Phosphoramidites based on phenyl-substituted 1,2-diols as ligands in palladium-catalyzed asymmetric allylations: The contribution of steric demand and chiral centers to the enantioselectivity

Article abstract of DOI:10.1016/j.tetlet.2011.08.122

A small family of readily available phosphoramidite ligands, including compounds with P-stereocenters, has been prepared from phenyl-substituted 1,2-diols as simple and cheap starting materials. Using these ligands, up to 84% ee was achieved in Pd-catalyz

Full text of DOI:10.1016/j.tetlet.2011.08.122

Tetrahedron Letters 52 (2011) 5706–5710
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Tetrahedron Letters
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Phosphoramidites based on phenyl-substituted 1,2-diols as ligands
in palladium-catalyzed asymmetric allylations: the contribution of steric
demand and chiral centers to the enantioselectivity
Konstantin N. Gavrilov a, , Sergey V. Zheglov a, Mariya N. Gavrilova a, Ilya V. Chuchelkin a,
⇑
Nikolay N. Groshkin a, Eugenie A. Rastorguev b, Vadim A. Davankov b
a Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan, Russian Federation
b Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
A small family of readily available phosphoramidite ligands, including compounds with P⁄-stereocenters,
has been prepared from phenyl-substituted 1,2-diols as simple and cheap starting materials. Using these
ligands, up to 84% ee was achieved in Pd-catalyzed asymmetric allylic substitution. The influence of
structural modules such as asymmetric atoms and steric demand on the enantioselectivity is discussed.
Ó 2011 Elsevier Ltd. All rights reserved.
Article history:
Received 23 June 2011
Revised 11 August 2011
Accepted 22 August 2011
Available online 28 August 2011
Keywords:
Asymmetric allylic substitution
Palladium
Phosphorus ligands
Phosphoramidites
The syntheses of drugs, chemical agents for plant protection,
food additives, flavors, liquid crystals, and enantiopure polymers
are based on modern approaches to optically pure compounds.
One of the leading approaches is asymmetric metal complex catal-
ysis.1 In turn, the activity and stereoselectivity of metal complex
catalysts depend largely on the successful design and synthesis
of appropriate chiral ligands, among which phosphorus-containing
compounds are noteworthy. Accordingly, one of the core research
activities in the field of asymmetric catalysis is the ongoing devel-
opment of new phosphorus ligands aimed at higher levels of effi-
ciency and selectivity to meet the increasing demands of both
academic and industrial sectors. Although the use of numerous chi-
ral phosphorus ligands has been reported, the tuning of existing li-
gands and/or the development of novel chiral ligands with
improved performance continue to attract the interest of synthetic
chemists.1b,2
Optically active phosphite-type compounds play important
roles, because of their intrinsic electronic properties and steric var-
iability. Indeed, various P–O and/or P–N bond containing phospho-
rus ligands can be constructed in large quantities through the use
of relatively simple condensation processes, and from inexpensive
starting materials. Another advantage of phosphite-type ligands is
that they are less sensitive to air and other oxidizing agents than
phosphines. Hence, this makes it possible to develop a protocol
for the ligand synthesis that does not necessitate the use of a glove
box. Furthermore, they are amenable to parallel synthesis, even in
solid phase synthesis. Such key advantages allow the preparation
and screening of extensive libraries of chiral ligands aiming at high
activities and selectivities for each particular reaction. In addition,
phosphite-type ligands are characterized by pronounced
p-acidity
and low cost.3,4
Phosphoramidites represent a highly versatile and readily
accessible class of chiral phosphite-type ligands. Their modular
structure enables the formation of a series of ligands and simple
fine-tuning for a specific catalytic reaction. Phosphoramidites
frequently show exceptional levels of stereocontrol, and their
monodentate nature is essential in combinatorial catalysis, where
a ligand-mixture approach is used. Phosphoramidites with a
BINOL-backbone are considered as so-called ‘privileged ligands’.4l,5
Biphenol-, SPINOL-, TADDOL-, BIFOL-, diphenylprolinol-based
phosphoramidites, as well as phosphoramidites DpenPhos and
CydamPhos, also have demonstrated high enantioselectivities in
transition metal catalyzed asymmetric transformations.6
Herein we report the synthesis and application of some phos-
phoramidites containing 1,3,2-dioxaphospholane rings based on
phenyl-substituted 1,2-diols, including the compounds possessing
a P⁄-stereocenter in Pd-catalyzed asymmetric allylic substitution.
Enantioselective Pd-catalyzed allylic substitution has emerged as
a powerful synthetic tool which is tolerant of various functional
⇑
Corresponding author. Tel.: +7 4912 280580; fax +7 4912 281435.
E-mail address: k.gavrilov@rsu.edu.ru (K.N. Gavrilov).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.122

K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 5706–5710
5707
groups in the substrate and operates with a wide range of C-, N-,
O-, S- and P-nucleophiles. On the one hand, this is a common
benchmark test for evaluating new chiral ligands. On the other,
Pd-catalyzed allylic substitution is a novel and highly efficient
strategy in the total synthesis of enantiopure natural and unnatural
products.1c,7
rized in Table 1. Compound 5 was a mixture of epimers with re-
spect to the phosphorus stereocenter and contained 71% of the
major P⁄-epimer, while ligand 7 was formed as a single stereoiso-
mer (Table 1). We did not establish the absolute configuration of
the P⁄-stereocenter in the structure of ligand 7. Nevertheless, con-
sidering the data presented in an article on the related compound,
(2R,5S)-2-chloro-4,4,5-triphenyl-1,3,2-dioxaphospholan,10 it can
be assumed that we obtained the (2R,5S)-epimer of 7. The 13C
NMR spectra of these ligands are characterized by similar spin-spin
coupling constants JC(4),P and JC(5),P (7.1 and 7.0 Hz for (2R,5S)-2-
chloro-4,4,5-triphenyl-1,3,2-dioxaphospholan, 9.0 and 8.9 Hz for 7,
respectively), which indicate that their asymmetric phosphorus
atoms have the same absolute configurations.11 It should be added
that the (R)-configuration of the P⁄-stereocenter in (2R,5S)-2-
chloro-4,4,5-triphenyl-1,3,2-dioxaphospholan has been proved by
single crystal X-ray diffraction.10 To estimate the steric demands
of phosphoramidites 5–7, we calculated their Tolman cone angles
using the reported semi-empirical quantum-mechanical AM1
method with full optimization of geometrical parameters.12 The
results obtained showed that the steric parameters (h) of ligands
5–7 gradually increased within the intervals of 117°–138°, peaking
at compound 7 bearing three phenyl substituents (Table 1).
In order to examine the influence of the asymmetric atoms and
steric demand, phosphoramidites 5–7 were tested in the asymmet-
ric Pd-catalyzed allylic substitution of (E)-1,3-diphenylallyl acetate
(10) as a benchmark catalytic process (Tables 2 and 3). The reac-
tions were run in THF or CH2Cl2. The results obtained showed that
A well-conceived ligand should possess one or more structural
features (modules) that may be varied readily in a systematic fash-
ion, in order to optimize the design for the given purpose. The de-
sign is informative to the extent that variations in the ligand
modules can be correlated to changes in the reactivity or selectiv-
ity of the catalyst. A set of such powerful modules includes asym-
metric atoms and steric demands.1b,2c,d Phosphoramidites 5–7
with a 1,2-diol-backbone illustrate successfully this concept.
The monodentate phosphoramidites 5–7 were synthesized via
one-step phosphorylation of the corresponding phenyl-substituted
1,2-diols 2–4 with hexaethylphosphorous triamide (1) (Scheme 1)
in toluene (in the case of 5 and 7) or under solvent-free conditions
(in the case of 6). This convenient method does not require an addi-
tional base and the only by-product is volatile HNEt2. The starting
optically active diols 2 and 3 are commercially available; diol 4 was
synthesized in two steps from (S)-mandelic acid.8 It should be
noted that (S,S)-hydrobenzoin (3) and (S)-1,1,2-triphenylethane-
1,2-diol (4) are important chiral auxiliaries and synthetic building
blocks.9 Since all the precursors are inexpensive and readily
available, the ligands 5–7 can be prepared on multigram scale.
The 1,2-diol-based phosphoramidites 5–7 are colorless liquids or
white solids, which are readily soluble in common organic sol-
vents. They were fully characterized by 1H, 13C, and 31P NMR spec-
troscopy, EI and/or MALDI TOF/TOF mass spectrometry as well as
by elemental analysis. Compounds 5–7 and their solutions must
be kept under anhydrous conditions due to their sensitivity toward
moisture.
2
2
Table 1
31P NMR chemical shifts (162.0 MHz, CDCl3, 25 °C) and cone angles h (°) of ligands
5–7.
Ligand
dP
h
The phosphoramidites 5–7 possess: (i) a 1,3,2-dioxaphospho-
lane ring with one to three phenyl substituents and an NEt2 substi-
tuent on the phosphorus atom, (ii) one or two C⁄-stereocenters,
(iii) chirogenic phosphorus donor atoms in the case of 5 and 7.
The 31P NMR spectroscopic data for compounds 5–7 are summa-
5
(29%)a
(71%)a
149.7
146.5
149.4
142.9
117
6
7
126
138
Percentage of P⁄-epimers.
a
N
N
P
N
HO
1
OH
+
+
OH
110 °C,
-2 Et2NH
OH
O
O
4
2
P
N
O
O
P
N
OH
OH
5
+
7
3
O
P
N
O
6
Scheme 1. Synthesis of phosphoramidites 5–7.

5708
K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 5706–5710
Table 2
Table 3
Pd-catalyzed allylic sulfonylation and alkylation of (E)-1,3-diphenylallyl acetate (10)a
Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate (10)a
Nu
*
Nu
*
OAc
Ph
OAc
Ph
NuX, cat
solvent
NuH, cat
solvent
Ph
Ph
Ph
Ph
Ph
Ph
10
10
11a,b
11c,d
Nu = N(Pr)2, 11c
Nu = N(CH2)4, 11d
N u= SO2pTol, X = Na, 11a
Nu = CH(CO2Me)2 X = H, 11b
Entry
Ligand
L/Pd
Solvent
Conversion (%)
ee (%)
Entry
Ligand
L/Pd
Solvent
Conversion (%)
ee (%)
Allylic amination with dipropylamineb
1
2
3
4
5
6
7
b
Allylic sulfonylation with sodium p-toluenesulfinate
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
1
2
1
2
1
2
1
2
2
2
1
2
1
2
2
CH2Cl2
CH2Cl2
THF
100
100
100
100
100
100
14
5 (ꢀ)
1
2
3
4
5
6
7
8
5
5
6
6
6
7
7
7
1
2
1
2
2
1
2
2
THF
THF
THF
THF
THF
THF
THF
THF
94c
95c
97c
80c
90c
40 (R)
50 (R)
30 (R)
65 (R)
80 (R)
35 (R)
50 (R)
62 (R)
2 (ꢀ)
9 (ꢀ)
THF
15 (ꢀ)
35 (ꢀ)
39 (ꢀ)
74 (ꢀ)
71 (ꢀ)
39 (ꢀ)c
47 (ꢀ)c
15 (+)
13 (+)
11 (+)
11 (+)
10 (+)d
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
THF
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
d
e
c
83
96c
81c
8
9
16
100
100
100
100
24
f
Allylic alkylation with dimethyl malonate (BSA, KOAc)
9
10
11
12
13
14
15
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
1
2
1
2
1
2
1
2
2
2
1
2
1
2
2
2
CH2Cl2
CH2Cl2
THF
100
100
—
5 (R)
8 (R)
—
2 (R)
30 (R)
80 (R)
20 (R)
40 (R)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
THF
10
44
100
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
THF
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
THF
100
100
16
30
100
98
100
100
94
100
100
90
e
Allylic amination with pyrrolidine
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
1
2
1
2
1
2
1
2
2
2
1
2
1
2
2
CH2Cl2
CH2Cl2
THF
100
100
100
100
100
100
72
5 (S)
3 (S)
84 (R)d
38 (R)d
70 (S)
37 (S)
40 (S)
32 (S)
26 (S)e
25 (S)e
29 (S)
19 (S)
49 (S)
57 (S)
60 (S)
65 (S)
60 (S)c
54 (S)c
63 (R)
57 (R)
60 (R)
54 (R)
49 (R)d
THF
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
THF
CH2Cl2
CH2Cl2
THF
THF
CH2Cl2
57
100
100
100
100
100
100
100
a
All reactions were carried out with 2 mol% of [Pd(allyl)Cl]2 at room temperature
for 48 h.
Enantiomeric excess of 11a was determined by HPLC (Daicel Chiralcel OJ, C6H14
i-PrOH = 4:1, 0.5 ml/min, 254 nm).
b
/
c
Isolated yield of 11a.
With complex 8 as the catalyst.
With complex 9 as the catalyst.
d
a
All reactions were carried out with 2 mol% of [Pd(allyl)Cl]2 at room temperature
for 48 h.
The conversion of substrate 10 and enantiomeric excess of 11c were deter-
mined by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH/HN(Et)2 = 1000:1:1, 0.4 mL/
min, 254 nm, t (+) = 8.2 min, t (–) = 9.1 min).
e
f
The conversion of substrate 10 and enantiomeric excess of 11b were deter-
mined by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH = 99:1, 0.6 ml/min, 254 nm).
b
c
With complex 8 as the catalyst.
With complex 9 as the catalyst.
The conversion of substrate 10 and enantiomeric excess of 11d were deter-
the efficiency of these ligands differs dramatically. In most cases li-
gand 5 demonstrated an excellent conversion, but its enantioselec-
tivity was poor (in allylic alkylation and amination, no more than
29% ee) or mediocre (in allylic sulfonylation, up to 50% ee, Table
2, entries 1 and 2). Presumably, this is caused by the rather low ste-
ric demand (h = 117°) of phosphacyclane 5, and by the low ratio of
its P⁄-epimers (Table 1).
At the same time, the use of phosphoramidites 6 and 7 resulted
in moderate to good enantioselectivities in most cases (Tables 2
and 3). Hence, with these ligands cationic palladium catalysts 8
and 9 were prepared (Scheme 2). Compounds 6 and 7 readily react
with [Pd(allyl)Cl]2 (CH2Cl2/THF, AgBF4 as chloride scavenger, room
temperature, 3 h) to give cationic complexes of the type [Pd(al-
lyl)(L)2]BF4 bearing two molecules of the monodentate phospho-
rous ligand. The 31P NMR spectra of isolated complexes (in
d
e
mined by HPLC (Daicel Chiralcel OD-H, OD-H, C6H14/i-PrOH/HN(Et)2 = 200:1:0.1,
0.9 mL/min, 254 nm).
1/2 [Pd(allyl)Cl]2, AgBF4
- AgCl
L
L
BF4
L
2
Pd
8 (L = 6)
9 (L = 7)
Scheme 2. Synthesis of cationic palladium complexes 8 and 9.
complex 8 was employed as the chiral auxiliary (Table 2, entry
5). When the reaction was carried out with [Pd(allyl)Cl]2 as the
precatalyst, ligand 6 afforded (R)-11a having a moderate enantio-
meric purity (up to 65% ee). On the whole, the palladium catalysts
with ligand 7 provided no more than 62% ee (Table 2, entries 6–8).
In the Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl
acetate with dimethyl malonate, the best result (quantitative con-
version and 84% ee) was obtained again with cationic complex 8
(Table 2, entry 17). It is clear that CH2Cl2 is the solvent of choice
(Table 2, entries 13–24). In all cases, the catalytic systems based
on phosphoramidite 6 led to the product 11b with (R)-configura
CDCl3) exhibited a singlet at dP 146.2 for 8 and an AB system (dP
140.9, d and dP 140.0, d, JP,P 102.1 Hz) for 9 either due to the fast
2
0
interconversion of the exo- and endo-isomers or to the absence of
one of them.13 The AB system in the 31P NMR spectrum of complex
9 indicates the nonequivalence of the two P⁄-monodentate ligands
7 in the coordination sphere of palladium.14 The MS spectroscopic
and elemental analysis data (see Supplementary data) were also in
good agreement with the proposed structures of 8 and 9.
In the allylic sulfonylation of (E)-1,3-diphenylallyl acetate,
product (R)-11a was obtained in 90% yield and 80% ee when

K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 5706–5710
5709
tion, and the optimal molar ratio was L/Pd = 2. P⁄-chiral ligand 7
showed lower enantioselectivities (up to 70% ee, Table 2, entry
19). Unlike the allylic alkylation with ligand 6, in the case of ligand
7 the product 11b had (S)-configuration, and the best asymmetric
induction was achieved with L/Pd = 1 (Table 2, entries 19–24). In
particular, the cationic complex 9 bearing two ligands 7 in a coor-
dination sphere of palladium provided low enantioselectivity (no
more than 26% ee, Table 2, entries 23 and 24).
Allylic amination of compound 10 with dipropylamine in the
presence of ligand 6 gave product (ꢀ)-11c with up to 74% ee. The
reaction in THF was more enantioselective, while a higher conver-
sion was achieved in CH2Cl2. The L/Pd molar ratio had virtually no
effect on the enantioselectivity (see Table 3, entries 5–10). At the
same time, ligand 7 demonstrated low enantioselectivity almost
irrespective of both the L/Pd molar ratio and the solvent (10–15%
ee, Table 3, entries 11–15). Interestingly, in this reaction, as in
the case of the above discussed allylic alkylation of (E)-1,3-diphen-
ylallyl acetate, phosphoramidites 6 and 7 favored the formation of
the opposite enantiomers of product 11c.
We also investigated the allylic amination of (E)-1,3-diphenylal-
lyl acetate with pyrrolidine as an N-nucleophile. In this reaction,
phosphoramidites 6 and 7 were moderate stereoinductors provid-
ing up to 65% and 63% ee, respectively (Table 2, entries 23 and 26).
As a rule, the conversion was quantitative. The enantiomeric excess
does not depend (or poorly depends) on the solvent and the molar
ratio L/Pd. As in the reactions with dimethyl malonate and dipro-
pylamine, compounds 6 and 7 afforded different enantiomers of
amine 11d. Accordingly, ligand 6 led to the (S)-enantiomer of
11d, and ligand 7 the (R)-enantiomer.
In conclusion, three monodentate phosphoramidites 5–7 based
on (S)-1-phenylethane-1,2-diol, (S,S)-hydrobenzoin and (S)-1,1,2-
triphenylethane-1,2-diol were obtained via a simple synthesis.
Some conclusions can be drawn from the results obtained with
these ligands in the Pd-catalyzed asymmetric allylation. As stated
above, ligand 5 gave poor or mediocre enantioselectivity due to
its low steric demand and low epimeric ratio. Among the phospho-
ramidites 6 and 7 the former was more efficient. It should be noted
that phosphacyclane 7 is more sterically demanding than 6 and has
a P⁄-stereocenter. Presumably, the low enantioselectivity in the
Pd-catalyzed allylic alkylation at a molar ratio L/Pd = 2 was caused
by steric hindrance in the [Pd(1,3-Ph2-allyl)(7)2]+ intermediate.15
In certain processes with participation of 7, for example, in the
allylic amination with dipropylamine, a mismatched combination
of P⁄- and C⁄-stereocenters takes place. At the same time, the
choice between 6 and 7 makes it possible to control the sign of
asymmetric induction in most cases. To sum up, the results ob-
tained with phosphoramidites 6 and 7 show the considerable po-
tential of such ligands in enantioselective catalysis. Indeed, in the
Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate with
dimethyl malonate they are more efficient than a series of BINOL-
based phosphoramidites and comparable with TADDOL-based
phosphoramidites.16 Enantioselectivity can be further improved
by introduction of bulky N-containing exocyclic substituents at
the phosphorus atom instead of the NEt2 group, including substit-
uents with additional C⁄-stereocenters. Such experiments are in
progress in our laboratory.
Gel 60 F254). 1H NMR (400.13 MHz, CDCl3, 25 °C): d = 1.11 (t,
J = 8.1 Hz, 6H, CH3); 3.12 (m, 4H, NCH2); 3.68 (m, 1H, OCH2); 4.51
(m, 1H, OCH2); 5.27 (br t, J = 6.1 Hz, 1H, OCH); 7.31 (m, 2H, CHAr);
7.39 (m, 3H, CHAr), major epimer; 1.10 (t, J = 7.9 Hz, 6H, CH3); 3.15
(m, 4H, NCH2); 3.71 (m, 1H, OCH2); 4.21 (m, 1H, OCH2); 5.11 (dd,
J = 9.9 Hz, J = 6.1 Hz, 1 H, OCH); 7.29 (m, 2H, CHAr); 7.38 (m, 3H,
CHAr), minor epimer. 13C{H} NMR (100.6 MHz, CDCl3, 25 °C):
dC = 15.0 (d, 3J = 3.0 Hz, CH3); 37.9 (d, 2J = 21.1 Hz, NCH2); 70.9 (d,
2J = 7.9 Hz, OCH2); 76.5 (d, 2J = 9.0 Hz, OCH); 125.6 (s, CHAr);
127.8 (s, CHAr); 128.3 (s, CHAr); 139.7 (d, 3J = 5.0 Hz, CAr), major epi-
mer; dC = 14.9 (d, 3J = 3.1 Hz, CH3); 37.8 (d, 2J = 21.0 Hz, NCH2); 68.7
(d, 2J = 6.0 Hz, OCH2); 77.2 (d, 2J = 5.9 Hz, OCH); 125.3 (s, CHAr);
127.9 (s, CHAr); 128.4 (s, CHAr); 137.6 (d, 3J = 4.0 Hz, CAr), minor epi-
mer. MS (EI, 70 eV): m/z (%) = 239 (100) [M] +. Anal. Calcd for
C
12H18NO2P: C, 60.24; H, 7.58; N, 5.85. Found: C, 60.48; H, 7.62;
N, 5.64.
Procedure for the preparation of ligand 6: A mixture of P(NEt2)3
(1) (2.74 ml, 10 mmol) and (S,S)-hydrobenzoin (3) (2.14 g,
10 mmol) was stirred at 110 °C for 45 min. Next the mixture was
stirred under vacuum (10 Torr, 90 °C) for 30 min to remove HNEt2
and cooled to 20 °C. The residue was purified by bulb-to-bulb dis-
tillation in vacuum (Tbath = 171–182 °C, 1 Torr) and then by flash
chromatography on aluminum oxide (toluene).
(4S,5S)-2-Diethylamino-4,5-diphenyl-1,3,2-dioxaphospholan (6):
White waxy solid; yield 2.18 g (69%); Rf 0.7 (EtOAc/hexane, 1:1,
Alugram Alox N/UV254). 1H NMR (400.13 MHz, CDCl3, 25 °C):
d = 1.19 (t, J = 8.0 Hz, 6H, CH3); 3.27 (m, 4H, NCH2); 4.84 (br s,
2H, OCH); 7.19–7.35 (m, 10H, CHAr). 13C{H} NMR (100.6 MHz,
CDCl3, 25 °C): dC = 15.4 (d, 3J = 4.0 Hz, CH3); 38.4 (d, 2J = 28.2 Hz,
NCH2); 82.6 (d, 2J = 9.1 Hz, OCH); 84.7 (d, 2J = 8.1 Hz, OCH); 126.4
(s, CHAr); 127.2 (s, CHAr); 128.2 (s, CHAr); 128.3 (s, CHAr); 128.4
(s, CHAr); 128.5 (s, CHAr); 136.7 (d, 3J = 6.0 Hz, CAr); 138.1 (d,
3J = 10.1 Hz, CAr). MS (EI, 70 eV): m/z (%) = 315 (8) [M]+, 181 (100)
[PhCH2CHPh] +. Anal. Calcd for C18H22NO2P: C, 68.56; H, 7.03; N,
4.44. Found: C, 68.71; H, 7.16; N, 4.54.
Procedure for the preparation of ligand 7: A solution of P(NEt2)3
(1) (2.74 ml, 10 mmol) and (S)-1,1,2-triphenylethan-1,2-diol (4)
(2.90 g, 10 mmol) in toluene (30 ml) was stirred under reflux for
2 h. Next the solution was cooled to 20 °C and filtered through a
short aluminum oxide plug. The filtrate was concentrated in vac-
uum (40 Torr) and the crude product was purified by flash chroma-
tography on silica gel (CH2Cl2) and then by careful trituration with
EtOAc/hexane (1:25). The precipitated white solid was separated
by centrifugation and dried in vacuum (1 Torr) for 1 h.
(5S)-2-Diethylamino-4,4,5-triphenyl-1,3,2-dioxaphospholan (7):
White powder; yield 2.54 g (65%); Rf 0.85 (EtOAc/hexane, 1:5, silica
gel 60 F254). 1H NMR (400.13 MHz, CDCl3, 25 °C): d = 1.04 (t,
J = 7.5, 6H, CH3), 3.04 (m, 4H, NCH2), 5.93 (s, 1 H, OCH), 6.92–
7.14 (m, 10H, CHAr), 7.31 (d, J = 8.0, 1H, CHAr), 7.38 (t, J = 7.9, 2H,
CHAr), 7.69 (d, J = 7.9, 2H, CHAr). 13C{H} NMR (100.6 MHz, CDCl3,
25 °C): dC = 15.0 (d, 3J = 3.0, CH3), 38.3 (d, 2J = 21.1, NCH2), 84.4
(d, 2J = 8.9, OCH), 90.6 (d, 2J = 9.0, OC), 126.7 (s, CHAr), 126.9 (s,
CHAr), 127.0 (s, CHAr), 127.4 (s, CHAr), 127.5 (s, CHAr), 127.7 (s,
CHAr), 127.8 (s, CHAr), 128.1 (s, CHAr), 128.2 (s, CHAr), 137.5 (d,
3J = 7.0, CAr), 141.1 (d, 3J = 3.1, CAr), 143.6 (s, CAr). MS (EI, 70 eV):
m/z (%) = 391 (1) [M]+, 257 (100) [Ph2CHCHPh]+. MS (MALDI TOF/
TOF): m/z (%) = 430 (100) [M+K]+, 273 (39) [Ph2CHC(OH)Ph]+, 257
(66) [Ph2CHCHPh]+. Anal. Calcd for C24H26NO2P: C, 73.64; H,
6.69; N, 3.58. Found: C, 73.87; H, 6.59; N, 3.46.
Experimental procedures for the preparation of ligands 5–7: Pro-
cedure for the preparation of ligand 5. A solution of P(NEt2)3 (1)
(2.74 ml, 10 mmol) and (S)-1-phenylethan-1,2-diol (2) (1.38 g,
10 mmol) in toluene (25 ml) was stirred under reflux for 1 h. All
volatiles were removed under vacuum and the crude product
was purified by flash chromatography on silica gel (EtOAc/hexane,
1:3) and then by bulb-to-bulb distillation under vacuum
(Tbath = 125–134 °C, 1 Torr).
Acknowledgments
We acknowledge the financial support from the Russian Foun-
dation for Basic Research (Grant No. 11-03-00347-a) and a grant
from the President of the Russian Federation for Young Candidates
of Sciences (No. MK-3889.2010.3).
(4S)-2-Diethylamino-4-phenyl-1,3,2-dioxaphospholan (5): Color-
less liquid; yield 1.77 g (74%); Rf 0.9 (EtOAc/hexane, 1:1, Silica

5710
K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 5706–5710
6. (a) Chapsal, B. D.; Hua, Z.; Ojima, I. Tetrahedron: Asymmetry 2006, 17, 642; (b)
Supplementary data
Vuagnoux-d’Augustin, M.; Kehrli, S.; Alexakis, A. Synlett 2007, 2057; (c) Qiao,
X.-C.; Zhu, S.-F.; Zhou, Q.-L. Tetrahedron:Asymmetry 2009, 20, 1254; (d)
Pellissier, H. Tetrahedron 2008, 64, 10279; (e) Kop-Weiershausen, T.; Lex, J.;
Neudörfl, J.-M.; Goldfuss, B. Beilstein J. Org. Chem. 2005, 1; (f) Bondarev, O. G.;
Goddard, R. Tetrahedron Lett. 2006, 47, 9013; (g) Liu, Y.; Ding, K. J. Am. Chem.
Soc. 2005, 127, 10488; (h) Zhao, B.; Wang, Z.; Ding, K. Adv. Synth. Catal. 2006,
348, 1049.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.122.
References and notes
7. (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809; (b) Crepy, K. V. L.;
Imamoto, T. Adv. Synth. Catal. 2003, 345, 79; (c) Graening, T.; Schmalz, H. G.
Angew. Chem., Int. Ed. 2003, 42, 2580; (d) Chapsal, B. D.; Ojima, I. Org. Lett. 2006,
8, 1395; (e) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258; (f) Dieguez, M.;
Pamies, O. Acc. Chem. Res. 2010, 43, 312; (g) Lam, F. L.; Kwong, F. Y.; Chan, A. S.
C. Chem. Commun. 2010, 46, 4649; (h) Fernandez-Perez, H.; Etayo, P.; Panossian,
A.; Vidal-Ferran, A. Chem. Rev. 2011, 111, 2119; (i) Lafrance, D.; Bowles, P.;
Leeman, K.; Rafka, R. Org. Lett. 2011, 13, 2322.
8. Braun, M.; Gräf, S.; Herzog, S. Org. Synth. Coll. 1998, 9, 507.
9. (a) Okano, K. Tetrahedron 2011, 67, 2483; (b) Braun, M.; Sacha, H.; Galle, D.;
Baskaran, S. Pure Appl. Chem. 1996, 68, 561; (c) Ridder, D.; Wunderlichb, H.;
Braun, M. Eur. J. Org. Chem. 1998, 1071.
10. Meier, T.; Braun, M.; Frank, W. Phosphorus, Sulfur, Silicon, Relat. Elem. 2009, 184,
2536.
11. Arzoumanian, H.; Buono, G.; Choukrad, M.; Petrignani, J.-F. Organometallics
1988, 7, 59.
12. (a) Tolman, C. A. Chem. Rev. 1977, 77, 313; (b) Polosukhin, A. I.; Kovalevskii, A.
I.; Gavrilov, K. N. Russ. J. Coord. Chem. 1999, 25, 758.
13. Tsarev, V. N.; Lyubimov, S. E.; Shiryaev, A. A.; Zheglov, S. V.; Bondarev, O. G.;
Davankov, V. A.; Kabro, A. A.; Moiseev, S. K.; Kalinin, V. N.; Gavrilov, K. N. Eur. J.
Org. Chem. 2004, 2214. and references cited therein.
1. (a) Brown, J. M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. I, pp 121–182; (b) Ohkuma, T.;
Kitamura, M.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-
VCH: New York, 2000; pp 1–110; (c) Trost, B. M.; Crawley, M. L. Chem. Rev.
2003, 103, 2921; (d) Blaser, H.-U.; Schmidt, E. Asymmetric Catalysis on Industrial
Scale; Wiley-VCH: Weinheim, 2004; (e) Burk, M. J. Acc. Chem. Res. 2000, 33, 363.
2. (a) Falciola, C. A.; Alexakis, A. Eur. J. Org. Chem. 2008, 3765; (b) Hargaden, G. C.;
Guiry, P. J. Chem. Rev. 2009, 109, 2505; (c) Au-Yeung, T. T.-L.; Chan, S.-S.; Chan,
A. S. C. Adv. Synth. Catal. 2003, 345, 537; (d) Caldentey, X.; Pericas, M. A. J. Org.
Chem. 2010, 75, 2628.
3. Claver, C.; Pamies, O.; Dieguez, M. In Börner, A., Ed.; Phosphorus Ligands in
Asymmetric Catalysis; Wiley-VCH: Weinheim, 2008; Vol. II, pp 507–528.
4. (a) Ansel, J.; Wills, M. Chem. Soc. Rev. 2002, 31, 259; (b) Alexakis, A.; Benhaim, C.
Eur. J. Org. Chem. 2002, 19, 3221; (c) Molt, O.; Schrader, T. Synthesis 2002, 2633;
(d) Reetz, M. T.; Mehler, G.; Meiswinkel, A.; Sell, T. Tetrahedron Lett. 2002, 43,
7941; (e) Dieguez, M.; Pamies, O.; Claver, C. Tetrahedron:Asymmetry 2004, 15,
2113; (f) Gavrilov, K. N.; Bondarev, O. G.; Polosukhin, A. I. Russ. Chem. Rev. 2004,
73, 671; (g) Jerphagnon, T.; Renaud, J.-L.; Bruneau, C. Tetrahedron: Asymmetry
2004, 15, 2101; (h) Reetz, M. T.; Mehler, G.; Bondarev, O. Chem. Commun. 2006,
2292; (i) de Vries, J. G.; Lefort, L. Chem. Eur. J. 2006, 12, 4722; (j) Jagt, R. B. C.;
Toullec, P. Y.; Geerdink, D.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J. Angew.
Chem., Int. Ed. 2006, 45, 2789; (k) Swennenhuis, B. H. G.; Chen, R.; van Leeuwen,
P. W. N. M.; de Vries, J. G.; Kamer, P. C. J. Org. Lett. 2008, 10, 989; (l) Teichert, J.
F.; Feringa, B. L. Angew. Chem., Int. Ed. 2010, 49, 2486; (m) van Leeuwen, P. W. N.
M.; Kamer, P. C. J.; Claver, C.; Pamies, O.; Dieguez, M. Chem. Rev. 2011, 111,
2077.
14. Gavrilov, K. N.; Lyubimov, S. E.; Zheglov, S. V.; Benetsky, E. B.; Davankov, V. A. J.
Mol. Catal. A: Chem. 2005, 231, 255.
15. Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH:
New York, 2000; pp 593–649.
16. (a) Mikhel, I. S.; Bernardinelli, G.; Alexakis, A. Inorg. Chim. Acta 2006, 359, 1826;
(b) Boele, M. D. K.; Kamer, P. C. J.; Lutz, M.; Spek, A. L.; de Vries, J. G.; van
Leeuwen, P. W. N. M.; van Strijdonck, G. P. F. Chem. Eur. J. 2004, 10, 6232.
5. Krausová, Z.; Sehnal, P.; Bondzic, B. P.; Chercheja, S.; Eilbracht, P.; Stará, I. G.;
´
Saman, D.; Stary, I. Eur. J. Org. Chem. 2011, 3849.