Conjugate phosphination of cyclic and acyclic acceptors using Rh(I)-phosphine or Rh(I)-carbene complexes. Probing the mechanism with chirality at the silicon atom or the phosphorus atom of the Si-P reagent

Article abstract of DOI:10.1016/j.tet.2009.04.038

The Rh(I)-catalyzed conjugate phosphinyl transfer from an Si-P reagent to an electron-deficient acceptor requires individual protocols for cyclic and acyclic α,β-unsaturated carbonyls and carboxyls. While 1,4-addition to cyclic acceptors is catalyzed by a

Full text of DOI:10.1016/j.tet.2009.04.038

Tetrahedron 65 (2009) 6510–6518
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Conjugate phosphination of cyclic and acyclic acceptors using Rh(I)–phosphine
or Rh(I)–carbene complexes. Probing the mechanism with chirality
at the silicon atom or the phosphorus atom of the Si–P reagent
*
Verena T. Trepohl, Roland Fro¨hlich, Martin Oestreich
Organisch-Chemisches Institut, Westfa¨lische Wilhelms-Universita¨t Mu¨nster, Corrensstraße 40, D-48149 Mu¨nster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The Rh(I)-catalyzed conjugate phosphinyl transfer from an Si–P reagent to an electron-deficient acceptor
Received 3 March 2009
Received in revised form 3 April 2009
Accepted 6 April 2009
requires individual protocols for cyclic and acyclic a,b-unsaturated carbonyls and carboxyls. While 1,4-ad-
dition to cyclic acceptors is catalyzed by a Rh(I)–phosphine complex, a Rh(I)–carbene complex is needed to
promote conjugate phosphination of acyclic acceptors. General procedures for both systems are reported.
Aside from monophosphine-derived Si–P reagents as phosphinide sources, dppe- as well as dppp-derived
reagent having two Si–P units do also participate in this reaction. The mechanism of this Rh(I)-catalyzed
activation of the Si–P reagent is still under debate. Control experiments with enantiopure silicon-stereogenic
and racemic phosphorus-stereogenic Si–P reagents support a catalysis commencing with transmetalation
rather than oxidative addition. Preparation and full characterization data of the Si–P compounds used in this
investigation is included.
Available online 17 April 2009
Dedicated to Professor Larry E. Overman on
the occasion of the 2008 Tetrahedron Prize
for Creativity in Organic Chemistry
Keywords:
Phosphorus
Ó 2009 Elsevier Ltd. All rights reserved.
Conjugate addition
Homogeneous catalysis
Reaction mechanism
Rhodium
Silicon
1. Introduction
linkages to Si–P reagents for the 1,4-addition of nucleophilic phos-
phorus.6 We assume that all these Rh(I) catalyses are likely to share
Transmetalation of a carbon nucleophile from a main group ele-
ment to a transition metal is one of the common principles in catal-
ysis to generate C–TM metal bonds (TM¼transition metal) for
subsequent C–C bond formation.1 In contrast to oxidative addition,
the oxidation state of the transition metal remains unchanged.
Among the prominent examples of transmetalation-based catalysis
are the Suzuki–Miyaura cross-coupling reaction2 (generation of
a C(sp2)–Pd(II) complex) and the Hayashi–Miyaura conjugate addi-
tion reaction3 (generation of a C(sp2)–Rh(I) complex). In both tran-
sition metal-catalyzed processes, the carbon nucleophile is released
from boron, usually a boronic acid. The latter Rh(I) catalysis is how-
ever not limited to the conjugate transfer of carbon nucleophiles.
After Rh(I)-catalyzed activation of B–B4 and Si–B5 bonds through
transmetalation, the thus-formed nucleophilic boron as well as sili-
con complexes also undergo conjugate C–B and (asymmetric) C–Si
bond formation, respectively. Aside from boron-based precursors, we
were recently able to further extend the scope of interelement
the basic mechanistic steps. We also note that an identical mecha-
nism of action might apply to closely related Pd(II)-catalyzed con-
jugate addition of carbon7 as well as phosphorus8 nucleophiles.
Hayashi et al. established the mechanism of the Rh(I)-cata-
lyzed 1,4-addition of boronic acids.9 Our approach to interelement
bond activation was guided by that, and we proposed a tentative
mechanism for the Rh(I)-catalyzed 1,4-addition of phosphorus
nucleophiles to electron-deficient
a,b-unsaturated carbonyl
compounds (Scheme 1).6 The active catalyst is the Rh(I)–OH
complex A, formed from a Rh(I) pre-catalyst in basic aqueous
media. The catalysis then commences with coordination of the
Si–P reagent B to A (A/C). In complex C, the slightly Lewis acidic
silicon atom is located in close proximity to the Lewis basic oxygen
(the hydroxy group might even be deprotonated). Intramolecular
attack of the oxygen at silicon then results in net transmetalation
to afford the phosphinide transfer complex E along with silanol D
(C/E). The a,b-unsaturated acceptor F is then captured by E, and
conjugate phosphinyl transfer yields Rh(I) enolate G (E/G). Its
hydrolysis completes the catalytic cycle, releasing adduct H (G/
H) and regenerating catalytically active A.
* Corresponding author.
E-mail address: martin.oestreich@uni-muenster.de (M. Oestreich).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.038

V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
6511
Scheme 1. Tentative catalytic cycle of conjugate phosphinyl transfer.
Figure 1. Molecular structure of silylphosphine 3b.
In this full account, we summarize our efforts toward the Rh(I)-
catalyzed conjugate transfer of Ph2P, Cy2P, and t-Bu2P groups from
Si–P reagents10 on cyclic6 and acyclic acceptors.11,12 We also provide
sound mechanistic evidence for the debated transmetalation
pathway.13
2. Results and discussion
2.1. Preparation of Si–P reagents
Si–P reagents had been employed as phosphinyl group sources
in the past, and there are a few protocols available. We accessed
silylphosphines 1–3 according to a procedure reported by Hayashi
et al. (left, Scheme 2).14 While high chemical yields were obtained
for t-BuMe2Si–Cl and i-Pr3Si–Cl as electrophiles, the related prep-
aration of 4–5 using Me2PhSi–Cl bearing an aryl group at the silicon
atom failed. Quantitative formation of Me2PhSi–SiPhMe2 indicated
a lithium–chlorine exchange at the silicon atom. Introducing the
silicon unit as the nucleophilic component resulted in the forma-
tion of the desired silylphosphines 4–5 in good yields (right,
Scheme 2). The molecular structure of 3b was secured by X-ray
analysis (Fig. 1).
Scheme 3. Preparation of bridged bis(silylphosphines) 8–10.
The phosphorus-stereogenic silylphosphine rac-13 was pre-
pared from rac-1216 (Scheme 4) analogous to our reported protocol
(right, Scheme 2).6
We decided to make silicon-stereogenic (SiR)-19 in highly
enantioenriched form by conventional resolution of diastereomeric
menthyl ethers17 followed by stereospecific substitutions at the
silicon atom (Scheme 5). Treatment of dichloromethylphenylsilane
(14) with tert-butyllithium afforded chlorosilane rac-15 in moderate
yield (14/rac-15). Using (ꢀ)-menthol (16) as the chiral auxiliary in
the resolution, its potassium salt was reacted with rac-15 to give
(SiSR)-17 as a mixture of diastereomers (dr¼50:50); (SiS)-17 was
obtained in diastereomerically pure form after several cycles of flash
chromatography on silica gel (rac-15/(SiSR)-17/(SiS)-17). Stereo-
specific, racemization-free reduction with DIBAL–H18 provided si-
lane (SiR)-1819 in excellent yield and a perfect enantiomeric excess of
>99% ((SiS)-17/(SiR)-18). Subsequent chlorination of (SiR)-18 using
a saturated solution of Cl2 in CCl4 furnished chlorosilane (SiS)-15
((SiR)-18/(SiS)-15).18 (SiS)-15 was directly converted into desired
(SiR)-19 with lithium diphenylphosphide ((SiS)-15/(SiR)-19). Both
Scheme 2. Preparation of silylphosphines 1–5.
Encouraged by our findings in the Rh(I)-catalyzed 1,4-addition
of simple silylphosphines to cyclic
a,b
-unsaturated ketones,6 we
envisioned novel bridged bis(silylphosphines) 8–10 as an in-
teresting entry into bisphosphine ligand structures. For this,
bidentate phosphines dppe (6) and dppp (7) were reductively
metalated with elementary lithium and then trapped with the
corresponding chlorosilane,15 furnishing bridged bis(silylphos-
phines) 8–10 in high overall yields yet as an isomeric mixture
(dr¼50:50) of meso- and rac-8–10.
Scheme 4. Preparation of phosphorus-stereogenic silylphosphine rac-13.

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V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
Scheme 5. Preparation of silicon-stereogenic silylphosphine (SiR)-19.
the stereochemical course of this final nucleophilic displacement
and the enantiomeric excess of (SiR)-19 were unequivocally de-
termined by HPLC analysis after known enantiospecific reduction
with LiBH4 ((SiR)-19/(SiR)-18).20
using 1a proceeded in high yields (73–89%, entries 1–3), slightly
better than with 2a (60–76%, entries 4–6). Transfer of a PCy2 group
worked equally well with 3b (79–92%, entries 7–9) and 4b (64–89%,
entries 10–12). Even 5c with an electron-rich Pt-Bu2 group partic-
ipated with moderate yields (48–58%, entries 13–15).
Unfortunately, extension of the substrate scope using less re-
active acyclic a,b-unsaturated acceptors failed under these reaction
conditions. This prompted us to seek a new Rh(I)–ligand combi-
nation, which would promote the conjugate phosphination of
acyclic electron-deficient alkenes (cf. Section 2.4 and Ref. 8).
2.2. Phosphinyl transfer to cyclic acceptors catalyzed by
a Rh(I)–phosphine complex
On the basis of the assumed mechanistic analogyof the conjugate
transfer of carbon,9 boron,4 silicon,5 and phosphorus nucleophiles,
wechose conditionssimilar tothose reported for the Rh(I)-catalyzed
1,4-addition of boronic acids. A series of control experiments
showed that both the presence of a base and the absence of strongly
coordinating counter ions were crucial for success.6 We were
pleased to find that the combination of cationic Rh(I) complex
[(dppp)Rh(cod)]ClO4 and an equimolar amount of the free ligand
dppp in the presence of Et3N as base promoted the desired 1,4-
addition (Scheme 6 and Table 1).
2.3. Rh(I)-catalyzed twofold phosphination using bridged
bis(silylphosphines)
Attracted by the remarkably facile preparation of bridged bis-
(silylphosphines) 8–10 (Scheme 3), we briefly explored the possi-
bility of twofold conjugate additions as an access to bidentate
phosphine ligand motifs (Scheme 7). To limit the number of
Due to oxygen-sensitivity in solution, we decided to oxidize the
intermediate trivalent phosphine adduct prior to purification
(phosphinyl/phosphinoyl oxidation), which afforded the corre-
sponding phosphine oxides 23–25. Protection by sulfurization with
S8 to give related phosphine sulfides was also possible.
Table 1
Conjugate phosphinyl transfer to cyclic acceptors 20–22a
Entry
Si–PR2
Acceptor
Product
Yieldb (%)
1
2
3
4
5
6
7
8
1a
1a
1a
2a
2a
2a
3b
3b
3b
4b
4b
4b
5c
5c
5c
20 (n¼1)
21 (n¼2)
22 (n¼3)
20 (n¼1)
21 (n¼2)
22 (n¼3)
20 (n¼1)
21 (n¼2)
22 (n¼3)
20 (n¼1)
21 (n¼2)
22 (n¼3)
20 (n¼1)
21 (n¼2)
22 (n¼3)
23a
24a
25a
23a
24a
25a
23b
24b
25b
23b
24b
25b
23c
24c
25c
88
73
89
72
60
76
79
87
92
64
84
89
48
55
58
After identification of a suitable catalyst system,6 we tested
a few representative
a,b-unsaturated cyclic ketones 20–22 using
several phosphinide sources (Table 1). The PPh2 group transfer
9
10
11
12
13
14
15
a
Reactions were conducted using [(dppp)Rh(cod)]ClO4 (5.0 mol %), dppp
(5.0 mol %), Et3N (1.0 equiv), and silylphosphine 1–5 (2.5 equiv) in 1,4-diox-
ane:H2O¼10:1 at 60 ꢁC for 2 days.
b
Isolated yield of analytically pure phosphine oxide after flash chromatography
Scheme 6. Conjugate phosphinyl transfer to
a,b-unsaturated cyclic ketones using
on silica gel.
a Rh(I)–phosphine complex (see Table 1 for details).

V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
6513
Scheme 7. Rh(I)-catalyzed conjugate phosphination using bridged bis(silylphosphines) 8–10.
diastereomers formed, we confined ourselves to using methyl vinyl
ketone (26) as the simplest acceptor possible. We note that, in
As summarized in Table 2, all electron-deficient acceptors gen-
erally gave good chemical yields. We made a number of observa-
tions, which agree with data obtained in the related Pd(II)-catalyzed
contrast to acyclic
b-substituted a,b-unsaturated carbonyls and
carboxyls, -unsubstituted systems do react in the presence of our
b
phosphination:8 (1)
a,b-unsaturated carboxyls are intrinsically less
Rh(I)–dppp catalyst.13 We were delighted to isolate the products 27
and 28, respectively, in excellent chemical yields albeit as a mixture
of meso and rac diastereomers, which were separated by flash
chromatography on silica gel (Scheme 7). As expected, cyclic 20–22
do react in good yields as well.
reactive than carbonyl compounds, which is why non-activated
carboxyls do not react at all.21 Gratifyingly, phosphinyl transfer to
activated 29–31 proceeded in decent yields (entries 1–5). (2) Iso-
lated yields were invariably higher for Z than for E-configured
precursors. (3) a,b-unsaturated imides 34 extended the scope (en-
tries 9 and 10), later allowing for auxiliary-based, diastereoselective
variants.22 (4) Both fumaric (E-35) and maleic ester (Z-35) reacted
cleanly (entries 11 and 12).
2.4. Phosphinyl transfer to acyclic acceptors catalyzed by
a Rh(I)–carbene complex
2.5. Mechanistic insight using silicon- and phosphorus-
stereogenic Si–P reagents as stereochemical probes
In an effort to also make acyclic acceptors susceptible for the
phosphinyl transfer, we screened a number of phosphine ligands
with little or no success. To our surprise, typical N-heterocyclic
carbene ligands brought about the formation of more reactive
Rh(I)–carbene complexes, which facilitated the desired 1,4-addi-
tion. For example, [Rh(cod)2]OTf (5.0 mol %), IPr$HCl (5.0 mol %),
and KOt-Bu (10 mol %) were used to generate the active catalyst,
which then effectively promoted C–P bond formation in the pres-
ence of Et3N (Scheme 8).
As outlined in the introduction (Section 1), we believe that the
Si–P bond is cleaved by transmetalation (A/C/E, Scheme 1), and
that there is no change of the oxidation state of the Rh(I) catalyst.
Conversely, Hayashi et al. had proposed an alternative Rh(I)/Rh(III)
cycle involving an oxidative addition of the Si–P bond to Rh(I).13 To
clarify this situation, we envisaged probing the Si–P bond activation
step with an enantiopure silicon-stereogenic Si*–P reagent, an
unconventional strategy that had assisted us in other mechanistic
investigations in the past.23 Analysis of the level of stereoselection
in the stereoselectivity-determining 1,4-addition itself (F/G)
would then reveal the true nature of the nucleophilic phosphinyl
A number of Z- and E-configured a,b-unsaturated active esters
29–31,21 ketones 32–33, imides 34, diesters 35, and nitroalkene 36
were included in our survey (Fig. 2). Z-configured acceptors were
accessed by Lindlar reduction.5b
Figure 2. Acyclic Z- and E-configured a,b-unsaturated acceptors investigated in this
Scheme 8. Conjugate phosphinyl transfer to acyclic acceptors (see Table 2 for details).
study.

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V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
Table 2
Conjugate phosphinyl transfer to acyclic acceptorsa
Entry
1
Acceptor
Product
Yieldb (%)
65
Z-29
2
3
E-29
Z-30
37
63
Figure 3. Possible scenarios after transmetalation or oxidative addition.
4
5
6
E-30
E-31
Z-32
54
88
86
7
8
Z-32
E-33
65
83
Scheme 9. Chirality at the silicon and the phosphorus atoms as stereochemical probes
in the 1,4-addition.
9
Z-34
73
experiment, (SiR)-19 was processed following our standard protocol
with the Rh(I)–phosphine combination for cyclic model substrate
21 (21/24a, Scheme 9). As expected for a transmetalation path-
way, absolutely no stereoinduction (0% ee) was detected. This
outcome clearly substantiates that the silicon moiety is released
from the catalytic cycle (D, Scheme 1) rather than being co-
ordinated to the catalyst. Oxidative addition is therefore unlikely.
Under identical reaction conditions, rac-13 performed well in
the 1,4-addition but diastereoselectivity (dr¼66:34) was somewhat
disappointing (21/rac-45, Scheme 9). The asymmetrically
substituted phosphorus atom is directly involved in the stereo-
chemistry-determining C–P bond formation, which is why one
might have expected higher stereocontrol.24
10
11
E-34
Z-35
70
95
12
E-35
E-36
77
75
13
a
Reactions were conducted using [Rh(cod)2]OTf (5.0 mol %), IPr$HCl (5.0 mol %),
KOt-Bu (10 mol %), Et3N (1.0 equiv), and 1a (2.5 equiv) in 1,4-dioxane:H2O¼10:1 at
60 ꢁC for 1 day.
3. Summary
b
Isolated yield of analytically pure phosphine oxide after flash chromatography
In summary, we developed an efficient methodology for the
on silica gel.
Rh(I)-catalyzed conjugate phosphination of a,b-unsaturated elec-
tron-deficient carbonyls and carboxyls. Cyclic acceptors react in the
presence of a Rh(I)–phosphine catalyst while acyclic acceptors re-
quire a Rh(I)–carbene complex as catalyst. The debated mechanism
of action, transmetalation versus oxidative addition, was probed
with a silicon-stereogenic Si*–P reagent. The absence of any ster-
eoinduction using a chiral phosphinide source strongly indicated
a transmetalation pathway. Extension of this methodology to the
development of enantioselective and substrate-controlled variants
are the focus of our current work.
transfer complex E (Scheme 1). For comparison, we also tested
a racemic phosphorus-stereogenic Si–P* reagent.
Our line of thought is further illustrated with two pairs of pos-
sible Rh(I) and Rh(III) intermediates, all of which are hypothetical
phosphinyl transfer complexes (Fig. 3). Use of a Si*–P reagent will
enable to distinguish between the transmetalation and the oxida-
tive addition pathways. While the former will produce achiral Rh(I)
Si
complex E, the latter will form chiral Rh(III) complex E*, and
stereoinduction in the subsequent conjugate addition step might
only be seen if silicon-stereogenic Rh(III) complex is operative.
Performing the same experiment with the Si–P* is not expressive
since both transmetalation and oxidative addition yield chiral
complexes, Rh(I) complex E* and Rh(III) complex PE*.
4. Experimental
4.1. General information
For these purposes, we had prepared silicon-stereogenic (SiR)-19
(ꢂ96% ee) in almost enantiomerically pure form (Scheme 5) and
phosphorus-stereogenic rac-13 (Scheme 4). In the decisive
Reagents obtained from commercial suppliers were used
without further purification unless otherwise noted. Racemic

V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
6515
tert-butylchlorophenylphosphine (rac-12)16 and racemic tert-
4.2.2. meso-/rac-1,2-Bis[(tert-butyldimethylsilyl)phenyl-
butylchloromethylphenylsilane (rac-15)25 were prepared accord-
ing to reported procedures. All reactions were performed in
flame-dried glassware under a static pressure of argon. Liquids
and solutions were transferred with syringes or double-ended
needles; 1,4-dioxane was purified following a standard pro-
cedure, both 1,4-dioxane and H2O were thoroughly degassed
prior to use. Et3N was distilled from CaH2 and stored at 4 ꢁC
under exclusion of air. Technical grade solvents for extraction or
flash chromatography (cyclohexane, tert-butyl methyl ether, ethyl
acetate, CH2Cl2, and methanol) were distilled before use. Ana-
lytical thin layer chromatography was performed on silica gel 60
F254 glass plates by Merck and flash chromatography was per-
phosphino]ethane (meso-/rac-9)
Pale yellowish oil; yield: 95%. 1ꢃ10ꢀ5 mbar at 250 ꢁC oven
temperature.1H NMR (400 MHz, CDCl3):
d
ꢀ0.19 (d, J¼5.9 Hz, 6H), 0.03
(d, J¼6.3 Hz, 6H), 0.85 (s, 9H), 0.89 (s, 9H), 1.81 (m, 2H), 2.31 (m, 2H),
7.18–7.38 (m, 8H), 7.40–7.48 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3):
d
ꢀ7.1, ꢀ6.3, 18.4 (d, JC–P¼11.5 Hz), 19.8 (d, JC–P¼19.8 Hz), 25.6, 27.0,
127.4 (d, JC–P¼9.2 Hz), 128.0 (d, JC–P¼4.3 Hz), 128.1 (d, JC–P¼5.2 Hz),
133.2 (d, JC–P¼9.4 Hz), 133.4 (d, JC–P¼3.0 Hz), 133.6 (d, JC–P¼9.4 Hz),
134.5 (d, JC–P¼14.4 Hz), 135.0 (d, JC–P¼10.4 Hz) ppm. 31P{1H} NMR
(121 MHz, CDCl3):
d
ꢀ79.5, ꢀ81.4 ppm. IR (ATR): 1437 (s) cmꢀ1. Anal.
Calcd for C26H44P2Si2 (474.75): C, 65.78; H, 9.84. Found: C, 65.52; H,
9.84.
formed on silica gel 60 (40–63 mm, 230–400 mesh, ASTM) by
Merck. 1H, 13C, and 31P NMR spectra were recorded in CDCl3 on
Bruker AM 300, AM 400, and DRX 500 instruments. Chemical
shifts are reported in ppm with the solvent reference as the in-
4.2.3. meso-/rac-1,3-Bis[(tert-butyldimethylsilyl)phenyl-
phosphino]propane (meso-/rac-10)
Pale yellowish oil; yield: 91%. 2ꢃ10ꢀ5 mbar at 250 ꢁC oven
ternal standard (
d
¼7.26 ppm for 1H NMR and
d
¼77.1 ppm for 13C
temperature. 1H NMR (300 MHz, CDCl3):
ꢀ0.15 (d, J¼2.7 Hz, 3H), 0.05 (d, J¼3.0 Hz, 3H), 0.09 (d, J¼3.0 Hz,
3H), 0.89 (s, 9H), 0.91 (s, 9H), 1.61–1.88 (m, 4H), 2.22–2.48 (m, 2H),
7.18–7.30 (m, 6H), 7.33–7.44 (m, 4H) ppm. 13C NMR (75 MHz,
d
ꢀ0.17 (d, J¼2.7 Hz, 3H),
NMR). Chemical shifts for 31P{1H} NMR are reported downfield in
ppm relative to external standard 85% H3PO4
(
d
¼0.0 ppm). In-
frared spectra were recorded on a Digilab Excalibur Series FTS
4000 spectrophotometer. Enantiomeric ratios were determined
by analytical HPLC analysis on an Agilent 1200 Series with
a chiral stationary phase using Daicel Chiralpak IC as well as
Daicel Chiralcel OJ-H columns (n-heptane–i-PrOH solvent mix-
tures). Optical rotations were measured on a Perkin Elmer 341
polarimeter. High resolution mass spectrometry (HRMS) and
electron spray ionization mass spectrometry (ESI-MS) were per-
formed by the Analytic Department at the Organisch-Chemisches
Institut, Universita¨t Mu¨nster.
CDCl3):
d
ꢀ7.3, ꢀ7.2, ꢀ6.3, ꢀ6.2, 18.5 (d, JC–P¼12.1 Hz), 21.5 (d, JC–P¼
13.1 Hz), 21.9 (d, JC–P¼13.7 Hz), 27.1, 27.2, 27.4, 28.0, 127.1, 127.2,
127.9 (d, JC–P¼7.5 Hz), 128.0 (d, JC–P¼7.5 Hz), 133.2, 133.4, 135.2 (d,
JC–P¼18.2 Hz), 135.5 (d, JC–P¼18.2 Hz) ppm. 31P{1H} NMR (121 MHz,
CDCl3):
d
ꢀ88.5, ꢀ89.5 ppm. IR (ATR): 1466 (s) cmꢀ1. Anal. Calcd for
C27H46P2Si2 (488.26): C, 66.35; H, 9.45. Found: C, 66.44; H, 9.61.
4.3. rac-(Dimethylphenylsilyl)-tert-butylphenylphosphine
(rac-13)
Full experimental data for silylphosphines 3–5 (Scheme 2) and
cyclic
b
-phosphinoyl ketones 23–25 (Table 1) are reported in the
To a large excess (w10 equiv) of freshly cut lithium wire (activated
with Me3SiCl) in THF (30 mL), chlorodimethylphenylsilane (4.25 g,
25.9 mmol,1.00 equiv) was added in one portion at room temperature.
The reaction mixture was maintained at ꢀ13 ꢁC for 18 h (dark red
coloration indicated formation of the corresponding lithium com-
pound). The mixture was allowed to warm to 0 ꢁC and was sonicated
for an additional hour. To separate the solution of the lithium reagent
from unreacted lithium metal, the supernatant was transferred to
a dropping funnel connected to a Schlenk flask via a double-ended
cannula. Prior to slow addition (2 h) of the lithium reagent at 0 ꢁC, the
Schlenk flask was charged with tert-butylchlorophenylphosphine (rac-
12, 5.00 g, 25.9 mmol, 1.00 equiv) and n-hexane (60 mL). The addition
was accompanied by a color change and precipitation of lithium
chloride. The reaction mixture was allowed to warm to room tem-
perature and was maintained at this temperature for another 2 h. After
evaporation of the solvents, the residue was purified via Kugelrohr
distillation (5ꢃ10ꢀ1 mbar at 225 ꢁC oven temperature) yielding rac-13
Electronic Supplementary Data of Ref. 6. For full experimental
data of acyclic
Ref. 8.
b-phosphinoyl compounds 40–44 (Table 2), see
4.2. Typical procedure for the preparation of bridged
bis[(triorganosilyl)phosphines] meso-/rac-8–10
To a large excess (w10 equiv) of freshly cut lithium wire (acti-
vated with Me3SiCl) in THF (30 mL), a solution of dppe (6, 2.00 g,
5.02 mmol, 1.00 equiv) or dppp (7, 2.07 g, 5.02 mmol, 1.00 equiv)
and THF (20 mL) was added with a syringe pump over a period of
2 h at 0 ꢁC. The reaction mixture was maintained at 0 ꢁC for 18 h
and successively sonicated for an additional hour. To separate the
reaction mixture from unreacted lithium metal, the supernatant
was transferred to another Schlenk flask via a double-ended can-
nula. To this solution, the corresponding chlorosilane (4.06 g,
21.1 mmol, 4.20 equiv) was added at 0 ꢁC with a syringe pump over
a period of 2 h. The addition was accompanied by a color change
and precipitation of lithium chloride. The reaction mixture was
allowed to warm to room temperature and subsequently heated at
reflux for further 30 min. After evaporation of the solvents, the
residue was purified via Kugelrohr distillation.
(5.67 g, 76%) as a colorless oil.1H NMR (400 MHz, CDCl3):
0.70 (s, 3H), 1.14 (d, J¼12.6 Hz, 9H), 7.31–7.42 (m, 6H), 7.49ꢀ7.59 (m,
4H) ppm.13C NMR (100 MHz, CDCl3):
d 0.35 (s, 3H),
d
ꢀ3.9, 0.9, 24.5 (d, JC–P¼16.5 Hz),
29.7 (d, JC–P¼13.0 Hz), 127.4 (d, JC–P¼7.4 Hz), 127.7, 128.0 (d, JC–P
¼
¼
5.9 Hz), 128.3 (d, JC–P¼6.2 Hz), 129.2, 132.9, 133.8, 135.5 (d, JC–P
16.2 Hz) ppm. 31P{1H} NMR (121 MHz, CDCl3):
d
ꢀ5.4 ppm. IR (ATR):
1445 (s) cmꢀ1. Anal. Calcd for C18H25PSi (300.45): C, 71.96; H, 8.39.
Found: C, 71.79; H, 8.31.
4.2.1. meso-/rac-1,2-Bis[(triisopropylsilyl)phenylphosphino]ethane
(meso-/rac-8)
4.4. (SiRS)-tert-Butyl-(L)-menthoxymethylphenylsilane
((SiRS)-17)
Colorless oil; yield: 70%. 6ꢃ10ꢀ6 mbar at 280 ꢁC oven temper-
ature. 1H NMR (400 MHz, CDCl3):
d
0.89 (d, J¼7.2 Hz, 18H), 0.96 (d,
J¼7.2 Hz, 18H), 1.10 (m, 6H), 1.89 (m, 2H), 2.51 (m, 2H), 7.11–7.26 (m,
A solution of (ꢀ)-menthol (16, 7.03 g, 45.0 mmol, 1.50 equiv,
>99% ee) in THF (30 mL) was added to a suspension of oil-free
potassium hydride (1.81 g, 45.0 mmol, 1.50 equiv) in THF (20 mL) at
0 ꢁC. For complete deprotonation, the mixture was heated at reflux
for 3 h. After cooling to room temperature, the mixture was treated
with racemic chlorosilane rac-15 (6.36 g, 30.0 mmol, 1.00 equiv) in
6H), 7.32–7.48 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3):
d
10.7, 12.6
(d, JCꢀP¼4.5 Hz), 18.5, 19.1 (d, JCꢀP¼7.8 Hz), 127.0, 127.1, 128.5, 132.9,
133.2, 133.5, 134.7, 135.0 ppm. 31P{1H} NMR (121 MHz, CDCl3):
d
ꢀ73.6, ꢀ74.8 ppm. IR (ATR): 1441 (s) cmꢀ1. Anal. Calcd for
C32H56P2Si2 (558.91): C, 68.77; H, 10.10. Found: C, 68.54; H, 10.01.

6516
V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
THF (50 mL). Heating at reflux for 16 h was followed by cooling to
ambient temperature, quenching with H2O (100 mL) and neutral-
ization (pH¼7) with 2 M HCl. The organic layer was separated and
the aqueous phase was extracted with tert-butyl methyl ether
(4ꢃ60 mL). The combined organic layers were washed with brine
(70 mL), dried (MgSO4), filtered and the volatiles were evaporated
under reduced pressure. The crude product was purified by flash
chromatography on silica gel with cyclohexane as eluent affording
the title compound (SiRS)-17 (8.47 g, 85%, dr¼50:50) as a colorless
oil. After repeated flash chromatography, (SiS)-17 (4.11 g, 41%,
dr>99:1) was separated as colorless oil. Rf¼0.35 (cyclohexane). 1H
7.01–7.10 (m, 5H), 7.30–7.41 (m, 6H), 7.66ꢀ7.71 (m, 4H) ppm. 13C
NMR (100 MHz, CDCl3):
d
ꢀ8.6 (d, JC–P¼1.9 Hz), 19.7 (d, JC–P¼
11.4 Hz), 27.5 (d, JC–P¼2.9 Hz), 126.4, 127.7, 127.9 (d, JC–P¼6.3 Hz),
128.4, 128.7, 129.2 132.6 (d, JC–P¼14.5 Hz), 134.2 (d, JC–P¼11.8 Hz),
135.5 (d, JC–P¼6.0 Hz), 136.1 (d, JC–P¼12.8 Hz), 136.5 (d, JC–P
¼
16.5 Hz), 136.8 (d, JC–P¼20.1 Hz) ppm.31 P{1H} NMR (162 MHz,
CDCl3):
d
ꢀ64.7 ppm. IR (ATR): 1441 (s) cmꢀ1. Anal. Calcd for
C23H27PSi (362.16): C, 76.20; H, 7.51. Found: C, 76.50; H, 7.59.
4.7. General procedure for the Rh(I)-catalyzed 1,4-addition
using bridged bis(silylphosphines) meso-/rac-8–10
NMR (400 MHz, CDCl3):
d
0.43 (s, 3H), 0.65 (d, J¼6.6 Hz, 3H), 0.74–
0.83 (m, 2H), 0.87 (d, J¼6.6 Hz, 3H), 0.90 (d, J¼7.1 Hz, 3H), 0.92 (s,
9H), 1.02 (m, 1H), 1.21 (m, 1H), 1.29 (m, 1H), 1.55–1.65 (m, 2H), 1.88
(m, 1H), 2.36 (qqd, J¼2.5, 7.0, 7.0 Hz, 1H), 3.51 (ddd, J¼4.5, 10.2,
10.2 Hz, 1H), 7.33–7.42 (m, 3H), 7.57–7.61 (m, 2H) ppm. 13C NMR
Under argon atmosphere, a Schlenk tube equipped with a mag-
netic stirring bar is charged with methyl vinyl ketone (26, 1.0 equiv)
dissolved in deoxygenated 1,4-dioxane:H2O¼10:1 (approximately
0.5 M based on substrate). After addition of [(dppp)Rh(cod)]ClO4
(5.0 mol %) and dppp (5.0 mol %), Et3N (1.0 equiv) and silylphos-
phine meso-/rac-8–10 (0.51 equiv) are successively added. The re-
action mixture is maintained at 60 ꢁC for 2 days. The reaction
mixture is cooled to room temperature and is directly oxidized with
H2O2 (30%, 2.0 equiv). After additional stirring for 4 h, H2O and
aqueous FeSO4 (0.5 M) are added. The organic layer is separated
and the aqueous phase is extracted with tert-butyl methyl ether
(3ꢃ). The combined organic phases are dried (MgSO4) and the
volatiles are removed under reduced pressure. Purification by flash
column chromatography on silica gel (CH2Cl2–methanol) provides
phosphine oxides 27 and 28.
(100 MHz, CDCl3):
d
ꢀ5.2, 15.8, 18.6, 21.4, 22.4, 22.6, 25.1, 26.1, 31.6,
34.5, 45.4, 50.5, 72.9, 127.3, 129.1, 134.6, 136.6 ppm. IR (ATR): 1110
(s) cmꢀ1
355.2428. Found: 355.2435.
.
HRMS (ESI) calculated for C21H36OSiNa ([MþNa]þ):
4.5. (SiR)-tert-Butylmethylphenylsilane ((SiR)-18)
A 100 mL Schlenk flask equipped with a magnetic stirring bar and
a reflux condenser was charged with (SiS)-17 (1.86 g, 5.60 mmol,
1.00 equiv, dr>99:1) and n-heptane (30 mL). DIBAL–H (1.0 M in n-
hexane, 22.4 mL, 22.4 mmol, 4.00 equiv) was added and the reaction
mixture was subsequently heated at reflux for 20 h. The reaction
mixture was quenched at ambient temperature by careful addition of
H2O (60 mL) followed by neutralization (pH¼7) with 2 M HCl. The
organic layer was separated and the aqueous phase was extracted
with tert-butyl methyl ether (4ꢃ50 mL). The combined organic layers
were washed with brine (40 mL), dried (MgSO4), filtered and the
volatiles were evaporated under reduced pressure. The crude product
was purified by flash chromatography on silica gel with cyclohexane
as eluent, furnishing highly enantiomerically enriched silane (SiR)-18
(916 mg, 92%, >99% ee) as a colorless oil. HPLC (Daicel Chiracel OJ-H
column, column temperature 12 ꢁC, solvent n-heptane:i-PrOH 99:1,
flow rate 0.7 mL minꢀ1): tR¼5.23 min for (SiS)-18 (minor enantiomer)
4.7.1. meso- and rac-4-({2-[(3-Oxobutyl)phenylphosphinoyl]-
ethyl}phenylphosphinoyl)butan-2-one (meso- and rac-27)
meso-27:26 pale yellow solid; yield: 37% (from 8), 42% (from 9);
Rf¼0.24 (CH2Cl2–methanol 50:1). Mp 120–121 ꢁC.1H NMR (500 MHz,
CDCl3):
d 1.87 (m, 2H), 2.03 (s, 6H), 2.08 (m, 2H), 2.11–2.21 (m, 4H),
2.41 (m, 2H), 2.73 (m, 2H), 7.47–7.59 (m, 6H), 7.61–7.67 (m, 4H) ppm.
13C NMR (100 MHz, CDCl3):
d
21.7 (d, JC–P¼32.2 Hz), 23.6 (d, JC–P¼
35.5 Hz), 29.5, 34.8, 128.9 (d, JC–P¼5.7 Hz), 129.0 (d, JC–P¼5.6 Hz),
129.4, 130.4 (d, JC–P¼4.6 Hz),130.5 (d, JC–P¼4.6 Hz),130.7,131.9,132.2,
205.6 (d, JC–P¼6.2 Hz) ppm. 31P{1H} NMR (162 MHz, CDCl3):
d
41.1 ppm. IR (ATR): 1704 (s) cmꢀ1. HRMS (ESI) calculated for
and tR¼6.27 min for (SiR)-18 (major enantiomer). Rf¼0.70 (cyclo-
C22H28O4P2Na ([MþNa]þ): 441.1355. Found: 441.1352.
20
hexane). [
d
a]
ꢀ25.6 (c 0.55, CHCl3). 1H NMR (400 MHz, CDCl3):
rac-27:26 pale yellow solid; yield: 36% (from 8), 40% (from 9);
Rf¼0.18 (CH2Cl2–methanol 50:1). Mp 120–121 ꢁC. 1H NMR
D
0.36 (d, J¼3.7 Hz, 3H), 0.96 (s, 9H), 4.16 (q, J¼3.7 Hz, 1H), 7.34–7.42
(m, 3H), 7.52–7.57 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3):
d
ꢀ8.5,
(500 MHz, CDCl3): d 1.84 (m, 2H), 2.08 (s, 6H), 2.12 (m, 2H), 2.20–
16.6, 26.8, 127.6, 129.2, 135.1, 135.5 ppm. IR (ATR): 2111 (s) cmꢀ1
.
2.36 (m, 4H), 2.49 (m, 2H), 2.81 (m, 2H), 7.41–7.46 (m, 4H), 7.50–7.57
HRMS (EI) calculated for C11H18Si ([M]þ):178.1172. Found: 178.1178.
(m, 6H) ppm. 13C NMR (100 MHz, CDCl3):
d
22.5 (d, JC–P¼29.3 Hz),
23.4 (d, JC–P¼35.5 Hz), 29.6, 34.9,128.8 (d, JC–P¼5.7 Hz),128.9(d, JC–P
¼
4.6. (SiR)-(tert-Butylmethylphenylsilyl)diphenylphosphine
((SiR)-19)
6.0 Hz), 129.6, 130.3 (d, JC–P¼4.5 Hz), 130.4 (d, JC–P¼4.5 Hz), 130.9,
132.2, 132.4, 205.7 (d, JC–P¼6.1 Hz) ppm. 31P{1H} NMR (162 MHz,
CDCl3):
d
40.9 ppm. IR (ATR): 1712 (s) cmꢀ1. HRMS (ESI) calculated
A saturated solution of Cl2 in CCl4 (6.0 mL) was added to a solu-
tion of (SiR)-18 (916 mg, 5.14 mmol, 1.00 equiv) in CCl4 (5.0 mL) at
0 ꢁC until the pale yellow color persisted. After 10 min, the reaction
mixture was purged with argon. Evaporation of the solvent under
reduced pressure provided chlorosilane (SiS)-15 as a colorless oil,
which was used without further purification. Simultaneously,
a 50 ml-Schlenk flask charged with diphenylphosphine (960 mg,
5.14 mmol, 1.00 equiv) in THF (20 mL) was cooled to ꢀ30 ꢁC and n-
butyllithium (1.6 M in hexane, 3.21 ml, 5.14 mmol, 1.00 equiv) was
added dropwise. The resulting red solution was allowed to warm to
room temperature and stirred for another hour. After cooling to 0 ꢁC,
a solution of freshly prepared (SiS)-15 and THF (5 mL) was slowly
added. The reaction mixture was heated at reflux for 1 h. After
evaporation of the solvents, the residue was purified via Kugelrohr
distillation (4ꢃ10ꢀ1 mbar at 220 ꢁC oven temperature), affording
(SiR)-19 as a pale yellowish, highly viscous oil (1.62 g, 87%). 1H NMR
for C22H28O4P2Na ([MþNa]þ): 441.1355. Found: 441.1354.
4.7.2. meso- and rac-4-({2-[(3-Oxobutyl)phenylphosphinoyl]-
propyl}phenylphosphinoyl)butan-2-one (meso- and rac-28)
meso-28:26 pale yellow oil; yield: 36%. Rf¼0.18 (CH2Cl2–metha-
nol 25:1). 1H NMR (300 MHz, CDCl3):
d 1.69 (m, 2H), 1.88–2.00 (m,
4H), 2.01 (s, 6H), 2.04–2.24 (m, 4H), 2.39 (m, 2H), 2.72 (m, 2H),
7.32–7.61 (m, 10H) ppm. 13C NMR (75 MHz, CDCl3):
d
23.7 (d, JC–P
¼
26.2 Hz), 28.9, 30.0 (d, JC–P¼11.9 Hz), 30.9 (d, JC–P¼11.9 Hz), 34.7 (d,
JC–P¼2.8 Hz), 128.8 (d, JC–P¼5.8 Hz), 131.1, 131.3 (d, JC–P¼19.0 Hz),
131.9 (d, JC–P¼2.5 Hz), 206.0 (d, JC–P¼12.3 Hz) ppm. 31P{1H} NMR
(121 MHz, CDCl3):
d
41.0 ppm. IR (ATR): 1710 (s) cmꢀ1. HRMS (ESI)
calculated for C23H30O4P2H ([MþH]þ): 433.1698. Found: 433.1691.
rac-28:26 pale yellow oil; yield: 35%. Rf¼0.13 (CH2Cl2–methanol
25:1). 1H NMR (300 MHz, CDCl3):
d 1.64 (m, 2H), 1.77–2.01 (m, 4H),
2.03 (s, 6H), 2.04–2.22 (m, 4H), 2.36 (m, 2H), 2.80 (m, 2H), 7.36ꢀ7.67
(400 MHz, CDCl3):
d
0.47 (d, J¼1.8 Hz, 3H), 0.80 (d, JC–P¼0.7 Hz, 9H),
(m, 10H) ppm. 13C NMR (75 MHz, CDCl3):
d
22.8 (d, JC–P¼26.1 Hz),

V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
6517
29.5, 29.8 (d, JC–P¼11.4 Hz), 30.7 (d, JC–P¼11.4 Hz), 34.8 (d, JC–P
¼
JC–P¼11.4 Hz), 128.8 (d, JC–P¼11.5 Hz), 130.6 (d, JC–P¼25.5 Hz), 131.0
(d, JC–P¼6.8 Hz), 131.1 (d, JC–P¼6.6 Hz), 131.6 (d, JC–P¼24.4 Hz), 131.9
(d, JC–P¼2.7 Hz), 132.0 (d, JC–P¼2.9 Hz), 170.5 (d, JC–P¼17.7 Hz) ppm.
2.4 Hz),128.7 (d, JC–P¼5.7 Hz),130.3,131.4 (d, JC–P¼19.2 Hz),131.8 (d,
JC–P¼2.5 Hz), 206.1 (d, JC–P¼12.1 Hz) ppm. 31P{1H} NMR (121 MHz,
CDCl3):
d
40.7 ppm. IR (ATR): 1712 (s) cmꢀ1. HRMS (ESI) calculated
31P{1H} NMR (121 MHz, CDCl3):
d 35.3 ppm. IR (ATR): 1758 (s)
for C23H30O4P2H ([MþH]þ): 433.1698. Found: 433.1689.
(C]O) cmꢀ1. Anal. Calcd for C18H18F3O3P (370.09): C, 58.38; H, 4.90.
Found: C, 58.45; H, 4.83.
4.8. General procedure for the Rh(I)-catalyzed 1,4-addition
of
a,
b-unsaturated acyclic acceptors
4.9. rac-3-(tert-Butylphenylphosphinoyl)cyclohexanone
(rac-45)
In a flame-dried Schlenk tube equipped with a magnetic stirring
bar, [Rh(cod)2]OTf (5.0 mol %), IPr$HCl (5.0 mol %) and KOt-Bu
(10 mol %) are dissolved in 1,4-dioxane (0.2 M based on substrate)
A Schlenk tube equipped with a magnetic stirring bar was
charged with 21 (38.8 mg, 0.415 mmol, 1.00 equiv) dissolved in
deoxygenated 1,4-dioxane: H2O¼10:1 (approximately 0.5 M based
on substrate). After addition of [(dppp)Rh(cod)]ClO4 (15.0 mg,
0.021 mmol, 5.0 mol %) and dppp (8.6 mg, 0.021 mmol, 5.0 mol %),
and stirred for 30 min at room temperature. The acyclic
a,b-
unsaturated acceptor (1.0 equiv), Et3N (1.0 equiv), silylphosphine
1a (2.5 equiv), and H2O (0.02 M based on substrate) are added in
this order. The mixture is maintained at 60 ꢁC for 16 h. The reaction
mixture is cooled to room temperature and is directly oxidized with
H2O2 (30%, 2.0 equiv). After additional stirring for 2 h, H2O and
aqueous FeSO4 (0.5 M) are added. The organic layer is separated
and the aqueous phase is extracted with tert-butyl methyl ether
(3ꢃ). The combined organic phases are dried (MgSO4) and the
volatiles are removed under reduced pressure. The residue is pu-
rified by flash chromatography on silica gel (cyclohexane–ethyl
acetate), yielding phosphine oxides 37–44.8
Et3N (58 mL, 41.9 mg, 0.415 mmol, 1.00 equiv) and silylphosphine
rac-13 (249 mg, 0.830 mmol, 2.50 equiv) were successively added.
The reaction mixture was maintained at 60 ꢁC for 2 days. The re-
action mixture was cooled to room temperature and directly oxi-
dized with H2O2 (30%, 85 mL, 0.830 mmol 2.00 equiv). After
additional stirring for 4 h, H2O (1 mL) and aqueous FeSO4 (1 mL)
were added. The organic layer was separated and the aqueous
phase was extracted with tert-butyl methyl ether (3ꢃ2 mL). The
combined organic phases were dried (MgSO4) and the volatiles
were removed in vacuo. Purification by flash column chromatog-
raphy on silica gel (ethyl acetate) provided phosphine oxide rac-45
as a mixture of diastereomers (88.9 mg, 77%, dr¼66:34) as a white
solid. Rf¼0.13 (CH2Cl2–methanol 50:1). Mp 77 ꢁC. 1H NMR
4.8.1. 3-Diphenylphosphinoyl-3-phenylpropionic acid 2,2,2-
trifluoroethyl ester (37)
White solid; yield: 65% (from Z-29), 37% (from E-29); Rf¼0.56
(cyclohexane–ethyl acetate 1:3). Mp 175 ꢁC. 1H NMR (400 MHz,
(400 MHz, CDCl3):
d
1.13 (d, J¼14.5 Hz, 6H), 1.17 (d, J¼14.5 Hz, 9H),
CDCl3):
d
3.01 (ddd, J¼3.7, 8.7, 16.7 Hz, 1H), 3.22 (ddd, J¼6.8, 11.3,
1.48–1.87 (m, 2H), 1.95–2.18 (m, 4H), 2.22–2.42 (m, 5H), 2.44–2.94
16.7 Hz, 1H), 4.04 (ddd, J¼3.7, 8.4, 11.3 Hz, 1H), 4.23 (m, 2H), 7.11–
(m, 4H), 7.41–7.51 (m, 5H), 7.61–7.72 (m, 3H) ppm. 13C NMR
7.30 (m, 7H), 7.33–7.40 (m, 3H), 7.51–7.62 (m, 3H), 7.89–7.99 (m,
(100 MHz, CDCl3):
d
24.5, 24.6, 25.7, 25.8, 26.1 (d, JC–P¼14.2 Hz),
2H) ppm. 13C NMR (100 MHz, CDCl3):
d
34.5, 42.9 (d, JC–P¼65.8 Hz),
26.6 (d, JC–P¼13.8 Hz), 33.5 (d, JC–P¼65.4 Hz), 33.6 (d, JC–P¼65.6 Hz),
35.6 (d, JC–P¼61.0 Hz), 35.8 (d, JC–P¼60.7 Hz), 40.4 (d, JC–P¼3.6 Hz),
40.8 (d, JC–P¼3.2 Hz), 40.9, 41.0, 128.4 (d, JC–P¼10.1 Hz), 128.5
(d, JC–P¼10.5 Hz), 129.3 (d, JC–P¼25.4 Hz), 130.0 (d, JC–P¼25.6 Hz),
131.2 (d, JC–P¼7.4 Hz), 131.3 (d, JC–P¼7.3 Hz), 131.5 (d, JC–P¼2.4 Hz),
60.5 (q, JC–F¼36.7 Hz), 122.6 (q, JC–F¼279 Hz), 127.5 (d, JC–P¼2.4 Hz),
128.1 (d, JC–P¼11.9 Hz),128.4 (d, JC–P¼1.9 Hz),128.9 (d, JC–P¼11.2 Hz),
129.5 (d, JC–P¼5.2 Hz), 130.4 (d, JC–P¼7.4 Hz), 131.1 (d, JC–P¼9.1 Hz),
131.3 (d, JC–P¼1.5 Hz), 131.4 (d, JC–P¼8.9 Hz), 131.6 (d, JC–P¼3.1 Hz),
132.2 (d, JC–P¼2.8 Hz), 134.4 (d, JCꢀP¼5.5 Hz), 169.8 (d,
131.6 (d, JC–P¼2.4 Hz), 209.9 (d, JC–P¼12.8 Hz), 210.0 (d, JC–P
¼
JCꢀP¼17.6 Hz) ppm. 31P{1H} NMR (121 MHz, CDCl3):
d
32.0 ppm. IR
12.3 Hz) ppm. 31P{1H} NMR (121 MHz, CDCl3):
d 48.5,48.7 ppm. IR
(ATR): 1754 (s) (C]O) cmꢀ1. Anal. Calcd for C23H20F3O3P (432.11): C,
(ATR): 1702 (s) cmꢀ1. HRMS (ESI) calculated for C16H23O2PNa
63.89; H, 4.66. Found: C, 63.82; H, 4.62.
([MþNa]þ): 301.1328. Found: 301.1319.
4.8.2. 3-Diphenylphosphinoylheptanoic acid 2,2,2-trifluoroethyl
ester (38)
4.10. X-ray data
Colorless oil; yield: 63% (from Z-30), 54% (from E-30); Rf¼0.66
4.10.1. General information
(cyclohexane–ethyl acetate 1:4).1H NMR (400 MHz, CDCl3):
d
0.75 (t,
Data set was collected with a Nonius KappaCCD diffractometer.
Programs used: data collection COLLECT (Nonius B.V., 1998), data
reduction Denzo-SMN,27a absorption correction Denzo,27b struc-
ture solution SHELXS-97,27c structure refinement SHELXL-97,27d
graphics SCHAKAL (Universita¨t Freiburg, 1997).
J¼7.1 Hz, 3H), 1.10–1.39 (m, 4H), 1.54 (m, 1H), 1.67 (m, 1H), 2.58 (ddd,
J¼7.9, 9.4, 17.2 Hz, 1H), 2.78 (ddd, J¼4.6, 14.6, 17.2 Hz, 1H), 2.94 (m,
1H), 4.19 (dq, J¼8.3, 12.7 Hz, 1H), 4.39 (dq, J¼8.3, 12.7 Hz, 1H), 7.42–
7.55 (m, 6H), 7.77–7.85 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3):
d
13.6, 22.4, 28.0 (d, JC–P¼1.7 Hz), 29.4 (d, JC–P¼10.0 Hz), 32.3, 33.8 (d,
Crystallographic data (excluding structure factors) for the struc-
tures reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication. CCDC-
718494 (3b) contain the supplementary crystallographic data for this
paper. This data can be obtained free of charge at www.ccdc.ca-
m.ac.uk/conts/retrieving.html [or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
þ44(1223)336-033; E-mail: deposit@ccdc.cam.ac.uk].
JC–P¼72.1 Hz), 60.5 (q, JC–F¼37.1 Hz), 122.6 (q, JC–F¼280 Hz), 128.7 (d,
JC–P¼11.7 Hz), 130.8 (d, JC–P¼9.0 Hz), 130.9 (d, JC–P¼8.9 Hz), 131.0,
131.1 (d, JC–P¼8.9 Hz), 131.8 (d, JC–P¼6.8 Hz), 131.9 (d, JC–P¼2.8 Hz),
132.0, 171.0 (d, JC–P¼13.2 Hz) ppm. 31P{1H} NMR (121 MHz, CDCl3):
d
36.1 ppm. IR (ATR): 1756 (s) (C]O) cmꢀ1. HRMS (ESI) calculated for
C21H24O3F3PNa ([MþNa]þ): 435.1307. Found: 435.1307.
4.8.3. 3-Diphenylphosphinoylbutyric acid 2,2,2-trifluoroethyl
ester (39)
4.10.2. X-ray crystal structure analysis for 3b
White solid; yield: 88%; Rf¼0.32 (cyclohexane–ethyl acetate 1:3).
Formula C21H43PSi, M¼354.61, colorless crystal 0.60ꢃ
Mp 90 ꢁC. 1H NMR (400 MHz, CDCl3):
d
1.23 (dd, J¼7.2, 16.1 Hz, 3H),
0.50ꢃ0.45 mm, a¼9.6011(2), b¼10.5024(2), c¼11.6826(3) Å,
a
¼
¼
2.57 (ddd, J¼6.4, 10.7, 16.7 Hz,1H), 2.76 (ddd, J¼3.4, 9.9, 16.7 Hz, 1H),
81.600 (1),
b
¼81.620(1),
g
¼75.210(1)ꢁ, V¼1119.50(4) Å3, rcalcd
2.90 (m,1H), 4.42 (m, 2H), 7.47–7.59 (m, 6H), 7.79–7.87 (m, 4H) ppm.
1.052 g cmꢀ3
,
m
¼1.566 mmꢀ1
,
empirical absorption correction
13C NMR (100 MHz, CDCl3):
73.9 Hz), 33.9, 60.4 (q, JC–F¼36.0 Hz),122.7 (d, JC–F¼275 Hz),128.7 (d,
d
12.8 (d, JC–P¼2.7 Hz), 29.2 (d, JC–P
¼
(0.453ꢄTꢄ0.539), Z¼2, triclinic, space group P1bar (No. 2),
l
¼1.54178 Å, T¼223(2) K,
u and 4 scans,12,250 reflections collected

6518
V.T. Trepohl et al. / Tetrahedron 65 (2009) 6510–6518
(ꢅh, ꢅk, ꢅl), [(sin
q)/l
]¼0.60 Åꢀ1, 3899 independent (Rint¼0.040)
12. Selected examples of 1,4-addition of R2P groups: (a) Thermal addition of R2PH:
Zabotina, E. Y.; de Kanter, F. J. J.; Bickelhaupt, F.; Wife, R. L. Tetrahedron 2001, 57,
10177–10180; (b) Thermal addition of R2PH$BH3: Join, B.; Delacroix, O.;
Gaumont, A.-C. Synlett 2005, 1881–1884; (c) Addition of metalated, borane-
protected R2PH: Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J.
Am. Chem. Soc. 1990, 112, 5244–5252; (d) For the Conant reaction (transfer of
P(V) nucleophile generated from R2PCl/glacial acetic acid), see: Conant, J. B.;
Braverman, J. B. S.; Hussey, R. E. J. Am. Chem. Soc. 1923, 45, 165–171.
13. Hayashi, M.; Matsuura, Y.; Watanabe, Y. J. Org. Chem. 2006, 71, 9248–9251.
14. Hayashi, M.; Matsuura, Y.; Watanabe, Y. Tetrahedron Lett. 2004, 45, 1409–
1411.
and 3781 observed reflections [Iꢂ2
s(I)], 214 refined parameters,
R¼0.043, wR2¼0.115, max (min) residual electron density 0.47
(ꢀ0.21) e Åꢀ3, hydrogen atoms calculated and refined as riding
atoms.
Acknowledgements
The research was supported by the International Research
Training Group Mu¨nster–Nagoya (GRK 1143) (predoctoral fellow-
ship to V.T.T., 2007–2009) and the Aventis Foundation (Karl-Win-
nacker fellowship to M.O., 2006–2008). Generous donation of
chemicals from Wacker AG (Burghausen, Germany) is gratefully
acknowledged.
15. Issleib, K.; Bo¨ttcher, W. Syn. React. Inorg. Metal-Org. Chem. 1976, 6, 179–190.
16. Heinicke, J.; Kadyov, R. J. Organomet. Chem. 1996, 520, 131–137.
17. (a) Sommer, L. H. Stereochemistry, Mechanism, and Silicon; McGraw-Hill: New
York, NY, 1965; (b) Sommer, L. H. Intra-Sci. Chem. Rep. 1973, 7, 1–44; (c) Corriu,
R. J. P.; Guerin, C.; Moreau, J. J. E. In Topics in Stereochemistry; Eliel, E. L., Ed.;
Wiley: New York, NY, 1984; Vol. 15, pp 43–198.
18. (a) Oestreich, M.; Auer, G.; Keller, M. Eur. J. Org. Chem. 2005, 184–195; (b)
Rendler, S.; Auer, G.; Keller, M.; Oestreich, M. Adv. Synth. Catal. 2006, 348,
1171–1182.
19. (a) Jankowski, P.; Schaumann, E.; Wicha, J.; Zarecki, A.; Adiwidjaja, G. Tetrahe-
dron: Asymmetry 1999, 10, 519–526; (b) Jankowski, P.; Schaumann, E.; Wicha, J.;
Zarecki, A.; Adiwidjaja, G.; Asztemborska, M. Chem. Commun. 2000, 1029–1030.
20. Dubac, J.; Escudie, J.; Couret, C.; Cavezzan, J.; Satge, J.; Mazerolles, P. Tetrahedron
1981, 37, 1141–1151.
References and notes
1. Handbook of Organopalladium Chemistry for Organic Synthesis; Negishi, E.-i., Ed.;
Wiley: New York, NY, 2002.
2. (a) Miyaura, N. Bull. Chem. Soc. Jpn. 2008, 81, 1535–1553; (b) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
21. Conventional
b-substituted a,b-unsaturated esters were reluctant to participate
while simple acrylic esters reacted in high chemical yields.
22. (a) Conjugate addition of lithiated R2PH$BH3: Le´autey, M.; Castelot-De-
liencourt, G.; Jubault, P.; Pannecoucke, X.; Quirion, J.-C. Tetrahedron Lett. 2002,
43, 9237–9240; (b) Conjugate addition of lithiated or sodiated (EtO)2P(O)H:
Castelot-Deliencourt, G.; Pannecoucke, X.; Quirion, J.-C. Tetrahedron Lett. 2001,
42, 1025–1028.
23. (a) Rendler, S.; Oestreich, M.; Butts, C. P.; Lloyd-Jones, G. C. J. Am. Chem. Soc. 2007,
129, 502–503; (b) Rendler, S.; Oestreich, M. Angew. Chem., Int. Ed. 2008, 47, 5997–
6000; (c) Weickgenannt, A.; Oestreich, M. Chem. Asian J. 2009, 4, 406–410.
24. For a remarkable reagent-controlled 1,4-addition of a metalated phosphorus-
stereogenic phosphine oxide, see: Haynes, R. K.; Lam, W. W.-L.; Yeung, L.-L.
Tetrahedron Lett. 1996, 37, 4729–4732.
25. West, R.; Boudjouk, P. J. Am. Chem. Soc. 1973, 95, 3983–3987.
26. The configurational assignment of meso and rac compounds is not secured.
27. (a) Otwinowski, Z.; Minor, W. Methods Enzymol. 1997, 276, 307–326; (b) Otwi-
nowski, Z.; Borek, D.; Majewski, W.; Minor, W. Acta Crystallogr. 2003, A59, 228–
234; (c) Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467–473; (d) Sheldrick, G. M.
Acta Crystallogr. 2008, A64, 112–122.
3. (a) Yoshida, K.; Hayashi, T. In Modern Rhodium-Catalyzed Organic Reactions;
Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005; pp 55–77; (b) Fagnou, K.;
Lautens, M. Chem. Rev. 2003, 103, 169–196.
4. Kabalka, G. W.; Das, B. C.; Das, S. Tetrahedron Lett. 2002, 43, 2323–2325.
5. (a) Walter, C.; Auer, G.; Oestreich, M. Angew. Chem., Int. Ed. 2006, 45, 5675–5677;
(b) Walter, C.; Oestreich, M. Angew. Chem., Int. Ed. 2008, 47, 3818–3820.
6. Trepohl, V. T.; Oestreich, M. Chem. Commun. 2007, 3300–3302.
7. (a) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Angew. Chem., Int. Ed. 2003, 42,
2768–2770; (b) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organometallics 2004,
23, 4317–4324.
8. Trepohl, V. T.; Mori, S.; Itami, K.; Oestreich, M. Org. Lett. 2009, 11, 1091–1094.
9. Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124,
5052–5058.
10. (a) Uncatalyzed: Couret, C.; Escudie, J.; Satge, J.; Ahn, N. T.; Soussan, G. J.
Organomet. Chem. 1975, 91, 11–30; (b) Fluoride-mediated: Hayashi, M.; Mat-
suura, Y.; Watanabe, Y. Tetrahedron Lett. 2004, 45, 9167–9169.
11. For a summary of conjugate phosphorus(III) and phosphorus(V) transfer, see:
Enders, D.; Saint-Dizier, A.; Lannou, M.-I.; Lenzen, A. Eur. J. Org. Chem. 2006, 29–49.