Novel chiral diphosphine ligands with a pinene core obtained via an allylphosphinite-allylphosphine oxide rearrangement

Article abstract of DOI:10.1016/j.tetasy.2004.05.045

A number of new chiral diphosphine ligands with a pinene framework were synthesized and tested in some transition metal-catalyzed asymmetric reactions (enantioselectivities up to 84% ee were achieved). The [2,3]-sigmatropic allylphosphinite-allyl phosphin

Full text of DOI:10.1016/j.tetasy.2004.05.045

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2279–2288
Novel chiral diphosphine ligands with a pinene core obtained via an
allylphosphinite–allylphosphine oxide rearrangement
Andrei Gavryushin, Kurt Polborn and Paul Knochel*
Department of Chemistry, Ludwig–Maximilians-University, Butenandtstrasse 5-13, D-81377 Munich, Germany
Received 2 April 2004; accepted 17 May 2004
Available online 10 July 2004
Abstract—A number of new chiral diphosphine ligands with a pinene framework were synthesized and tested in some transition
metal-catalyzed asymmetric reactions (enantioselectivities up to 84% ee were achieved). The [2,3]-sigmatropic allylphosphinite–allyl
phosphine oxide rearrangement was applied as a key step of the synthesis. An improved procedure for the phosphine oxide
reduction and a new protocol for the deprotection of phosphine–borane complexes were developed.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
retrosynthetic analysis of the pinene-derived ligands is
shown in Figure 1.
Chiral diphosphine ligands have been extensively stud-
ied and used over the last few decades as ligands for
transition metals in catalytic processes for the synthesis
of enantiopure compounds.1 Natural homochiral terp-
enes present an inexpensive and reliable source for the
synthesis of new ligands, although so far, most of the
known syntheses of chiral ligands from terpenes start
from camphor.2
hydroboration,
PPh2
PPh2
P(O)Ph2
[2,3]-rearrangement
oxidation,
reduction,
substitution
OH
OH
A
B
hydroboration,
oxidation,
reduction,
PPh2
PPh2
P(O)Ph2 [2,3]-rearrangement
substitution
More than 50 years ago, Arbuzov and Nikonorov, dis-
covered the thermal rearrangement of allyldiarylphos-
phinites to allyldiphenylphosphine oxides.3 We have
shown that this reaction proceeds highly diastereo-
selectively and is a convenient tool for the transforma-
tion of easily available chiral allylic alcohols into chiral
diarylphosphines. Several new chiral ligands were syn-
thesized in this way.4;5 Herein, we report the application
of this reaction to the synthesis of new chiral diphos-
phines starting from naturally occurring allylic alcohols.
Thermal [2,3]-sigmatropic rearrangement of diphenyl-
phosphinites,4 obtained in situ from chiral myrtenol and
trans-pinocarveol gave the corresponding allylphos-
phine oxides in excellent yields. Hydroboration–oxida-
tion gave diphenylphosphinoyl alcohols as single
diastereomers, which were transformed into the corre-
sponding diphosphines in four synthetic steps. The short
C
D
Figure 1. Retrosynthetic pathway for the pinene-derived ligands.
Starting from pinene-derived alcohols, myrtenol, and
pinocarveol, we were able to obtain two types of ligands
with the opposite configuration of the phosphorus-
containing substituents, attached to the pinene scaffold
(Fig. 2).
Ph Ph
P
Ph Ph
P
Cy Cy
P
Ph Ph
P
Ph
Ph
I
Cy
P
P
P
P
Ph
Ph
PI
Cy
1
3
2
4
Figure 2. Ligands obtained from pinene-derived alcohols.
Novel diphosphine ligands were tested in a number
of transition-metal catalyzed asymmetric reactions.
Enantioselectivities up to 84% ee were achieved.
* Corresponding author. Tel.: +49-89-2180-77679; fax: +49-89-2180-
77680; e-mail: paul.knochel@cup.uni-muenchen.de
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.045

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A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
2. Results and discussion
we could obtain full conversion within 1–2 h. Since the
reaction mixture is homogeneous, it can be conveniently
monitored by 31P NMR. Excess of PMHS and its oxi-
dized derivates of various polarity made the chromato-
graphical purification of the product troublesome until
we found that stirring of the mixture after the reaction
with 20–25% HF completely removed both the titanium
and silicon compounds, leaving the borane protection
intact. By this method, alcohol 8 was obtained in nearly
quantitative yield.
2.1. Synthesis of (2R,3R)-2-diphenylphosphanyl-3-
[(diphenylphosphanyl)-methyl]-bicyclo[3.1.1]heptane
The elaboration of the remaining asymmetric centers in
the synthesis of ligand 1 (Scheme 1) is based on the
known hydroboration of pinenes, which occurs with
high diastereoselectivity.6 The formation of diphen-
ylphosphinite from trans-pinocarveol22 5 and its thermal
rearrangement were performed in toluene according to a
one-pot procedure,5 and gave allylphosphine oxide 6.
The hydroboration7;8 of the allylphosphine oxide with
borane–dimethyl sulfide readily occurred in toluene at
60 °C. We found that for the oxidation9 of the borane
adduct, m-chloroperbenzoic acid in CH2Cl2 is much
more efficient than the conventional NaOH–H2O2 mix-
ture. After the removal of the excess of the acids (aq
Na2S2O5, then NaOH) and the usual work-up, the
desired diphenylphosphinoyl alcohol was crystallized
from ether in 62% overall yield. Its relative configuration
of the single diastereomer formed was established by
X-ray analysis (Fig. 3).10
Alcohol 8 was converted into the mesylate by treatment
with excess methanesulfonyl chloride and triethylamine
in cold CH2Cl2. Dilution of the reaction mixture with
ether, filtration through silica gel and removal of the
excess of MsCl in vacuo afforded the unstable mesylate
sufficiently pure for direct use in the next step.
Reaction of the mesylate with diphenylphosphine and
t-BuOK in THF followed by protection gave the desired
diphosphine–borane in an acceptable yield. The product
was purified by flash chromatography (Al2O3, CH2Cl2–
pentane) and recrystallized from Et2O in 55% overall
yield, mp 195–196 °C. Attempts to use more convenient
phosphine-borane nucleophiles in polar aprotic sol-
vents12 proved unsuccessful, with only the starting
material being recovered.
PPh2:BH3
OH
P(O)Ph2
P(O)Ph2
OH
OH
iv)
i)
ii,iii)
8
Whereas deprotection of monophosphine–boranes nor-
mally proceeds easily, bis-phosphine boranes, especially
electron-rich, can present a significant problem for de-
protection. Although a complementary acid-mediated
method of their decomplexation is known,12;13 we were
looking for a simplified procedure avoiding the use of
aqueous solutions, which usually contaminates the
product with the phosphine oxide. Inexpensive N,N0-bis-
3-(aminopropyl)-piperazine turned out to be an excel-
lent solution: complete deprotection of the bis-borane
could be performed at 100 °C within 1 h. Dilution of the
mixture with ether, filtration through dry silica in argon
and evaporation gave the desired diphosphine in nearly
quantitative yield.
6
7
5
PPh2
PPh2
PPh2:BH3
PPh2:BH3
OMs
PPh2:BH3
vii)
v), vi)
vi)
1
9
10
Scheme 1. Reagents and conditions: (i) Ph2PCl, DMAP, toluene,
80 °C, 6 h; (ii) BH3–Me2S, 60 °C, 6 h; (iii) mCPBA, CH2Cl2, 10–15 °C,
62% overall; (iv) PMHS, Ti(Oi-Pr)4, PhMe, 100 °C, 2 h, BH3–Me2S,
then 25% HF, 25 °C, 12 h, 96%; (v) MsCl, Et3N, CH2Cl2, À20 °C, 2 h;
(vi) Ph2PH, t-BuOK, THF, 50 °C, 18 h, BH3–Me2S, 55% for two steps;
(vii) N,N0-bis-(3-aminopropyl)-piperazine, 100 °C, 2 h, 95%.
2.2. Synthesis of (2S,3S)-2-diphenylphosphanyl-3-
[(diphenylphosphanyl)-methyl]-bicyclo[3.1.1]heptane
The rearrangement of the diphenylphosphinite, ob-
tained from myrtenol (Scheme 2) required harsher
conditions (100 °C, 48 h against 6 h at 80 °C) compared
to the trans-pinocarveol derivative, but led to the desired
allylphosphine oxide in excellent yield. Hydroboration
of product 12 with borane in THF gave a diastereomeric
mixture of products in 3:1 ratio. Use of more bulky
14
9-BBN
gave after oxidation, alcohol 13 as a single
diastereomer. The anticipated cis-configuration of the
substituents was confirmed by X-ray analysis (Fig. 4).15
Interestingly, the borane adduct of alkene 12 and 9-BBN
is unusually air-stable crystalline solid, which can be
easily purified by recrystallization.
Figure 3. ORTEP diagram of alcohol 7.
Phosphine oxide 7 was reduced quantitatively into the
corresponding phosphine by
a mixture of poly-
methylhydrosiloxane–Ti(Oi-Pr)4, although under the
originally described conditions11 (THF, reflux) the
reaction was very sluggish. In toluene at 100 °C however
The remaining steps of the synthesis were performed
using the same sequence as for the ligand 1. In this way,

A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
2281
OH
OH
PCy2:BH3
OH
P(O)Ph2
OH
P(O)Ph2
OH
P(O)Cy2
iv)
i)
ii), iii)
i)
P(O)Ph2
ii)
11
13
12
17
13
16
PPh2:BH3
PCy2:BH3
OH
PPh2:BH3
PPh2:BH3
PPh2
PPh2
PCy2
iii), iv)
v)
PPh2:BH3
vii)
PPh2
v), vi)
2
14
15
18
3
Scheme 2. Reagents and conditions: (i) Ph2PCl, DMAP, PhMe,
100 °C, 48 h, 90%; (ii) 9-BBN, THF, 75 °C, 48 h; (iii) mCPBA, CH2Cl2,
10–15 °C, 67% for two steps; (iv) PMHS, Ti(Oi-Pr)4, PhMe, 100 °C,
2 h, BH3–Me2S, then 25% HF, 25 °C, 12 h, 95%; (v) MsCl, Et3N,
CH2Cl2, À20 °C, 2 h; (vi) Ph2PH, t-BuOK, THF, 50 °C, 18 h, BH3–
Me2S, 48% for two steps; (vii) N,N0-bis-(3-aminopropyl)-piperazine,
100 °C, 2 h, 96%.
Scheme 3. Reagents and conditions: (i) Raney Ni, MeOH, H2, 50 bar,
50 °C, 48 h, 97%; (ii) PMHS, Ti(Oi-Pr)4, PhMe, 100 °C, 2 h, BH3–
Me2S, then 25% HF, 25 °C, 12 h, 93%; (iii) MsCl, Et3N, CH2Cl2,
À20 °C, 2 h; (iv) Ph2PH, t-BuOK, THF, 50 °C, 18 h, BH3–Me2S, 44%
for two steps; (v) N,N0-bis-(3-aminopropyl)-piperazine, 100 °C, 12 h,
96%.
PCy2:BH3
P(O)Cy2
P(O)Ph2
OH
i)
OH
ii)
OH
C
C1
20
19
PCy2:BH3
7
PCy2
C1
C
iii), iv)
v)
PPh2:BH3
C2
PPh2
C
C
C
C1
4
21
C1
C1
C1
C
C
C
P
Scheme 4. Reagents and conditions: (i) Raney Ni, MeOH, H2, 50 bar,
50 °C, 48 h, 98%; (ii) PMHS, Ti(Oi-Pr)4, PhMe, 100 °C, 2 h, BH3–
Me2S, then 25% HF, 25 °C, 12 h, 94%; (iii) MsCl, Et3N, CH2Cl2,
À20 °C, 2 h; (iv) Ph2PH, t-BuOK, THF, 50 °C, 18 h, BH3–Me2S, 48%
for two steps; (v) N,N0-bis-(3-aminopropyl)-piperazine, 100 °C, 12 h,
95%.
C1
C2
C1
C2
C
O
C1
C1
O
Figure 4. ORTEP diagram of alcohol 13.
enantiomeric excess of the hydrogenation reaction is
strongly dependent on the solvent, we performed the
optimization of the solvent system for these reactions
with ligand 7 as the model compound. Hydrogena-
tion of methyl (Z)-acetamidocinnamate was performed
at room temperature and 1 bar pressure, with
Rh(COD)2BF4 as the metal source, using 2 mol % of the
preformed catalyst. Screening of the solvents (Table 1)
showed that the highest enantioselectivities were
achieved in a toluene–methanol 10:1 mixture. This
mixture was used for the testing of all other ligands in
the Rh-catalyzed hydrogenation of acetamidocinnamic
and acetamidoacrylic esters.
chiral diphosphine 2 with the opposite configuration of
the phosphine substituents on the pinene core was
obtained.
2.3. Synthesis of diphenyphosphanyl–dicyclohexylphos-
phanyl ‘mixed’ ligands
The introduction of the dicyclohexylphosphine moiety
instead of diarylphosphine often significantly changed
the ligands properties due to steric reasons and different
electron densities on the phosphorus atom.16;17 Hydro-
genation18 of diphenylphosphinoyl alcohols 7 and 13
proceeded quantitatively over Raney Ni in methanol.
Reduction of the products with PMHS–Ti(Oi-Pr)4 fol-
lowed by borane protection, formation of the mesylates,
and nucleophilic substitution with the phosphide anion
gave the desired phosphine–borane complexes, which
were finally deprotected by heating with bis-3-(amino-
propyl)-piperazine to obtain the corresponding phos-
phines in slightly less (44–48%) overall yields than for
the bis-(diphenylphosphine) analogs. The syntheses of
new ‘mixed’ phosphines are given on Schemes 3 and 4.
Solvent optimization for the hydrogenation of dimethyl
itaconate showed that methanol and toluene–THF
mixtures give similar results (Table 2). The further
Table 1. Solvent optimization for Rh-catalyzed hydrogenation of
methyl acetamidocinnamate
Entry
Solvent system
Enantiomeric
excess (%)
1
2
3
4
5
6
MeOH
38
29
47
52
49
78
CH2Cl2–MeOH 10:1
THF–MeOH 10:1
PhMe–MeOH 1:1
PhMe–THF 5:1
PhMe–MeOH 10:1
2.4. Asymmetric catalysis
We examined the performances of the newly synthesized
ligands in the Rh-catalyzed asymmetric reduction of
three substrates: methyl acetamidocinnamate, dimethyl
itaconate, and methyl acetamidoacrylate. Since the
Reagents and conditions: 0.5 mmol methyl acetamidocinnamate,
0.01 mmol Rh(COD)2BF4, 0.011 mmol of ligand 7 in 5 mL solvent, rt,
1 bar H2, 12 h.

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A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
Table 2. Solvent optimization for Rh-catalyzed hydrogenation of
dimethyl itaconate
Table 5. Rh-catalyzed asymmetric hydrogenation of dimethyl itaco-
nate
Entry
Solvent system
Enantiomeric
excess (%)
Entry
Ligand
Enantiomeric
excess (%)
1
2
3
4
PhMe
58
66
78
81
1
2
3
4
1
2
3
4
18 (S)
81 (S)
17 (R)
54 (S)
PhMe–MeOH
PhMe–THF
MeOH
Reagents and conditions: 0.5 mmol dimethyl itaconate, 0.01 mmol
Rh(COD)2BF4, 0.011 mmol of ligand 7, 5 mL of solvent, rt, 1 bar H2,
12 h.
Reagents and conditions: 0.5 mmol dimethyl itaconate, 0.01 mmol
Rh(COD)2BF4, 0.011 mmol of ligand in 5 mL MeOH, rt, 1 bar H2,
12 h.
Data of hydrogenation of dimethyl itaconate reveal a
very strong difference between the diastereomeric bis-
diphenylphosphine ligands 1 and 2: 18% and 81% ee,
correspondingly (Table 5).
testing reactions for this substrate with other ligands
were performed in methanol.
Test results for our ligands in Rh-catalyzed catalytic
asymmetric hydrogenation of acetamidocinnamic ester
are given in Table 3. Reactions were performed at 1 bar
H2 pressure and room temperature for 12 h. In all cases,
full conversion was achieved. As we can conclude from
the testing data, the additional steric hindrance created
by the methyl groups of pinene core forces the phos-
phorus atom to take a more advantageous position for
high enantioselectivity. Introduction of cyclohexyl rings
instead of phenyl impairs the enantioselectivity of the
reaction in both cases.
Introduction to the ligand 1 cyclohexyl groups in place
of the phenyls (ligand 3) caused dramatical changes in
the reaction course, leading to the opposite enantiomer
of the product.
Besides the application of the newly synthesized ligands
in hydrogenation of C@C double bonds, we examined
their performance in the asymmetric hydrogenation of
C@O and C@N bonds. For Ru-catalyzed catalytic
hydrogenation
of
benzoyl
acetate
(0.5 mol %
Ru(COD)(C4H7)2, 0.5 mol % ligand 2, 0.3 M HBr in
MeOH, 50 bar H2, rt, 16 h)19 the product was obtained
with full conversion, but only 37% ee. Full conversion,
but poor enantioselectivity was achieved in the Rh-cat-
alyzed hydrogenation of acetophenone benzoylhydraz-
Table 3. Rh-catalyzed asymmetric hydrogenation of methyl acetami-
docinnamate
Entry
Ligand
Enantiomeric
excess (%)
one with ligand
1
(1 mol % ligand, 1 mol %
Rh(COD)2BF4, MeOH, 50 bar H2, rt, 16 h, 30% ee,20
and Pd-catalyzed allylic substitution of 1,3-diphenyl-
propenyl acetate with dimethyl malonate (1 mol %
[Pd(allyl)Cl]2, 2 mol % of ligand, 5 mol % KOAc, 3 equiv
BSA, rt, 1 h, 33% ee).21
1
2
3
4
1
2
3
4
84 (R)
78 (S)
51 (R)
46 (S)
Reagents and conditions: 0.5 mmol methyl acetamidocinnamate,
0.01 mmol Rh(COD)2BF4, 0.011 mmol of ligand in 5 mL PhMe–
MeOH (10:1), rt, 1 bar H2, 12 h.
3. Conclusion
For the hydrogenation of acetamidoacrylic ester (Table
4, the same reaction conditions) the situation changed
significantly: both ligands 1 and 2 essentially gave the
same enantioselectivity, while the introduction of
cyclohexyl rings led to an improvement of ee in one case
(ligand 3) and a dramatic drop in another (ligand 4).
Conversely to the reaction with acetamidocinnamic
ester, all the ligands gave the same enantiomer of the
product.
Starting from naturally occurring terpenes, we have
synthesized a number of new chiral diphosphine ligands
with a pinene framework and tested them in some
transition metal-catalyzed asymmetric reactions. For the
catalytic asymmetric hydrogenations, enantioselectivi-
ties up to 84% ee were achieved. In the key step of the
synthesis, we applied the [2,3]-sigmatropic allylphosph-
inite–allyl phosphine oxide rearrangement, which afford-
ed a simple one-step conversion of allylic alcohols into
phosphine oxides. A formerly reported method for
phosphine oxide reduction has been significantly im-
proved upon in terms of easiness and scalability. We
also reported a new, simple and practical protocol for
the deprotection of phosphine–borane complexes, suit-
able for preparation of diphosphines, including poly-
alkyl-substituted electron-rich ones.
Table 4. Rh-catalyzed asymmetric hydrogenation of methyl acetami-
doacrylate
Entry
Ligand
Enantiomeric
excess (%)
1
2
3
4
1
2
3
4
60 (R)
61 (R)
79 (R)
7 (R)
4. Experimental
Reagents and conditions: 0.5 mmol of methyl acetamidoacrylate,
0.01 mmol Rh(COD)2BF4, 0.011 mmol of ligand, 5 mL PhMe–MeOH
(10:1), rt, 1 bar H2, 12 h.
All reactions were carried out under argon using stan-
dard Schlenk techniques. 1H and 13C NMR spectra were

A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
2283
recorded on a Bruker AMX 300 instrument. 31P NMR
spectra were recorded on a VARIAN Mercury 200
instrument. Chemical shifts (d) are given as ppm relative
to the residual solvent peak. IR spectra were recorded
on a Perkin–Elmer 1420 Infrared Spectrometer. Mass
spectra were recorded on a FINNIGAN MAT 95 Q
spectrometer. Optical rotations were measured on a
Perkin–Elmer 241 polarimeter. Column chromatogra-
phy was performed on MERCK silica gel 60 (230–
400 mesh ASTM). Thin layer chromatography was
performed on MERCK TLC-plates silica gel 60 F-254.
Enantiomeric excesses were determined by by chiral GC
50 °C for 18 h. BH3–Me2S (2.0 mL, 20 mmol) was added
and the reaction mixture transferred into a 250 mL
Erlenmeyer flask with methanol (10 mL). When gas
evolution ceased, saturated NH4Cl (50 mL) was added
and the aqueous layer extracted twice with dichloro-
methane (20 mL portions). The combined organic
extracts were washed with saturated brine, dried over
MgSO4, and evaporated. The residue was dissolved in a
small amount of a dichloromethane–pentane mixture
(1:1) and passed through alumina (Fluka, Brockmann
grade III). The filtrate was concentrated on a rotary
evaporator to dryness and treated as specified for the
substance. Yields 44–55%.
(Chiralsil L-Val and TFA–cyclodextrine columns).
4.1. Typical procedure for the conversion of phosphine
oxides into phosphine–borane complexes
4.3. Typical procedure for the deprotection of a phos-
phine–borane with N,N0-bis(3-aminopropyl)-piperazine
Into a 50 mL Schlenk flask was placed a phosphine
oxide (5 mmol), dry toluene (20 mL), poly-
methylhydrosiloxane (2 mL, 33 mmol), and titanium
isopropoxide (1.5 mL, 20 mmol). The mixture was
heated at 100 °C for 2–4 h, until 31P NMR showed
complete reduction, after which it was cooled and BH3–
Me2S (1 mL, 10 mmol) then added. After 5 min, the
mixture was carefully poured into a 250 mL Erlenmeyer
flask with methanol (5 mL). When gas evolution ceased,
the solution was transferred into a 250 mL Nalgeneâ
bottle with a mixture of 48% HF (20 mL) and H2O
(20 mL), and stirred for 12 h at room temperature. The
aqueous phase was extracted with toluene (15 mL) and
the combined organic phases washed with saturated
NaHCO3, brine, dried over MgSO4, and evaporated.
The residue was redissolved in a small amount of ether
and filtered through silica gel, washed with ether, and
evaporated and dried in vacuo to obtain a phosphine–
borane complex as a viscous oil, which gradually
solidified. Yields 93–96%.
A phosphine–borane (1 mmol) was placed into a 10 mL
Schlenk tube and dissolved in toluene (2 mL). To the
solution, N,N0-bis(3-aminopropyl)-piperazine (1 mL,
excess) was added. The mixture was heated at 100 °C for
the time stated, cooled down and diluted with ether
(10 mL). The solution was filtered under an Ar atmo-
sphere through a pad of previously dried silica and
evaporated. The resulting phosphine was obtained as
white foam or very viscous oil and stored under argon.
Yields 95–96%.
4.4. Typical procedure for the hydrogenation of a
diphenylphosphine oxide over Raney Ni
Raney Ni (6.0 g, 50% in water, Acros) was washed three
times with 20 mL portions of methanol and transferred
in methanol into a 200 mL stainless steel autoclave. The
diphenylphosphine oxide (8 mmol) was added, and the
autoclave charged with hydrogen to 50 bar pressure.
Hydrogenation was performed at 50 °C for 48 h, the
autoclave depressurized, the contents filtered through a
pad of Celite and the precipitate washed successively
with methanol. The filtrate was evaporated to give the
product as a colourless solid in practically quantitative
yield.
4.2. Typical procedure for the synthesis of bis-phosphine
boranes from phosphine–borane alcohols
Into a 100 mL Schlenk flask was placed a phosphine–
borane alcohol (5 mmol) and dry dichloromethane
(40 mL). Cooled to À20 °C, dry triethylamine (2.4 mL,
17 mmol) was added. Methanesulfonyl chloride (1.2 mL,
17 mmol) was added at this temperature dropwise with
good stirring. The mixture was left at À20 °C for 2 h
and, while still cold, poured into dry ether (200 mL).
After 5 min, the white precipitate was filtered off
through a pad of silica gel, the filter cake washed with
ether (100 mL), and the filtrate concentrated on rotary
evaporator to about 10 mL. The residual solvents and
the excess MsCl were removed by oil pump vacuo dur-
ing 5 h. The mesylate was used in the next step without
further purification.
4.5. Synthesis of [(1S,2R,3R,5R)-3-(diphenylphosphino)-
6,6-dimethylbicyclo[3.1.1]hept-2-yl]-methyl(diphenyl)-
phosphine 1
4.5.1. (1S,2R,3S,5R)-2-(Diphenylphosphinoylmethyl)-6,6-
dimethyl-bicyclo[3.1.1]heptan-3-ol 7. 4-Dimethylamino-
pyridine (10.2 g, 84 mmol) was placed into a 250 mL
Schlenk flask and dissolved under argon in dry toluene
(100 mL). trans-Pinocarveol (12.7 g, 84 mmol) was add-
ed, the mixture cooled to À30 °C, at which point di-
phenyl chlorophosphine (15.2 mL, 84 mmol, Strem 98%,
distilled in vacuo prior to use) was added dropwise in
5 min. The mixture was allowed to reach ambient tem-
perature and heated at 80 °C for 6 h. 31P NMR showed
complete rearrangement (diphenylphosphinite: 126 ppm,
diphenylphosphine oxide: 29 ppm). The hot mixture was
filtered through a pad of Celite and the filter cake washed
In a 100 mL Schlenk flask, t-BuOK (1.40 g, 12.5 mmol)
was dissolved in THF (25 mL), and diphenylphosphine
(2.33 g, 12.5 mmol) then added. The orange solution was
cooled to À20 °C and the solution of the mesylate in
10 mL THF slowly added. The mixture was heated at

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A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
with toluene. The filtrate was concentrated to about
70 mL and borane–dimethyl sulfide complex (12 mL,
120 mmol) was added carefully. The solution was heated
at 50 °C for 6 h, cooled down and carefully poured into a
1 L Erlenmeyer flask with methanol (70 mL). After 4 h,
the solution was evaporated in vacuo and the residue
redissolved in dichloromethane (80 mL). meta-Chloro-
perbenzoic acid (70–75%, Acros, 25 g, 106 mmol) was
dissolved separately in dichloromethane (200 mL), the
solution was dried over MgSO4 and placed into 0.5 L
two-necked flask with a dropping funnel and thermo-
meter. The flask was immersed into an acetone–dry ice
cooling bath and the solution of the hydroborated
adduct added slowly so that the temperature didn’t
exceed 15 °C. After completion of the addition, the
mixture was stirred for 1 h, and filtered. The filtrate was
stirred with a solution of 80 g of Na2S2O5 in 200 mL H2O
for 10 min, the layers separated and the organic phase
washed twice with 100 mL portions of 2 M NaOH, then
with saturated brine, dried, and evaporated. The semi-
solid residue was stirred 24 h with ether (200 mL), the
precipitate filtered off, washed with ether, and dried in
vacuo. Yield 18.4 g (62%), white solid.
Mp 107–107.5 °C, ½aŠ ¼ 13:0 (c 0.75, CH2Cl2); IR
D
ꢀ
(KBr): m 3432 (br s), 3255 (br s), 2922 (s), 2386 (s), 1436
(vs), 1105 (m), 1062 (m), 1031 (m), 736 (vs), 691 (s). H
1
NMR (CDCl3): d 7.78–7.62 (m, 4H), 7.56–7.40 (m, 6H),
4.20–4.10 (br s, 1H), 2.70–2.40 (m, 1H), 2.48 (br s, 1H),
2.33–2.20 (m, 2H), 1.93 (s, 1H), 1.86 (s, 1H), 1.79 (s,
1H), 1.75 (s, 1H), 1.17 (s, 3H), 1.15 (s, 1H), 1.11 (s, 1H),
0.96 (s, 3H). 13C NMR (CDCl3): d 132.8 (d, J ¼ 8:8 Hz),
132.3 (d, J ¼ 8:8 Hz), 131.8, 131.6, 131.1, 129.3 (d,
J ¼ 4:7 Hz), 129.2 (d, J ¼ 4:7 Hz), 128.8, 71.1 (d,
J ¼ 5:6 Hz), 48.5, 48.4, 41.1, 38.1, 33.8, 33.3, 32.5, 27.4,
24.1. 31P NMR (81 MHz, CDCl3): d 15.4 (br s). MS (EI,
70 eV) m=z (%): 108 (16), 183 (34), 185 (17), 186 (11), 199
(100), 200 (82), 338 (11). HRMS: 351.2051 (C22H29BOP,
[MÀH]þ).
4.5.3. (1S,2R,3R,5R)-3-Diphenylphosphanyl-2-[(diphenyl-
phosphanyl)-methyl]-6,6-dimethyl-bicyclo[3.1.1]heptane
bis-borane complex 10. Compound 8 was transformed
into the corresponding bis-phosphine borane 10
according to Section 4.2. The residue after evaporation
was quickly dissolved in ether (25 mL). Within minutes,
crystallization of the product started. After 12 h, the
crystals were filtered off, washed with a small amount of
ether, and dried in vacuo. Yield 1.47 g (55%), colourless
crystals.
Mp 200–200.5 °C, ½aŠ ¼ À4:2 (c 0.75, CHCl3); IR
D
ꢀ
(KBr): m 3351 (br s), 1438 (s), 1173 (vs), 1120 (s), 740
1
(vs), 546 (s). H NMR (CDCl3): d 7.71–7.63 (m, 4H),
7.50–7.36 (m, 6H), 5.56 (br s, 1H), 4.34–4.24 (m, 1H),
3.64 (br s, 1H), 2.56–2.38 (m, 2H), 2.29–2.13 (m, 2H),
1.94–1.86 (m, 1H), 1.14 (s, 3H), 0.99 (s, 1H), 0.96 (s,
1H), 0.91 (s, 3H). 13C NMR (CDCl3): d 134.6, 133.2,
132.7, 132.4–132.3 (m), 131.5 (d, J ¼ 9:2 Hz), 130.8 (d,
J ¼ 9:2 Hz), 129.3 (m), 129.1 (m), 70.2, 51.3 (d,
J ¼ 14:4 Hz), 48.3, 41.8, 38.7, 38.0 (d, J ¼ 69 Hz), 37.0,
34.5, 27.9, 24.2. 31P NMR (81 MHz, CDCl3): d 36.0. MS
(EI, 70 eV) m=z (%): 155(20), 201(78), 202(100), 215(32),
311(57). HRMS: 355.1809 (C22H28O2P, [MþH]þ).
Mp 195–196 °C, ½aŠ ¼ þ17:9 (c 0.48, CH2Cl2); IR
D
ꢀ
(KBr): m 3435 (br s), 2919 (w), 2401 (s), 2383 (s), 1436 (s),
1106 (m), 1054 (m), 739 (s), 698 (vs), 500 (m). 1H NMR
(CDCl3): d 7.93–7.79 (m, 2H), 7.71–7.50 (m, 4H), 7.47–
7.21 (m, 8H), 7.22–7.00 (m, 4H), 6.90–6.77 (m, 2H),
3.70–3.45 (m, 1H), 3.26 (br s, 1H), 3.10–2.85 (m, 1H),
2.16–1.90 (m, 1H), 1.80–0.73 (m, 6H), 0.91 (s, 3H), 0.87
(s, 3H). 13C NMR (CDCl3): d 131.5, 131.4, 131.2, 131.1,
130.7, 130.4, 130.2, 130.0 (d, J ¼ 8:8 Hz), 129.8, 129.6
(m), 129.4, 129.3, 129.3, 129.2, 129.0, 128.8, 128.5
(d, J ¼ 9:4 Hz), 128.1, 127.6 (d, J ¼ 10:0 Hz), 127.3 (d,
J ¼ 10:0 Hz), 44.5, 38.9, 37.2, 33.9, 32.7, 28.1, 27.2 (d,
J ¼ 10:6 Hz), 26.8 (d, J ¼ 10:6 Hz), 25.6 (d, J ¼ 8:5 Hz),
19.9.); 31P NMR (81 MHz, CDCl3): d 17.5 (br s), 19.0
(br s). MS (EI, 70 eV) m=z (%): 183 (24), 185 (14), 262
(11), 429 (100), 430 (30), 519 (17). HRMS: 534.2953
(C34H42B2P2, [M]þ).
A sample of [(1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-
en-2-yl]methyl-(diphenyl)-phosphine oxide 6 was taken
from the reaction mixture after the rearrangement
reaction finished and purified by column chromatogra-
phy (CH2Cl2–Et2O 1:1). White hygroscopic solid.
ꢀ
Mp 50–52 °C, ½aŠ ¼ À10:1 (c 0.85, CH2Cl2); IR (KBr): m
D
2984 (m), 2914 (s), 1437 (s), 1194 (vs), 1119 (s), 735 (m),
719 (s), 696 (s), 533 (m). 1H NMR (CDCl3): d 7.73–7.63
(m, 4H), 7.43–7.30 (m, 6H), 5.30–5.25 (m, 1H), 3.07–2.95
(m, 2H), 2.15–2.02 (m, 2H), 1.90–1.82 (m, 1H), 1.08 (s,
3H), 0.86 (s, 1H), 0.83 (s, 1H), 0.62 (s, 3H). 13C NMR
(CDCl3): d 138.6 (d, J ¼ 11 Hz), 134.5 (d, J ¼ 28 Hz),
133.2 (d, J ¼ 28 Hz), 131.8, 131.4, 131.3, 131.2, 128.9–
128.6 (m), 122.3 (d, J ¼ 11 Hz), 47.4, 40.5, 39.8, 38.9,
38.4, 31.9 (d, J ¼ 9 Hz), 26.5, 21.4. 31P NMR (81 MHz,
CDCl3): d 29.4. MS (EI, 70 eV) m=z (%): 77 (17), 91 (16),
155 (19), 201 (55), 202 (100), 203 (22), 293 (12), 321 (18),
336 (17). HRMS: 336.1660 (C22H25OP, [M]þ).
4.5.4.
(1S,2R,3R,5R)-[3-(Diphenylphosphino)-6,6-di-
methylbicyclo[3.1.1]hept-2-yl]-methyl(diphenyl)-phosphine
1. Compound 1 was obtained from 10 according to
Section 4.3. Yield 0.48 g (95%), colourless, very viscous
oil.
ꢀ
½aŠ ¼ þ19:8 (c 1.25, CH2Cl2); IR (KBr): m 3436 (br s),
D
2912 (s), 1479 (w), 1433 (s), 696 (s), 741 (vs), 513 (m). 1H
NMR (CDCl3): d 7.49–7.36 (m, 4H), 7.25–7.00 (m,
16H), 6.85–6.78 (m, 2H), 3.24–3.10 (m, 1H), 2.53–2.37
(m, 3H), 2.36–2.32 (m, 1H), 2.10–2.00 (m, 1H), 1.76
(br s, 1H), 1.58–1.40 (m, 2H), 1.27 (d, J ¼ 10:1 Hz,
1H), 1.10 (s, 3H), 0.91 (s, 3H). 13C NMR (CDCl3):
4.5.2. (1S,2R,3S,5R)-2-(Diphenylphosphanylmethyl)-6,6-
dimethyl-bicyclo[3.1.1]heptan-3-ol-borane complex 8.
Compound 8 was obtained from 7 according to Sec-
tion 4.1. Yield 1.69 g (96%), colourless semi-solid mass,
slowly crystallized during the storage.
d
139.3 (d, J ¼ 14:1 Hz), 138.2 (d, J ¼ 11:8 Hz),
137.4 (d, J ¼ 13:5 Hz), 137.0 (d, J ¼ 14:7 Hz), 133.4
(d, J ¼ 20:8 Hz), 132.1 (d, J ¼ 19:4 Hz), 131.4 (d,

A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
2285
J ¼ 18:5 Hz), 127.9–127.0 (m), 124.3, 45.3 (d,
J ¼ 14:4 Hz), 40.1, 37.2, 35.1–34.8 (m), 31.7 (d,
J ¼ 17:0 Hz), 29.8–29.3 (m), 27.2–27.0 (m), 26.6, 26.1,
solid residue was stirred 24 h with ether (100 mL), the
precipitate was filtered off, washed with ether, and dried
in vacuo. Yield 5.65 g (67%), white solid.
20.0. 31P NMR (81 MHz, CDCl3):
d
À15.6 (d,
J ¼ 3:4 Hz), À16.2 (d, J ¼ 3:4 Hz). MS (EI, 70 eV) m=z
(%): 183 (25), 185 (11), 262 (9), 429 (100), 431 (27).
HRMS: 506.2288 (C34H36P2, [M]þ).
Mp 185.5–186 °C, ½aŠ ¼ þ56:6 (c 0.66, CH2Cl2); IR
D
ꢀ
(KBr): m 3370 (br s), 2882 (s), 1437 (s), 1162 (s), 720 (s),
1
700 (s), 538 (vs), 1117 (m). H NMR (CDCl3): d 7.94–
7.82 (m, 2H), 7.80–7.67 (m, 2H), 7.50–7.23 (m, 6H),
4.81 (br s, 1H), 3.83 (br s, 1H), 3.52–3.25 (m, 2H),
2.58 (br s, 1H), 2.27 (br s, 1H), 2.12–1.90 (m, 2H), 1.87–
1.65 (m, 3H), 1.19 (s, 3H), 0.98 (s, 3H). 13C NMR
(CDCl3): d 135.9, 134.6, 134.2, 132.9, 132.0, 131.7,
131.1 (d, J ¼ 8:7 Hz), 130.4 (d, J ¼ 8:7 Hz), 129.5 (d,
J ¼ 11:0 Hz), 129.1 (d, J ¼ 11:0 Hz), 89.0, 65.4 (d,
J ¼ 12:0 Hz), 46.1, 41.5 (d, J ¼ 3:8 Hz), 40.0 (d,
J ¼ 5:0 Hz), 39.5, 29.4, 29.0, 28.7, 28.5, 27.0, 21.3. 31P
NMR (CDCl3): d 39.1. MS (EI, 70 eV) m=z (%): 155 (17),
201 (42), 202 (100), 203 (22), 255 (19), 324 (72), 325 (18).
HRMS: 335.1825 (C22H28OP, [M]þ).
4.6. Synthesis of (1S,2S,S,R)-3-(diphenylphosphino)-6,6-
dimethylbicyclo[3.1.1]hept-2-yl]-methyl(diphenyl)-phos-
phine 2
4.6.1.
(1R,3S,5R)-6,6-dimethyl-2-methylenebicyclo-
[3.1.1]hept-3-yl](diphenyl)phosphine oxide 12. Into a
250 mL Schlenk flask under argon was placed 4-di-
methylaminopyridine (7.60 g, 62 mmol) in toluene
(120 mL). (À)-Myrtenol (9.50 g, 62 mmol) (Dragoco,
>99% ee) was added and the solution cooled down to
À30 °C. At this temperature, diphenylchlorophosphine
(11.2 mL, 62 mmol, Strem 98%, distilled in vacuo prior
to use) was added dropwise in 5 min. The mixture was
allowed to reach room temperature and heated at 100 °C
for 48 h, then filtered hot through a pad of Celite and the
precipitate was washed with 50 mL of hot toluene. The
filtrate evaporated in vacuo, the residue filtered off and
washed with ether. Yield 20.8 g (90%), white crystalline
solid.
4.6.3. (1S,2S,3R,5S)[3-(Diphenylphosphanyl)-6,6-dimeth-
yl-bicyclo[3.1. 1]hept-2-yl]-methanol-borane complex 14.
Compound 13 was transformed according to Section 4.1
into the corresponding phosphine–borane complex 14.
Yield 1.68 g (95%), colourless, very viscous oil.
ꢀ
½aŠ ¼ þ86:8 (c 1.15, CH2Cl2); IR (KBr): m 3434 (s, br s),
D
2932 (s), 2387 (m), 1437 (s), 1105 (vs), 1070 (vs), 1027 (s),
1
740 (m), 695 (vs). H NMR (CDCl3): d 7.82–7.72 (m,
Mp 189.5–190 °C, ½aŠ ¼ À35:0 (c 1.05, CH2Cl2). IR
2H), 7.61–7.52 (m, 2H), 7.41–7.32 (m, 3H), 7.27–7.18
(m, 3H), 3.55–3.35 (m, 2H), 2.61 (br s, 1H), 2.17–2.00
(m, 2H), 1.94–1.77 (m, 2H), 1.43–0.99 (m, 4H), 1.12 (s,
3H), 0.95 (s, 3H). 13C NMR (CDCl3): d 132.8 (d,
J ¼ 8:8 Hz), 132.3 (d, J ¼ 8:8 Hz), 131.8, 131.6, 131.1,
129.3 (d, J ¼ 4:7 Hz), 129.2 (d, J ¼ 4:7 Hz), 128.8, 71.1
(d, J ¼ 5:6 Hz), 48.5, 48.4, 41.1, 38.1, 33.8, 33.3, 32.5,
27.4, 24.1. 31P NMR (81 MHz, CDCl3): d 21.0 (br s). MS
(EI, 70 eV) m=z (%): 40 (48), 108 (55), 183 (100), 185
(41), 186 (69), 213 (80), 267 (85). HRMS: 351.2047
(C22H29BOP, [MÀH]þ).
D
ꢀ
(KBr): m 3435 (br s), 3054 (w), 2981 (m), 2920 (s), 1631
(w), 1437 (s), 1174 (s), 1116 (s), 720 (s), 701 (vs), 538 (s),
1
606 (m). H NMR (CDCl3): d 7.88–7.82 (m, 4H), 7.50–
7.43 (m, 6H), 4.56 (d, J ¼ 3:4 Hz, 1H), 3.91 (s, 1H), 3.64
(br s, 1H), 2.41–1.94 (m, 6H), 1.24 (s, 3H), 0.77 (s, 3H).
13C NMR (CDCl3): d 145.4 (d, J ¼ 8:5 Hz), 134.5 (d,
J ¼ 10:0 Hz), 133.2 (d, J ¼ 13:2 Hz), 132.2 (d,
J ¼ 8:5 Hz), 131.7 (m), 131.5 (d, J ¼ 8:5 Hz), 129.1 (d,
J ¼ 11:2 Hz), 128.6 (d, J ¼ 11:2 Hz), 112.3 (d,
J ¼ 7:6 Hz), 52.0, 41.0, 39.9, 34.9 (d, J ¼ 67 Hz), 26.9,
26.5, 26.1, 21.7. 31P NMR (81 MHz, CDCl3): d 37.0. MS
(EI, 70 eV) m=z (%): 155 (19), 201 (68), 202 (100), 203
(76), 267 (33), 293 (22), 335 (29), 336 (28). HRMS:
336.1647 (C22H25OP, [M]þ).
4.7. (1S,2S,3S,5R)-3-(Diphenylphosphino)-6,6-dimethyl-
bicyclo[3.1.1]hept-2-yl]-methyl(diphenyl)-phosphine bis-
borane complex 15
4.6.2.
(1S,2S,3S,5R)[3-(Diphenylphosphinoyl)-6,6-di-
Bis-phosphine borane 15 was synthesized from 14
according to Section 4.2. The residue after evaporation
was quickly dissolved in 25 mL of ether. Within minutes,
crystallization of the product started; after 12 h the
crystals were filtered off, washed with small amount of
ether and dried in vacuo. Yield 1.29 g (48%), colourless
crystals.
methyl-bicyclo[3.1.1]hept-2-yl]-methanol 13. Phosphine
oxide 12 (8.0 g, 20 mmol) was dissolved under argon in
0.5 M THF solution of 9-BBN (Aldrich, 50 mL,
25 mmol) and the mixture heated at 70 °C in a sealed
tube for 12 h. Into a 0.5 L three-necked flask was placed
the dried solution of meta-chloroperbenzoic acid (25 g,
106 mmol, 70–75% Acros) in dichloromethane (250 mL),
the flask was cooled to 15 °C in acetone–dry ice cooling
bath and the solution of the hydroborated phosphine
oxide added at such a rate that temperature did not
exceed 20 °C. After the end of the addition, the mixture
was stirred for 1 h and filtered. The filtrate was stirred
for 15 min with a solution of 80 g Na2S2O5 in 200 mL
H2O. The layers were separated and the organic phase
washed twice with 100 mL portions of 2 M NaOH, then
with saturated brine, dried, and evaporated. The semi-
Mp 195.5–196 °C, ½aŠ ¼ À47:3 (c 0.69, CH2Cl2); IR
D
ꢀ
(KBr): m 3436 (m, br s), 2919 (m), 2383 (s), 2401 (s), 1437
(s), 1106 (m), 1054 (m), 739 (s), 698 (vs), 500 (m). H
1
NMR (CDCl3): d 7.90–7.80 (m, 2H), 7.62–7.53 (m, 2H),
7.52–7.44 (m, 2H), 7.33–7.09 (m, 10H), 7.10–6.98 (m,
2H), 6.86–6.73 (m, 2H), 3.58–3.35 (m, 1H), 3.13–2.81
(m, 2H), 2.25–2.00(m, 1H), 1.99–1.86 (m, 1H), 1.77 (br s,
1H), 1.64 (br s, 1H), 1.20 (d, J ¼ 10:3 Hz), 1.09 (s, 1H),
0.87 (s, 3H), 0.71 (s, 1H), 0.50 (s, 3H). 13C NMR

2286
A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
ꢀ
(CDCl3): d 133.5 (d, J ¼ 9:4 Hz), 133.0, 132.9, 132.8,
132.7, 132.1, 131.8, 131.7, 131.6, 131.3, 131.0, 130.9–
130.7 (m), 130.2 (d, J ¼ 10:3 Hz), 129.9 (d, J ¼ 9:7 Hz),
129.5, 129.1, 129.0, 128.2, 44.2, 40.7 (d, J ¼ 8:5 Hz),
39.1, 37.4, 29.0, 28.5, 27.9, 27.5, 27.2, 23.0. 31P NMR
(81 MHz, CDCl3): d 17.4 (br s), 19.0 (br s). MS (EI,
70 eV) m=z (%): 183 (24), 185 (14), 262 (10), 429 (100),
430 (30), 519 (17). HRMS: 534.2926 (C34H42B2P2, [M]þ).
½aŠ ¼ þ2:6 (c 0.91, CH2Cl2); IR (KBr): m 3436 (s, br s),
D
2930 (vs), 2380 (m), 1634 (w, br s), 1449 (m), 1070 (m).
1H NMR (CDCl3): d 4.01–3.92 (m, 1H), 3.80–3.70 (m,
1H), 3.00–2.80 (m, 1H), 2.55–2.37 (m, 1H), 2.31–1.06
(m, 33H), 1.01 (s, 3H). 13C NMR (CDCl3): d 63.3, 49.3,
43.5, 41.3, 40.0, 37.1, 33.2, 32.8, 32.4, 28.8, 28.0, 27.7,
27.2–27.0 (m), 25.2, 21.3, 21.0, 20.4. 31P NMR (CDCl3):
d 17.2 (br s). MS (EI, 70 eV) m=z (%): 117 (31), 170 (35),
198 (47), 225 (35), 279 (39), 319 (49), 333 (58), 334 (53),
361 (100), 377 (77). HRMS: 363.3014 (C22H41BOP,
[MÀH]þ).
4.7.1. (1S,2S,3S,5R)-3-(Diphenylphosphino)-6,6-dimeth-
ylbicyclo[3.1.1]hept-2-yl]-methyl(diphenyl)-phosphine 2.
Compound 15 was transformed into the corresponding
phosphine 2 according to the Section 4.3. Heating time
2 h. Yield 0.49 g (96%), colourless, very viscous oil.
4.9. (1S,2S,3S,5R)-Dicyclohexyl(2-[(diphenylphosphino)-
methyl]-6,6-dimethylbicyclo-[3.1.1]hept-3-ylphosphine
borane complex 18
ꢀ
½aŠ ¼ þ4:0 (c 0.75, CH2Cl2); IR (KBr): m 3436 (m, br s),
D
2929 (vs), 2854 (m), 2371 (w), 1448 (w), 1064 (w). H
Compound 17 was transformed into the corresponding
bis-phosphine borane 18 according to the Section 4.2.
The residue after evaporation was dissolved in dichloro-
methane (10 mL). Methanol (50 mL) was added and the
solution concentrated on a rotary evaporator to half
volume and left in a fridge at 0 °C. After 12 h, the pre-
cipitate was filtered off, washed with a small amount of
ether, and dried in vacuo. Yield 1.31 g (48%), colourless
crystals.
1
NMR (CDCl3): d 7.55–7.47 (m, 2H), 7.45–7.35 (m, 2H),
7.33–7.23 (m, 2H), 7.22–7.10 (m, 10H), 7.10–7.00 (m,
2H), 6.84–6.74 (m, 2H), 3.22 (t, J ¼ 9:1 Hz, 1H), 2.65 (t,
J ¼ 13:1 Hz, 1H), 2.54–2.40 (m, 2H), 2.32–2.21 (m, 1H),
2.14–2.03 (m, 1H), 1.82–1.71 (m, 1H), 1.69–1.58 (m,
1H), 1.28 (d, J ¼ 9:8 Hz, 1H), 1.08 (s, 3H), 1.04 (s, 3H).
13C NMR (CDCl3): d 138.8 (d, J ¼ 12:9 Hz), 137.9 (d,
J ¼ 12:6 Hz), 137.1 (d, J ¼ 13:5 Hz), 136.7 (d,
J ¼ 14:7 Hz), 133.3 (d, J ¼ 20:8 Hz), 132.1, 131.8, 131.6,
128.1–126.7 (m), 43.6 (d, J ¼ 13:5 Hz), 40.1, 38.6–38.3
(m), 38.2, 30.3–29.2 (m), 27.1–26.6 (m), 26.6 (d,
J ¼ 31:7 Hz), 22.2. 31P NMR (81 MHz, CDCl3): d À15.7
(d, J ¼ 3:2 Hz), À16.3 (d, J ¼ 3:2 Hz). MS (EI, 70 eV)
m=z (%): 201 (29), 262 (24), 276 (20), 321 (21), 429 (100),
430 (29). HRMS: 506.2288 (C34H36P2, [M]þ).
Mp 204–205 °C (dec.), ½aŠ ¼ þ14:4 (c 0.73, CH2Cl2); IR
D
ꢀ
(KBr): m 3436 (m, br s), 2930 (vs), 2853 (m), 2378 (s),
1437 (m), 1070 (m), 738 (m), 695 (m). 1H NMR
(CDCl3): d 7.98–7.88 (m, 2H), 7.68–7.58 (m, 2H), 7.51–
7.42 (m, 3H), 7.35–7.23 (m, 3H), 3.68–3.42 (m, 1H),
3.09–2.91 (m, 1H), 2.43–2.14 (m, 4H), 1.91–0.57 (m,
31H), 0.53–0.29 (m, 1H). 13C NMR (CDCl3): d 132.7 (d,
J ¼ 8:3 Hz), 131.9, 131.2, 131.1, 130.4, 129.9 (d,
J ¼ 9:6 Hz), 129.7, 129.0, 129.0 (d, J ¼ 9:6 Hz), 44.8,
41.0, 39.3, 37.4, 34.7 (d, J ¼ 32:0 Hz), 32.7 (d,
J ¼ 32:0 Hz), 28.2–25.8 (m), 23.4, 22.0–21.3 (m). 31P
NMR (CDCl3): d 16.8 (br s), 28.7 (br s). MS (EI, 70 eV)
m=z (%): 183 (7), 435 (100), 436 (27), 530 (14), 531 (42),
532 (19). HRMS: 531.3467 (C34H50BP2, [MÀBH4]þ).
4.8. Synthesis of (1S,2S,3S,5R)-dicyclohexyl(2-[(diphenyl-
phosphino)methyl]-6,6-dimethylbicyclo-[3.1.1]hept-3-yl-
phosphine 3
4.8.1. (1S,2S,3S,5R)-3-(Dicyclohexylphosphoryl)-6,6-di-
methyl-bicyclo[3.1.1]hept-2-yl]methanol 16. According
to the Section 4.4, compound 13 was transformed into
adduct 16. Yield 2.87 g (98%), white solid.
4.10. (1S,2S,3S,5R)-Dicyclohexyl(2-[(diphenylphosphino)-
methyl]-6,6-dimethylbicyclo-[3.1.1]hept-3-ylphosphine 3
Mp 164–165 °C, ½aŠ ¼ þ12:9 (c 1.35, CH2Cl2). IR
D
(KBr): m 3401 (m, br s), 3281 (m, br s), 2954 (vs), 2928
(s), 1447 (m), 1143 (s), 1060 (w), 567 (w). 1H NMR
(CDCl3): d 6.05 (br s, 1H), 3.92 (br s, 1H), 3.66–3.48 (m,
1H), 3.00–2.78 (m, 1H), 2.59 (br s, 1H), 2.31–1.05 (m,
36H), 0.94 (s, 3H). 13C NMR (CDCl3): d 65.8, 46.3, 42.7,
39.7, 39.1, 37.8, 37.0, 35.6, 34.8, 28.3, 27.3, 27.2–24.9
(m), 20.5. 31P NMR (81 MHz, CDCl3): d 62.0. MS (EI,
70 eV) m=z (%): 214 (45), 241 (30), 267 (31), 335 (22), 283
(32), 336 (100), 337 (33). HRMS: 367.2767 (C22H40PO2,
[MþH]þ).
Phosphine 3 was obtained from the borane complex 18
according to the Section 4.3. Heating time 12 h. Yield
0.49 g (95%), colourless, very viscous oil.
ꢀ
½aŠ ¼ þ4:5 (c 0.93, CH2Cl2), IR (KBr): m 2923 (vs),
D
2849 (s), 1447 (m), 1434 (m), 1262 (m), 1096 (m), 1027
1
(m), 738 (s), 696 (s). H NMR (CDCl3): d 7.64–7.52 (m,
2H), 7.47–7.35 (m, 2H), 7.35–7.21 (m, 3H), 7.20–7.10
(m, 3H), 3.40–3.20 (m, 1H), 2.60–2.23 (m, 3H), 2.22–
2.08 (m, 1H), 1.98–1.81 (m, 1H), 1.80–0.46 (m, 32H). 13C
NMR (CDCl3): d 138.8 (d, J ¼ 12:3 Hz), 137.4 (d,
J ¼ 13:8 Hz), 133.3 (d, J ¼ 20:8 Hz), 131.7 (d,
J ¼ 18:8 Hz), 128.2–126.8 (m), 43.4 (d, J ¼ 12:3 Hz),
40.8–39.7 (m), 38.0, 32.8–32.1 (m), 29.7 (d, J ¼ 17:6 Hz),
29.0 (d, J ¼ 12:3 Hz), 28.9–28.4 (m), 28.0 (d,
J ¼ 10:3 Hz), 27.1, 27.0–26.0 (m), 25.4 (d, J ¼ 17:0 Hz).
31P NMR (81 MHz, CDCl3): d À3.4 (s), À17.4 (s). MS
4.8.2.
(1S,2S,3S,5R)-3-(Dicyclohexylphosphoryl)-6,6-
dimethylbicyclo[3.1.1]hept-2-yl]methanol borane complex
(17). Compound 17 was obtained from phosphine oxide
16 according to Section 4.1. Yield 1.72 g (94%), colour-
less, very viscous oil.

A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
2287
(EI, 70 eV) m=z (%): 41(5), 55 (7), 183 (6), 185 (5), 435
(100), 436 (26), 437 (4), 451 (8). HRMS: 518.3222
(C34H48P2, [M]þ).
132.5 (d, J ¼ 9:4 Hz), 132.2, 132.0 (d, J ¼ 8:8 Hz), 131.5,
131.2, 131.0, 130.3, 129.1 (d, J ¼ 10:0 Hz), 128.9 (d,
J ¼ 10:0 Hz), 46.9, 40.8, 38.4, 35.9, 34.6 (d,
J ¼ 30:8 Hz), 33.9 (d, J ¼ 27:8 Hz), 30.2, 29.7, 29.4,
29.2, 28.8, 28.4–27.5 (m), 26.4 (d, J ¼ 22:0 Hz), 24.6–
24.0 (m), 21.5. 31P NMR (81 MHz, CDCl3): d 16.0 (br s),
33.5 (br s). MS (EI, 70 eV) m=z (%): 185 (5), 435 (100),
436 (33), 531 (25), 532 (9). HRMS: 531.3499
(C34H50BP2, [MÀBH4]þ).
4.11. Synthesis of (1S,2R,3R,5R)-Dicyclohexyl-[3-(diph-
enylphosphino)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]meth-
ylphosphine 4
4.11.1. (1S,2R,3S,5R)-2-[(Dicyclohexylphosphinoyl)-me-
thyl]-6,6-dimethylbicyclo[3.1.1]heptan-3-ol 19. According
to the Section 4.4, compound 7 was transformed into
adduct 19. Yield 2.84 g (97%), white solid.
4.11.4. (1S,2R,3R,5R)-Dicyclohexyl-{[3-(diphenylphosph-
ino)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methyl}phosphine
4. Phosphine 4 was obtained from compound 21
according to the Section 4.3. Heating time 12 h. Yield
0.50 g (96%), viscous oil.
Mp 160–161 °C, ½aŠ ¼ À20:8 (c 0.85, CH2Cl2). IR
D
ꢀ
(KBr): m 3435 (m, br s), 3231 (m, br s), 2927 (vs), 2854
1
(s), 1450 (m), 1147 (s), 1028 (m). H NMR (CDCl3): d
5.94 (s, 1H), 4.05 (bs, 1H), 2.49–2.19 (m, 3H), 2.08–1.54
(m, 17H), 1.52–1.06 (m, 14H), 1.16 (s, 3H), 0.90 (s, 3H).
13C NMR (CDCl3): d 70.9, 51.0, 50.2, 42.9, 39.8, 38.7,
38.1, 37.7 (d, J ¼ 14:7 Hz), 36.8, 35.2, 31.7 (d,
J ¼ 57:5 Hz), 28.9, 28.3–26.7 (m), 26.3, 25.3. 31P NMR
(81 MHz, CDCl3): d 61.0. MS (EI, 70 eV) m=z (%): 39
(6), 55 (10), 146 (9), 214 (18), 268 (6), 323 (100), 324 (23).
HRMS: 367.2728 (C22H40PO2, [MþH]þ).
½aŠ ¼ þ26:5 (c 1.8, CH2Cl2); IR (KBr): m 2921 (vs),
D
2850 (s), 1446 (m), 1433 (m), 737 (m), 696 (s), 511 (w).
1H NMR (CDCl3): d 7.42–7.32 (m, 4H), 7.26–7.17
(m, 6H), 2.73–2.60 (m, 3H), 2.49–2.20 (m, 7H),
2.07–1.37 (m, 16H), 1.29–0.98 (m, 15H), 0.94 (s, 3H).
13C NMR (CDCl3): d 138.4 (d, J ¼ 11:5 Hz), 137.8
(d, J ¼ 14:1 Hz), 132.4 (d, J ¼ 19:1 Hz), 131.8 (d,
J ¼ 18:2 Hz), 127.5, 127.4–126.8 (m), 55.5, 52.4,
46.3, 40.4, 39.9, 37.2, 36.4, 32.7–30.3 (m), 29.6, 29.3,
28.2, 27.7, 27.4–26.3 (m), 25.5 (d, J ¼ 23:8 Hz),
24.4–23.7 (m), 20.3. 31P NMR (81 MHz, CDCl3): d À3.8
(s), À17.5 (s). MS (EI, 70 eV) m=z (%): 41(6), 55 (8), 183
(6), 185 (5), 435 (100), 436 (25). HRMS: 518.3240
(C34H48P2, [M]þ).
4.11.2. (1S,2R,3S,5R)-2-[(dicyclohexylphosphoryl)-meth-
yl]-6,6-dimethylbicyclo[3.1.1]heptan-3-ol-borane complex
20. Phosphine oxide 19 was transformed according to
Section 4.3 into the corresponding phosphine–borane
complex 20. Yield 1.70 g (93%), colourless solid.
Mp 103–104 °C, ½aŠ ¼ À13:6 (c 1.03, CH2Cl2); IR
D
ꢀ
(KBr): m 1435 (vs, br s), 2915 (m, br s), 1637 (w, br s),
4.12. Typical procedure for the catalytic asymmetric
hydrogenation reaction
1
1435 (m), 1183 (w, br s), 695 (s). H NMR (CDCl3): d
4.01–3.92 (m, 1H), 2.50–2.08 (m, 4H), 1.97–1.47 (m,
19H), 1.42–1.05 (m, 18H), 0.84 (s, 3H). 13C NMR
(CDCl3): d 69.4, 47.7, 47.4, 39.7, 36.5 (d, J ¼ 24:3 Hz),
32.1–30.3 (m), 26.6–24.3 (m), 22.8. 31P NMR (81 MHz,
CDCl3): d 34 (br s). MS (EI, 70 eV) m=z (%): 55 (33), 130
(76), 131 (47), 212 (100), 251 (26), 323 (27), 350 (31).
HRMS: 363.2978 (C22H41BOP, [MÀH]þ).
In a 10-mL Schlenk tube, Rh(COD)2BF4 (4.1 mg,
0.01 mmol) and of the tested phosphine (0.011 mmol)
were stirred in dry CH2Cl2 (1 mL) for 10 min. The sol-
vent was removed in vacuo and the residue dissolved in
5 mL of MeOH. In a 10 mL Schlenk flask under Ar,
0.5 mmol of the substrate was dissolved in 5 mL of the
appropriate solvent (toluene for acetamidocinnamic and
acetamidoacrylic esters, methanol for dimethyl itaco-
nate), and the flask was filled with hydrogen. The cat-
alyst solution (0.5 mL, 1 lmol, 2 mol %) was added and
the mixture stirred for 12 h in hydrogen atmosphere.
The products were isolated by flash chromatography
and analyzed by chiral GC.
4.11.3. 1S,2R,3R,5R)-Dicyclohexyl[3-(diphenylphosph-
ino)-6,6-dimethylbicyclo[3.1.1]hept-2-yl]methylphosphine
bis-borane complex 21. Compound 20 was converted
into the corresponding bis-phosphine borane 21
according to the Section 4.2. The residue after evapo-
ration was quickly dissolved in ether (25 mL). In some
minutes, crystallization of the product starts. After 12 h,
the precipitate was filtered off, washed with small
amount of ether, and dried in vacuo. Yield 1.21 g (44%),
colourless crystals.
Methyl N-acetylphenylalaninate: column Chiralsil L-Val
(Chrompak, 25 m ꢀ 0.12 lm ꢀ 0.22 lm); 140 °C const.
Retention time: (R)-enantiomer 10.5 min, (S)-enantio-
mer 11.3 min.
Mp 228–229 °C, ½aŠ ¼ þ206:6 (c 0.49, CH2Cl2); IR
Methyl N-acetylalaninate: column Chiralsil
120 °C const., (R)-enantiomer 1.94 min, (S)-enantiomer
2.06 min.
L-Val,
D
ꢀ
(KBr): m 3436 (m, br s), 2930 (vs), 2852 (m), 2380 (s),
1436 (m), 1069 (w), 1056 (w), 742 (w), 695 (m). 1H NMR
(CDCl3): d 7.79–7.69 (m, 4H), 7.48–7.37 (m, 6H), 3.29–
3.00 (m, 3H), 2.60–2.45 (m, 1H), 2.28–2.08 (m, 2H),
2.07–1.79 (m, 8H), 1.78–1.56 (m, 6H), 1.55–1.05 (m,
18H), 1.02 (s, 3H), 1.00 (s, 3H). 13C NMR (CDCl3): d
Dimethyl itaconate: column TFA–cyclodextrine; 60 °C
for 3 min, then ramp 2 °C/min to 100 °C, (R)-enantiomer
19.0 min, (S)-enantiomer 19.6 min.

2288
A. Gavryushin et al. / Tetrahedron: Asymmetry 15 (2004) 2279–2288
7. Feeder, N.; Hutton, G.; Warren, S. Tetrahedron Lett.
1994, 35, 5911–5914.
Acknowledgements
8. Bell, A.; Davidson, A.; Earnshaw, C.; Norrish, H. K.;
Torr, R. S.; Trowbridge, D. B.; Warren, S. J. Chem. Soc.,
Perkin Trans. 1 1983, 2879–2891.
9. Tanaka, H.; Kawai, K.; Fujiwara, K.; Murai, A. Tetra-
hedron 2002, 58, 10017–10031.
10. Cambridge database Number CCDC 231395.
11. Coumbe, T.; Lawrence, N. J.; Muhammad, F. Tetra-
hedron Lett. 1994, 35(4), 625–628.
We thank Bayer AG (Leverkusen) for financial support.
We thank also the BASF AG (Ludwigshafen), Cheme-
tall GmbH (Frankfurt), Dragoco (Holzminden), and
€
Degussa-Huls AG (Hanau) for the generous gift of
chemicals.
12. McKinstry, L.; Livinghouse, T. Tetrahedron 1995, 51,
7655–7666.
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