NOBIN-based chiral phosphite-type ligands and their application in asymmetric catalysis

Article abstract of DOI:10.1016/j.tetlet.2015.06.047

P?-Monodentate diamidophosphite and diastereomeric P,N-containing phosphite ligands have been synthesized from enantiomerically pure N-Bn-NOBIN and used as asymmetric inductors in Pd-catalyzed allylic substitution and Cu-catalyzed conjugate addition react

Full text of DOI:10.1016/j.tetlet.2015.06.047

Accepted Manuscript
NOBIN-based chiral phosphite-type ligands and their application in asymmetric
catalysis
Konstantin N. Gavrilov, Alexei A. Shiryaev, Sergey V. Zheglov, Marina S.
Bochelyuk, Ilya V. Chuchelkin, Viktor A. Tafeenko, Vladimir V. Chernyshev,
Ilya A. Zamilatskov, Igor S. Mikhel
PII:
S0040-4039(15)01053-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.06.047
TETL 46439
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 January 2015
9 June 2015
17 June 2015
Please cite this article as: Gavrilov, K.N., Shiryaev, A.A., Zheglov, S.V., Bochelyuk, M.S., Chuchelkin, I.V.,
Tafeenko, V.A., Chernyshev, V.V., Zamilatskov, I.A., Mikhel, I.S., NOBIN-based chiral phosphite-type ligands
and their application in asymmetric catalysis, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.
2015.06.047
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NOBIN-based chiral phosphite-type ligands and their application in
asymmetric catalysis
Konstantin N. Gavrilov,a∗ Alexei A. Shiryaev,a Sergey V. Zheglov,a Marina S. Bochelyuk,a
Ilya V. Chuchelkin,a Viktor A. Tafeenko,b Vladimir V. Chernyshev,b Ilya A. Zamilatskov,c
Igor S. Mikhelc
a Department of Chemistry, Ryazan State University, 46 Svoboda Street, 390000 Ryazan,
Russian Federation
b Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1-3,
119991 Moscow, Russian Federation
c A. N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of
Sciences, Leninskiy prospekt 31, 119071 Moscow, Russian Federation.
Abstract: P*-monodentate diamidophosphite and diastereomeric P,N-containing phosphite
ligands have been synthesized from enantiomerically pure N-Bn-NOBIN and used as asymmetric
inductors in Pd-catalyzed allylic substitution and Cu-catalyzed conjugate addition reactions. The
best results (up to 93% ee) were obtained for the Pd-catalyzed allylic alkylation of (E)-1,3-
diphenylallyl acetate with 1-cyclohexenylpyrrolidine. The reactions of P,N-containing ligands
1
with Pd(COD)Cl2 at molar ratios of L/M = 1 and 2 were studied using H, 13C and 31P NMR
spectroscopy as well as HRESI mass spectrometry, showing the trans-PdCl2L2 complex was the
only product.
Keywords: Asymmetric allylic substitution; Palladium; Asymmetric conjugate addition; Copper;
Phosphorus ligands.
Сhiral phosphite ligands are extremely attractive for transition-metal-mediated
asymmetric catalysis. Indeed they can be simply prepared from readily accessible precursors, are
less sensitive to air and other oxidizing agents than typical phosphanes, and are inexpensive.
This has allowed the generation of extensive libraries of structurally diverse chiral ligands. In
addition, phosphite-type ligands are characterized by a highly modular structure and pronounced
∗ Corresponding author. Tel.: +7-4912-280580; fax +7-4912-281435; e-mail: k.gavrilov@rsu.edu.ru
2

π-acceptor capacity. See, for example, selected review articles1-6 and literature reports regarding
chiral phosphites,7-13 phosphoramidites14-19 and diamidophosphites.20,21
The careful selection of a suitable chiral backbone has become crucial in the design of
any modern stereoinducer for enantioselective catalysis.22 Several naturally occuring building
blocks, as well as binaphthyl and biphenyl derivatives, have been widely used in the
development of phosphite-type chiral ligands.1-3,8,9,14,22 Conversely, there are only a few
examples of phosphite-type ligands LA–C (Figure 1) based on the NOBIN [(2'-amino-[1,1'-
binaphthalen]-2-ol)] chiral synthon23-29 which is surprising since chiral phosphanes with the
NOBIN framework are well-known.30-37
Figure 1. Phosphite-type ligands with the NOBIN backbone.
Herein, we describe the synthesis of new NOBIN-derived P*-monodentate
diamidophosphite and P,N-bidentate phosphite ligands as well as their catalytic performance in
asymmetric Pd-catalyzed allylic alkylation and Cu-catalyzed conjugate addition reactions. The
Pd-catalyzed allylic substitution reaction is a powerful and well-established synthetic tool, which
is tolerant of various functional groups and operates with a wide range of nucleophiles. As a
consequence this reaction is widely used in the synthesis of enantiomerically pure natural and
unnatural compounds.7,38-47 In particular, the products of alkylation with dimethyl malonate,
which proceeds under mild conditions and without involvement of the C*-stereocenter, can
easily be converted to esters and amides of chiral unsaturated carboxylic acids.46 The Pd-
catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate with 1-cyclohexenylpyrrolidine has
also been used as a key step in the synthesis of a selective antimuscarinic agent.47,48 Finally, this
represents a common benchmark test for initial ligand screening and the enantiomeric excesses
obtained are the simplest indexes for the evaluation of new chiral ligands.7,45,49 Another target,
the hydrometallation – Cu-catalyzed 1,4-addition reaction is an operationally simple and
convenient process which is tolerant of many functional groups and has been used for the highly
enantioselective one-step synthesis of steroid derivatives.50-53
3

N
N
P
N
+
N
PhCH3
N
P
O
- 2 Et2NH
2
NH
OH
- Et3N.HCl
HN
O
O
P
(
)-1
Ra
(
)-1
or Sa
O
2.5 Et3N, PhCH3
O
P
(
,
)-3
(
,
)-3
Ra Ra
and Ra Sa
+
Cl
O
Scheme 1. Synthesis of ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3.
Starting from (Ra)- or (Sa)-BINOL, both enantiomers of N-Bn-NOBIN ((Ra)-1 and (Sa)-
1)) were readily prepared following known methodology.36,37,54,55 With these enantiomers in
hand, P*-monodentate diamidophosphite 2 as well as P,N-containing phosphites (Ra,Ra)-3 and
(Ra,Sa)-3 were prepared in a single-step (Scheme 1). Diamidophosphite 2 was synthesized by the
direct phosphorylation of (Ra)-1 with N,N,N',N',N'',N''-hexaethylphosphanetriamine in boiling
toluene. This method did not require additional base and the only by-product was volatile HNEt2.
Compounds (Ra,Ra)-3 and (Ra,Sa)-3 were obtained by phosphorylation of the corresponding
enantiomer of N-Bn-NOBIN with (Ra)-4-chlorodinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine56
in toluene, utilising Et3N as a HCl scavenger. Compounds 2, (Ra,Ra)-3 and (Ra,Sa)-3 were
obtained as white solids and were found to be sufficiently stable to allow manipulation in the
open air and could be stored under dry conditions at room temperature for at least a few months
with minimal degradation. Phosphites (Ra,Ra)-3 and (Ra,Sa)-3 readily formed solvates with
toluene. Therefore, crystallization from heptane and extended drying under high vacuum were
required for the preparation of analytically pure material.
1
Ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3 were fully characterized by 31P, H and 13C NMR
spectroscopy 2D-NMR (COSY, NOESY, HSQC and HMBC), MALDI TOF/TOF mass
spectrometry as well as elemental analysis. The data collected was in accordance with the
proposed structures. Diamidophosphite 2 with a P*-stereocenter was formed as single
stereoisomer, as indicated by the narrow singlet at δ 152.6 observed in the 31P NMR spectrum in
P
CDCl3. It should be emphasized that during the preparation of (Ra,Ra)-3 and (Ra,Sa)-3,
phosphorylation occured exclusively at the hydroxyl group. Note, the presence of signals
4

3
characteristic of the protons of the peripheral amino group (δ 4.32, d, J = 6.1 Hz, 2H, NCH2
H
1
and δ 4.02, t, 3J = 6.1 Hz, 1H, NH) in the H NMR spectrum of solvate (Ra,Ra)-3 with toluene
H
(see ESI).
Figure 2. The molecular structure of diamidophosphite 2, showing the atomic numbering of non-
carbon atoms and 40% probability displacement ellipsoids. H atoms have been omitted for
clarity.
Single crystals suitable for X-ray crystal structure analysis were obtained for
diamidophosphite 2 by crystallisation from toluene at – 20 °C. This analysis showed that ligand
2 crystallizes in the chiral orthorhombic space group P212121. The N-Bn-NOBIN framework
corresponded to the (R)-enantiomer and the absolute configuration at phosphorus was (S) (Figure
2). Note that similar ligands LC (Figure 1) containing the (Sa)-N-Ph-NOBIN core were found to
have P*-stereocenters with the (R)-configuration, irrespective of the absolute configuration of
the bis(1-phenylethyl)amine fragment.29 The mean planes of the two naphthalene cores were
inclined to each other at 61.2(2)° and the P1–O2 bond length was 1.665(3) Å. The exocyclic P1–
N4 bond (1.649(3) Å) was considerably shorter than the P1–N3 bond (1.730(3) Å) within the
1,3,2-oxazaphosphepine ring, which exhibited a boat conformation. The exocyclic nitrogen atom
N4 was planar, whereas the N3 nitrogen was slightly pyramidal (sums of all angles were
360.0(5)° and 354.6(5)°, respectively). The O2–P1–N3 and O2–P1–N4 angles (96.15(14) and
98.52(16)°) showed significant distortions from the tetrahedral arrangements around the P*-
stereocenter meaning the phosphorus lone pair was not hindered by bulky substituents. A search
5

of the Cambridge Structural Database (CSD, Version 5.3557 for compounds containing
asymmetric phosphorus atoms bonded to the NOBIN fragment has showed no hits.
Table 1. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate 4 with dimethyl
malonate a
Entry
Ligand
L/Pd
Conversion (%)
ee (%) b,c
1
2
3
4
5
6
7
8
9
1
2
1
2
1
2
1
2
1
2
42
47
57
86
0
4 (R)
55 (R)
78 (R)
88 (R)
-
2
2
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Sa)-3
(Ra,Sa)-3
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Sa)-3
(Ra,Sa)-3
0
-
50
40
70
38
57 (R) d
13 (R) d
50 (R) e
31 (R) e
10
a Reactions were carried out with 2 mol% of [Pd(allyl)Cl]2 in CH2Cl2 at 18 °C for 48 h, BSA
(0.11 mL, 0.44 mmol), KOAc (0.002 g).
b Conversion and ee were determined by HPLC (Daicel Chiralcel OD-H, C6H14/i-PrOH = 99/1,
0.3 mL/min, 254 nm, t(R) = 28.0 min, t(S) = 29.3 min).
c The absolute configuration was assigned by comparison of the HPLC retention times reported
in the literature.75
d Equimolar mixture of ligand (Ra,Ra)-3 and ZnTPP.
e Equimolar mixture of ligand (Ra,Sa)-3 and ZnTPP.
The N-Bn-NOBIN-derived ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3 were evaluated in the Pd-
catalyzed asymmetric allylic alkylation reaction of (E)-1,3-diphenylallyl acetate 4 with dimethyl
malonate using [Pd(allyl)Cl]2 as a palladium source (Table 1). The nucleophile was generated in
situ using N,O–bis(trimethylsilyl) acetamide (BSA) and a catalytic amount of KOAc. P*-
Monodentate ligand 2 showed moderate conversion and enantioselectivity (up to 47%
conversion, 55% ee, Table 1, entries 1, 2). P,N-Bidentate phosphite (Ra,Ra)-3 showed
significantly higher conversion and asymmetric induction (up to 86% conversion, 88% ee, Table
1, entries 3, 4). In all cases the molar ratio L/Pd = 2 was found to be optimal and the major
substitution product had the (R)-configuration. Rather surprisingly the diastereomeric ligand
(Ra,Sa)-3 generated an inactive catalytic species (Table 1, entries 5, 6).
It is well known that asymmetric catalysts are often very sensitive to small changes in
reaction conditions and the addition of suitable achiral compounds which support the chiral
catalyst system can be beneficial to the yields and enantioselectivities obtained.58,59 We observed
6

that the addition of an equimolar amount of zinc(II) 5,10,15,20-tetraphenylporphyrin (ZnTPP) to
ligands (Ra,Ra)-3 or ((Ra,Sa)-3 prior to addition of [Pd(allyl)Cl]2 had a pronounced influence on
both the conversion and asymmetric induction. In particular, (Ra,Ra)-3 proved to be less efficient
in the presence of ZnTPP (up to 50% conversion, 57% ee Table 1, entries 7, 8). At the same
time, (Ra,Sa)-3 now afforded product (R)-5 with moderate conversion and enantiomeric purity
(up to 70% conversion, 50% ee, Table 1, entries 9, 10). It should be noted that N-Zn
13
coordination was not observed by 1H, C and NOESY NMR analyses of equimolar mixtures of
(Ra,Ra)-3 or (Ra,Sa)-3 with ZnTPP in CDCl3. Therefore, we can speculate that the large aromatic
surface of the zinc(II) porphyrin molecule likely plays an important role by creating a pocket that
directs the substrate. It is appropriate to assume that π-π interactions between ZnTPP and the
aromatic groups of the substrate and (or) ligand can participate here.60
Table 2. Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate 4 with 1-
cyclohexenylpyrrolidinea
Conversion
(%) b
ee (%)
6a/6b
11/85
16/44
24/84
4/9
Entry
Ligand
L/Pd
T (°C)
anti/syn c,d
1
2
3
4
5
6
7
8
1
2
1
2
1
2
1
2
18
18
30
30
18
18
30
30
64
80
92
98
39
52
93
79/21
71/29
73/27
54/46
56/44
80/20
50/50
63/37
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Sa)-3
(Ra,Sa)-3
(Ra,Sa)-3
(Ra,Sa)-3
9/78
49/93
21/25
12/39
98
a Reactions were carried out with 2 mol% of [Pd(allyl)Cl]2 in CH2Cl2 for 48 h.
b Conversion and ee were determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH = 96/4,
0.5 mL/min, 254 nm, t(S,R)-6b = 14.0 min, t(R,S)-6b = 15.1 min; t(S,S)-6a = 16.9 min, t(R,R)-6a
= 19.0 min).
c Determined by 1H NMR.
d The absolute configuration of the predominant enantiomers of the anti- and syn-products was
assigned by comparison of the HPLC retention times reported in the literature.62, 63
Ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3 were also applied to the Pd-catalyzed allylic alkylation
of (E)-1,3-diphenylallyl acetate 4 with 1-cyclohexenylpyrrolidine (Table 2). Enamines can serve
as convenient nucleophiles for Pd-catalyzed asymmetric allylic alkylations, avoiding the need to
generate unstablilized ketone enolates using strong bases. However, successful examples of Pd-
catalyzed enantioselective allylic substitution with enamines are scarce, and this transformation
7

remains a challenge.20,47,61-63 Ligand 2 gave no conversion in this reaction, while ligands (Ra,Ra)-
3 and (Ra,Sa)-3 led to the desired product as a mixture of anti- and syn- diastereomers 6a (up to
49% ee) and 6b (up to 93% ee), respectively, with low to good conversion and diastereomeric
ratios. While the best diastereoselectivity and asymmetric induction were obtained with ligand
(Ra,Sa)-3 (Table 2, entry 6), its diastereoisomer (Ra,Ra)-3 produced better conversion at room
temperature (Table 2, entries 1, 2 and 5, 6). The optimal L/Pd molar ratio was found to be 1 for
(Ra,Ra)-3, and 2 for (Ra,Sa)-3. Excellent conversion was obtained at elevated temperatures, but
the degree of diastereoselectivity was reduced in all cases. For the most part, better
enantioselectivity was observed at 18 °C. To the best of our knowledge, the reaction with 1-
cyclohexenylpyrrolidine is the second example using phosphite-type ligands in the Pd-catalyzed
asymmetric allylic alkylation with enamine nucleophiles.20
Table 3. Pd-catalyzed allylic alkylation of cinnamyl acetate 7 with ethyl 2-oxocyclohexane-1-
carboxylate 8 a
Entry
Ligand
L/Pd
Conversion (%)
ee (%) b,c
1
2
3
4
5
6
2
2
1
2
1
2
1
2
44
0
47
68
0
65 (R)
-
62 (S)
(Ra,Sa)-3
(Ra,Sa)-3
(Ra,Ra)-3
(Ra,Ra)-3
29 (S)
-
-
0
a Reactions were carried out with 2 mol% of [Pd(allyl)Cl]2 in toluene at 20 °C for 48 h, BSA
(0.25 mL, 1 mmol), Zn(OAc)2 (0.005 g).
b Conversion and ee were determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH = 95/5,
0.4 mL/min, 254 nm, t(R) = 14.3 min, t(S) = 16.4 min).
c The absolute configuration was assigned by comparison of the HPLC retention times reported
in the literature.63
Ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3 were also screened in the allylic alkylation of
cinnamyl acetate 7 with ethyl 2-oxocyclohexane-1-carboxylate 8. It should be noted that the Pd-
catalyzed enantioselective synthesis of a quaternary carbon center is still a formidable challenge
(Table 3).38,63,65 Both P*-monodentate diamidophosphite 2 and phosphite (Ra,Sa)-3 gave similar
results, furnishing quaternary-substituted products (R)-9 and (S)-9 in 44% conversion, 65% ee
and 47% conversion, 62% ee, respectively (Table 3, entries 1, 3). For both ligands L/Pd = 1 was
found as the optimal molar ratio. Unfortunately, phosphite (Ra,Ra)-3 gave no conversion.
8

Table 4. Hydrometallation of 4-phenyl-1-butene 10 ‒ Cu-catalyzed conjugate addition to
cyclohex-2-enone 11 a
Entry
Ligand
L/Cu
Yield (%)
ee (%) b,c
1
2
3
4
5
6
2
2
1
2
1
2
1
2
71
86
0
91
82
44
44 (R)
36 (R)
-
18 (S)
15 (R)
5 (R)
(Ra,Ra)-3
(Ra,Ra)-3
(Ra,Sa)-3
(Ra,Sa)-3
.
a Reactions were carried out with 5 mol% of (CuOTf)2 C6H6 in CH2Cl2 at 20 °C for 14 h.
b The ee was determined by HPLC (Kromasil 5-CelluCoat, C6H14/i-PrOH = 95/5, 1.0 mL/min,
210 nm, t(R) = 7.6 min, t(S) = 8.1 min).
c The absolute configuration was assigned by comparison of the HPLC retention times reported
in the literature.50
Finally, the Cu-catalyzed conjugate addition of an alkylzirconium reagent (generated in situ by
hydrometallation of 4-phenyl-1-butene 10 with Schwartz reagent) to cyclohex-2-enone 11 was
investigated (Table 4). The reaction of P*-monodentate ligand 2 in the presence of
.
(CuOTf)2 C6H6 gave product 12 in up to 44% ee (Table 4, entries 1, 2). Conversely, phosphites
(Ra,Ra)-3 and (Ra,Sa)-3 showed variable yields and low enantioselectivity (Table 4, entries 3–6).
It should be noted that the asymmetric induction of this reaction is difficult to control. Indeed,
subtle differences in the structure of the phosphoramidite ligands have been reported to have a
large effect on the enantioselectivity.50
The presence of phosphorus and nitrogen donor centers in (Ra,Ra)-3 and (Ra,Sa)-3 makes
it theoretically possible that P,N-bidentate chelate or bridging coordination modes are occurring.
In order to shed light on the coordination properties of (Ra,Ra)-3 and (Ra,Sa)-3, we carried out
investigations of the palladium complexes obtained from these ligands. As a main precursor to
study the coordination behavior of (Ra,Ra)-3 and (Ra,Sa)-3, Pd(COD)Cl2 (COD - cycloocta-1,5-
diene) was selected, which is known to give stable complexes with phosphites and
phosphoramidites.66-69 However, the solutions produced by the interaction of (Ra,Ra)-3 and
(Ra,Sa)-3 with Pd(COD)Cl2 at the molar ratio L/Pd = 1 contained Pd(COD)Cl2, as well as
cycloocta-1,5-diene which was liberated during complex formation. This was indicated by the 1H
and 13C spectra of the resulting solutions, which contained resonances of equal intensity for
9

Pd(COD)Cl2 δ 6.33 (br. s., 4H), 2.93-2.88 (m, 4H), 2.59-2.55 (m, 4H) ppm and δ 116.6, 30.9
H
C
ppm 70 and COD δ 5.62 (br. s., 4H), 2.40 (br. s., 8H) ppm and δ 128.1, 28.0 ppm. Addition of a
H
C
further equivalent of ligand (Ra,Ra)-3 or (Ra,Sa)-3 led to the complete disappearance of the
Pd(COD)Cl2 signals. 31P NMR spectra of reaction mixtures each contained one signal at δP 107.4
ppm for 13a and δP 101.6 ppm for 13b whose position was independent of the L/Pd molar ratio
used. This provided evidence for the immediate formation of PdCl2L2 complexes with P-
monodentate ligand coordination.
Scheme 2. Synthesis of complexes 13a,b
Therefore, the complex formation of (Ra,Ra)-3 and (Ra,Sa)-3 with Pd(COD)Cl2 can be
represented by Scheme 2. The trans geometry of 13a,b was assigned on the basis of the presence
of virtual triplets for some of the 13C signals (see ESI).71-73 HRESI mass spectrometry was used
to confirm the elemental composition of both complexes. These results allowed us to conclude
that phosphites (Ra,Ra)-3 and (Ra,Sa)-3 act as P-monodentate ligands, and the nitrogen donor site
has no influence on the coordination behavior of the ligands.
To conclude, we have developed phosphite-type chiral ligands bearing the N-Bn-NOBIN
moiety74 and applied them to Pd-catalyzed asymmetric allylations and Cu-catalyzed conjugate
addition reactions. High enantioselectivities were achieved using (E)-1,3-diphenylallyl acetate as
a substrate and 1-cyclohexenylpyrrolidine and dimethyl malonate as nucleophiles (ee up to 93%
and 88%, respectively). The marked influence of small amounts of ZnTPP as an achiral additive
on the Pd-catalyzed allylic alkylation was discovered. Additional studies highlighting the
potential of these ligands in other asymmetric reactions are currently underway.
Acknowledgements
We acknowledge the financial support from the Russian Science Foundation (Grant No.
14-13-01383).
References and notes
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74. Experimental procedures for the preparation of ligands 2, (Ra,Ra)-3 and (Ra,Sa)-3:
Procedure for the preparation of ligand 2: A solution of P(NEt2)3 (0.55 mL, 2 mmol) and (Ra)-
N-Bn-NOBIN ((Ra)-1) (0.75 g, 2 mmol) in toluene (6 mL) was stirred at reflux for 90 min. The
solution was cooled to 20 °C, filtered through a short plug of Al2O3, and the column washed
twice with toluene (4 mL). The solvent was evaporated under reduced pressure (40 Torr). The
residue was purified by crystallization from heptane at - 20 °C. (Ra)-5-Benzyl-4-(diethylamino)-
4,5-dihydrodinaphtho[2,1-d:1',2'-f][1,3,2]oxazaphosphepine (2): White powder; yield 0.68 g
(71%); R 0.67 (hexane/ EtOAc, 2/1, silica gel 60 F254); [α]D25 = - 278.4 (c 0.5, toluene). 31P{H}
f
1
NMR (CDCl3, 162.0 MHz): δ = 152.6. H NMR (CDCl3, 600.1 MHz): δ = 1.10 (t, 3JH,H = 7.1,
P
H
13

2
3
3
6 H, CH3); 2.97 (ddq, 3JH,H = 7.1, JH,H = 14.1, JH,P = 11.1, 2 H, NCH2); 3.05 (ddq, JH,H = 7.1,
2JH,H = 14.1, 3JH,P = 9.7, 2 H, NCH2); 4.58 (dd, 2JH,H = 15.5, 3JH,P = 3.5, 1 H, NCH2Ph); 4.72 (dd,
3
2JH,H = 15.5, JH,P = 9.7, 1 H, NCH2Ph); 6.65-6.62 (m, 4 H, CHPh); 6.82-6.79 (m, 1 H, CHPh);
3
6.92 (d, JH,H = 8.6, 1 H, CHAr); 7.16-7.13 (m, 1 H, CHAr); 7.24-7.21 (m, 1 H, CHAr); 7.36 (d,
3JH,H = 8.6, 1 H, CHAr); 7.40-7.37 (m, 1 H, CHAr); 7.43-7.40 (m, 1 H, CHAr); 7.60 (d, 3JH,H = 8.8,
1 H, CHAr); 7.63 (d, 3JH,H = 8.7, 1 H, CHAr); 7.83 (d, 3JH,H = 8.5, 1 H, CHAr); 7.85 (d, 3JH,H = 7.9,
3
3
1 H, CHAr); 7.96 (d, JH,H = 8.3, 1 H, CHAr); 8.03 (d, JH,H = 8.7, 1 H, CHAr). 13С{H} NMR
(CDCl3, 150.9 MHz): δ = 15.22 (d, 3JC,P = 2.7, СH3); 38.94 (d, 2JC,P = 20.9, NCH2); 51.11 (d,
C
2JC,P = 43.3, NCH2Ph); 122.03 (d, 3JC,P = 1.8, CHAr); 123.26 (s, CHAr); 124.22 (s, CHAr); 124.63
3
(s, CHAr); 125.63 (s, CHAr); 125.77 (s, CHAr); 126.27 (d, JC,P = 4.0, CAr); 126.41 (s, CHPh);
126.96 (s, CHAr); 127.47 (d, 4JC,P = 0.6, CHPh); 127.54 (s, CHAr); 127.67 (s, CHPh); 127.88 (s,
CHAr); 128.09 (s, CHAr); 128.56 (s, CHAr); 128.64 (s, CAr); 129.83 (s, CHAr); 130.98 (s, CAr);
131.00 (d, 5JC,P = 0.6, CAr); 132.83 (s, CAr); 133.16 (d, 4JC,P = 1.8, CAr); 138.51 (d, 3JC,P = 10.4,
PNCH2C); 140.82 (d, 2JC,P = 6.3, PNC); 150.96 (d, 2JC,P = 1.6, POC). MS (MALDI TOF/TOF):
m/z (%) = 495 (100) [M + H2O + H] +. C31H29N2OP: calcd: C, 78.13; H, 6.13; N, 5.88; found: C,
78.41; H, 6.18; N, 5.64. Procedure for the preparation of ligands (Ra,Ra)-3 and (Ra,Sa)-3: A
solution of the appropriate enantiomer of N-Bn-NOBIN ((Ra)-1 or (Sa)-1)) (0.75 g, 2 mmol) in
toluene (4 mL) was added dropwise to a vigorously stirred solution of (Ra)-4-
chlorodinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine (0.70 g, 2 mmol) and Et3N (0.70 mL, 5
mmol) in toluene (6 mL). The mixture that obtained was stirred for 24 h at 20 °C, then heated to
40 °C for 1 h before being cooled to 20 °C. The resulting suspension was filtered through a short
plug of Al2O3, and the column washed twice with toluene (6 mL). The solvent was evaporated
under reduced pressure (40 Torr). The residue was purified by crystallization from heptane. (Ra)-
4-((Ra)-(2'-(Benzylamino)-[1,1'-binaphthalen]-2-yl)oxy)dinaphtho[2,1-d:1',2'-
f][1,3,2]dioxaphosphepine ((Ra,Ra)-3): White powder; yield 1.04 g (75%); R 0.65 (hexane/
f
EtOAc, 2/1, silica gel 60 F254); [α]D24 = - 247.5 (c 1.0, toluene). 31P{H} NMR (CDCl3, 162.0
1
MHz): δ = 145.1. H NMR (CDCl3, 400.1 MHz): δ = 4.03 (br s, 1 H, NH); 4.32 (s, 2 H,
P
H
NCH2); 6.35 (d, 3JH,H = 8.8, 1 H, CHAr); 7.06 - 7.00 (m, 4 H, CHAr); 7.13 - 7.08 (m, 2 H, CHAr);
3
7.17 (d, JH,H = 9.1, 1 H, CHAr); 7.26 - 7.20 (m, 4 H, CHAr); 7.32 - 7.28 (m, 3 H, CHAr); 7.44 -
7.34 (m, 4 H, CHAr); 7.50 - 7.46 (m, 1 H, CHAr); 7.57 (d, 3JH,H = 8.8, 1 H, CHAr); 7.63 (d, 3JH,H
=
3
8.8, 1 H, CHAr); 7.96 - 7.84 (m, 6 H, CHAr); 8.01 (d, JH,H = 8.8, 1 H, CHAr). 13С{H} NMR
(CDCl3, 100.6 MHz): δ = 47.61 (s, NCH2); 111.76 (s, CAr); 113.84 (s, CHAr); 121.41 (s, CHAr);
C
121.49 (s, CHAr); 121.65 (s, CHAr); 121.82 (s, CHAr); 121.93 (s, CHAr); 122.40 (d, JC,P = 1.7,
CAr); 123.11 (d, JC,P = 3.8, CAr); 123.99 (s, CHAr); 124.24 (d, JC,P = 4.5, CAr); 124.69 (s, CHAr);
124.98 (s, CHAr); 125.37 (s, CHAr); 125.84 (s, CHAr); 125.87 (s, CHAr); 126.12 (s, CHAr); 126.55
14

(s, CHAr); 126.61 (s, CHAr); 126.65 (s, CHAr); 126.78 (s, CHAr); 126.93 (s, CHAr); 127.12 (s,
CHAr); 127.35 (s, CAr); 127.97 (s, CHAr); 128.18 (s, CHAr); 128.20 (s, CHAr); 128.22 (s, CHAr);
128.26 (s, CHAr); 129.44 (s, CHAr); 129.70 (s, CHAr); 130.11 (s, CHAr); 130.16 (s, CHAr); 131.06
(s, CAr); 131.41 (s, CAr); 131.42 (s, CAr); 132.26 (s, CAr); 132.67 (s, CAr); 133.66 (s, CAr); 134.15
2
2
(s, CAr); 139.48 (s, CAr); 144.46 (s, CAr); 147.01 (d, JC,P = 2.1, POC); 147.48 (d, JC,P = 4.6,
2
+
POC); 148.59 (d, JC,P = 8.0, POC). MS (MALDI TOF/TOF): m/z (%) = 690 (100) [M + H] ,
+
599 (22) [M – Bn + H] . C47H32NO3P: calcd: C, 81.84; H, 4.68; N, 2.03; found: C, 82.05; H,
4.82; N, 2.11. (Ra)-4-((Sa)-(2'-(Benzylamino)-[1,1'-binaphthalen]-2-yl)oxy)dinaphtho[2,1-d:1',2'-
f][1,3,2]dioxaphosphepine ((Ra,Sa)-3): White powder; yield 1.24 g (90%); R 0.68 (hexane/
f
EtOAc, 2/1, silica gel 60 F254); [α]D24 = - 597.1 (c 1.0, toluene). 31P{H} NMR (CDCl3, 162.0
1
MHz): δ = 145.6. H NMR (CDCl3, 400.1 MHz): δ = 4.06 (br s, 1 H, NH); 4.39 (s, 2 H,
P
H
3
3
NCH2); 6.04 (d, JH,H = 8.8, 1 H, CHAr); 6.99 (d, JH,H = 8.8, 1 H, CHAr); 7.07 - 7.04 (m, 3 H,
3
CHAr); 7.26 - 7.16 (m, 7 H, CHAr); 7.51 - 7.29 (m, 9 H, CHAr); 7.53 (d, JH,H = 8.8, 1 H, CHAr);
3
3
7.81 (d, JH,H = 8.0, 1 H, CHAr); 7.97 - 7.88 (m, 5 H, CHAr) ; 8.00 (d, JH,H = 8.8, 1 H, CHAr).
13С{H} NMR (CDCl3, 150.9 MHz): δ = 47.80 (s, NCH2); 111.68 (s, CAr); 114.21 (s, CHAr);
C
121.74 (d, JC,P = 1.1, CHAr); 121.89 (s, CHAr); 121.98 (s, CAr); 122.27 (d, JC,P = 4.7, CHAr);
122.54 (d, JC,P = 2.3, CAr); 123.75 (d, JC,P = 4.8, CAr); 124.37 (d, JC,P = 5.1, CAr); 124.48 (s,
CHAr); 124.74 (s, CHAr); 125.04 (s, CHAr); 125.57 (s, CHAr); 125.89 (s, CHAr); 126.08 (s, CHAr);
126.19 (s, CHAr); 126.74 (s, CHAr); 126.80 (s, CHAr); 126.84 (s, CHAr); 126.86 (s, CHAr); 127.06
(s, CAr); 127.21 (s, CHAr); 127.53 (s, CAr); 128.09 (s, CHAr); 128.25 (s, CHAr); 128.26 (s, CHAr);
128.29 (s, CHAr); 128.37 (s, CHAr); 129.07 (s, CHAr); 129.36 (s, CHAr); 130.06 (s, CHAr); 130.13
(s, CHAr); 130.30 (s, CHAr); 131.16 (s, CAr); 131.51 (s, CAr); 131.71 (s, CAr); 132.30 (s, CAr);
132.78 (d, JC,P = 1.1, CAr); 133.66 (s, CAr); 134.51 (d, JC,P = 1.0, CAr); 139.55 (s, CAr); 144.75 (s,
CAr); 147.16 (d, 2JC,P = 2.6, POC); 147.49 (d, 2JC,P = 4.7, POC); 148.75 (d, 2JC,P = 8.8, POC). MS
+
+
(MALDI TOF/TOF): m/z (%) = 690 (100) [M + H] , 599 (11) [M – Bn + H] . C47H32NO3P:
calcd: C, 81.84; H, 4.68; N, 2.03; found: C, 82.13; H, 4.74; N, 2.18.
75. Thiesen, K. E.; Maitra, K.; Olmstead, M. M.; Attar, S. Organometallics 2010, 29, 6334 -
6342.
15

Graphical abstract.
1