Pd-catalyzed asymmetric reactions using resorcinol- and hydroquinone-based P,P-bidentate diamidophosphites

Article abstract of DOI:10.1016/j.tetlet.2010.11.111

Readily available isomeric bisdiamidophosphites with P-stereocentres have been prepared using resorcinol and hydroquinone as simple and cheap starting materials. Palladium catalytic systems containing these P,P-bidentate ligands afforded 99% and 70% ees i

Full text of DOI:10.1016/j.tetlet.2010.11.111

Tetrahedron Letters 52 (2011) 964–968
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Pd-catalyzed asymmetric reactions using resorcinol- and hydroquinone-based
* *
P ,P -bidentate diamidophosphites
Konstantin N. Gavrilov a, , Sergey V. Zheglov a, Alexei A. Shiryaev a, Nikolay N. Groshkin a,
⇑
Eugenie A. Rastorguev b, Eduard B. Benetskiy 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
Article history:
Readily available isomeric bisdiamidophosphites with P*-stereocentres have been prepared using resor-
Received 9 August 2010
Revised 9 November 2010
Accepted 19 November 2010
Available online 24 November 2010
cinol and hydroquinone as simple and cheap starting materials. Palladium catalytic systems containing
*
*
these P ,P -bidentate ligands afforded 99% and 70% ees in asymmetric allylic substitution and desymmet-
rization processes, respectively. The influence of the precatalyst, substrate, nucleophile, and solvent on
the enantioselectivity is discussed.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric allylic substitution
Desymmetrization
Palladium
Phosphorus ligands
Diamidophosphites
*
*
The development of asymmetric transition metal catalyzed
reactions has played a significant role in allowing synthetic access
to optically pure compounds, especially to biologically important
molecules.1 The dramatic growth of enantioselective catalysis calls
for continuation of the search for new and improved chiral ligands.
A key factor in the design of new ligands is their stability and the
ease with which they can be accessed. To be economically viable,
ligands should be synthesized in one to three steps from readily
available starting materials.2 Phosphite-type compounds are
highly attractive ligands that meet all these requirements. Indeed,
the most important advantages of phosphite-type ligands include
only a few examples of efficient P ,P -bidentate phosphite-type
ligands with stereogenic phosphorus atoms in the literature.4h,7
*
*
We recently reported the synthesis of several P ,P -bidentate
diamidophosphites and demonstrated that they can serve as a
new class of very promising ligands for enantioselective catalysis.8
Encouraged by these observations, we have prepared P*,P*-biden-
tate diamidophosphite compounds 1 and 2 as ligands for applica-
tion in Pd-catalyzed asymmetric reactions. It should be noted
that ligands 1 and 2 have some important advantages; resorcinol
and hydroquinone were chosen as suitable building blocks for their
synthesis forming a rigid bridge between the two phosphite-type
moieties.
their pronounced
p-acidity, stability to oxidation, as well as their
synthetic availability and low cost.3,4 In contrast to monodentate
phosphites, libraries of chiral bidentate phosphite-type ligands
are scarce, despite the importance of bidentate phosphorus ligands
in asymmetric transition metal catalyzed reactions.1a,b,5 This is
attributed to the intrinsically more complicated synthesis of biden-
tate ligands compared to monodentate ligands, and is especially
true for bidentate ligands with chirogenic phosphorus donor
atoms. In their complexes, the asymmetric phosphorus atoms bind
directly to the metal atom. This factor eliminates potentially
inefficient secondary transfer of chirality from the ligand backbone
and, thus provides a more efficient chiral environment at the site
where the enantioselection originates.6 Nevertheless, there are
Enantioselective Pd-catalyzed allylic substitution has emerged
as a powerful synthetic tool, which is tolerant of various func-
tional 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 novel groups of stereoselectors. On
the other, Pd-catalyzed allylic substitution is a novel and highly
efficient strategy in the total synthesis of natural products.1c,6,9
For example, the Pd-catalyzed allylic alkylation of cyclohex-2-
enyl ethyl carbonate with dimethyl malonate provides easy
access to chiral cyclohexene derivatives, which may serve as
building blocks for the synthesis of (+)-juvabione and (ꢀ)-wine
lactone. The Pd-catalyzed desymmetrization of N,N0-ditosyl-
meso-cyclopent-4-ene-1,3-diol biscarbamate has been success-
fully used in key steps during the synthesis of mannostatin A
and (ꢀ)-swainsonine.1c,9b
⇑
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 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.111

K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 964–968
965
In contrast to phosphine ligands, whose syntheses can often re-
quire multiple steps,10 phosphite-type compounds can be assem-
bled in a much easier way by simple condensation processes, in
particular, by reacting phenols, alcohols or amines with phospho-
rus halides. Thus, bisphosphites can be readily prepared by reac-
tion between different phosphorochloridites and benzenediols.11
Using this strategy, ligands 1 and 2 were synthesized in reasonable
yields from (5S)-2-chloro-3-phenyl-1,3-diaza-2-phosphabicy-
clo[3.3.0]octane (Scheme 1). This phosphorylating reagent was ob-
tained from readily accessible (S)-(2-anilinomethyl)pyrrolidine as
the starting material according to the reported procedure.12 The
reactions were performed in the presence of Et3N as a HCl scaven-
ger in toluene. Both ligands were stable during purification on sil-
ica gel using standard eluents and could be prepared on gram scale.
They were stable on prolonged storage at room temperature. The
elemental analyses, 1H, 13C, and 31P NMR spectra and EI and/or
ESI mass spectra were in agreement with the assigned structures
of 1 and 2.
(S)
..
8/
N
(R)
N
P
X
X = exocyclic substituent
Figure 1. Stereochemistry of the phosphabicyclic part in ligands 1 and 2.
diamidophosphite 1 (Table 1, entries 4 and 5 and 1–3). It should
be noted that chiral allylic sulfones are exceptionally versatile
intermediates in organic synthesis.1c
The results obtained encouraged us to investigate further the
asymmetric allylic substitution of 3 with different nucleophiles.
In particular, when dimethyl malonate was employed as a C-nucle-
ophile, up to 96% ee was achieved (Table 1, entries 6–17). In con-
trast to allylic sulfonylation, ligand 1 was generally a more
efficient stereoselector. We also examined the effect of solvents,
L/Pd molar ratio, and precatalysts. When the reaction was per-
formed using 1 and CH2Cl2 as solvent, the alkylated product 4a
was furnished in high enantiomeric excess. At the same time, for
bisdiamidophosphite 2 the nature of the solvent did not have a sig-
nificant effect on the reaction rate or asymmetric induction. In all
cases, the enantioselectivity was poorly sensitive to the L/Pd molar
ratio. When the reaction was carried out using ligand 1 and
[Pd2(dba)3]ꢁCHCl3 as the precatalyst, the enantioselectivity in-
creased considerably to 96% (Table 1, entry 10). In the catalytic
performance of ligand 2 with participation of [Pd2(dba)3]ꢁCHCl3
the asymmetric induction was not changed, but the conversion
dropped dramatically (Table 1, entries 16 and 17).
Bisdiamidophosphites 1 and 2 were next evaluated in the Pd-
catalyzed allylic amination of (E)-1,3-diphenylallyl acetate (3) with
dipropylamine and pyrrolidine as N-nucleophiles (Table 2). As a
rule, both reactions were characterized by the quantitative conver-
sion of the starting substrate regardless of the L/Pd molar ratio and
nature of the solvent. At the same time, the asymmetric induction
was strongly dependent on the nature of the ligand, solvent,
and precatalyst. In all cases, the enantioselectivity was higher in
THF than in CH2Cl2. With [Pd2(dba)3]ꢁCHCl3 as the precatalyst,
During the phosphorylation, exclusive formation of stereospe-
cific bisdiamidophosphites 1 and 2 with (R) configuration at the
P*-stereocentres occurred. The 31P NMR spectra of their solutions
in CDCl3 exhibited narrow singlets at dP 124.1 and 122.3, respec-
tively. The 13C NMR spectra of these compounds were character-
2
ized by large spin–spin coupling constants JC(8),P (35.1 and
36.0 Hz), which are indicative of the cis orientation of the phospho-
rus lone pair with respect to the C(8) atom. Correspondingly, the
pseudoequatorially oriented exocyclic substituent at the phospho-
rus atom and the –(CH2)3– part of the pyrrolidine fragment of the
phosphabicyclic skeleton are in the trans arrangement (Fig. 1).12,13
With these bisdiamidophosphites in hand, initial studies were
carried out with 1 and 2 as stereoselectors for Pd-catalyzed allylic
sulfonylation of racemic (E)-1,3-diphenylallyl acetate (3) with p-
TolSO2Na as an S-nucleophile in THF. Compound 3 was chosen as
the substrate because allylic substitution itself has been performed
with a wide range of ligands, allowing the efficiency of the various
ligand systems to be compared directly.1b,d,9c The sulfonylation
proceeded smoothly to afford sulfone 4a in good yields and excel-
lent enantioselectivity (up to 99% for the R-enantiomer, Table 1).
When the reaction was carried out using 2 as the ligand, the
enantioselectivity was higher than in the case of bis-
3
2
N
7
Cl
2
4
P
N
5
1
8
6
+
+
HO
OH
HO
OH
2.2 Et3N, PhCH3
- 2 Et3N.HCl
N
N
O
P
O
P
P
N
N
O
O
N
P
N
N
N
1
2
*
*
Scheme 1. Synthesis of P ,P -bidentate bisdiamidophosphites.

966
K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 964–968
Table 1
Table 2
Pd-catalyzed allylic sulfonylation and alkylation of (E)-1,3-diphenylallyl acetate (3)a
Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate (3)a
OAc
Ph
Nu
*
Nu
*
OAc
NuH, cat
Ph
NuX, cat
Solvent
Ph
Ph
Ph
Ph
Ph
Ph
Solvent
3
3
4c,d
4a,b
Nu = N(Pr)2, 4c
Nu = N(CH2)4, 4d
Nu = SO2pTol, X = Na, 4a
Nu = CH(CO2Me)2 X = H, 4b
Entry Ligand Precatalyst
L/Pd Solvent Conversion (%) ee (%)
Entry Ligand Precatalyst
L/Pd Solvent Conversion (%) ee (%)
Allylic amination with dipropylamineb
Allylic sulfonylation with sodium p-toluenesulfinatec
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
2
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2
CH2Cl2
THF
98
98
100
100
50 (+)
60 (+)
86 (+)
83 (+)
26 (+)
60 (+)
29 (+)
14 (+)
66 (+)
32 (+)
1
2
3
4
5
1
1
1
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
THF
THF
THF
THF
THF
93b
92b
40b
88b
92b
72 (R)
80 (R)
72 (R)
98 (R)
99 (R)
[Pd2(dba)3]ꢁCHCl3 1.5
THF
[Pd(allyl)Cl]2
1
[Pd2(dba)3]ꢁCHCl3 1.5
CH2Cl2 100
THF 55
CH2Cl2 100
CH2Cl2 100
THF
THF
[Pd(allyl)Cl]2
2
[Pd2(dba)3]ꢁCHCl3 1.5
Allylic alkylation with dimethyl malonate (BSA, KOAc)d
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
6
7
8
1
1
1
1
1
1
2
2
2
2
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2 100
CH2Cl2
THF
84 (S)
82 (S)
70 (S)
67 (S)
96 (S)
65 (S)
79 (S)
83 (S)
83 (S)
89 (S)
90 (S)
82 (S)
100
100
85
80
10
Allylic amination with pyrrolidinec
9
THF
100
10
11
12
13
14
15
16
17
[Pd2(dba)3]ꢁCHCl3 1.5
CH2Cl2 100
THF 98
CH2Cl2 100
CH2Cl2 100
11
12
13
14
15
16
17
18
19
1
1
1
1
1
2
2
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2 100
CH2Cl2 100
THF
THF
40 (R)
63 (R)
53 (R)
78 (R)
51 (R)
76 (R)
75 (R)
78 (R)
80 (R)
[Pd2(dba)3]ꢁCHCl3 1.5
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
83
100
THF
THF
CH2Cl2
THF
100
100
32
[Pd2(dba)3]ꢁCHCl3 1.5
CH2Cl2 100
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2
CH2Cl2
THF
99
99
98
[Pd2(dba)3]ꢁCHCl3 1.5
[Pd2(dba)3]ꢁCHCl3 1.5
37
THF
100
Bold indicates best results.
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 or [Pd2(dba)3]ꢁCHCl3
Bold indicates best results.
a
at room temperature for 48 h.
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 or [Pd2(dba)3]ꢁCHCl3
b
Isolated yield of 4a.
at room temperature for 48 h.
c
b
Enantiomeric excess of 4a was determined by HPLC (Daicel Chiralcel OJ, C6H14
i-PrOH = 4:1, 0.5 ml/min, 254 nm).
The conversion of substrate 3 and enantiomeric excess of 4b were determined
by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH = 99:1, 0.6 ml/min, 254 nm).
/
The conversion of substrate 3 and enantiomeric excess of 4c were determined
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).
d
c
The conversion of substrate 3 and enantiomeric excess of 4d were determined
by HPLC (Daicel Chiralcel OD-H, OD-H, C6H14/i-PrOH/HN(Et)2 = 200:1:0.1, 0.9 mL/
min, 254 nm).
enantioselectivities were lower (Table 2, entries 5, 6, and 15). In
the process involving the participation of dipropylamine, ligand 1
afforded product 4c with good enantiomeric purity (up to 86%
ee), but the analogous catalyst based on ligand 2 provided no more
than 66% ee (Table 2, entries 1–10). When pyrrolidine was used as
the nucleophile, both 1 and 2 delivered almost equal enantioselec-
tivity (78% and 80%, respectively, Table 2, entries 14 and 19).
Unlike allylic alkylation and amination, successful examples of
Pd-catalyzed asymmetric allylic etherification with aliphatic alco-
hols are very scarce, and this process remains a challenge for syn-
thetic chemists.14 We investigated the asymmetric allylic
etherification between benzyl alcohol and 3 in the presence of
Cs2CO3 as a base, as shown in Table 3. As a whole, the new catalytic
systems led to the expected product 4e with good to excellent con-
version and good enantioselectivity (up to 80%, Table 3, entry 4).
We found that there was no obvious trend in the influence of
the nature of the solvent and the L/Pd molar ratio on the
asymmetric induction, but conversion was higher in CH2Cl2. Bis-
diamidophosphite 1 provided higher asymmetric induction than
isomeric ligand 2 (up to 80% and 67% ee, respectively). To the best
of our knowledge, this is the first example of the use of phosphite-
type ligands in Pd-catalyzed asymmetric allylic etherification.
We also screened ligands 1 and 2 in the Pd-catalyzed allylic
alkylation of a cyclic substrate, namely cyclohex-2-enyl ethyl car-
bonate (5), with dimethyl malonate (Table 4). The enantioselectiv-
ity for a cyclic substrate 5 is usually more difficult to control than
for hindered acyclic substrate 3.15 The best result (up to 90%
conversion and 92% ee) was obtained with bisdiamidophosphite
1 (Table 4, entry 2). It is clear that CH2Cl2 is the solvent of choice
(Table 4, entries 2 and 4). Interestingly, in CH2Cl2, an increase of
Table 3
Pd-catalyzed allylic etherification of (E)-1,3-diphenylallyl acetate (3) with benzyl
a,b
alcohol
OAc
Ph
OCH2Ph
PhCH2OH, cat
Solvent
*
Ph
Ph
Ph
4e
3
Entry Ligand Precatalyst
L/Pd Solvent Conversion (%) ee (%)c
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
2
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2 100
CH2Cl2 100
THF
75 (II)
65 (II)
58 (II)
80 (II)
65 (II)
68 (II)
67 (II)
55 (II)
60 (II)
60 (II)
39
84
THF
[Pd2(dba)3]ꢁCHCl3 1.5
CH2Cl2 100
THF
[Pd2(dba)3]ꢁCHCl3 1.5
88
98
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2
CH2Cl2 100
THF
THF
76
100
10
Bold indicates best results.
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 or [Pd2(dba)3]ꢁCHCl3
at room temperature for 48 h (Cs2CO3).
b
The conversion of substrate 3 and enantiomeric excess of 4e were determined
by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH = 200:1, 0.8 mL/min, 254 nm,
t(I) = 8 min, t(II) = 10 min).
c
The absolute configuration of the product 4e was not assigned.
the L/Pd molar ratio led to a dramatic increase in conversion and
enantioselectivity (Table 4, entries 1 and 2). Isomeric ligand 2 gave
much lower enantioselectivities (28–37%, Table 4, entries 6–9).

K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 964–968
967
Table 4
ation of (E)-1,3-diphenylallyl acetate (3), [Pd2(dba)3]ꢁCHCl3 was the
preferred precatalyst (Table 5, entries 1–4 and 5–11). With
[Pd2(dba)3]ꢁCHCl3 as the catalytic precursor, the best ee values
were observed in THF, and an increase of the L/Pd molar ratio led
to a gradual increase of the asymmetric induction (Table 5, entries
8–10). The enantioselectivity could be further improved by con-
trolling the reaction temperature. Thus, when the reaction was car-
ried out at 0 °C instead of 35 °C, the enantioselectivity increased
from 47% to 70% (Table 5, entries 10 and 11).
Pd-catalyzed allylic alkylation of cyclohex-2-enyl ethyl carbonate (5) with dimethyl
malonatea,b
O
MeO2C
CO2Me
O
O
CH2(CO2Me)2
Solvent
, cat
*
In conclusion, P*,P*-bidentate diamidophosphites 1 and 2 have
been successfully developed for the Pd-catalyzed enantioselective
reactions of several different substrates. These ligands can be pre-
pared efficiently from a readily available phosphorylating reagent
and resorcinol or hydroquinone as convenient building blocks.
Excellent performance of the catalyst systems was observed with
various nucleophiles in the Pd-catalyzed asymmetric allylation of
(E)-1,3-diphenylallyl acetate (up to 99% ee). Moreover, good enanti-
oselectivity (up to 92% ee) was also obtained in the allylic alkylation
of a more difficult cyclic substrate. In addition, the first example of
successful Pd-catalyzed asymmetric allylic etherification (up to 80%
ee) with participation of phosphite-type ligands was found. Note
that ligand 1 is a pincer-type bisdiamidophosphite ligand, and it
is a very efficient stereoselector among other chiral pincer phos-
phites.16 Further studies to explore the scope of ligands 1 and 2 in
other asymmetric catalytic reactions are currently in progress.
General procedure for the preparation of ligands 1 and 2: To a
5
6
Entry Ligand Precatalyst
L/Pd Solvent Conversion (%) ee (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
2
2
2
2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
CH2Cl2 57
CH2Cl2 90
27 (R)
92 (R)
43 (R)
60 (R)
40 (R)
31 (R)
28 (R)
37 (R)
33 (R)
THF
THF
88
78
[Pd2(dba)3]ꢁCHCl3 1.5
CH2Cl2 34
CH2Cl2 47
CH2Cl2 70
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
1
2
1
2
THF
THF
68
64
Bold indicates best results.
a
All reactions were carried out with 2 mol % of [Pd(allyl)Cl]2 or [Pd2(dba)3]ꢁCHCl3
at room temperature for 48 h (BSA, KOAc).
b
The conversion of the substrate 5 and enantiomeric excess of 6 were deter-
mined by HPLC (Chiralpak AD, C6H14/i-PrOH = 200:1, 1 mL/min, 219 nm,
t(R) = 11.3 min, t(S) = 12.1 min).
solution
of
(5S)-2-chloro-3-phenyl-1,3-diaza-2-phosphabicy-
Table 5
clo[3.3.0]octane (2.41 g, 10 mmol) and Et3N (1.53 ml, 11 mmol)
in toluene (30 ml), a solution of resorcinol or hydroquinone
(0.55 g, 5 mmol) in toluene (15 ml) was added dropwise over a
period of 20 min with vigorous stirring. The resulting mixture
was refluxed for 10 min and cooled to room temperature, then
precipitated Et3NꢁHCl was removed by filtration. The filtrate
was concentrated in vacuo (40 Torr). Products 1 and 2 were
purified by column chromatography on silica gel (EtOAc/hexane,
1:5 and 1:6, respectively) and dried under vacuum (1 Torr) for
2 h.
Pd-catalyzed desymmetrization of N,N0-ditosyl-meso-cyclopent-4-ene-1,3-diol bisc-
arbamate (8)a
Ts
Ts
HN
NH
O
O
HO
OH
+ TsNCO
Solvent
O
O
7
8
1,3-Bis[(2R,5S)-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octyl-
oxy]benzene (1): White powder; yield 1.81 g (70%); mp 112–
114 °C; Rf 0.55 (EtOAc/hexane, 1:5). 1H NMR (CDCl3, 25 °C):
d = 1.58 (dq, 2H, J = 11.4 Hz, J = 6.8 Hz); 1.85 (m, 4H); 1.95 (m,
2H); 3.15 (m, 2H); 3.25 (m, 2H); 3.46 (dd, 2H, J = 8.7 Hz,
J = 6.5 Hz); 3.64 (m, 2H); 3.74 (q, 2H, J = 6.5 Hz); 6.63 (m, 3H);
6.93 (br t, 2H, J = 9.8 Hz); 7.08 (m, 4H); 7.31 (m, 5H). 13C{H} NMR
(CDCl3, 25 °C): dC = 26.2 (d, C(7), 3J = 4.4 Hz); 31.6 (s, C(6)); 47.7
(d, C(8), 2J = 35.1 Hz); 53.7 (d, C(4), 2J = 7.7 Hz); 62.5 (d, C(5),
Ts
N
Ts
N
H
H
H
H
cat
+
O
O
Solvent, Et3N
- CO2, - TsNH2
O
O
(S,R)-9
(R,S)-9
Entry
Precatalyst
L/Pd
Solvent
Yield (%)
ee (%)b,c
2J = 8.8 Hz); 115.0 (d, CHPh
3J = 4.9 Hz); 116.5 (d, CHAr 3J = 4.4 Hz); 119.0 (s, CHPh); 128.8 (s,
CHPh); 129.0 (s, CHAr); 145.1 (d, CPh
2J = 15.4 Hz); 154.2 (d, CAr
,
3J = 12.6 Hz); 115.5 (d, CHAr
,
1
2
3
4
5
6
7
8
9
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd(allyl)Cl]2
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
[Pd2(dba)3]ꢁCHCl3
1
2
1
2
1
1.5
2
1
1.5
2
CH2Cl2
CH2Cl2
THF
68
55
59
73
59
64
86
92
59
78
62
34 (II)
30 (II)
21 (II)
22 (II)
40 (II)
30 (II)
39 (II)
25 (II)
43 (II)
47 (II)
70 (II)
,
,
,
THF
2J = 3.8 Hz). MS (EI, 70 eV): m/z (%) = 519 (9) [M]+, 205 (100)
[C10H15N2P]+. MS (ESI): m/z (%) = 519 (100) [M]+, 205 (37)
[C10H15N2P]+. Calcd for C28H32N4O2P2: C, 64.86; H, 6.22; N, 10.80.
Found: C, 65.01; H, 6.28; N, 10.68.
CH2Cl2
CH2Cl2
CH2Cl2
THF
THF
THF
1,4-Bis[(2R,5S)-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octyl-
oxy]benzene (2): White foamy solid; yield 1.97 g (76%); mp 90–
92 °C; Rf 0.35 (EtOAc/hexane, 1:6). 1H NMR (CDCl3, 25 °C):
d = 1.52 (m, 2H); 1.84 (m, 6H); 3.07 (m, 2H); 3.27 (m, 4H); 3.52
(m, 2H); 3.62 (m, 2H); 6.68 (br s, 4H); 6.88 (br t, 2H, J = 6.2 Hz);
7.04 (m, 4H); 7.27 (m, 4H). 13C{H} NMR (CDCl3, 25 °C): dC = 26.2
(d, C(7), 3J = 4.1 Hz); 31.7 (s, C(6)); 47.7 (d, C(8), 2J = 36.0 Hz);
10
11d
2
THF
Bold indicates best results.
a
All reactions were carried out with ligand 1 and 5 mol % of [Pd(allyl)Cl]2 or
[Pd2(dba)3]ꢁCHCl3 at 35 °C for 24 h.
b
The enantiomeric excess of 9 was determined by HPLC (Kromasil 5-CelluCoat,
C6H14/i-PrOH = 9:1, 2 mL/min, 219 nm, t(I) = 15 min, t(II) = 18 min).
53.8 (d, C(4), 2J = 8.0 Hz); 62.6 (d, C(5), 2J = 9.1 Hz); 114.9 (d, CHPh
3J = 13.0 Hz); 119.0 (s, CHPh); 122.3 (d, CHAr 3J = 4.0 Hz); 129.0 (s,
2J = 5.9 Hz). MS
,
c
The absolute configuration of the product 9 was not assigned.
d
,
Reaction carried out at 0 °C.
CHPh); 145.1 (d, CPh, ,
2J = 15.9 Hz); 148.9 (d, CAr
(EI, 70 eV): m/z (%) = 519 (4) [M]+, 205 (100) [C10H15N2P]+. Calcd
for C28H32N4O2P2: C, 64.86; H, 6.22; N, 10.80. Found: C, 65.06; H,
6.34; N, 11.02.
P*,P*-Bidentate diamidophosphite 1 also took part in desym-
metrization reactions (Table 5). As in the Pd-catalyzed allylic alkyl-

968
K. N. Gavrilov et al. / Tetrahedron Letters 52 (2011) 964–968
8. (a) Gavrilov, K. N.; Zheglov, S. V.; Vologzhanin, P. A.; Maksimova, M. G.;
Acknowledgments
Safronov, A. S.; Lyubimov, S. E.; Davankov, V. A.; Schäffner, B.; Börner, A.
Tetrahedron Lett. 2008, 49, 3120; (b) Gavrilov, K. N.; Zheglov, S. V.; Vologzhanin,
P. A.; Rastorguev, E. A.; Shiryaev, A. A.; Maksimova, M. G.; Lyubimov, S. E.;
Benetsky, E. B.; Safronov, A. S.; Petrovskii, P. V.; Davankov, V. A.; Schäffner, B.;
Börner, A. Russ. Chem. Bull., Int. Ed. 2008, 57, 2311; (c) Gavrilov, K. N.; Zheglov, S.
V.; Benetsky, E. B.; Safronov, A. S.; Rastorguev, E. A.; Groshkin, N. N.; Davankov,
V. A.; Schäffner, B.; Börner, A. Tetrahedron: Asymmetry 2009, 20, 2490; (d)
Gavrilov, K. N.; Rastorguev, E. A.; Shiryaev, A. A.; Grishina, T. B.; Safronov, A. S.;
Lyubimov, S. E.; Davankov, V. A. Russ. Chem. Bull., Int. Ed. 2009, 58, 1325.
9. (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809; (b) Graening, T.;
Schmalz, H.-G. Angew. Chem., Int. Ed. 2003, 42, 2580; (c) Lu, Z.; Ma, S. Angew.
Chem., Int. Ed. 2008, 47, 258.
We acknowledge the financial support from the Russian Foun-
dation for Basic Research (Grant No. 08-03-00416-a) and a grant
from the President of the Russian Federation for Young Candidates
of Sciences (No. MK-3889.2010.3).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.11.111.
10. Cobley, C. J.; Gardner, K.; Klosin, J.; Praquin, C.; Hill, C.; Whiteker, G. T.; Zanotti-
Gerosa, A. J. Org. Chem. 2004, 69, 4031.
11. (a) Baber, R. A.; Bedford, R. B.; Betham, M.; Blake, M. E.; Coles, S. J.; Haddow, M.
F.; Hursthouse, M. B.; Orpen, A. G.; Pilarski, L. T.; Pringle, P. G.; Wingad, R. L.
Chem. Commun. 2006, 3880; (b) Rubio, M.; Suarez, A.; del Rio, D.; Galindo, A.;
Alvarez, E.; Pizzano, A. Dalton Trans. 2007, 407.
12. 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.
References and notes
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.
13. (a) Arzoumanian, H.; Buono, G.; Choukrad, M.; Petrignani, J.-F. Organometallics
1988, 7, 59; (b) Brunel, J. M.; Constantieux, T.; Buono, G. J. Org. Chem. 1999, 64,
8940; (c) Ngono, C. J.; Constantieux, T.; Buono, G. Eur. J. Org. Chem. 2006, 1499;
(d) Gavrilov, K. N.; Benetsky, E. B.; Grishina, T. B.; Zheglov, S. V.; Rastorguev, E.
A.; Petrovskii, P. V.; Macaev, F. Z.; Davankov, V. A. Tetrahedron: Asymmetry
2007, 18, 2557; (e) Kimura, M.; Uozumi, Y. J. Org. Chem. 2007, 72, 707; (f) Barta,
K.; Holscher, M.; Francio, G.; Leitner, W. Eur. J. Org. Chem. 2009, 4102.
14. (a) Lam, F. L.; Au-Yeung, T. T.-L.; Kwong, F. Y.; Zhou, Z.; Wong, K. Y.; Chan, A. S.
C. Angew. Chem., Int. Ed. 2008, 47, 1280; (b) Kato, M.; Nakamura, T.; Ogata, K.;
Fukuzawa, S. Eur. J. Org. Chem. 2009, 5232; (c) Caldentey, X.; Pericas, M. A. J.
Org. Chem. 2010, 75, 2628; (d) Liu, Z.; Du, H. Org. Lett. 2010, 12, 3054.
15. (a) Mata, Y.; Dieguez, M.; Pamies, O.; Claver, C. Adv. Synth. Catal. 2005, 347,
1943; (b) Mazuela, J.; Paptchikhine, A.; Tolstoy, P.; Pamies, O.; Dieguez, M.;
Andersson, P. G. Chem. Eur. J. 2010, 16, 620.
16. (a) Ini, S.; Oliver, A. G.; Tilley, T. D.; Bergman, R. G. Organometallics 2001, 20,
3839; (b) Wallner, O. A.; Olsson, V. J.; Eriksson, L.; Szabo, K. J. Inorg. Chim. Acta
2006, 359, 1767; (c) Aydin, J.; Kumar, K. S.; Sayah, M. J.; Wallner, O. A.; Szabo, K.
J. J. Org. Chem. 2007, 72, 4689; (d) Aydin, J.; Ryden, A.; Szabo, K. J. Tetrahedron:
Asymmetry 2008, 19, 1867; (e) Li, J.; Lutz, M.; Spek, A. L.; van Klink, G. P. M.; van
Koten, G.; Gebbink, R. J. M. K. Organometallics 2010, 29, 1379; (f) Niu, J.-L.;
Chen, Q.-T.; Hao, X.-Q.; Zhao, Q.-X.; Gong, J.-F.; Song, M.-P. Organometallics
2010, 29, 2148.
2. Noel, T.; Bert, K.; Van der Eycken, E.; Van der Eycken, J. Eur. J. Org. Chem. 2010,
4056.
3. Claver, C.; Pamies, O.; Dieguez, M. In Phosphorus Ligands in Asymmetric
Catalysis; Börner, A., Ed.; 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) Teichert, J. F.; Feringa, B. L. Angew. Chem., Int.
Ed. 2010, 49, 2486.
5. Goudriaan, P. E.; van Leeuwen, P. W. N. M.; Birkholz, M.-N.; Reek, J. N. H. Eur. J.
Inorg. Chem. 2008, 2939.
6. Crepy, K. V. L.; Imamoto, T. Adv. Synth. Catal. 2003, 345, 79.
7. (a) Pastor, S. D.; Rodebaugh, R. K.; Odorisio, P. A.; Pugin, B.; Rihs, G.; Togni, A.
Helv. Chim. Acta 1991, 74, 1175; (b) Dros, A. C.; Meetsma, A.; Kellogg, R. M.
Tetrahedron 1999, 55, 3071.