Nonsimple relationships between the P*-chiral diamidophosphite and the arylphosphine moieties in Pd-catalyzed asymmetric reactions: Combinatorial approach and P,P*-bidentate phosphine-diamidophosphites

Article abstract of DOI:10.1016/j.tet.2013.12.006

A small family of P,P^*-bidentate C₁-symmetric ligands containing 1,3,2-diazaphospholidine rings with stereogenic phosphorus atoms has been prepared. Palladium catalytic systems with these phosphine-diamidophosphites afforded 95% and

Full text of DOI:10.1016/j.tet.2013.12.006

Accepted Manuscript
Nonsimple relationships between the P*-chiral diamidophosphite and the
arylphosphine moieties in Pd-catalyzed asymmetric reactions: combinatorial approach
and P,P*-bidentate phosphine-diamidophosphites
Konstantin N. Gavrilov, Alexei A. Shiryaev, Sergey V. Zheglov, Vladislav K. Gavrilov,
Nikolay N. Groshkin, Marina G. Maksimova, Alexandr N. Volov, Ilya A. Zamilatskov
PII:
S0040-4020(13)01846-2
10.1016/j.tet.2013.12.006
TET 25090
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 June 2013
Revised Date: 21 November 2013
Accepted Date: 2 December 2013
Please cite this article as: Gavrilov KN, Shiryaev AA, Zheglov SV, Gavrilov VK, Groshkin NN,
Maksimova MG, Volov AN, Zamilatskov IA, Nonsimple relationships between the P*-chiral
diamidophosphite and the arylphosphine moieties in Pd-catalyzed asymmetric reactions: combinatorial
approach and P,P*-bidentate phosphine-diamidophosphites, Tetrahedron (2014), doi: 10.1016/
j.tet.2013.12.006.
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ACCEPTED MANUSCRIPT
Graphical abstract.
Nonsimple relationships between the P*-chiral
diamidophosphite and the arylphosphine moieties in Pd-
catalyzed asymmetric reactions: combinatorial approach and
P,P*-bidentate phosphine-diamidophosphites
Konstantin N. Gavrilov, Alexei A. Shiryaev, Sergey V. Zheglov, Vladislav K. Gavrilov,
Nikolay N. Groshkin, Marina G. Maksimova, Alexandr N. Volov, Ilya A. Zamilatskov
Nu
* Ph
Ph
up to 95% ee
O
O
Ts
N
O
N
*
N
OR =
O
P
O
O
O
Ph P
2
O
Ph2P
O
*
OR
Ph2P
Ph2P
up to 63% ee
1

ACCEPTED MANUSCRIPT
Nonsimple relationships between the P*-chiral diamidophosphite and the
arylphosphine moieties in Pd-catalyzed asymmetric reactions: combinatorial
approach and P,P*-bidentate phosphine-diamidophosphites
a1
a
a
a
Konstantin N. Gavrilov, Alexei A. Shiryaev, Sergey V. Zheglov, Vladislav K. Gavrilov,
a
a
b
b
Nikolay N. Groshkin, Marina G. Maksimova, Alexandr N. Volov, Ilya A. Zamilatskov
a
Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan,
Russian Federation
b
A. N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of
Sciences, Leninskiy prospekt 31, 119071 Moscow, Russian Federation.
1
Abstract: A small family of P,P*-bidentate C -symmetric ligands containing 1,3,2-
diazaphospholidine rings with stereogenic phosphorus atoms has been prepared. Palladium
catalytic systems with these phosphine-diamidophosphites afforded 95% and 63% ees in
asymmetric allylic substitution and desymmetrization processes, respectively. The influence of the
nature of both the phosphine and diamidophosphite moieties of these compounds on the
enantioselectivity is discussed. The ”mixed-ligand approach” in Pd-catalyzed asymmetric
3
allylation with participation of some new P*-monodentate diamidophosphites and PPh is also
considered.
Keywords: Asymmetric allylic substitution; Desymmetrization; Palladium; Phosphine-
diamidophosphites.
1
. Introduction
Preparation of enantiopure or enantioenriched organic and organoelement compounds is a
trend in synthetic chemistry. This is due to the practical importance of such substances as main
components of pharmaceuticals, agrochemicals, food additives and perfumery compositions.
Asymmetric synthesis involving the use of chiral catalysts is the main stream in the preparation
of enantioenriched compounds. Such an approach was successfully effected, in particular, in
1-5
enantioselective metal complex catalysis. Activity and stereoselectivity of metal complex
catalysts were significantly determined by a proper strategy of design and synthesis of the
1
Corresponding author. Tel.: +7-4912-280580; fax +7-4912-281435; e-mail: k.gavrilov@rsu.edu.ru
2

ACCEPTED MANUSCRIPT
corresponding chiral ligands, first of all, phosphorus-containing ones, thousands of
1
-10
representatives of which were used in various asymmetric reactions.
Beyond doubt, C -symmetric bis-phosphines are extremely powerful and versatile
ligands for metal-mediated asymmetric transformations.
of facts have demonstrated that, regarding enantioselectivities, C
2
2
,4,11,12
However, a sufficient number
-symmetric ligands are not
2
necessarily intrinsically better than their analogs lacking any symmetry element. In certain
cases, ligands with two different coordinating groups should allow for a better
1
3,14
stereocontrol.
application of C
This has led to growing interest in the design, preparation and catalytic
1
-symmetric P,P-bidentate ligands. In particular, phosphorus compounds with
phosphine and phosphite-type moieties are examples of nonsymmetric ligands that differ in the
electronics and the sterics of their respective binding groups. Many of them are easier to prepare
than bis-phosphines and they can induce high enantioselectivity and have desirable stability
characteristics. These ligands have afforded excellent results in various asymmetric
14,15
transformations, first of all in hydrogenation, hydroformylation and conjugate addition.
Phosphine-phosphites and phosphine-phosphoramidites (where the phosphite-type
moieties have three P–O bonds and two P–O bonds plus one P–N bond, respectively) are well-
14,15
known groups of such unsymmetrical ligands.
To the best of our knowledge, there are no
examples of phosphine-diamidophosphites (phosphite-type species with one P–O bond and two
P–N bonds). It is rather important that diamidophosphites have different properties from
phosphites or phosphoramidites. For example, nitrogen substituents create more steric bulk
around the phosphorus than oxygen, since nitrogen substitution may be greater. Furthermore, the
replacement of the oxygen atom in the first coordination sphere of the phosphorus by a nitrogen
16,17
atom increases the electron density on the phosphorus center.
Inclusion of the phosphorus
atom into a cyclic structure, in particular a five-membered 1,3,2-diazaphospholidine ring, is a
key feature, since it increases its stability toward air and moisture. Also, these compounds
display balanced electronic characteristics since they are both good π-acceptors (due to the
*
accessibility of low-lying π PN orbitals) as well as good σ-donors. The possibility of varying the
nature of the substituents at the nitrogen and phosphorus atoms allows control over the steric and
electronic parameters. Thus, interest in diamidophosphites with 1,3,2-diazaphospholidine rings
for asymmetric catalysis lies not only in their robustness but also in the tunability of their
1
6-24
donor- acceptors properties, as well as their geometry.
Moreover, their modular nature allows a facile systematic variation of the configuration
of the C*- and, if the donor phosphorus atom is asymmetric, of the P*-stereocentres. It is very
important that in complexes with P*-chirogenic ligands the asymmetric phosphorus atom binds
directly to the metal atom. This factor eliminates potentially inefficient secondary transfer of
3

ACCEPTED MANUSCRIPT
chirality from the ligand backbone and, thus, provides a more efficient chiral environment at the
12,25,26
site where the enantioselection originates.
Note that phosphine-phosphites and phosphine-
phosphoramidites with phosphine P*-atoms were used successfully in Pd-catalyzed allylation,
Rh-catalyzed hydroformylation, Rh- and Ir-catalyzed hydrogenation and some other
1
4,15,27-34
enantioselective reactions.
1
At the same time, C -symmetric P,P-bidentate ligands
bearing P*-chirogenic phosphorus atoms in the phosphite-type moieties, are unknown.
In this paper, we report on the preparation of a small series of novel P,P*-bidentate
phosphine-diamidophosphites containing 1,3,2-diazaphospholidine rings, which we subsequently
explored in Pd-catalyzed asymmetric allylation and desymmetrization reactions. The
enantioselective Pd-catalyzed allylic substitution has emerged as a powerful synthetic tool,
which is tolerant of various functional groups in the substrate and which operates with a wide
range of nucleophiles. As a result, Pd-catalyzed allylic substitution is a versatile and highly
3,6,14,35-41
efficient strategy in the total synthesis of enantiopure natural and unnatural products.
This is a common benchmark test for initial ligand screening. From a functional point of view,
the enantiomeric excesses obtained are the simplest indexes for evaluating new chiral
1
4,40,42
ligands.
It should be added that Pd-catalyzed desymmetrization of N,N'-ditosyl-meso-
cyclopent-4-ene-1,3-diol biscarbamate has been successfully used as a key step in the synthesis
3,36
of mannostatin A and (-)-swainsonine.
We also report the application of some new P*-monodentate diamidophosphites and PPh
3
in Pd-catalyzed enantioselective processes using the so-called ”mixed-ligand approach”. This
strategy has been exploited with success in Rh-catalyzed asymmetric reactions: it has been
shown that the combination of two different P-monodentate ligands, in particular one chiral and
the other achiral, may in certain situations afford a more stereoselective and/or more active
43,44
45,46
catalyst.
Such an approach is less common for palladium catalysis.
2
. Results and discussion
The novel P*-mono- and P,P*-bidentate diamidophosphite ligands 3a-g were prepared
via condensation reactions between the phosphorylating reagent 1 and naphthalen-2-ol 2a,
alcohols 2b,c or hydroxy-phosphines 2d-g in THF or toluene in the presence of an excess of
3
Et N as an HCl scavenger and DMAP as a catalyst. Scheme 1 shows the synthesis of these
4

ACCEPTED MANUSCRIPT
Scheme 1. Synthesis of P*-mono- and P,P*-bidentate diamidophosphites 3a-g.
compounds. The use of DMAP is advantageous, as it decreases the reaction time and also
47
reduces the amount of byproducts. However, in order to guarantee the elimination of possible
impurities, the resulting mixtures were purified by chromatography through basic aluminum
oxide. New stereoselectors were obtained as colorless oils for 3a,b and 3d,e and as white solids
for 3c and 3f,g in good yields (74 - 86%). They can be stored under dry conditions at room
temperature for at least a few months with minimal degradation. Ligands 3e-g readily form
solvates with toluene. Therefore, long time of high vacuum drying is required for the preparation
of analytically pure material. Note that we turned our attention to design and synthesis of ligands
3
b,c with long-chain exocyclic substituents in view of the high efficiency of a similar P*-chiral
48
diamidophosphite stereoselector bearing a fluorous ponytail. We also synthesized ligand 5
Scheme 2) as a phosphine-diamidophosphate analog of 3f with a P=O structural fragment.
(
Scheme 2. Synthesis of phosphine-diamidophosphate 5.
1
13
31
Compounds 3a-g and 5 have been fully characterized by H, C, and P NMR
spectroscopy, MALDI TOF/TOF or EI mass spectrometry as well as by elemental analysis, and
the data collected are in accord with the structures proposed for them. In particular, all NMR
5

ACCEPTED MANUSCRIPT
spectra suggest that the new P,P*-bidentate phosphine-diamidophosphites show C -symmetry.
1
3
1
31
P NMR data are summarized in Table 1. In the P NMR spectra 3d-g two different phosphine
31
Table 1. Р NMR spectroscopic data for ligands 3a-g, 5 and complexes 6d-f in CDCl
3
Compound
δР
JP,P*, Hz
a
3
a (96%)
4%)
124.5 (s)
(
120.5 (s)
3
b
122.5 (s)
3
c
122.6 (s)
a
3
d (85%)
125.9 (d), - 17.8 (d)
117.6 (s), - 16.2 (s)
120.0 (s), - 15.7 (s)
127.2 (s), - 12.9 (s)
119.0 (s), - 14.4 (s)
130.6 (d), - 13.6 (d)
117.2 (d), - 15.4 (d)
17.7 (s), - 13.5 (s)
137.7 (br. d), 11.4 (br. d)
137.3 (br. d), 11.1 (br. d.)
127.8 (d), 12.8 (d)
127.6 (d), 15.3 (d)
132.7 (d), 22.5 (d)
131.9 (d), 24.0 (d)
123.5 (d), 21.9 (d)
122.1 (d), 20.8 (d)
8.5
–
(15%)
3
e
–
a
3
f (84%)
16%)
–
(
–
a
3
g (86%)
5.1
13.6
–
(14%)
5
b
b
6
d (48%)
79.4
81.8
65.5
68.1
63.2
63.7
64.3
64.2
(52%)
6
e (42%)
(58%)
a
b
b
6
f (85%) (60%)
(
a
25%)
b
(
15%) (11%)
b
(
4%)
a
Percentage of Р*-epimers.
Percentage of exo- and endo-isomers.
b
and diamidophosphite moieties displayed two distinct singlets in a narrow range around δ - 12.9
Р
–
- 17.8 and 117.2 – 130.6 ppm, respectively. Compounds 3a, 3d and 3f,g are mixtures of
epimers with respect to the phosphorus stereocentre, and contain 84-96% of the major Р*-
epimers, while ligands 3b,c and 3e are formed as single stereoisomers (Table 1). Ligands 3b,c
and 3e and the major epimers of ligands 3a, 3d and 3f,g have the P*-stereocentres with the (R)-
13
configuration. Indeed, the C NMR spectra of these compounds are characterized by large spin-
6

ACCEPTED MANUSCRIPT
2
spin coupling constants J
(32.4 – 38.4 Hz, see Experimental section). These values suggest
C(8),P
an anti-orientation of the pseudoequatorial exocyclic substituent at the phosphorus atom and the
(CH - part of the pyrrolidine fragment of the phosphabicyclic skeleton and, consequently, the
-
2 3
)
syn-orientation of the phosphorus lone pair with respect to the C(8) atom. On the contrary, the
minor epimers of 3a, 3d and 3f,g contain asymmetric phosphorus atoms with the (S)-
13
configuration, as evidenced by the fact that their C NMR spectra have small coupling constants
2
18,20,22,48-50
J
C(8),P (3.2 – 4.5 Hz, see Experimental section).
It is worth noting that for both epimers
of 3g it is possible to observe the long range spin–spin coupling between two distant phosphorus
51
atoms (Table 1) as new example of such quite rare phenomenon. We did not establish the
absolute configuration of the P*-stereocentre in the structure of ligand 5, nevertheless,
considering the data presented in the literature on related compounds it can be assumed that this
52
phosphine-diamidophosphate has an asymmetric phosphorus atom with the (R)-configuration.
Compounds 3d-f readily reacted with [Pd(allyl)Cl] (CH Cl /THF, AgBF as a chloride
scavenger, room temperature, 3.5 h) to give cationic metallochelates 6d-f of the type
2
2
2
4
31
[
Pd(allyl)(L)]BF (Scheme 3). The AX systems were observed in the P NMR spectra of
4
Scheme 3. Synthesis of cationic palladium complexes 6d-f.
complexes 6d-f due to the presence of the two different phosphine and diamidophosphite
phosphorus atoms in the coordination sphere of the palladium. Duplication of the AX systems in
31
the P NMR spectra of complexes 6d-f (Table 1) indicated the presence of their exo- and endo-
2
0,53
isomers.
The MALDI TOF/TOF mass spectrometry and elemental analysis data (see
Experimental section) were also in good agreement with the proposed structures of 6d-f.
To investigate the ability of the present diamidophosphite ligands to induce
enantioselectivity in catalytic processes, their performance in representative Pd-catalyzed
asymmetric allylation and desymmetrization reactions has been examined. First, compounds 3a-f
and 6d-f have been tested in Pd-catalyzed allylic sulfonylation of the substrate (E)-1,3-
diphenylallyl acetate 7 as a test reaction (Table 2). The substrate was added to a solution
Table 2. Pd-catalyzed allylic sulfonylation of (E)-1,3-diphenylallyl acetate 7 with sodium para-
a
toluene sulfinate
7

ACCEPTED MANUSCRIPT
b
Entry
Ligand
L/Pd
Yield (%)
Ee (%)
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3b
3b
3b
3b
3c
3c
3d
3d
3d
3e
3e
3e
3f
1
2
1
2
1
2
1
2
1
2
1
2
1
1
2
1
1
2
1
1
2
95
80
72
70
80
95
23
25
51
55
93
94
90
25
30
26
80
69
88
25
28
69 (S)
57 (S) c
10 (S)
d
11 (S)
80 (S)
70 (S) e
20 (S) f
30 (S)
77 (S)
61 (S)
2 (S)
3 (S)
5 (S)
57 (S)
34 (S)
68 (S)
55 (S)
33 (S) i
92 (S)
60 (R)
65 (R)
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
g
h
3f
3f
3g
3g
a
All reactions were carried out with 2 mol% of [Pd(allyl)Cl]
h.
Enantiomeric excess of 8a was determined by HPLC (Daicel Chiralcel OD-H, C
/1, 0.5 mL/min, 254 nm, t(R) = 16.3 min, t(S) = 18.5 min).
2
in THF at room temperature for 48
b
6
H14/i-PrOH =
4
c
Mixture of ligands 3a and PPh (0.005 mmol each).
3
d
e
f
Mixture of ligands 3a and PPh (0.01 mmol each).
3
Mixture of ligands 3b and PPh
Mixture of ligands 3b and PPh
3
(0.005 mmol each).
(0.01 mmol each).
3
g
h
i
With complex 6d as the catalyst.
With complex 6e as the catalyst.
With complex 6f as the catalyst.
2
containing the palladium pre-catalyst [Pd(allyl)Cl] and the appropriate ligand. Finally, the
anhydrous sodium para-toluene sulfinate as the S-nucleophile was added to the reaction mixture.
P*-monodentate ligands 3a-c demonstrated moderate to good levels of asymmetric induction (up
to 69%, 80% and 77% ee, respectively, Table 2, entries 1, 5 and 9). The best asymmetric
induction was achieved with L/Pd = 2 molar ratio in all cases. The hetero-combinations of PPh
3
8

ACCEPTED MANUSCRIPT
and of the diamidophosphites 3a,b behaved poorly in this reaction, providing sulfone (S)-8a with
moderate or low yields and low enantiomeric excesses (see entries 3,4 and 7,8). The results
obtained with P,P*-bidentate phosphine-diamidophosphites 3d-g demonstrated that the
efficiency of these ligands differs dramatically. In particular, the palladium catalysts derived
from 3d showed excellent activity, but insignificant enantioselectivity (no more than 5% ee)
regardless of the L/Pd molar ratio. At the same time, homologous ligand 3e afforded a
considerably greater asymmetric induction (up to 68% ee, Table 2, entries 11-16). Complex 6f
was the most efficient stereoselector, and (S)-8a was formed in 88% yield and 92% ee (Table 2,
entry 19). Interestingly, the application of the hydroxy-phosphine 2f (precursor of P,P*-bidentate
ligand 3f) in the asymmetric sulfonylation process afforded 8a in only 13% yield and 4% ee
favoring the (R)-enantiomer; palladium complexes with phosphine-diamidophosphate 5 gave no
conversion (see Supplementary data, Table S1, entries 1-4). Remarkably, compound 3g induced
reversal of the enantioselectivity in the synthesis of 8a, compared to diastereomeric ligand 3f
(
Table 2, entries 17-21).
In the next step, the novel diamidophosphites were studied in the traditional reaction
between (E)-1,3-diphenylallyl acetate 7 and dimethyl malonate as the C-nucleophile. Dimethyl
malonate was treated with 7 in the presence of [Pd(allyl)Cl] and the corresponding ligand. As
2
Table 3. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate 7 with dimethyl
a
malonate
b
Entry
Ligand
L/Pd
Solvent
Conversion (%)
Ee (%)
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
1
2
1
2
1
2
1
2
1
2
1
2
1
CH
CH Cl
THF
THF
CH
CH
THF
THF
CH
CH
THF
THF
CH Cl
2
Cl
2
100
100
78
90
87
90
0
30
100
100
75
100
100
65 (S)
73 (S)
71 (S)
70 (S) c
60 (S)
2
2
2
Cl
Cl
2
d
2
2
76 (S)
c
-
d
50 (S)
2
Cl
Cl
2
87 (S)
86 (S)
82 (S)
92 (S) e
73 (S)
1
1
1
1
0
1
2
3
2
2
2
2
9

ACCEPTED MANUSCRIPT
f
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3b
3b
3b
3c
3c
3c
3c
3d
3d
3d
3d
3d
3d
3e
3e
3e
3e
3e
3e
3f
2
1
2
1
2
1
2
1
2
1
2
1
1
1
2
1
2
1
1
1
2
1
2
1
1
1
2
1
2
CH
THF
THF
CH
CH
THF
THF
CH Cl
CH Cl
THF
THF
CH
THF
CH
CH
THF
THF
CH Cl
THF
CH Cl
CH Cl
THF
2
Cl
2
50
30
54
100
100
87
70
10
16
0
40 (S)
e
75 (S) f
67 (S)
93 (S)
90 (S)
87 (S)
84 (S)
3 (S)
2 (S)
-
2
Cl
Cl
2
2
2
2
2
2
2
0
22
0
-
g
2
Cl
2
15 (S)
g
-
2
2
Cl
Cl
2
100
60
62
10
71
55
100
100
40
35
95
46
80
81
50
35
47 (S)
54 (S)
70 (S)
47 (S)
50 (S)
41 (S)
2
h
2
2
h
88 (S)
95 (S)
34 (S)
35 (S) i
95 (S) i
80 (S)
33 (R)
32 (R)
13 (R)
44 (R)
2
2
3f
3f
3f
3f
2
2
THF
CH
THF
CH
CH
2 2
Cl
3f
3g
3g
3g
3g
2
2
Cl
Cl
2
2
THF
THF
a
All reactions were carried out with 2 mol% of [Pd(allyl)Cl]
BSA, KOAc).
2
at room temperature for 48 h
(
b
The conversion of substrate 7 and enantiomeric excess of 8b were determined by HPLC
Daicel Chiralcel OD-H, C 14/i-PrOH = 99/1, 0.3 mL/min, 254 nm, t(R) = 28.0 min, t(S) = 29.3
(
6
H
min).
c
Mixture of ligands 3a and PPh (0.005 mmol each).
3
d
e
f
Mixture of ligands 3a and PPh (0.01 mmol each).
3
Mixture of ligands 3b and PPh
Mixture of ligands 3b and PPh
3
(0.005 mmol each).
(0.01 mmol each).
3
g
h
i
With complex 6d as the catalyst.
With complex 6e as the catalyst.
With complex 6f as the catalyst.
seen from Table 3, both P*-monodentate ligands 3b and 3c induced very good conversion and
asymmetric induction (82-92% and 84-93% ee for (S)-8b, respectively, entries 9-12 and 17-20).
The analogous palladium catalysts based on P*-monodentate diamidophosphite 3a with a
naphthalen-2-ol fragment proved to be less efficient: no more than 73% ee was achieved in this
case (Table 3, entries 1-4). Note that the 1:1 combination of 3a and PPh
3
induced a peculiar
outcome: the reaction rate and enantioselectivity were approximately the same in CH Cl , but
2
2
1
0

ACCEPTED MANUSCRIPT
decreased in THF compared to 3a alone (Table 3, entries 1-4 and 5-8). In addition, a decrease in
the conversion and selectivity was observed for the hetero-combination 3b/PPh
entries 9-12 and 13-16). As in the case of the allylic sulfonylation, phosphine-diamidophosphite
d and phosphine-diamidophosphate 5 were completely inefficient (see Table 3, entries 21-26
3
(compare
3
and Supplementary data, Table S1, entries 9-12); compound 3e showed moderate asymmetric
induction again (ee varies from 41% to 70%, entries 27-32). Also, P,P*-bidentate phosphine-
diamidophosphite 3f provided an excellent enantioselectivity (up to 95% ee for (S)-8b, Table 3,
entry 34) and quantitative conversion. It is clear that CH
2
2
Cl is the solvent of choice (entries 33,
3
2
5
4 and 37). It is appropriate to mention here that under the same conditions hydroxy-phosphine
f (precursor of 3f) gave malonate 8b with a smaller conversion and asymmetric induction (53–
7% ee) (Supplementary data, Table S1, entries 5, 6) as well as with opposite absolute
configuration. Diastereomeric ligand 3g afforded product (R)-8b with mediocre enantiomeric
purity (13-44% ee) probably due to the mismatched combination of the (2R,5S)-stereocentres of
a
the phosphabicyclic cores with the (S )-binaphthyl framework.
Table 4 shows the results obtained when pyrrolidine was used as the N-nucleophile.
Table 4. Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate 7 with pyrrolidine
a
b
Entry Ligand L/Pd
Solvent
Conversion (%)
Ee (%)
1
2
3
4
5
6
7
3a
3a
3a
3a
3a
3a
3a
1
2
1
2
1
2
1
CH Cl
100
100
100
98
100
100
30
62 (R)
72 (R)
70 (R)
69 (R) c
22 (R)
2
2
CH Cl
2
2
THF
THF
CH
CH
2
Cl
Cl
2
d
2
2
50 (R) c
THF
25 (R)
1
1

ACCEPTED MANUSCRIPT
d
8
9
3a
3b
3b
3b
3b
3b
3b
3b
3b
3c
3c
3d
3d
3d
3d
3d
3d
3e
3e
3e
3e
3e
3e
3f
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
1
1
2
1
2
1
1
1
2
1
2
1
1
1
2
1
2
THF
40
100
100
100
100
63
65
35
32
100
100
55
69
38
46
26
42
70
80
55
70
100
99
100
100
55
43
100
87
35 (R)
80 (R)
81 (R)
84 (R)
CH
CH
2
Cl
Cl
2
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
2
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
THF
THF
79 (R) e
CH
CH
2
Cl
Cl
2
68 (R)
43 (R)
f
2
2
e
THF
THF
55 (R) f
57 (R)
87 (R)
89 (R)
35 (R)
57 (R)
25 (R)
31 (R)
25 (R)
15 (R)
11 (R)
9 (R)
5 (R)
CH Cl
2
2
CH Cl
2
2
CH
CH
2
2
Cl
Cl
2
2
2
THF
THF
g
CH
2
Cl
g
THF
CH Cl
2
2
CH Cl
2
2
THF
THF
13 (R)
50 (R)
60 (R)
h
CH
2
Cl
2
h
THF
CH
CH
2
2
Cl
Cl
2
65 (R)
63 (R)
47 (R)
43 (R) i
44 (R) i
49 (R)
61 (S)
55 (S)
38 (S)
43 (S)
3f
3f
3f
3f
2
THF
THF
CH Cl
2
2
3f
THF
3g
3g
3g
3g
CH Cl
2
2
55
56
89
54
CH
2
Cl
2
THF
THF
a
c
All reactions were carried out with 2 mol% of [Pd(allyl)Cl]
The conversion of substrate 7 and enantiomeric excess of 8c were determined by HPLC (Daicel
2
at room temperature for 48 h.
Chiralcel OD-H, C H /i-PrOH/HN(Et) = 200/1/0.1, 0.9 mL/min, 254 nm, t(R) = 5.0 min, t(S) =
6
14
2
6
.1 min).
c
Mixture of ligands 3a and PPh
3
(0.005 mmol each).
(0.01 mmol each).
(0.005 mmol each).
(0.01 mmol each).
d
e
f
Mixture of ligands 3a and PPh
Mixture of ligands 3b and PPh
Mixture of ligands 3b and PPh
3
3
3
g
h
i
With complex 6d as the catalyst.
With complex 6e as the catalyst.
With complex 6f as the catalyst.
Catalytic performance in the Pd-catalyzed allylic amination of 7 with participation of P*-
monodentate ligands 3a-c and pyrrolidine followed the same trend as for the allylic sulfonylation
and alkylation of 7. Moderate to good enantioselectivity was observed when employing
diamidophosphites 3a-c (up to 72%, 84% and 89% ee, respectively, Table 4, entries 2, 11 and
1
2

ACCEPTED MANUSCRIPT
1
8). The resulting product 8c proved to have the same (R)-configuration in all cases. In general,
both the conversion of 7 and asymmetric induction were poorly sensitive to the L/Pd molar ratio
and solvent, but for ligand 3c CH Cl is undoubtedly preferable. Again, the catalysts arising from
the hetero-combinations of 3a/PPh and 3b/PPh were by far less active and stereoselective than
2
2
3
3
with only 3a or 3b (entries 5-8 and 13-16). Ligand 5 with phosphine and diamidophosphate
moieties exhibited very low conversion and enantioselectivity (Supplementary data, Table S1,
entries 17-20). As for the P,P*-bidentate phosphine-diamidophosphites 3d-g, all of them gave
amine (R)-8c ((S)-8c in the case of 3g) with similar enantiomeric purity (57-65% ee) and modest
to quantitative conversion. Although the L/Pd molar ratio and solvent do not have a profound
influence on the efficiency of chiral transfer, for 3f,g the highest results were obtained in
CH
see Supplementary data, Table S1 and Table 4).
To understand, why the ”mixed-ligand approach”» was unsuccessful, we decided to study
the Pd-π-allyl complexes which contain ligand 3b or 3b and PPh , as these are the key
The formation of the palladium
complexes was investigated by adding 3b (2 or 4 equiv.) or the 3b/PPh mixture (2 equiv. each)
to a solution of [Pd(allyl)Cl] (1 equiv.) in CD Cl . Complexation studies were then performed
by means of P NMR spectroscopy. Signals of both the exo- and endo-isomers of the neutral
2 2
Cl . As usual, ligand 3f showed higher activity and enantioselectivity than its precursor 2f
(
3
3
,54
intermediates in the allylic substitution reactions studied.
3
2
2
2
3
1
3
1
[
Pd(allyl)(3b)Cl] complex were visible in the P NMR spectrum of the resulting solution based
on homo-combination at molar ratio 3b/Pd = 1 (δ 121.9 and 121.5 ppm, 47% and 53%,
respectively). When homo-combination at molar ratio 3b/Pd = 2 was employed, two peaks (δ
17.9 and 116.8 ppm, 4% and 96%, respectively) of the cationic two-ligated specie
Р
Р
1
2
0
31
[
Pd(allyl)(3b)
spectrum of the reaction mixture containing hetero-combination 3b/PPh
intensive singlets δ 104.2, 31.8, 25.2, 24.1, 21.3 and a minor AX system (δ
8.7 ppm, d, JP,P* 30.9 Hz, 4%) which correspond, probably, to the expected hetero-complex
Pd(allyl)(PPh )(3b)]Cl. Thus, no selective formation of the hetero-complex was observed. It is,
2
]Cl was observed, also due to the presence of both isomers. The P NMR
showed a set of
98.3 ppm, d and
3
Р
Р
3
[
3
perhaps, one of the reasons for the rather low efficiency of the P*-monodentate
diamidophosphites/PPh hetero-combinations in Pd-catalyzed asymmetric allylation. Indeed, the
3
electronic disparity of the two different phosphorus ligands in the first coordination sphere of
palladium is able to impact positively on the stereoselectivity of the reaction. In fact, the
nucleophilic attack is expected to proceed preferentially trans to the ligand with the higher trans-
4
6
influence, because of the higher electrophilicity of the corresponding π-allyl terminus.
We evaluated the small P*-chiral diamidophosphite ligand library in the Pd-catalyzed
desymmetrization of N,N'-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate 10 (Table 5). The
1
3

ACCEPTED MANUSCRIPT
Table 5. Pd-catalyzed desymmetrization of N,N'-ditosyl-meso-cyclopent-4-ene-1,3-diol
a
biscarbamate 10
b,c
Entry
Ligand
L/Pd
Yield (%)
Ee (%)
1
2
3
4
5
6
7
8
9
3b
3b
3c
3c
3d
3d
3e
3e
3f
1
2
1
2
1
2
1
2
1
2
1
2
49
56
39
43
76
72
59
71
87
92
89
94
12 (II)
23 (II)
15 (II)
27 (II)
30 (II)
28 (II)
12 (II)
10 (II)
45 (I)
1
1
1
0
1
2
3f
3g
3g
40 (I)
63 (II)
50 (II)
a
°
All reactions were carried out with 5 mol% of [Pd (dba) ]·CHCl in THF at 35 C for 24 h.
2
3
3
b
The enantiomeric excess of 11 was determined by HPLC (Kromasil 5-CelluCoat, C
9/1, 2 mL/min, 219 nm, t(I) = 13 min, t(II) = 17 min).
6
H14/i-PrOH
=
с
The absolute configuration of the product 11 was not assigned.
2 3 3
reaction was performed in THF in the presence of [Pd (dba) ]·CHCl as the pre-catalyst. The
stereochemistry of this transformation revealed some remarkable trends. In contrast to the Pd-
catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate 7, P*-monodentate
ligands 3b,c provided poor asymmetric induction (12-27% ee, Table 5, entries 1-4). Similarly,
with participation of the P,P*-bidentate phosphine-diamidophosphites 3d,e low
enantioselectivity (no more than 30% ee, entries 5-8) was observed irrespective of the L/Rh
molar ratio. The use of both diastereomers 3f,g of the P,P*-ligand with a binaphthyl backbone
made it possible to obtain product 11 in good yield and the opposite absolute configuration
(Table 5, entries 9-12). Unlike the allylation of 7, in the Pd-catalyzed desymmetrization of
1
4

ACCEPTED MANUSCRIPT
substrate 10, compound 3g afforded the resulting product 11 with a higher enantiomeric purity
than diastereomeric ligand 3f (up to 63% and 45% ee, respectively).
3
. Conclusion
To sum up all of the above-considered data, the following conclusions can be drawn: i)
we have designed and synthesized the first representatives of a novel class of C -symmetric P,P-
1
bidentate ligands. These ligands have three main advantages: the diamidophosphite nature of
their phosphite-type moieties, the P*-chirogenic phosphorus atoms and the 1,3,2-
diazaphospholidine rings with balanced electronic characteristics; ii) some new P*-monodentate
diamidophosphites 3a-c with naphthyl or long-chain substituents have been successfully
prepared. These ligands demonstrated moderate to high levels of asymmetric induction in Pd-
catalyzed asymmetric allylation, but low enantioselectivity in Pd-catalyzed desymmetrization;
46
iii) in accordance with the literature precedent in Pd-catalyzed allylic substitution reactions, the
hetero-combination of P*-monodentate diamidophosphite/PPh , as a rule, induced a lower
3
reaction rate and a diminished enantiomeric excess compared to the homo-combination of the
corresponding diamidophosphite; iv) homologous P,P*-bidentate phosphine-diamidophosphites
3
d,e with achiral phosphine moieties showed moderate-to-poor enantioselectivity, their catalytic
performance is highly affected by the nature of the nucleophile. At the same time, diastereomeric
P,P*-bidentate phosphine-diamidophosphites 3f,g are the most promising asymmetric inductors.
In asymmetric Pd-catalyzed allylic substitution, 3f,g and 3a-c are very efficient and
complementary groups of ligands, whereas in the Pd-catalyzed desymmetrization 3f,g are
substantially better stereoselectors than 3a-c. As opposed to 3f, its precursor 2f and analog 5 with
a P=O fragment provided much lower activity and enantioselectivity. Thus, the binaphthyl
backbone in the efficient P,P*-bidentate ligands 3f,g forms an axially chiral phosphine basis and
an additional P*-donor atom and/or C*-stereocenters in the diamidophosphite species should be
present in their structures for achieving high catalytic enantioselectivity.
Remarkably, in the Pd-mediated asymmetric allylic alkylation of (E)-1,3-diphenylallyl
acetate 7 with dimethyl malonate, the best of the phosphine-phosphites and phosphine-
14,27,53
phosphoramidites tested to date gave maximum ee values of 83% and 90%, respectively.
Hence, the enantioselectivity produced by phosphine-diamidophosphite 3f (95% ee) is the best
so far achieved in this reaction using unsymmetrical P,P-bidentate ligands with phosphine and
phosphite-type moieties. As a whole, diastereomeric stereoselectors 3f,g hold a noteworthy
position among such ligands, and further studies to explore the scope of 3f,g in other asymmetric
catalytic reactions are currently in progress.
1
5

ACCEPTED MANUSCRIPT
4
. Experimental section
4
.1. General comments
3
1
13
1
13
P, C and H NMR spectra were recorded on a Bruker MSL-300 (75.5 MHz for C), a
31
13
1
Bruker AMX 400 (162.0 MHz for P, 100.6 MHz for C and 400.13 MHz for H) and a Bruker
3
1
13
1
Avance III 600 (242.9 MHz for P, 150.9 MHz for C and 600.13 MHz for H) instruments.
1
13
Complete assignment of all the resonances in the H and C NMR spectra was achieved by the
use of APT and DEPT techniques (together with COSY and HSQC techniques for compounds
18,20,30,31,49
3
a, 3e-g and 5) and published data.
Chemical shifts (ppm) were given relative to
1
13
31
Me Si ( H and C) and 85% H PO ( P NMR). Data are represented as follows: chemical shift,
4
3
4
n
multiplicity (br = broad, s = singlet, d = doublet, t = triplet, m = multiplet); coupling constants J
in Hertz (Hz) integration, ”n” values are reported in the case of their unambiguous
determination. IR spectra were recorded on a Specord M80 instrument. Mass spectra were
recorded on a Varian MAT 311 spectrometer (EI) and a Bruker Daltonics Ultraflex spectrometer
(MALDI TOF/TOF). HPLC analyses were performed on Agilent 1100 and Stayer instruments
using Chiralcel® and Kromasil® columns. Elemental analyses were performed on a CHN-
microanalyzer Carlo Erba EA1108 CHNS-O.
All manipulations were carried out under a dry argon atmosphere in flame-dried
glassware and in freshly dried and distilled solvents. For example, toluene and tetrahydrofuran
were freshly distilled from sodium benzophenone ketyl before use; dichloromethane was
distilled from NaH. Triethylamine and pyrrolidine were distilled over KOH and then over a
4
small amount of LiAlH before use. Thin-layer chromatography was performed on E. Merck pre-
coated silica gel 60 F254 and Macherey-Nagel Alugram Alox N/UV254 plates. Column
chromatography was performed using silica gel MN Kieselgel 60 (230 – 400 mesh) and MN-
Aluminum oxide, basic, Brockmann Activity 1. Phosphorylating reagents, (5S)-2-chloro-3-
phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane
1,
(2S,5S)-2-chloro-3-phenyl-1,3-diaza-2-
phosphabicyclo[3.3.0]octane-2-oxide 4 and ligands 3a-g, 5 were prepared analogously to known
2
0,48,55,56
procedures.
reduction
(2-(Diphenylphosphino)phenyl)methanol 2e was prepared by the NaBH
4
57
of
2-(diphenylphosphino)benzaldehyde.
(R)-2’-(Diphenylphosphino)-1,1’-
binaphthyl-2-ol 2f and (S)-2’-(diphenylphosphino)-1,1’-binaphthyl-2-ol 2g were prepared in four
5
8
steps, starting from the (R)- and (S)-BINOL, respectively. The [Pd(allyl)Cl]
2
, starting substrate
Pd-catalyzed reactions: allylic
sulfonylation of (E)-1,3-diphenylallyl acetate 7 with sodium para-toluene sulfinate, alkylation
5
9,60
7
2 3 3
, and [Pd (dba) ]·CHCl were obtained as published.
1
6

ACCEPTED MANUSCRIPT
with dimethyl malonate, amination with pyrrolidine and desymmetrization of N,N’-ditosyl-meso-
cyclopent-4-ene-1,3-diol biscarbamate 10 were performed according to the appropriate
20,61, 23
procedures.
Naphthalen-2-ol 2a, decan-1-ol 2b, hexadecan-1-ol 2c, 2-(diphenylphosphino)phenol 2d,
-(diphenylphosphino)benzaldehyde, (R)- and (S)-BINOL, DMAP (4-dimethylamino-pyridine),
2
triphenylphosphine, sodium para-toluene sulfinate, dimethyl malonate, BSA (N,O-
bis(trimethylsilyl) acetamide), meso-cyclopent-4-ene-1,3-diol 9 and tosyl isocyanate were
purchased from Aldrich and Acros Organics and used without further purification.
4
.2. General procedure for the preparation of ligands 3a-g and 5
A solution of the appropriate alcohol 2a-g (2 mmol) in THF (for 2a-c and 2f in the case
of ligand 5 synthesis) or toluene (for 2d-g) (5 mL) was added dropwise to a vigorously stirred
3
solution of the appropriate phosphorylating reagent 1 or 4 (2 mmol), Et N (0.5 mL, 3.6 mmol),
and DMAP (0.025 g, 0.2 mmol) in the same solvent (10 mL). The mixture was then heated to
boiling point, refluxed for 30 min (1 h 30 min in the case of ligand 5 synthesis), and cooled to 20
°
C. The resulting suspension was filtered through a short plug of aluminum oxide, the column
was washed twice with THF or toluene (6 mL), and the solvent evaporated under reduced
pressure (40 Torr). The product was dried in vacuum (1 Torr) for 1h (16 h of further high
-3
vacuum (10 Torr) drying is necessary for the preparation of analytically pure samples of 3e-g).
Ligand 5 was additionally purified by column chromatography on aluminum oxide
(
2 2
CH Cl /hexane, 3:1).
4
.2.1.
(2R,5S)-2-(Naphthalene-2-yloxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo[3.3.0]octane (3a). Yield: 0.60 g (86%) as colorless oil. IR: νmax (CHCl ) 3038,
3
-
1
1
°
3
1
1
021, 2923, 2851, 1464, 1432, 1078, 835, 740 cm . H NMR (600.13 MHz, CDCl
3
, 24 C): δ =
.50-1.56 (m, 1 H, C(6)H), 1.83-1.90 (m, 2 H, С(7)H ), 1.91-1.97 (m, 1 H, C(6)H), 3.13-3.16 (m,
2
H, С(4)H), 3.35-3.42 (m, 2 H, С(4)H and С(8)H), 3.64-3.67 (m, 1 H, С(5)H), 3.70-3.75 (m, 1
3
H, С(8)H), 6.96 (t, J = 7.2 Hz, 1 H, CHPh), 7.12-7.16 (m, 3 H, CHAr and 2 CHPh), 7.31-7.36 (m,
3
3
1
H, CH and 2 CH ), 7.38-7.41 (m, 1 H, CH ), 7.43-7.46 (m, 1 H, CH ), 7.69 (d, J = 7.8 Hz,
Ar
Ph
Ar
Ar
3
3
13
H, CHAr), 7.72 (d, J = 8.9 Hz, 1 H, CHAr), 7.80 (d, J = 8.4 Hz, 1 H, CHAr). C NMR (150.9
°
3
2
3
MHz, CDCl , 25 C): δ = 26.4 (d, J = 4.4 Hz, С(7)), 32.0 (s, C(6)), 48.0 (d, J = 35.6 Hz, С(8)),
2
2
3
3
5
3.8 (d, J = 7.9 Hz, С(4)), 62.9 (d, J = 8.8 Hz, С(5)), 115.4 (d, J = 12.8 Hz, CH ), 117.7 (d, J
Ph
3
=
6.3 Hz, CHNaphth), 119.4 (s, CHPh), 122.9 (d, J = 3.5 Hz, CHNaphth), 124.4 (s, CHNaphth), 126.0
(s, CHNaphth), 127.1 (s, CHNaphth), 127.6 (s, CHNaphth), 128.8 (s, CHNaphth), 129.3 (s, CHPh), 130.2
1
7

ACCEPTED MANUSCRIPT
2
2
(
s, CNaphth), 134.3 (s, CNaphth), 145.3 (d, J = 15.2 Hz, C ), 151.6 (d, J = 4.8 Hz, CNaphth) (major
Ph
+
epimer). MS (MALDI TOF/TOF): m/z (%) = 367 (41) [M + H
2
O + H] , 177 (100)
+
[
PhNHCH
2
CH(CH
2
)
3
NH + H] . Anal. Calcd for C21
H
21
N
2
OP: C, 72.40; H, 6.08; N, 8.04. Found:
C, 72.67; H, 6.01; N, 8.16.
4
.2.2. (2R,5S)-2-(Decyloxy)-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane (3b).
Yield: 0.57 g (79%) as colorless viscous oil. IR: νmax (CHCl ) 3033, 2953, 2920, 2870, 2861,
3
-1
1
°
3
1
441, 1378, 1065, 745 cm . H NMR (400.13 MHz , CDCl
3
, 27 C): δ = 0.87 (t, J = 6.8 Hz, 3
H, CH ), 1.17-1.32 (br. M, 14 H, (CH ), 1.46-1.53 (m, 2 H, CH
3
2
)
7
2
); 1.60-1.66 (m, 1 H), 1.70-
1
.76 (m, 1 H), 1.79-1.85 (m, 1 H), 1.98-2.05 (m, 1 H) (С(6)H , С(7)H ); 3.12-3.21 (m, 2 H,
2
2
2 2
CH O); 3.48-3.60 (m, 2 H), 3.63-3.69 (m, 1 H), 3.71-3.76 (m, 1 H), 4.10-4.16 (m, 1 H) (С(4)H ,
3
3
3
2
С(5)H, С(8)H ); 6.82 (t, J = 7.2 Hz, 1 H, CHPh), 7.01 (br. d, J = 7.4 Hz, 2 H, CHPh), 7.22 (t, J
13
°
=
7.6 Hz, 2 H, CH ). C NMR (75.5 MHz, CDCl , 26 C): δ = 14.1 (s, CH ), 22.7 (s, CH ), 26.1
Ph
3
3
2
3
(
s, CH
2
), 26.2 (d, J = 3.8 Hz, С(7)), 29.3 (s, CH
2
), 29.4 (s, CH
2
), 29.5 (s, CH
2
2
), 29.6 (s, CH ),
3
2
2
3
0.9 (d, J = 3.8 Hz, CH
2
), 31.9 (s, C(6)), 32.1 (s, CH
2
), 48.8 (d, J = 37.0 Hz, С(8)), 54.9 (d, J
2
2
3
=
6.8 Hz, С(4)), 62.3 (d, J = 3.8 Hz, CH O), 63.3 (d, J = 9.1 Hz, С(5)), 114.8 (d, J = 12.1 Hz,
2
2
CHPh), 118.7 (s, CHPh), 129.1 (s, CHPh), 145.9 (d, J = 15.8 Hz, CPh). MS (EI, 70 eV): m/z (%) =
+
+
+
+
3
63 (16) [M + H] , 362 (37) [M] , 222 (91) [M – C10
H20] , 205 (100) [M – OC10H21] . Anal.
Calcd for C H N OP: C, 69.58; H, 9.73; N, 7.73. Found: C, 69.87; H, 9.92; N, 7.68.
21
35
2
4
0
1
.2.3. (2R,5S)-2-(Hexadecyloxy)-3-phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane (3c). Yield:
.66 g (74%) as milky-white waxy solid. IR: νmax (CHCl ) 3030, 2950, 2924, 2869, 2861, 1443,
3
-
1
1
°
3
372, 1062, 745 cm . H NMR (400.13 MHz , CDCl
), 1.19-1.33 (br. M, 26 H, (CH 13), 1.45-1.53 (m, 2 H, CH
m, 1 H), 1.80-1.86 (m, 1 H), 1.98-2.05 (m, 1 H) (С(6)H , С(7)H
.49-3.60 (m, 2 H), 3.64-3.69 (m, 1 H), 3.70-3.75 (m, 1 H), 4.10-4.16 (m, 1 H) (С(4)H
3
, 25 C): δ = 0.88 (t, J = 6.4 Hz, 3 H,
); 1.56-1.63 (m, 1 H), 1.70-1.76
); 3.13-3.22 (m, 2 H, CH O);
, С(5)H,
2
); 6.81 (t, J = 7.2 Hz, 1 H, CHPh), 7.0 (br. D, J = 7.5 Hz, 2 H, CHPh), 7.22 (t, J = 7.6 Hz,
CH
3
2
)
2
(
2
2
2
3
2
3
3
3
С(8)H
1
3
°
2
H, CHPh). C NMR (100.6 MHz, CDCl
3
, 27 C): δ = 14.0 (s, CH
3
), 22.6 (s, CH
2
), 25.9 (s,
), 29.6
2
), 31.8 (s, C(6)), 32.0 (s, CH ), 48.6 (d, J = 38.4 Hz,
3
CH
2
), 26.0 (d, J = 3.8 Hz, С(7)), 29.1 (s, CH
2
), 29.2 (s, CH ), 29.4 (s, CH
2
2
), 29.5 (s, CH
2
3
2
(
br. S, (CH
2
)
6
), 30.8 (d, J = 3.3 Hz, CH
2
2
2
2
С(8)), 54.7 (d, J = 7.1 Hz, С(4)), 62.2 (d, J = 3.0 Hz, CH O), 63.1 (d, J = 8.7 Hz, С(5)), 114.6
2
3
2
(
(
(
d, J = 11.7 Hz, CHPh), 118.6 (s, CHPh), 128.9 (s, CHPh), 145.7 (d, J = 15.5 Hz, CPh). MS
+
+
2
MALDI TOF/TOF): m/z (%) = 465 (28) [M + H O + H] , 229 (100) [M – OC16H32 + Na] , 177
+
27) [PhNHCH CH(CH ) NH + H] . Anal. Calcd for C H N OP: C, 72.60; H, 10.61; N, 6.27.
2
2 3
27 47
2
Found: C, 72.90; H, 10.72; N, 6.45.
1
8

ACCEPTED MANUSCRIPT
4
.2.4.
(2R,5S)-2-(2-(Diphenylphosphino)phenoxy)-3-phenyl-1,3-diaza-2-
3
phosphabicyclo[3.3.0]octane (3d). Yield: 0.82 g (85%) as colorless viscous oil. IR: νmax (CHCl )
-1
1
°
3
3
053, 3031, 2922, 2854, 1460, 1440, 1077, 740 cm . H NMR (400.13 MHz , CDCl , 25 C): δ
=
1.45-1.52 (m, 1 H), 1.66-1.74 (m, 2 H), 1.78-1.85 (m, 1 H), (С(6)H
2
, С(7)H
2
); 2.98-3.11 (m, 2
3
H), 3.40-3.50 (m, 2 H), 3.60-3.66 (m, 1 H), (С(4)H
2
, С(5)H, С(8)H
2
); 6.85 (t, J = 7.2 Hz, 1 H,
3
13
CH ), 6.93 (t, J = 7.4 Hz, 1 H, CH ), 6.96-7.04 (m, 3 H, CH ), 7.19-7.37 (m, 14 H, CH ). C
Ar
Ar
Ar
Ar
°
3
2
3
NMR (75.5 MHz, CDCl , 25 C): δ = 26.3 (d, J = 4.5 Hz, С(7)), 31.8 (s, C(6)), 48.0 (d, J =
2
2
3
3
3.6 Hz, С(8)), 53.7 (d, J = 6.8 Hz, С(4)), 62.9 (d, J = 9.1 Hz, С(5)), 115.6 (d, J = 13.6 Hz,
CHPhN), 119.3 (s, CHPhN), 120.2 (dd, J = 10.2 Hz, J = 1.9 Hz, CH ), 123.0 (s, CH ), 128.1 (s,
Ar
Ar
CHAr), 128.2 (s, CHAr), 128.3 (s, CHAr), 128.4 (s, CHAr), 129.1 (s, CHPhN), 130.1 (s, CHAr), 133.6
2
2
1
(
d, J = 20.3 Hz, CHAr), 133.7 (d, J = 20.4 Hz, CHAr), 134.3 (s, CHAr), 137.5 (d, J = 12.6 Hz,
1
2
2
2
C ), 137.6 (d, J = 12.7 Hz, C ), 145.2 (d, J = 15.4 Hz, C ), 157.1 (dd, J = 19.3 Hz, J = 2.2
Ar
Ar
PhN
3
2
Hz, СAr) (major epimer) and 25.4 (d, J = 3.8 Hz, С(7)), 28.4 (s, C(6)), 43.8 (d, J = 4.5 Hz,
2
2
3
С(8)), 51.5 (d, J = 6.0 Hz, С(4)), 65.8 (d, J = 11.3 Hz, С(5)), 117.3 (d, J = 12.8 Hz, CHPhN),
1
18.2 (s, CHPhN), 120.7 (br. S, CH ), 122.2 (s, CH ), 128.4 (s, CH ), 128.5 (s, CH ), 128.6 (s,
Ar
Ar
Ar
Ar
2
CHAr), 128.7 (s, CHAr), 128.8 (s, CHPhN), 129.9 (s, CHAr), 133.4 (d, J = 19.4 Hz, CHAr), 133.5
2
1
1
(
d, J = 19.1 Hz, CHAr), 134.1 (s, CHAr), 136.4 (d, J = 11.5 Hz, CAr), 136.2 (d, J = 11.8 Hz,
2
2
2
C ), 146.5 (d, J = 14.9 Hz, C ), 158.5 (dd, J = 18.7 Hz, J = 2.3 Hz, С ) (minor epimer).
Ar
PhN
Ar
+
+
MS (MALDI TOF/TOF): m/z (%) = 501 (26) [M + H
2
O + H] , 279 (100) [Ph
2 6 4
PC H OH + H] ,
+
1
5
77 (39) [PhNHCH
2
CH(CH
2
)
3
NH + H] . Anal. Calcd for C29
H
28
N
2
OP : C, 72.19; H, 5.85; N,
2
.81. Found: C, 72.32; H, 5.90; N, 5.65.
4
.2.5.
(2R,5S)-2-(2-(Diphenylphosphino)phenylmethoxy)-3-phenyl-1,3-diaza-2-
phosphabicyclo[3.3.0]octane (3e). Yield: 0.83 g (84%) as colorless viscous oil. IR: νmax (CHCl
3
)
-1
1
°
3
055, 3029, 2922, 2850, 1460, 1443, 1065, 742 cm . H NMR (600.13 MHz , CDCl
1.54-1.60 (m, 1 H, C(6)H), 1.71-1.82 (m, 2 H, С(7)H ), 1.94-2.0 (m, 1 H, C(6)H), 3.05-3.14
m, 2 H, С(4)H and С(8)H), 3.50-3.57 (m, 2 H, С(4)H and С(8)H), 3.88-3.92 (m, 1 H, С(5)H),
3
, 25 C): δ
=
2
(
2
3
2
3
4
.72 (dd, JH,H = 13.4 Hz, JH,P = 5.4 Hz, 1 H, СHO), 4.99 (ddd, JH,H = 13.4 Hz, JH,P = 6.0 Hz,
4
3
3
J
H,P = 2.1 Hz, 1 H, СHO), 6.82 (t, J = 6.4 Hz, 1 H, CHAr), 6.85 (t, J = 7.2 Hz, 1 H, CHPhN), 7.0
3
3
(
d, J = 7.4 Hz, 2 H, CH ), 7.15 (t, J = 7.2 Hz, 1 H, CH ), 7.21-7.26 (m, 3 H, CH and 2
PhN Ar Ar
1
3
CHPhN), 7.28-7.39 (m, 10 H, CHAr), 7.6-7.62 (m, 1 H, CHAr). C NMR (150.9 MHz, CDCl
3
, 23
°
3
2
2
C): δ = 26.3 (d, J = 4.1 Hz, С(7)), 32.1 (s, C(6)), 48.4 (d, J = 37.6 Hz, С(8)), 54.9 (d, J = 7.6
2
3
2
3
Hz, С(4)), 61.8 (dd, J = 27.5 Hz, J = 4.8 Hz, СH O), 63.2 (d, J = 8.8 Hz, С(5)), 114.9 (d, J =
2
1
2.2 Hz, CHPhN), 118.8 (s, CHPhN), 127.0 (d, J = 5.3 Hz, CHAr), 127.1 (s, CHAr), 128.6 (d, J = 6.9
1
9

ACCEPTED MANUSCRIPT
Hz, CH ), 128.7 (s, CH ), 128.8 (s, CH ), 128.9 (s, CH ), 129.0 (s, CHPhN), 132.6 (s, CHAr),
Ar
Ar
Ar
Ar
2
2
1
1
33.9 (d, J = 19.8 Hz, CHAr), 134.1 (d, J = 19.6 Hz, CHAr), 136.1 (d, J = 9.8 Hz, CAr), 136.2
1
2
3
2
(
d, J = 10.1 Hz, CAr), 143.0 (dd, J = 21.7 Hz, J = 2.6 Hz, СAr), 145.7 (d, J = 16.3 Hz, CPhN).
+
+
MS (MALDI TOF/TOF): m/z (%) = 535 (100) [M + K] , 497 (17) [M + H] . Anal. Calcd for
C
30
H
30
N
2 2
OP : C, 72.57; H, 6.09; N, 5.64. Found: C, 72.85; H, 6.16; N, 5.44.
4
a
.2.6. (2R,5S,R )-2-[1-(2-(Diphenylphosphino)naphthalene-1-yl)naphthalene-2-yloxy]-3-
phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane (3f). Yield: 1.01 g (77%) as white solid, m. p.
°
-1 1
9
3
8-100 C. IR: νmax (CHCl ) 3050, 3036, 2920, 2853, 1464, 1448, 1080, 833, 737 cm . H NMR
°
(
600.13 MHz, CDCl , 24 C): δ = 1.51-1.57 (m, 1 H, C(6)H), 1.59-1.65 (m, 1 H, С(7)H), 1.67-
3
1
.72 (m, 1 H, С(7)H), 1.85-1.91 (m, 1 H, C(6)H), 2.55-2.61 (m, 1 H, С(8)H), 2.99-3.03 (m, 1 H,
3
С(4)H), 3.19-3.25 (m, 1 H, С(8)H), 3.39 (t, J = 8.1 Hz, 1 H, С(4)H), 3.79-3.84 (m, 1 H, С(5)H),
3
3
3
6
.45 (d, J = 7.8 Hz, 2 H, CH ), 6.76 (t, J = 7.5 Hz, 1 H, CH ), 6.92 (d, J = 8.4 Hz, 1 H,
PhN PhN
3
CHAr), 6.97 (t, J = 7.8 Hz, 2 H, CHPhN), 7.07-7.11 (m, 3 H, CHAr), 7.13-7.17 (m, 2 H, CHAr),
3
3
7
.18-7.25 (m, 5 H, CHAr), 7.29-7.34 (m, 4 H, CHAr), 7.42 (dd, J = 8.7 Hz, J = 2.7 Hz, 1 H,
3
3
3
CH ), 7.48 (d, J = 8.4 Hz, 1 H, CH ), 7.52 (t, J = 7.8 Hz, 1 H, CH ), 7.88 (t, J = 7.8 Hz, 2
Ar
Ar
Ar
13
°
3
H, CHAr), 7.91-7.94 (m, 2 H, CHAr). C NMR (150.9 MHz, CDCl
3
, 24 C): δ = 26.0 (d, J = 4.1
2
2
2
Hz, С(7)), 31.4 (s, C(6)), 47.6 (d, J = 34.7 Hz, С(8)), 53.8 (d, J = 7.2 Hz, С(4)), 62.4 (d, J =
3
8
1
1
.5 Hz, С(5)), 114.8 (d, J = 12.7 Hz, CHPhN), 118.8 (s, CHPhN), 121.8 (d, J = 8.5 Hz, CHAr),
24.0 (s, CHAr), 125.9 (d, J = 7.4 Hz, CHAr), 126.1 (s, CHAr), 126.5 (s, CHAr), 127.4 (s, CHAr),
27.6 (s, CHAr), 127.7 (s, CHAr), 127.8 (s, CHAr), 127.9 (s, CHAr), 128.0 (s, CHAr), 128.1 (s,
CHAr), 128.3 (s, CHAr), 128.9 (s, CHPhN), 129.0 (s, CHAr), 129.2 (s, CHAr), 129.9 (s, CAr), 130.7
2
2
(
s, CHAr), 133.1 (d, J = 18.0 Hz, CHAr), 133.3 (d, J = 8.0 Hz, CAr), 133.5 (d, J = 20.2 Hz,
CHAr), 133.7 (s, CAr), 134.3 (s, CAr), 136.3 (d, J = 9.8 Hz, CAr), 138.3 (d, J = 14.0 Hz, CAr), 138.4
2
(
d, J = 13.3 Hz, CAr), 142.2 (d, J = 35.5 Hz, CAr), 144.8 (d, J = 16.2 Hz, CPhN), 150.0 (s, CAr
)
2
2
(
major epimer) and 27.9 (s, С(7)), 31.4 (s, C(6)), 42.4 (d, J = 4.2 Hz, С(8)), 51.3 (d, J = 6.0 Hz,
2
3
С(4)), 65.3 (d, J = 10.9 Hz, С(5)), 117.7 (d, J = 12.1 Hz, CHPhN), 120.6 (s, CHPhN), 121.5 (d, J
13.3 Hz, CHAr), 123.7 (s, CHAr), 125.3 (s, CHAr), 125.7 (s, CHAr), 125.8 (d, J = 5.3 Hz, CHAr),
27.0 (s, CHAr), 127.1 (s, CHAr), 128.1 (s, CHAr), 128.2 (s, CHAr), 129.3 (s, CHAr), 129.5 (s, CAr),
=
1
1
1
2
2
29.6 (s, CHPhN), 130.3 (s, CH ), 133.5 (d, J = 19.8 Hz, CH ), 133.6 (d, J = 20.1 Hz, CH ),
Ar
Ar
Ar
33.8 (s, CAr), 134.1 (s, CAr), 136.2 (d, J = 11.0 Hz, CAr), 137.7 (d, J = 13.0 Hz, CAr), 138.5 (d, J
2
=
14.2 Hz, CAr), 142.5 (d, J = 35.1 Hz, CAr), 145.1 (d, J = 13.7 Hz, CPhN), 150.0 (s, CAr) (minor
+
epimer). MS (MALDI TOF/TOF): m/z (%) = 677 (5) [M + H O + H] , 455 (15)
2
+
+
[
(C10
H
6
OH)C10
H
6
PPh
2
+
H] , 437 (100) [(C10
H
6
)C10
H
6
PPh
2
] , 229 (42) [M
–
2
0

ACCEPTED MANUSCRIPT
+
(
C H O)C H PPh + Na] . Anal. Calcd for C H N OP : C, 78.41; H, 5.51; N, 4.25. Found: C,
1
0
5
10
6
2
43 36
2
2
7
8.72; H, 5.26; N, 4.17.
4
a
.2.7. (2R,5S,S )-2-[1-(2-(Diphenylphosphino)naphthalene-1-yl)naphthalene-2-yloxy]-3-
phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane (3g). Yield: 1.05 g (80%) as white solid, m. p.
°
-1 1
1
04-106 C. IR: νmax (CHCl
3
) 3050, 3037, 2922, 2853, 1464, 1447, 1078, 833, 738 cm . H
°
NMR (600.13 MHz, CDCl , 24 C): δ = 1.27-1.33 (m, 1 H, C(6)H), 1.37-1.49 (m, 3 H, C(6)H
3
3
and С(7)H
2
), 2.32-2.38 (m, 1 H, С(8)H), 2.84-2.95 (m, 3 H, С(4)H, С(5)H and С(8)H), 3.21 (t, J
3
3
=
7.8 Hz, 1 H, С(4)H), 6.81-6.86 (m, 3 H, CHPhN), 6.89 (d, J = 8.4 Hz, 1 H, CHAr), 7.02 (t, J =
3
7
7
7
2
.4 Hz, 1 H, CH ), 7.06-7.19 (m, 9 H, 7 CH and 2 CH ), 7.29 (t, J = 8.1 Hz, 3 H, CH ),
Ar Ar PhN Ar
3
3
.34 (t, J = 7.8 Hz, 3 H, CHAr), 7.44-7.49 (m, 2 H, CHAr), 7.58 (d, J = 8.4 Hz, 1 H, CHAr), 7.84-
3
13
°
3
.88 (m, 3 H, CHAr), 7.98 (d, J = 8.4 Hz, 1 H, CHAr). C NMR (150.9 MHz, CDCl , 25 C): δ =
3
2
2
5.9 (d, J = 3.9 Hz, С(7)), 30.8 (s, C(6)), 47.0 (d, J = 32.4 Hz, С(8)), 52.9 (d, J = 6.6 Hz,
2
3
С(4)), 62.0 (d, J = 8.0 Hz, С(5)), 115.2 (d, J = 13.0 Hz, CHPhN), 119.0 (s, CHPhN), 122.6 (d, J =
.0 Hz, CHAr), 124.0 (s, CHAr), 125.7 (s, CHAr), 125.8 (s, CHAr), 126.1 (s, CHAr), 126.4 (s,
CH ), 127.6 (d, J = 5.9 Hz, CH ), 127.7 (s, CH ), 127.8 (s, CH ), 127.9 (s, CH ), 128.0 (s,
8
Ar
Ar
Ar
Ar
Ar
2
CHAr), 128.9 (s, CHPhN), 129.4 (s, CHAr), 129.9 (s, CAr), 130.6 (d, J = 2.4 Hz, CHAr), 133.1 (d, J
2
=
18.9 Hz, CHAr), 133.4 (d, J = 19.9 Hz, CHAr), 133.5 (s, CAr), 133.6 (s, CAr), 134.4 (s, CAr),
1
3
3
36.4 (d, J = 10.1 Hz, C ), 137.8 (d, J = 13.7 Hz, C ), 139.0 (d, J = 14.6 Hz, C ), 142.5 (d, J =
Ar Ar Ar
2
5.8 Hz, CAr), 145.0 (d, J = 15.4 Hz, CPhN), 149.5 (s, CAr) (major epimer) and 27.5 (s, C(7)),
2
2
2
1.6 (s, C(6)), 43.4 (d, J = 3.2 Hz, С(8)), 51.0 (d, J = 6.3 Hz, С(4)), 65.5 (d, J = 10.9 Hz,
3
С(5)), 117.2 (d, J = 13.3 Hz, CHPhN), 120.2 (s, CHPhN), 120.4 (d, J = 13.1 Hz, CHAr), 123.5 (s,
CHAr), 125.5 (s, CHAr), 125.8 (d, J = 3.9 Hz, CHAr), 126.3 (s, CHAr), 126.7 (s, CHAr), 127.2 (d, J
=
2.7 Hz, CHAr), 127.5 (s, CHAr), 128.0 (s, CHAr), 128.1 (s, CHAr), 128.2 (s, CHAr), 128.3 (s,
CHAr), 129.0 (s, CHAr), 129.2 (s, CHPhN), 130.0 (s, CAr), 130.3 (d, J = 2.1 Hz, CHAr), 133.3 (s,
2
2
C
Ar), 133.4 (s, CAr), 133.7 (dd, J = 19.6 Hz, J = 2.4 Hz, СAr), 133.9 (d, J = 20.7 Hz, CHAr),
1
1
34.3 (d, J = 3.5 Hz, CAr), 135.8 (d, J = 11.9 Hz, CAr), 137.3 (d, J = 13.0 Hz, CAr), 138.7 (d, J =
2
4.3 Hz, CAr), 142.6 (d, J = 34.1 Hz, CAr), 145.1 (d, J = 16.9 Hz, CPhN), 149.7 (s, CAr) (minor
+
epimer). MS (MALDI TOF/TOF): m/z (%) = 677 (13) [M + H
2
O + H] , 455 (10)
+
+
[
(
(C H OH)C H PPh
+
+
H] , 437 (100) [(C H )C H PPh ] , 229 (23) [M
–
10
6
10
6
2
10
6
10
6
2
C
10
H
5
O)C10
H
6
PPh
2
+ Na] . Anal. Calcd for C43
H
36
N
2
2
OP : C, 78.41; H, 5.51; N, 4.25. Found: C,
7
8.61; H, 5.59; N, 4.09.
4
a
.2.8. (2R,5S,R )-2-[1-(2-(Diphenylphosphino)naphthalene-1-yl)naphthalene-2-yloxy]-3-
phenyl-1,3-diaza-2-phosphabicyclo[3.3.0]octane-2-oxide (5). Yield: 0.96 g (71%) as white solid,
2
1

ACCEPTED MANUSCRIPT
°
m. p. 138-140 C. IR: νmax (CHCl
3
) 3051, 3030, 2923, 2851, 1468, 1446, 1229, 1077, 830, 740
-1
1
°
cm . H NMR (600.13 MHz, CDCl
С(7)H
.33 (m, 1 H, С(4)H), 3.40-3.45 (m, 1 H, С(5)H), 3.57-3.62 (m, 1 H, С(8)H), 6.53 (d, J = 7.8
3
, 24 C): δ = 1.61-1.66 (m, 1 H, C(6)H), 1.77-1.82 (m, 2 H,
2
), 1.92-1.97 (m, 1 H, С(6)H), 2.61-2.67 (m, 1 H, С(8)H), 3.13-3.17 (m, 1 H, С(4)H), 3.29-
3
3
3
3
3
Hz, 2 H, CHPhN), 6.79 (t, J = 7.5 Hz, 1 H, CHPhN), 6.85 (t, J = 7.8 Hz, 2 H, CHPhN), 6.92 (d, J =
3
9
.0 Hz, 1 H, CHAr), 7.03 (t, J = 7.2 Hz, 2 H, CHAr), 7.13-7.21 (m, 7 H, CHAr), 7.24-7.29 (m, 2
3
H, CH ), 7.31-7.36 (m, 2 H, CH ), 7.37-7.41 (m, 2 H, CH ), 7.55 (t, J = 7.8 Hz, 1 H, CH ),
Ar
Ar
Ar
Ar
3
3
7
.62 (d, J = 9.0 Hz, 1 H, CHAr), 7.84 (d, J = 8.4 Hz, 1 H, CHAr), 7.89-7.94 (m, 2 H, CHAr), 7.98
3
13
°
3
(
d, J = 9.0 Hz, 1 H, CHAr). C NMR (150.9 MHz, CDCl
3
, 24 C): δ = 25.7 (d, J = 3.9 Hz,
3
2
2
С(7)), 32.0 (d, J = 3.9 Hz, С(6)), 46.7 (d, J = 3.2 Hz, С(8)), 50.4 (d, J = 19.3 Hz, С(4)), 56.3
2
3
(
(
(
(
d, J = 10.4 Hz, С(5)), 115.6 (d, J = 5.1 Hz, CHPhN), 119.0 (s, CHAr), 120.8 (s, CHPhN), 124.9
s, CHAr), 126.3 (d, J = 8.5 Hz, CHAr), 126.5 (s, CHAr), 126.8 (s, CHAr), 127.4 (s, CHAr), 127.6
d, J = 2.7 Hz, CH ), 127.7 (s, CH ), 127.8 (s, CH ), 127.9 (s, CH ), 128.0 (s, CH ), 128.1
Ar
Ar
Ar
Ar
Ar
s, CHAr), 128.2 (s, CHAr), 128.3 (s, CHAr), 128.8 (s, CHPhN), 129.9 (s, CHAr), 130.5 (d, J = 2.4
2
2
Hz, CHAr), 133.1 (d, J = 18.3 Hz, CHAr), 133.4 (d, J = 20.4 Hz, CHAr), 133.7 (s, CAr), 134.2 (d,
J = 1.5 Hz, C ), 135.9 (d, J = 10.1 Hz, C ), 137.9 (d, J = 13.0 Hz, C ), 138.2 (d, J = 13.9 Hz,
Ar
Ar
Ar
2
C
Ar), 140.7 (d, J = 5.7 Hz, CPhN), 141.0 (d, J = 35.5 Hz, CAr), 147.4 (dd, J = 7.9 Hz, J = 2.4 Hz,
+
+
С
Ar). MS (MALDI TOF/TOF): m/z (%) = 675 (78) [M + H] , 437 (100) [(C10
H
6
)C10
H
6
PPh
2
] ,
+
1
4
77 (89) [PhNHCH CH(CH ) NH + H] . Anal. Calcd for C H N O P : C, 76.55; H, 5.38; N,
2
2 3
43 36
2
2 2
.15. Found: C, 76.76; H, 5.43; N, 4.24.
4
.3. General procedure for the synthesis of the palladium complexes with ligands 3b and
3
1
3
PPh for the P NMR experiments
3
Palladium complexes with diamidophosphite 3b and PPh were synthesized for the NMR
investigations as follows: a solution of the diamidophosphite ligand or a solution of the mixture
of ligands a) 3b (0.016 g, 0.044 mmol), b) 3b (0.032 g, 0.088 mmol), c) 3b (0.016 g, 0.044
mmol) and PPh
3
(0.012 g, 0.044 mmol)) in CD
2
Cl
2
(0.3 mL) was added dropwise to a stirred
Cl (0.3 mL). The resulting
solution of [Pd(allyl)Cl]
2
((0.008 g, 0.022 mmol) in each case) in CD
2
2
solution (0.6 mL) was then transferred to an NMR tube and spectroscopic experiments were
carried out.
4
.4 General procedure for the synthesis of the cationic palladium complexes 6d-f
2
2

ACCEPTED MANUSCRIPT
A solution of the corresponding P,P*-bidentate ligand (0.2 mmol) in CH Cl (2 mL) was
2
2
added dropwise over 30 min to a stirred solution of [Pd(allyl)Cl]
2
(0.037 g, 0.1 mmol) in CH
2
Cl
2
°
°
(
1 mL) at 20 C. The reaction mixture was stirred for a further 1 h at 20 C. A solution of AgBF
4
(0.2 mmol, 0.039 g) in THF (2 mL) was added dropwise over 30 min to the resulting solution,
°
and the reaction mixture was stirred for 1.5 h at 20 C. The precipitate of AgCl formed was
separated by filtration. Solvent excess was removed in vacuum (40 Torr) to a volume of ~0.3
mL, and ether (7 mL) was added. The precipitate formed was separated by centrifugation,
washed with ether (2 × 5 mL), and dried in air and in vacuum (1 Torr).
4
.4.1. [Pd(allyl)(3d)]BF
TOF/TOF): m/z (%) = 647 (94) [M – BF
C H BF N OP Pd: C, 53.62; H, 4.64; N, 3.91. Found: C, 53.83; H, 4.59; N, 4.07.
4
(6d). Yield: 0.13 g (91%) as sand-colored powder. MS (MALDI
+
+
4
2 4
+ H O] , 629 (100) [M – BF ] . Anal. Calcd for
32
33
4
2
2
4
.4.2. [Pd(allyl)(3e)]BF
4
(6e). Yield: 0.14 g (94%) as sand-colored powder. MS (MALDI
+
+
TOF/TOF): m/z (%) = 643 (68) [M – BF ] , 602 (100) [M – All – BF ] . Anal. Calcd for
4
4
33 4 2 2
C H35BF N OP Pd: C, 54.23; H, 4.83; N, 3.83. Found: C, 54.48; H, 4.68; N, 4.09.
4
.4.3. [Pd(allyl)(3f)]BF (6f). Yield: 0.17 g (95%) as light yellow powder. MS (MALDI
4
+
+
TOF/TOF): m/z (%) = 805 (100) [M – BF
4 4
] , 764 (28) [M – All – BF ] . Anal. Calcd for
C
46
H
41BF
4
N
2
OP Pd: C, 61.87; H, 4.63; N, 3.14. Found: C, 62.02; H, 4.82; N, 2.88.
2
4
.5. Catalytic reactions
4
.5.1. Pd-catalyzed allylic sulfonylation of (E)-1,3-diphenylallyl acetate 7 with sodium
para-toluene sulfinate. A solution of [Pd(allyl)Cl] (0.0019 g, 0.005 mmol) and the appropriate
2
ligand (0.01 mmol or 0.02 mmol) in THF (1.5 mL) was stirred for 40 min. (E)-1,3-Diphenylallyl
acetate (0.05 mL, 0.25 mmol) was added and the solution stirred for 15 min, then sodium para-
toluene sulfinate (0.089 g, 0.5 mmol) was added and the reaction mixture stirred for a further 48
h, quenched with brine (3 mL) and extracted with THF (3 x 2 mL). The organic layer was
washed with brine (2 x 2 mL) and dried over MgSO
4
. The solvent was evaporated at reduced
pressure (40 Torr). Crystallization of the residue from EtOH, followed by desiccation in vacuum
6
2,63
(10 Torr, 12 h), gave (E)-1,3-diphenyl-3-tosylprop-1-ene 8a as white crystals.
The
enantiomeric excess of 8a was determined by HPLC (Daicel Chiralcel OD-H column, C
PrOH = 4/1, 0.5 mL/min, 254 nm, t(R) = 16.3 min, t(S) = 18.5 min).
6
H14/i-
2
3

ACCEPTED MANUSCRIPT
4
.5.2. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate 7 with dimethyl
2
malonate. A solution of [Pd(allyl)Cl] (0.0019 g, 0.005 mmol) and the appropriate ligand (0.01
mmol or 0.02 mmol) in the appropriate solvent (1.5 mL) was stirred for 40 min. (E)-1,3-
Diphenylallyl acetate (0.05 mL, 0.25 mmol) was added and the solution stirred for 15 min.
Dimethyl malonate (0.05 mL, 0.44 mmol), BSA (0.11 mL, 0.44 mmol) and potassium acetate
(
0.002 g) were added. The reaction mixture was stirred for 48 h, diluted with CH
2 2
Cl or THF (2
mL) and filtered through a thin layer of silica gel. The filtrate was evaporated at reduced pressure
(40 Torr) and dried in vacuum (10 Torr, 12 h) affording a residue containing (E)-dimethyl 2-
6
4,65
(1,3-diphenylallyl)malonate 8b.
In order to evaluate ee and conversion, the obtained residue
was dissolved in an appropriate eluent mixture (8 mL) and a sample was taken for HPLC
6
analysis (Daicel Chiralcel OD-H column, C H14/i-PrOH = 99/1, 0.3 mL/min, 254 nm, t(R) = 28.0
min, t(S) = 29.3 min).
4
.5.3. Pd-catalyzed allylic amination of (E)-1,3-diphenylallyl acetate 7 with pyrrolidine.
A solution of [Pd(allyl)Cl] (0.0019 g, 0.005 mmol) and the appropriate ligand (0.01 mmol or
2
0
.02 mmol) in the appropriate solvent (1.5 mL) was stirred for 40 min. (E)-1,3-Diphenylallyl
acetate (0.05 mL, 0.25 mmol) was added and the solution stirred for 15 min, then freshly
distilled pyrrolidine (0.06 mL, 0.75 mmol) was added. The reaction mixture was stirred for 48 h,
diluted with CH
2 2
Cl or THF (2 mL) and filtered through a thin layer of silica gel. The filtrate was
evaporated at reduced pressure (40 Torr) and dried in vacuum (10 Torr, 12 h) affording a residue
6
6,67
containing (E)-1-(1,3-diphenylallyl)pyrrolidine 8c.
the obtained residue was dissolved in an appropriate eluent mixture (8 mL) and a sample was
taken for HPLC analysis (Daicel Chiralcel OD-H column, C 14/i-PrOH/HN(Et) = 200/1/0.1,
.9 mL/min, 254 nm, t(R) = 5.0 min, t(S) = 6.1 min).
In order to evaluate ee and conversion,
6
H
2
0
4
.5.4. Pd-catalyzed desymmetrization of N,N’-ditosyl-meso-cyclopent-4-ene-1,3-diol
.
biscarbamate 10. A solution of [Pd
2
(dba)
3
] CHCl
3
(0.005 g, 0.005 mmol) and appropriate ligand
(0.01 mmol or 0.02 mmol) in THF (1 mL) was stirred for 40 min. The resulting solution was
°
brought to the 35 C and a solution of N,N’-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate
0 and Et N (14 µL, 0.099 mmol) in THF (0.5 mL) was added (compound 10 was prepared in
1
3
situ as follows: to a solution of the meso-cyclopent-4-ene-1,3-diol 9 (0.01 g, 0.099 mmol) in
THF (0.5 mL), tosyl isocyanate (35 µL, 0.232 mmol) was added; the mixture was stirred at room
°
temperature for 15 min, heated to 55 C for 1 h and cooled down to room temperature). The
reaction mixture was stirred for 24 h. The solvent was removed at reduced pressure (40 Torr) and
the residue was purified by flash chromatography on a short pad of silica gel (EtOAc/hexane,
2
4

ACCEPTED MANUSCRIPT
68
1
:4) and dried in vacuum (1 Torr) for 2 h gave the desired product 11 as a slightly brown solid.
The enantiomeric excess of 11 was determined by HPLC (Kromasil 5-CelluCoat column,
C
6
H
14/i-PrOH = 9/1, 2 mL/min, 219 nm, t(I) = 13 min, t(II) = 17 min).
Acknowledgements
The reported study was partially supported by RFBR, research projects No. 11-03-00347-
a and No. 12-03-31205-mol-a.
References and notes
1
. Brown, J. M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto,
H., Eds.; Springer: Berlin, 1999; Vol. I, pp 121-182.
. Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
Wiley-VCH: New York, NY, 2000; pp 1-110.
2
3
4
2
5
2
6
. Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921.
. Blaser, H.-U.; Schmidt, E. Asymmetric Catalysis on Industrial Scale; Wiley-VCH: Weinheim,
004.
. van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Claver, C.; Pamies, O.; Dieguez, M. Chem. Rev.
011, 111, 2077.
. Claver, C.; Pamies, O.; Dieguez, M. In Phosphorus Ligands in Asymmetric Catalysis; Börner,
A., Ed.; Wiley-VCH: Weinheim, 2008; Vol. II, pp 507-528.
7
8
9
1
1
1
1
1
1
. Falciola, C. A.; Alexakis, A. Eur. J. Org. Chem. 2008, 3765.
. Hargaden, G. C.; Guiry, P. J. Chem. Rev. 2009, 109, 2505.
. Bini, L.; Muller, C.; Vogt, D. Chem. Commun. 2010, 8325.
0. Teichert, J. F.; Feringa, B. L. Angew. Chem., Int. Ed. 2010, 49, 2486.
1. Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
2. Zhou, Q.-L. Privileged Chiral Ligands and Catalysts; Wiley-VCH: Weinheim, 2011.
3. Pavlov, V. A. Tetrahedron 2008, 64, 1147.
4. Fernandez-Perez, H.; Etayo, P.; Panossian, A.; Vidal-Ferran, A. Chem. Rev. 2011, 111, 2119.
5. Boaz, N. W.; Ponasik, J. A. In Phosphorus Ligands in Asymmetric Catalysis; Börner, A.,
Ed.; Wiley-VCH: Weinheim, 2008; Vol. II, pp 451-476.
6. Ayora, I.; Ceder, R. M.; Espinel, M.; Muller, G.; Rocamora, M.; Serrano, M.
Organometallics 2011, 30, 115.
7. Trost, B. M.; Lam, T. M. J. Am. Chem. Soc. 2012, 134, 11319.
1
1
2
5

ACCEPTED MANUSCRIPT
1
1
2
8. Brunel, J. M.; Constantieux, T.; Buono, G. J. Org. Chem. 1999, 64, 8940.
9. Hilgraf, R.; Pfaltz, A. Synlett 1999, 1814.
0. 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.
2
2
1. Hilgraf, R.; Pfaltz, A. Adv. Synth. Catal. 2005, 347, 61.
2. Buono, G.; Toselli, N.; Martin, D. In Phosphorus Ligands in Asymmetric Catalysis; Börner,
A., Ed.; Wiley-VCH: Weinheim, 2008; Vol. II, pp 529-546.
3. Gavrilov, K. N.; Zheglov, S. V.; Shiryaev, A. A.; Groshkin, N. N.; Rastorguev, E. A.;
Benetskiy, E. B.; Davankov, V. A. Tetrahedron Lett. 2011, 52, 964.
2
2
2
2
4. Trost, B. M.; Lam, T. M.; Herbage M. A. J. Am. Chem. Soc. 2013, 135, 2459.
5. Crepy, K. V. L.; Imamoto, T. Adv. Synth. Catal. 2003, 345, 79.
6. Gavrilov, K. N.; Shiryaev, A. A.; Zheglov, S. V.; Potapova, O. V.; Chuchelkin, I. V.;
Novikov, I. M.; Rastorguev, E. A.; Davankov, V. A. Tetrahedron: Asymmetry 2013, 24, 409.
7. Deerenberg, S.; Schrekker, H. S.; van Strijdonck, G. P. F.; Kamer, P. C. J.; van Leeuwen, P.
W. N. M.; Fraanje, J.; Goubitz, K. J. Org. Chem. 2000, 65, 4810.
2
2
2
3
3
2
3
8. Deerenberg, S.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Organometallics 2000, 19, 2065.
9. Suarez, A.; Pizzano, A. Tetrahedron: Asymmetry 2001, 12, 2501.
0. Suarez, A.; Mendez-Rojas, M. A.; Pizzano, A. Organometallics 2002, 21, 4611.
1. Vargas, S.; Rubio, M.; Suarez, A.; del Rio, D.; Alvarez, E.; Pizzano, A. Organometallics
006, 25, 961.
2. Rubio, M.; Suarez, A.; Alvarez, E.; Bianchini, C.; Oberhauser, W.; Peruzzini, M.; Pizzano,
A. Organometallics 2007, 26, 6428.
3. Yu, S.-Bo; Hu, X.-P.; Deng, J.; Wang, D.-Y.; Duan, Z.-C.; Zheng, Z. Tetrahedron:
Asymmetry 2009, 20, 621.
3
3
1
3
3
3
3
3
4
4
4
4. Hou, C.-J.; Guo, W.-L.; Hu, X.-P.; Deng, J.; Zheng, Z. Tetrahedron: Asymmetry 2011, 22,
95.
5. McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809.
6. Graening, T.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2003, 42, 2580.
7. Chapsal, B. D.; Ojima, I. Org. Lett. 2006, 8, 1395.
8. Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258.
9. Dieguez, M.; Pamies, O. Acc. Chem. Res. 2010, 43, 312.
0. Lam, F. L.; Kwong, F. Y.; Chan, A. S. C. Chem. Commun. 2010, 4649.
1. Lafrance, D.; Bowles, P.; Leeman, K.; Rafka, R. Org. Lett. 2011, 13, 2322.
2. Nemoto, T.; Hamada, Y. Tetrahedron 2011, 67, 667.
2
6

ACCEPTED MANUSCRIPT
4
4
3. Reetz, M. T. Angew. Chem., Int. Ed. 2008, 47, 2556.
4. Reetz, M. T. In Phosphorus Ligands in Asymmetric Catalysis; Börner, A., Ed.; Wiley-VCH:
Weinheim, 2008; Vol. III, pp 1135-1171.
5. Pignataro, L.; Lynikaite, B.; Colombo, R.; Carboni, S.; Krupicka, M.; Piarulli, U.; Gennari,
C. Chem. Commun. 2009, 3539.
4
4
1
4
4
6. Alberico, E.; Gladiali, S.; Taras, R.; Junge, K.; Beller, M. Tetrahedron: Asymmetry 2010, 21,
406.
7. Bravo, M. J.; Ceder, R. M.; Muller, G.; Rocamora, M. Organometallics 2013, 32, 2632.
8. Gavrilov, K. N.; Benetskiy, E. B.; Grishina, T. B.; Rastorguev, E. A.; Maksimova, M. G.;
Zheglov, S. V.; Davankov, V. A.; Schaffner, B.; Borner, A.; Rosset, S.; Bailat, G.; Alexakis, A.
Eur. J. Org. Chem. 2009, 3923.
4
5
5
5
5
5
9. Barta, K.; Hölscher, M.; Franciò, G.; Leitner, W. Eur. J. Org. Chem. 2009, 4102.
0. Kimura, M.; Uozumi, Y. J. Org. Chem. 2007, 72,707.
1. Doskocz, M.; Malinowska, B.; Młynarz, P.; Lejczak, B.; Kafarski, P. Tetrahedron Lett. 2010,
1, 3406.
2. Legrand, O.; Brunel, J. M.; Buono, G. Tetrahedron 2000, 56, 595.
3. Wassenaar, J.; van Zutphen, S.; Mora, G.; Le Floch, P.; Siegler, M. A.; Spek, A. L.; Reek, J.
N. H. Organometallics 2009, 28, 2724.
5
5
5
4. Pamies, O.; Dieguez, M. Chem. Eur. J. 2008, 14, 944.
5. Peyronel, J.-F.; Samuel, O.; Fiaud, J.-C. J. Org. Chem. 1987, 52, 5320.
6. Gavrilov, K. N.; Zheglov, S. V.; Shiryaev, A. A.; Potapova, O. V.; Gavrilov, V. K.; Volov,
A. N.; Zamilatskov, I. A. Izv. Akad. Nauk. Ser. Khim. 2013, 1096.
5
5
5
6
6
6
7. Landvatter, E. F.; Rauchfuss, T. B. Organometallics 1982, 1, 506.
8. Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945.
9. Auburn, P. R.; McKenzie, P. B.; Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2033.
0. Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A. J. Organomet. Chem. 1974,
5, 253.
1. Gavrilov, K. N.; Lyubimov, S. E.; Zheglov, S. V.; Benetsky, E. B.; Davankov, V. A. J. Mol.
Catal. A: Chemical 2005, 231, 255.
2. Seebach, D.; Devaquet, E.; Ernst, A.; Hayakawa, M.; Kuhnle, F. N. M.; Schweizer, W. B.;
Weber B. Helv. Chim. Acta 1995, 78, 1636.
6
6
6
6
3. Wolfe, J. A.; Hitchcock, S. R. Tetrahedron: Asymmetry 2010, 21, 2690.
4. Breeden, S.; Wills, M. J. Org. Chem. 1999, 64, 9735.
5. Mei, L.-Y.; Yuan, Z.-L.; Shi, M. Organometallics 2011, 30, 6466.
2
7

ACCEPTED MANUSCRIPT
6
2
6
2
6
6. Smyth, D.; Tye, H.; Eldred, C.; Alcock, N. W.; Wills, M. J. Chem. Soc., Perkin Trans. 1
001, 2840.
7. Chen, J.; Lang, F.; Li, D.; Cun, L.; Zhu, J.; Deng, J.; Liao, J. Tetrahedron: Asymmetry 2009,
0, 1953.
8. Trost, B. M.; Van Vranken, D. L.; Binge1, C. J. Am. Chem. Soc., 1992, 114, 9327
2
8

ACCEPTED MANUSCRIPT
Tetrahedron
Nonsimple relationships between the P*-chiral diamidophosphite
and the arylphosphine moieties in Pd-catalyzed asymmetric
reactions: combinatorial approach and P,P*-bidentate phosphine-
diamidophosphites
Konstantin N. Gavrilov, Alexei A. Shiryaev, Sergey V. Zheglov, Vladislav K. Gavrilov,
Nikolay N. Groshkin, Marina G. Maksimova, Alexandr N. Volov, Ilya A. Zamilatskov
Supplementary data