P,N-bidentate phosphites with a chiral ketimine fragment, their application in enantioselective allylic substitution and comparison with phosphine analogues

Article abstract of DOI:10.1055/s-2007-966066

Novel chiral P,N-bidentate arylphosphites have been prepared by a one-step phosphorylation of appropriate hydroxy ketimines based on (R)-(+)-camphor. Metal chelate complexes [Rh(CO)(PN)Cl] and [Pd(PN)(allyl)]BF₄ with the ligands were obtained a

Full text of DOI:10.1055/s-2007-966066

PAPER
1717
P,N-Bidentate Phosphites with a Chiral Ketimine Fragment, Their
Application in Enantioselective Allylic Substitution and Comparison with
Phosphine Analogues
E
nantioselective
A
o
pplication o
n
f
P,N-Bident
s
t
ites antin Gavrilov,a Vasily Tsarev,*b Sergey Zheglov,a Alexander Korlyukov,b Mikhail Antipin,b Vadim Davankovb
a
Department of Chemistry, Ryazan State Pedagogic University, 46 Svoboda str., Ryazan 390000, Russian Federation
Fax +7(491)2775498; E-mail: chem@ttc.ryazan.ru
Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilova str., Moscow 119991, Russian Federation
Fax +7(495)1356471; E-mail: tsarev@ineos.ac.ru
b
Received 19 December 2006; revised 11 April 2007
aryl phosphite 2c, containing a ketimine substituent,
based on (R)-(+)-camphor and the results of its prelimi-
nary testing in palladium-catalyzed asymmetric allyla-
tion.9 Developing this topic further, in the present work
we discuss the synthesis of a new series of such ligands
and their application in palladuim-catalyzed asymmetric
allylation. Moreover, we will make a direct comparison of
the new chiral iminophosphites with their phosphine ana-
logues.
Abstract: Novel chiral P,N-bidentate arylphosphites have been
prepared by a one-step phosphorylation of appropriate hydroxy
ketimines based on (R)-(+)-camphor. Metal chelate complexes
[Rh(CO)(PN)Cl] and [Pd(PN)(allyl)]BF4 with the ligands were ob-
tained and the new compounds were fully characterized by 1H, 13
C
and 31P NMR, IR, MS (EI, FAB and ESI techniques) and X-ray
crystal structure analysis. Using these ligands, up to 73% ee has
been achieved in the asymmetric palladium-catalyzed sulfonylation
of 1,3-diphenyl-2-propenyl acetate with sodium p-toluenesulfinate.
In the enantioselective alkylation of the same substrate with di-
methyl malonate, up to 94% enantioselectivity has been achieved.
Novel P,N-bidentate chiral aryl phosphites were easily
obtained by phosphorylation of appropriate iminoalcohols
2a and 2b or the iminophenol 2c with an easily accessible
bis(2,6-dimethylphenyl)chlorophosphite (1; Scheme 1).
Usually, this chlorophosphite is synthesized from 2,6-
dimethylphenol and PCl3 in the presence of triethylamine
in benzene.10,11 We have improved the procedure and de-
veloped a novel, versatile, solvent-free method for the
synthesis of phosphorochloridite (1) through the use of a
catalytic amount of 1-methylpyrrolidin-2-one. The reac-
tion time is three-fold shorter and no solvent is required.
Hence, this simple, economical and time-saving proce-
dure represents a handy method for the synthesis of con-
venient and cheap phosphorylating reagents, based on
substituted phenols.
Key words: allylations, asymmetric catalysis, chiral ketimines,
palladium, P,N-ligands
Imino phosphines constitute an important group of chiral
P,N-bidentate ligands for asymmetric catalysis by metal
complexes.1–3 The vast majority of such compounds con-
tain an aldimine fragment, whereas systems with ketimine
units are fairly uncommon.4–6 Imino phosphites have been
successfully used in enantioselective catalysis because of
their high p-acidity, resistance to undesired oxidation,
synthetic accessibility, and low cost.3,7,8 However, all
these ligands contain a peripheral aldimine group; phos-
phites with a ketimine fragment were not known until re-
cently. In 2004 we reported the synthesis of the first chiral
4
3
O
O
2
2a–c, Et3N, C6H6
5
P
Cl
P
O
N
O
O
1
6
– Et3N⋅HCl
3a–c
1
5'
3'
4'
1'
2'
HO
N
HO
N
HO
N
2c
2a
2b
Scheme 1 Synthesis of iminophosphites 2a–c
SYNTHESIS 2007, No. 11, pp 1717–1723
x
x.
x
x
.
2
0
0
7
Advanced online publication: 11.05.2007
DOI: 10.1055/s-2007-966066; Art ID: Z26206SS
© Georg Thieme Verlag Stuttgart · New York

1718
K. Gavrilov et al.
PAPER
The resulting iminophosphites 3a–c are stable under dry In general, 31P NMR and IR spectral data indicate that
conditions. For instance, the 31P NMR spectrum of com- ligands 3a–c have rather similar electronic demands.
pound 3c, recorded several months after its synthesis,
showed no signals of any decomposition products. It is
(Figure 1).
Complex 4a was characterized by X-ray diffraction
noteworthy that all starting reagents are inexpensive; imi-
noalcohols 2a, 2b and iminophenol 2c were obtained by
one-pot synthesis from 2-aminoethanol, (S)-isoleucinol or
2-aminophenol and (R)-(+)-camphor. In contrast to the
use of hydrochloric acid12 in the synthesis of 1c described
previously,9 we applied anhydrous zinc(II) chloride13 as a
catalyst in the synthesis of ketimines 2a–c. Despite mod-
erate yields, this procedure has the advantage of avoiding
a three-step synthesis through the N-nitroimine of (R)-
camphor.14
As for complexation patterns, ligands 3a–c represent typ-
ical chelating agents. Thus, their reactions with
[Rh(CO)2Cl]2 and with [Pd(allyl)Cl]2 in the presence of
AgBF4 gave neutral (4a–c) and cationic (5a–c) metal che-
lates with a cis-orientation of the P and N donor atoms
(Scheme 2). This is evident from the 31P NMR data for the
complexes (Table 1).
Table 1 Selected Spectroscopic Data for Compounds 4a–c and
5a–c
Compound
31P NMRa
IR
dP
1JP–Rh (Hz)
287.4
281.3
297.6
–
n(CO) (cm–1)
Figure 1 Molecular structure of complex 4a. Atoms are given by
thermal ellipsoids at 50% probability. Principal bonds and angles
averaged over two independent molecules (Å and °): Rh(1)–C(1K)
1.827(7), Rh(1)–N(1) 2.137(5), Rh(1)–P(1) 2.168(1), Rh(1)–Cl(1)
2.387(1), P(1)–O(1) 1.599(4), P(1)–O(2) 1.599(4), P(1)–O(3)
1.604(5), C(1K)–O(1K) 1.143(8); C(1K)–Rh(1)–N(1) 173.3(2),
N(1)–Rh(1)–P(1) 87.9(1), P(1)–Rh(1)–Cl(1) 168.4(6), O–P(1)–O
100.7(2).
4a
4b
4c
5a
121.5
119.7
137.8
2028
2024
2026
–
127.1 (5%),
124.8 (95%)
Compound 4a crystallized in the chiral space group P21,
with two independent molecules per unit cell. Both of the
independent molecules are characterized by the same R
configuration of the C(1) and C(4) atoms. In both of the
independent molecules, the conformation of metallocy-
cles may be described as a distorted boat. In one of the two
independent molecules, the deviation of the C(1¢) and
N(1) atoms from the basal plane are equal to 0.99 and 1.53
Å, respectively, while in the second, the Rh(1A) and
C(2¢A) atoms are deviated to 1.00 and 0.69 Å, respective-
ly.
5b
5c
120.9 (82%),
119.8 (18%)
–
–
–
–
143.5 (54%),
141.5 (46%)
a Recorded in CHCl3.
The 31P NMR and IR spectral data of compounds 4a–c in-
dicate features15 typical of aryl phosphites of the type
3a–c which have pronounced p-electron-withdrawing
ligands, and which have been shown to be important for
attaining high chemical and optical yields in some areas of
asymmetric catalysis.2,3 Interestingly, the spectral param-
eters of 4a–c strongly depend on the structural features.
Thus, the electron-donating sec-butyl substituent in 4b
causes an appropriate drop in the 1JP–Rh and n(CO) values.
The Rh(1) atom has a distorted square-planar configura-
tion. The deviation of the said atom from the plane of P(1),
N(1), O(1K) and Cl(1) atoms is equal to 0.18 Å (averaged
value for the two independent molecules). Such a distor-
tion of the Rh(1) coordination polyhedron may be ex-
–
+
OC
P
Cl
N
½ [Rh(CO)2Cl]2
– CO
BF4
½ [Pd(allyl)Cl]2, AgBF4
– AgCl
Rh
3a–c
Pd
N
P
4a–c
5a–c
Scheme 2 Synthesis of complexes 4a–c and 5a–c
Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York

PAPER
Enantioselective Application of P,N-Bidentate Phosphites
1719
plained by the high extent of steric overcrowding due to
the presence of the bulky P,N-ligand.
Table 2 Enantioselective Allylic Sulfonylation of 6 with Sodium
p-Toluene Sulfinate (in THF)
The P(1) atom has a distorted pyramidal configuration
(the sum of the three O–P–Rh angles is equal to 352°).
Due to the presence of bulky 1,7,7-trimethylbicy-
clo[2.2.1]heptane and 2,6-dimethylphenyl groups, the
P(1)–Rh(1)–Cl(1) angle is noticeably distorted in compar-
ison to those in previously investigated complexes with
P,N-ligands.16–19 The Rh(1)–P(1) bond length is close to
that found in complexes with the 1,3-diaza-2-phosphabi-
cyclo[3.3.0]octane ligand.17 The configuration at the N(1)
atom is planar (the sum of angles at this atom is 359.3, on
average). The P(1)–N(1) distance is almost identical to
those found in previously investigated complexes.
Entry Catalyst
Ratio L/Pd Isolated yield ee (%)
(%)
1
2
3
4
5
6
[Pd(allyl)Cl]2/3a
1:1
2:1
1:1
2:1
1:1
1:1
31
25
29
42
80
41
7 (S)
3 (S)
[Pd(allyl)Cl]2/3a
[Pd(allyl)Cl]2/3b
[Pd(allyl)Cl]2/3b
[Pd(allyl)Cl]2/3c
5c
6 (R)
12 (R)
73 (R)
65 (R)
The 31P NMR spectra of complexes 5a–c contain two sin-
glets (Table 1), assigned to their exo- and endo-isomers.15
The averaged coordination shifts [DdP = dP(complex) –
dP(ligand)] for complexes 5a–c, are equal to –9.3, –13.9
and 2.7 ppm, respectively, and indicate the presence of a
P–Pd bond in all cases. Large coordination shifts
DdC = dC(complex) – dC(ligand) of 14.6 and 13.5 ppm for
the signals of the imino C-2 atoms in the 13C NMR spectra
of complexes 5a and 5c, respectively, also suggest coordi-
nation of the peripheral imino group to palladium. ESI and
FAB MS data are consistent with the mononuclear struc-
tures of complexes 5a–c.
bly higher than in THF (see Table 3, entries 13, 15–17).
As in the allylic sulfonylation, ligand 3a again showed
low asymmetric induction (£36% ee, Table 3). In contrast,
3b provided appreciable enantioselectivity of up to 82%
ee (Table 3, entry 9). In this reaction, complex 5b and the
catalytic system [Pd(allyl)Cl]2/2L gave almost identical
optical yields of 8 (see Table 3, entries 9 and 12), dichlo-
romethane being a solvent of choice. The dramatic supe-
riority in asymmetric induction of 3b over 3a is due to the
bulky sec-butyl substituent bearing an additional C-ste-
reocenter. The highest enantioselectivities were obtained
using iminophosphite 3c. The 2-aminophenol fragment in
its structure reduces the degree of conformational free-
dom and leads to the high degree of rigidity necessary for
efficient transfer of chirality during the catalytic process.
Iminophosphites 3a–c (L), their complexes 5a–c, and sys-
tems [Pd(allyl)Cl]2/2L and [Pd(allyl)Cl]2/4L generated in
situ, were used in the palladium-catalyzed reactions of
enantioselective allylic substitution (Scheme 3). The re-
sults obtained are summarized in Tables 2 and Table 3.
Particularly good chemical and optical yields (up to 80%
and 73% ee, respectively; see Table 2, entry 5) were ob-
tained using 3c in the sulfonylation of 1,3-diphenylallyl
acetate (6) with sodium p-toluene sulfinate. Ligands 3a
and 3b afforded essentially racemic product 7 (Table 2).
P
O
N
P
N
Still better results (up to 94% ee and a nearly stoichio-
metric conversion) were obtained with ligand 3c in the
alkylation of allyl acetate 6 with dimethyl malonate (see
Table 3, entry 15). The yields were found to be dependent
on the nature of the nucleophile, the catalyst and on the
solvent. For instance, in both catalytic reactions, the
asymmetric induction increases significantly when
passing from complex 5c to the catalytic system
[Pd(allyl)Cl]2/2L (see Table 2, entries 5 and 6; Table 3,
entries 13 and 16, 15 and 17). This favorable effect can be
10
9
P
N
11
–
associated with the replacement of the outer-sphere BF4
anion by Cl–. Furthermore, the enantioselectivity of allylic
alkylation in dichloromethane was found to be apprecia-
Figure 2 (R)-(+)-Camphor-based iminophosphine ligands
Me
CH2(CO2Me)2,
MeO2C
CO2Me
Ph
OAc
Ph
BSA, cat*
SO2
NaSO2(p-Tol), cat*
Ph
*
Ph
*
Ph
Ph
7
6
8
Scheme 3 Enantioselective palladium-catalyzed allylic sulfonylation and alkylation of 1,3-diphenylallyl acetate (6)
Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York

1720
K. Gavrilov et al.
PAPER
Table 3 Enantioselective Allylic Alkylation of 6 with Dimethyl Malonate
Entry
1
Catalyst
Ratio L/Pd
1:1
Solvent
THF
Conversion (%)
ee (%)
12 (S)
30 (S)
15 (S)
22 (S)
7 (S)
[Pd(allyl)Cl]2/3a
[Pd(allyl)Cl]2/3a
[Pd(allyl)Cl]2/3a
[Pd(allyl)Cl]2/3a
5a
18
29
93
94
50
65
36
14
34
36
19
65
98
97
99
54
43
2
2:1
THF
3
1:1
CH2Cl2
CH2Cl2
THF
4
2:1
5
1:1
6
5a
1:1
CH2Cl2
THF
36 (S)
2 (R)
7
[Pd(allyl)Cl]2/3b
[Pd(allyl)Cl]2/3b
[Pd(allyl)Cl]2/3b
[Pd(allyl)Cl]2/3b
5b
1:1
8
2:1
THF
21 (R)
82 (R)
55 (R)
59 (R)
80 (R)
82 (R)
92 (R)
94 (R)
51 (R)
78 (R)
9
1:1
CH2Cl2
CH2Cl2
THF
10
11
12
13
14
15
16
17
2:1
1:1
5b
1:1
CH2Cl2
THF
[Pd(allyl)Cl]2/3c
[Pd(allyl)Cl]2/3c
[Pd(allyl)Cl]2/3c
5c
1:1
2:1
THF
1:1
CH2Cl2
THF
1:1
5c
1:1
CH2Cl2
It is useful to compare the stereoselectivity of iminophos- new generation of phosphorus-containing ligands for
phites 3a–c to related iminophosphine ligands 9–11 metal-complex asymmetric catalysis.2,3,24,25
(Figure 2). Under comparable conditions to the catalytic
In conclusion, a significant improvement in the general
procedures used for the synthesis of both phosphorylation
reagents and chiral ketimines has been developed. It al-
lows the synthesis of chiral P,N-bidentate phosphite-type
ligands to be performed faster and reduces the number of
stages required for the synthesis of chiral ligand building
blocks from cheap starting materials. Hence, the new pro-
allylic alkylation described for compounds 3a–c, xan-
thene-containing ligand 920 yielded racemic 8, while
phosphine 10, which is the closest analogue of phosphite
3c, gave up to 51% ee and noticeably lower conversion
(74–80%).4 The highest enantioselectivity among ligands
9–11 was achieved with compound 11 (69%),21 however,
this is still lower than those obtained with iminophos-
cedure offers great opportunities for the convenient syn-
phites 3b and 3c. In addition, synthesis of ligands 9–11 is
thesis of a broad variety of structurally diverse bidentate
more complex and proceeds in significantly lower
ligands.
yields.4,20,21 Therefore, iminophosphites 3b and 3c are su-
Taking the palladium-catalyzed allylic substitution of 1,3-
diphenylallyl acetate as a test case, it has been demonstrat-
perior to phosphines 9–11. It should be noted that regio-
and enantioselectivities of phosphorus-containing oxazo-
ed that the new ligands outperform their phosphine ana-
lines in the palladium-catalyzed allylic alkylation of cin-
logues and possess high potential for asymmetric
namyl acetate could be considerably improved by the
catalysis. To this end, further tuning of the ketimino phos-
introduction of a diarylphosphite group instead of a di-
phites, and studies on their application in various transi-
tion-metal-catalyzed processes, are in progress in our
laboratories.
arylphosphane fragment.22 Feringa et al. convincingly
demonstrated that, compared to state of the art bidentate
phosphines such as DuPhos, PhanePhos and JosiPhos,
readily accessible and stable, monodentate BINOL-based
phosphoramidites can lead to both higher rates and/or
higher enantioselectivities in the asymmetric hydrogena-
tion of a- and b-dehydroamino acid derivatives.23 These
facts, when taken together, testify that highly diverse and
extraordinarily inexpensive chiral phosphites represent a
IR spectra were recorded in CHCl3 on a Specord M80 instrument
(polyethylene cell). 31P, 13C and 1H NMR spectra were recorded on
a Bruker AMX-400 instrument (162.0 MHz for 31P, 100.6 MHz for
1
13C and 400.13 MHz for H). The complete assignment of all the
resonances in 13C NMR spectra was achieved using DEPT tech-
niques. Chemical shifts (ppm) are given relative to TMS (1H and 13
C
Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York

PAPER
Enantioselective Application of P,N-Bidentate Phosphites
1721
NMR) and 85% H3PO4 in D2O (31P NMR). Mass spectra were re-
corded with an AMD 402 spectrometer (FAB) and a Finnigan LCQ
Advantage spectrometer (electrospray ionization technique, ESI).
Elemental analyses were performed at the Laboratory of Microanal-
ysis (Institute of Organoelement Compounds, Moscow). Optical
yields of product 7 were determined using HPLC [(R,R)-WHELK-
01 column] according to the literature.26 Conversion of substrate 6
and optical purity of product 8 were determined using HPLC
(Daicel Chiralcel OD-H column) as described previously.27
Synthesis of Ligands 3a–c; General Procedure
Bis(2,6-dimethylphenyl)chlorophosphite (0.83 g, 2.7 mmol) and
Et3N (0.4 mL, 2.7 mmol) were dissolved in benzene (20 mL) and
the solution was cooled to 0 °C and stirred vigorously. The appro-
priate iminoalcohol 2a, 2b or iminophenol 2c (2.7 mmol) was added
and the resulting mixture was stirred for 10 min at 0 °C and then
heated to boiling point. After cooling to r.t., the Et3N·HCl was fil-
tered off and the solvent was removed under vacuum (40 Torr). The
residue was concentrated and dried under vacuum (1 Torr, 2 h).
All reactions were carried out in an atmosphere of dry argon using
anhydrous solvents. (2S,3S)-2-Amino-3-methylpentan-1-ol [(S)-
isoleucinol] and iminophenol (2c) were prepared as published pre-
viously.28,12 Et3N was distilled over KOH and LiAlH4 immediately
before use. [Rh(CO)2Cl]2 and [Pd(allyl)Cl]2 were prepared as
described earlier. Crystals of 4a suitable for X-ray analysis were ob-
tained by slow recrystallization from CH2Cl2–hexanes. Starting
substrate 6 was synthesised as published.30 2-Aminoethanol, 2-ami-
nophenol, (R)-(+)-camphor, dimethyl malonate, BSA [N,O-bis(tri-
methylsilyl)acetamide] and sodium p-toluene sulfinate were
purchased from Aldrich and Acros Organics and used without fur-
ther purification.
Bis(2¢¢,6¢¢-dimethylphenyl) (E)-2¢-({(1R,4R)-1,7,7-Trimethyl-
bicyclo[2.2.1]heptan-2-ylidene}amino)ethyl Phosphite (3a)
Yield: 1.03 g (97%); yellow oil.
13C NMR (100 MHz, CDCl3): d = 11.2, 18.7, 19.4 (CH3), 17.5, 17.6
29
29
(Ar-CH3), 27.2 (C-5), 31.9 (C-6), 35.6 (C-3), 43.6 (C-4), 46.8 (C-7),
3
52.7 (d, J = 3.4 Hz, CH2N), 53.6 (C-1), 62.2 (CH2O), 123.8 (Ar-
CH), 128.6 (Ar-CH), 130.3 (d, 3J = 2.4 Hz, Ar-C), 148.9 (Ar-CO),
184.2 (C-2).
31P NMR (162 MHz, CDCl3): d = 135.2.
MS (EI, 70 eV): m/z (%) = 468 (30) [M + H]+, 346 (100) [M –
Me2C6H3O]+, 178 (59) [CH2CH2N=C10H17]+.
Bis-(2,6-dimethylphenyl)chlorophosphite (1)
Anal. Calcd for C28H38NO3P: C, 71.92; H, 8.19; N, 3.0. Found: C,
71.73; H, 8.28; N, 3.22.
1-Methylpyrrolidin-2-one (0.01 g, 0.1 mmol) was added to a stirred
mixture of 2,6-dimethylphenol (4.89 g, 40 mmol) and PCl3 (1.76
mL, 20 mmol). The mixture was refluxed for 30 min until it became
completely homogeneous. All volatiles were then removed under
vacuum (1 Torr) at r.t. and the residue was twice fractionally dis-
tilled under high vacuum.
Bis(2¢¢,6¢¢-dimethylphenyl) (E,2¢S,3¢S)-3¢-Methyl-2¢-({(1R,4R)-
1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene}amino)pentyl
Phosphite (3b)
Yield: 1.01 g (95%); yellow oil.
13C NMR (100 MHz, CDCl3): d = 11.1, 18.8, 19.5 (CH3), 11.4 (C-
5¢), 15.7 [CH3 (s-Bu)], 17.4, 17.5, 17.6, 17.7 (Ar-CH3), 25.0 (C-4¢),
27.2 (C-5), 32.1 (C-6), 35.9 (C-3), 36.7 (C-3¢), 43.7 (C-4), 46.3 (C-
7), 53.6 (C-1), 64.3 (C-1¢), 66.1 (d, 3J = 3.6 Hz, C-2¢), 123.6, 123.7
Yield: 4.63 g (75%); colorless oil; bp 133–135 °C/1 Torr.
31P NMR (162 MHz, CDCl3): d = 174.3.
The spectroscopic and physicochemical characteristics of this sub-
stance fully correspond to published data.10,11
3
(Ar-CH), 128.6, 128.7 (Ar-CH), 130.3 (br d, J = 2.8 Hz, Ar-C),
148.9 (d, 2J = 2.4 Hz), 149.0 (Ar-CO), 181.6 (C-2).
31P NMR (162 MHz, CDCl3): d = 134.2.
Synthesis of Iminoalcohols 2a and 2b; General Procedure
A mixture of (R)-camphor (6.09 g, 40 mmol), appropriate aminoal-
cohol (40 mmol) and anhydrous ZnCl2 (0.55 g, 4 mmol) in o-xylene
(80 mL) was heated under reflux in a Dean–Stark apparatus for 25
h. The solvent was removed and the residue was stirred at 150 °C
for 1.5 h. The dark-red paste obtained was cooled to r.t. and unre-
acted starting materials were removed under vacuum (aspirator) at
temperatures <180 °C. The residue was then twice fractionally dis-
tilled under high vacuum.
MS (EI, 70 eV): m/z (%) = 524 (38) [M + H]+, 402 (100) [M –
Me2C6H3O]+, 234 (89) [CH2CH(s-Bu)N=C10H17 – H]+.
Anal. Calcd for C32H46NO3P: C, 73.39; H, 8.85; N, 2.67. Found: C,
73.64; H, 8.98; N, 2.53.
Bis(2¢¢,6¢¢-dimethylphenyl) (E)-2¢-({(1R,4R)-1,7,7-Trimethylbi-
cyclo[2.2.1]heptan-2-ylidene}amino)phenyl Phosphite (3c)
Yield: 1.21 g (87%); pale-yellow oil.
13C NMR (100 MHz, CDCl3): d = 10.8, 18.8, 19.5 (CH3), 17.2, 17.4,
17.5, 17.6 (Ar-CH3), 27.1 (C-5), 31.5 (C-6), 36.9 (C-3), 43.7 (C-4),
47.4 (C-7), 54.2 (C-1), 121.1–148.5 (Ar-C), 186.8 (C-2).
(E)-2¢-{[(1R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-
ylidene]amino}ethanol (2a)
Yield: 2.73 g (35%); colorless crystals; bp 108–110 °C/1 Torr; mp
66–67 °C.
31P NMR (162 MHz, CDCl3): d = 139.8.
MS (FAB): m/z (%) = 515 (7) [M]+, 394 (10) [M – Me2C6H3O]+,
290 (24) [(Me2C6H3O)2POH]+, 243 (27) [M – (Me2C6H3O)2P + H]+,
122 (100) [Me2C6H3OH]+.
The spectroscopic and physicochemical characteristics of this sub-
stance fully correspond to published data.12
(E,2¢S,3¢S)-3¢-Methyl-2¢-({(1R,4R)-1,7,7-trimethylbicy-
clo[2.2.1]heptan-2-ylidene}amino)pentan-1¢-ol (2b)
Yield: 4.22 g (42%); pale-yellow oil; bp 120–122 °C/1 Torr.
Anal. Calcd for C32H38NO3P: C, 74.54; H, 7.43; N, 2.72. Found: C,
74.33; H, 7.58; N, 2.54.
1H NMR (400 MHz, CDCl3): d = 0.73 (s, 3 H, CH3), 0.83 [t, J = 7.2
Hz, 3 H, CH2CH3 (s-Bu)], 0.90 (s, 3 H, CH3), 0.92 [d, J = 6.8 Hz,
3 H, CHCH3 (s-Bu)], 0.94 (s, 3 H, CH3), 1.20 (ddd, J = 17.4, 9.7,
4.0 Hz, 1 H, CH2), 1.24 [m, 2 H, CH2CH3 (s-Bu)], 1.33 (ddd,
J = 18.1, 9.7, 4.3 Hz, 1 H, CH2), 1.66 (td, J = 12.6, 4.3 Hz, 1 H,
CH2), 1.70 [m, 1 H, CHCH3 (s-Bu)], 1.79–1.87 (m, 2 H, CH2), 1.94
(m, 1 H, CH), 2.33 (br d, J = 17.1 Hz, 1 H, CH2), 2.68 (br s, 1 H,
OH), 2.94 (m, 1 H, CHN), 3.74 (m, 2 H, CH2O).
Synthesis of Rhodium Complexes 4a and 4b for NMR and IR
Experiments; General Procedure
Rhodium complexes with ligands 3b and 3c were synthesized as
follows: a solution of the ligand (0.36 mmol) in CHCl3 (0.5 mL) was
added dropwise to a stirred solution of [Rh(CO)2Cl]2 (0.18 mmol)
in CHCl3 (0.5 mL). A sample of the resulting solution (0.5 mL) was
transferred to a NMR tube or IR cuvette and spectral experiments
were carried out.
Anal. Calcd for C16H29NO: C, 76.44; H, 11.63; N, 5.57. Found: C,
76.23; H, 11.51; N, 5.71.
Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York

1722
K. Gavrilov et al.
PAPER
[Rh(CO)(h2-3a)Cl] (4a)
h. Upon completion, the reaction was quenched with brine (10 mL)
and extracted with THF (3 × 7 mL). The organic layer was washed
with brine (2 × 7 mL), dried over MgSO4 and the solvent was evap-
orated at reduced pressure (40 Torr). Crystallization of the residue
from EtOH followed by desiccation in vacuo (10 Torr, 12 h) gave
the product 7 as colorless crystals. All spectral data of compound 7
were in a good agreement with the literature.26 Enantiomeric excess
was determined by HPLC [(R,R)-Whelk-01 column; i-PrOH–
C6H14, 1:4; 1 mL/min; 254 nm] according to published data.26
A solution of the ligand 3a (0.36 mmol) in CHCl3 (5 mL) was added
dropwise to a stirred solution of [Rh(CO)2Cl]2 (0.07 g, 0.18 mmol)
in CHCl3 (5 mL) at r.t. The reaction mixture was stirred for 30 min
then the excess solvent was removed under vacuum (40 Torr) and
hexane (10 mL) was added to the residue. The precipitate obtained
was separated by centrifugation, washed with hexane (2 × 10 mL)
and dried under vacuum (1 Torr).
Yield: 0.22 g (96%); colorless solid; mp 182–184 °C (dec.).
Anal. Calcd for C29H38ClNO4PRh: C, 54.94; H, 6.04; N, 2.21.
Found: C, 55.18; H, 6.15; N, 2.27.
Palladium-Catalyzed Allylic Alkylation of 1,3-Diphenylallyl
Acetate with Dimethyl Malonate; General Procedure
A solution of [Pd(allyl)Cl]2 (0.0037 g, 0.01 mmol) and the appropri-
ate ligand (0.02 mmol) in THF (5 mL) was stirred for 40 min [alter-
natively, the appropriate pre-synthesized complex (0.02 mmol) was
dissolved in THF (5 mL)]. 1,3-Diphenylallyl acetate (6; 0.1 mL,
0.50 mmol) was added to the solution and the reaction mixture was
stirred for 15 min. Dimethyl malonate (0.10 mL, 0.87 mmol), BSA
(0.22 mL, 0.87 mmol) and sodium acetate (0.002 g) were added and
the reaction mixture was stirred for 48 h, diluted with THF (5 mL)
and filtered through celite. The filtrate was evaporated at reduced
pressure (40 Torr) giving, after a desiccation in vacuo (10 Torr, 12
h), the product 8 as a colorless oil that solidified upon standing. All
spectral data of compound 8 were in a good agreement with the lit-
erature.31 Enantiomeric excess was determined by HPLC (Daicel
Chiralcel OD-H; i-PrOH–C6H14, 1:99; 0.5 mL/min; 254 nm) ac-
cording to published data.27
Synthesis of Palladium Complexes 5a–c; General Procedure
A solution of the corresponding ligand (0.4 mmol) in CHCl3 (5 mL)
was added dropwise to a stirred solution of [Pd(allyl)Cl]2 (0.073 g,
0.2 mmol) in CHCl3 (5 mL) at r.t. The reaction mixture was stirred
for 1 h then AgBF4 (0.078g, 0.4 mmol) in THF (5 mL) was added.
The reaction mixture was stirred for 0.5 h and filtered. The solvents
were then removed under vacuum (40 Torr) and the solid was
washed with Et2O (2 × 10 mL) and dried under vacuum (1 Torr, 1
h).
[Pd(allyl)(h2-3a)]BF4 (5a)
Yield: 0.24 g (95%); colorless solid; mp 162–164 °C (dec.).
13C NMR (100 MHz, CDCl3): d = 10.8, 18.5, 19.5 (CH3), 17.7, 17.8
(Ar-CH3), 26.3 (C-5), 30.8 (C-6), 40.4 (C-3), 43.0 (C-4), 49.7 (C-7),
53.6 [allyl-CH2 (trans to N)], 54.5 (CH2N), 55.7 (C-1), 67.6
(CH2O), 84.6 [d, 2J = 44.7 Hz, allyl-CH2 (trans to P)], 121.5 (allyl-
CH), 125.4 (Ar-CH), 129.1 (Ar-CH), 129.7 (Ar-C), 148.4 (d,
2J = 15.2 Hz, Ar-CO), 198.8 (C-2).
X-ray Crystal Data for 4a
Empirical formula C29H38ClNO4PRh; formula weight 633.93; T =
120 K; crystal system = monoclinic; space group P21; unit cell di-
mensions a = 13.8284(17) Å, b = 14.1591(17) Å, c = 14.7757(18)
Å, b = 98.693(3)°; V = 2859.8(6) Å3; Z = 4; D (calculated) = 1.472
gcm–3; m (MoKa) = 7.81 cm–1; F(000) = 1312. Reflections collected
22794; independent reflections 13624 [R(int) = 0.0177]; Collected
with a SMART CCD 1000 diffractometer using MoKa radiation
(l = 0.71072 Å, w-scans with 0.3° step and 10 s exposure for each
frame). Absorbtion correction was applied semi-empirically from
equivalents. The structure of 4a was solved by direct method and re-
fined by full-matrix technique against F2 in anisotropic approxima-
tion using SHELXTL 5.1 program package.32 The positions of
hydrogen atoms were calculated geometrically and included in re-
finement in rigid body approximation. The refinement converged to
wR2 = 0.0957 with goodness-of-fit = 1.037 for all independent re-
flections [R1 = 0.0400 was calculated for 11920 observed reflec-
tions with I>2s(I)]. The absolute configuration of 4a was
determined by use of the Flack parameter. Crystallographic data
(excluding structure factors) for 4a have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion no. CCDC-295731. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge, CB2
MS (ESI): m/z (%) = 615 (100) [M – BF4]+.
Anal. Calcd for C31H43BF4NO3PPd: C, 53.05; H, 6.18; N, 2.0.
Found: C, 52.95; H, 6.3; N, 2.21.
[Pd(allyl)(h2-3b)]BF4 (5b)
Yield: 0.28 g (92%); colorless solid; mp 158–160 °C (dec.).
MS (ESI): m/z (%) = 671 (100) [M – BF4]+.
Anal. Calcd C35H51BF4NO3PPd: C, 55.46; H, 6.78; N, 1.85. Found:
C, 55.61; H, 6.71; N, 2.01.
[Pd(allyl)(h2-3c)]BF4 (5c)
Yield: 0.24 g (88%); yellow solid; mp 152–154 °C (dec.).
13C NMR (100 MHz, CDCl3): d = 9.5, 18.1, 18.5 (CH3), 17.1, 17.5,
17.6, 17.8 (Ar-CH3), 29.0 (C-5), 32.0 (C-6), 38.1 (C-3), 42.3 (C-4),
48.0 (C-7), 51.2 [allyl-CH2 (trans to N)], 55.3 (C-1), 81.5 [d,
2
2J = 41.2 Hz, allyl-CH2 (trans to P)], 120.3 (d, J = 8.9 Hz, allyl-
CH), 121.2-149.9 (Ar-C), 200.3 (C-2).
MS (FAB): m/z (%) = 662 (100) [M – BF4]+, 621 (12) [M – BF4 –
1EZ,
UK
[Fax:
+44(1223)336033;
E-mail:
depos-
allyl]+, 515 (15) [L]+.
it@ccdc.cam.ac.uk].
Anal. Calcd for C35H43BF4NO3PPd: C, 56.06; H, 5.78; N, 1.87.
Found: C, 55.87; H, 5.57; N, 2.06.
Acknowledgment
Palladium-Catalyzed Allylic Sulfonylation of 1,3-Diphenylallyl
Acetate with Sodium p-Toluenesulfinate; General Procedure
A solution of [Pd(allyl)Cl]2 (0.0037 g, 0.01 mmol) and the appropri-
ate ligand (0.02–0.04 mmol) in THF (5 mL) was stirred for 40 min
[alternatively, the pre-synthesized appropriate complex 5c (0.02
mmol) was dissolved in THF (5 mL)]. 1,3-Diphenylallyl acetate (6;
0.1 mL, 0.5 mmol) was added to the solution and the reaction mix-
ture was stirred for 15 min. Sodium p-toluenesulfinate (0.178 g,
1.00 mmol) was added and the reaction mixture was stirred for 48
The authors thank Dr. A. V. Korostylev (Leibniz-Institut für Orga-
nische Katalyse an der Universität Rostock, Germany) for his assi-
stance in preparing the manuscript. The authors gratefully
acknowledge receiving the chiral HPLC columns: (R,R)-WHELK-
01 from Regis Technologies (USA) and the Chiralcel OD-H from
Daicel Chemical Industries, Ltd. (Japan). This work was partially
supported by the Russian Foundation for Basic Research (Grant No.
06-03-90898-Mol-a).
Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York

PAPER
Enantioselective Application of P,N-Bidentate Phosphites
1723
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Synthesis 2007, No. 11, 1717–1723 © Thieme Stuttgart · New York