25.36 (d, J = 13, P-CH2CH2, rac), 25.34
(i-Pr CH3, meso), 25.33 (i-Pr CH3, rac), 25.17 (i-Pr CH3, meso),
25.12 (i-Pr CH3, rac), 24.9 (d, J = 15, P-CH2CH2, meso), 23.9
(i-Pr CH3, rac/meso).
Anal. Calcd for C38H64P2:C,78.30;H,11.07.Found:C,78.07;H,
11.15. HRMS: calcd for C38H63P2 (M - H)þ m/z 581.4405, found
m/z 581.4403. NMR data for one diastereomer are as follows.
31P{1H} NMR (CDCl3): δ -68.0. 1H NMR (CDCl3): δ 7.35 (4H,
Ar),4.8(broadd,JPH =240,2H, P-H), 1.53 (36H, t-Bu CH3),1.48
(m, 4H, CH2), 1.30 (18H, t-Bu CH3). 13C{1H} NMR (CDCl3):
δ 154.2 (quat, Ar), 149.0 (quat, Ar), 132.9 (m, quat Ar), 122.0
Is(PhCH2)(O)P(CH2)5P(O)(CH2Ph)Is (3e). Amounts: 35 mg
(0.05 mmol) of 2e; 22 mg (0.03 mmol) of 3e, 39 mg (0.075 mmol,
2.5 equiv) of 6 in C6D6. HRMS (ESþ): calcd for C49H71O2P2
(MHþ) m/z 753.4929, found m/z 753.4912. 31P{1H} NMR
(CDCl3): δ 44.6 (rac), 44.3 (meso), ∼1.3/1 (rac/meso). 1H
NMR (C6D6): δ 7.25-7.17 (m, 10H, Ar, rac/meso), 7.09 (d,
J = 4, 4H, Ar, meso), 7.07 (d, J = 4, 4H, Ar, rac), 3.88 (sep, J =
7, 4H, i-Pr CH, rac/meso), 3.47-3.32 (m, 4H, CH2Ph, rac/meso),
(23) Powell, J.; James, N.; Smith, S. J. Synthesis 1986, 338–340.
(24) More of the mixed tertiary/primary phosphine Mes*HP-
(CH2)2PH2 was formed than expected from the observed ratio of
intermediate chlorophosphines. It is possible that P-C cleavage oc-
curred during the LiAlH4 reduction step. Such processes have been
observed previously: Reiter, S. A.; Nogai, S. D.; Schmidbaur, H. Z.
Anorg. Allg. Chem. 2005, 631, 2595–2600. Kyba, E. P.; Liu, S. T. Inorg.
Chem. 1985, 24, 1613–1616.

Article
Organometallics, Vol. 29, No. 11, 2010 2473
(CH, Ar), 38.2 (quat, CMe3), 34.9 (quat CMe3), 33.5 (apparent t,
J = 7, o-CMe3), 31.3 (p-CMe3), 25.5 (CH2). IR (KBr): 2959, 2868,
and Dartmouth College for a Presidential Scholarship,
a Dean of Faculty Research Grant, and a Zabriskie
Fellowship.
2390 (P-H), 1594, 1361, 1261, 1100, 806, 661, 467 cm-1
.
Acknowledgment. We thank the National Science
Foundation for support, and the Department of Educa-
tion for a GAANN fellowship for T.W.C. A.J.S. thanks
the Beckman Foundation for a Beckman Scholarship
Supporting Information Available: Text, tables, and figures
giving additional experimental details and NMR spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.