Bisphenylene homologues of BINOL-based phosphoramidites: synthesis, stereostructure, and application in catalysis

Article abstract of DOI:10.1016/j.tetlet.2010.02.041

Bis-ortho- and bis-meta-phenylene homologues of BINOL-based N,N-dimethylphosphoramidites were prepared from the corresponding diols by treatment with hexamethyltriaminophosphane. Phosphoramidites derived from bulkier secondary amines were synthesized by 5

Full text of DOI:10.1016/j.tetlet.2010.02.041

Tetrahedron Letters 51 (2010) 1966–1970
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Bisphenylene homologues of BINOL-based phosphoramidites: synthesis,
stereostructure, and application in catalysis
b
a
b
c
Natalia Miklášová a, , Ondrej Julínek , Michaela Mešková , Vladimír Setnicka , Marie Urbanová ,
ˇ
ˇ
Martin Putala a,
*
a Department of Organic Chemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, 842 15 Bratislava, Slovak Republic
b Department of Analytical Chemistry, Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
c Department of Physics and Measurements, Institute of Chemical Technology, Technická 5, 166 28 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Bis-ortho- and bis-meta-phenylene homologues of BINOL-based N,N-dimethylphosphoramidites were
prepared from the corresponding diols by treatment with hexamethyltriaminophosphane. Phosphorami-
dites derived from bulkier secondary amines were synthesized by 5-phenyl-1H-tetrazole-promoted
amine exchange. All the phosphoramidites were obtained as single diastereomers. Their configurations
at the C(naphthyl)–C(phenyl) axes were determined by vibrational circular dichroism (VCD) spectros-
copy. Preliminary testing of the ligands in copper-catalyzed conjugate addition of diethylzinc to acyclic
enones and nitrostyrene gave the corresponding products in up to 74% ee.
Received 29 November 2009
Revised 19 January 2010
Accepted 5 February 2010
Available online 12 February 2010
Ó 2010 Elsevier Ltd. All rights reserved.
BINOL-based phosphoramidites are privileged ligands in
enantioselective organic reactions such as asymmetric rhodium-
catalyzed hydrogenations of alkenes,1 palladium- and nickel-cata-
lyzed hydrovinylations of alkenes,2 and copper-catalyzed
alkylations of imines3 and activated alkenes (conjugate addition).4
Two types of structural modifications of the basic MonoPhos (1)
structural motif have been reported which affect positively the
enantioselectivity of catalyzed reactions (Fig. 1): (a) replacement
of the phosphoramidite dimethylamino group with a bulkier sec-
ondary amine, including examples containing additional stereo-
genic center(s) (e.g., 2);5,6 (b) introduction of sterically
demanding groups to positions 3 and 30 of the binaphthyl skeleton,
for example, 3.6,7
We examined several methods for the preparation of phospho-
ramidites from diols 6 and 7: (i) preparation of the corresponding
chlorophosphite and in situ reaction with a secondary amine or (ii)
direct reaction with aminophosphanyl dichloride (both under var-
ious conditions),10 and (iii) reaction with triaminophosphane.11
Figure 1. Structural modifications of BINOL-based phosphoramidites.
Having developed an effective procedure for the introduction of
aryl groups at positions 2 and 20 of 1,10-binaphthyl,8 we aimed to
prepare and characterize bisphenylene homologues of BINOL-
based phosphoramidites 4 and 5 and explore their potential as li-
gands in asymmetric catalysis.
For the preparation of BINOL bis-ortho-phenylene homologue
(R)-6 and bis-meta-phenylene homologue (S)-7 (Scheme 1), we
exploited the previously described efficient diarylation of diiodide
(R)- or (S)-8 via Negishi cross-coupling,8 followed by demethyla-
tion of (R)-9 and (S)-10 with excess boron tribromide in dilute
dichloromethane solution.9
* Corresponding author. Tel.: +421 2 60296323; fax: +421 2 60296337.
E-mail address: putala@fns.uniba.sk (M. Putala).
Present address: Department of Chemical Theory of Drugs, Faculty of Pharmacy,
Scheme 1. Preparation of BINOL bisphenylene homologues (R)-6 and (S)-7.
Reagents and conditions: (a) o- or m-MeOC6H4ZnCl (6 equiv), 5% Pd(PPh3)4, THF,
MW, 120 °C, 40–60 min; (b) BBr3 (10 equiv), CH2Cl2,0 °C, 4 h.
ˇ
Comenius University in Bratislava, Kalinciakova 8, 832 32 Bratislava, Slovak Republic.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.041

N. Miklášová et al. / Tetrahedron Letters 51 (2010) 1966–1970
1967
While the first two methods gave complex mixtures of products
including oligomers, the latter allowed the preparation of the de-
sired phosphoramidites 4a and 5a in reasonable yields (Scheme
2), when hexamethyltriaminophosphane (HMPT)12 was used.
However, reactions with triaminophosphanes derived from bulkier
secondary amines did not proceed.
In order to prepare other dialkylphosphoramidites, we treated
dimethylphosphoramidites (R)-4a and (S)-5a with secondary
amines (piperidine and morpholine) in the presence of 5-phenyl-
1H-tetrazole.13 The target phosphoramidites (R)-4 and (S)-5 were
obtained in low to moderate yields depending on the number of
chromatographic steps (Table 1).14
can be observed in the 1H NMR spectra at decreased temperature.
For instance, bis(ortho-methoxyphenyl) derivative (R)-9 exists at
ꢀ50 °C in CDCl3 as a mixture of three interconvertible diastereo-
mers (R,R,R), (R,S,R), and (R,S,S) in the ratio 16:60:24. However,
all phosphoramidites 4 and 5 were obtained as single diastereo-
mers, exhibiting sharp signals in 1H NMR spectra within wide tem-
perature ranges. We failed to obtain crystals suitable for X-ray
structure analysis. Therefore, the configuration around the naph-
thyl–phenyl axes was determined using vibrational circular
dichroism (VCD) by making a comparison of the experimental with
the calculated spectra obtained by density functional theory.15 We
calculated and measured the VCD spectra of the phosphoramidites
(R)-4a and (S)-5a with the aim of determining the configuration at
the naphthyl–phenyl stereogenic axes.
Intermediate methoxy derivatives 9 and 10 exhibit atropiso-
merization by rotation around the naphthyl–phenyl axes which
Conformational analysis of the (S,R,R), (S,R,S), and (S,S,S) config-
urations of 5a revealed only one abundant conformer with (R,R)
configuration at the naphthyl–phenyl stereogenic axes, the struc-
ture of which is shown in Figure 2a. Conformers with (R,S) config-
uration were energetically unfavorable and their populations were
<1%. No conformer with (S,S) configuration was found, the connec-
tion between the phenyl groups limits the conformational flexibil-
Scheme 2. Preparation of N,N-dimethylphosphoramidites (R)-4a and (S)-5a by
reaction with HMPT. Reagents and conditions: P(NMe2)3 (1.25 equiv), NH4Cl
(2.5 mol %), C6H6, rt, 7 h.
Table 1
Preparation of phosphoramidites (R)-4 and (S)-5 by amine exchangea
Entry
Amine
Product
Yield (%)
1
2
3
4
Piperidine
Morpholine
Piperidine
Morpholine
(R)-4b
(R)-4c
(S)-5b
(S)-5c
29
50
51
25
a
Reagents and conditions: HNR2 (2 equiv), 5-phenyl-1H-tetrazole (1.5 equiv),
toluene, reflux, 6–9 h.
**
**
Figure 2. B3LYP/6-31G structures of the (S,R,R)-5a (a) and the major conformer,
(R,S,S)-4a (b).
Figure 3. B3LYP/6-31G IR and VCD spectra of (S,R,R)-5a and the experimental IR
and VCD spectra measured in CDCl3 (0.13 mol Lꢀ1).

1968
N. Miklášová et al. / Tetrahedron Letters 51 (2010) 1966–1970
ity of the molecule and precludes this configuration. The VCD and
IR absorption spectra of a single abundant conformer of 5a with
of the reaction conditions was performed on diethylzinc addition
to chalcone with ligand (S)-5a in toluene as the solvent (Table 2).
The results showed that copper(II) triflate was the best copper
source (in terms of both the yield and the enantioselectivity, en-
tries 2 and 3). Increasing the catalyst loading improved both the
yield and ee of the product (entries 1–3). Decreasing the tempera-
ture from ꢀ10 °C to ꢀ30 °C decreased remarkably the catalyst
activity and stereoselectivity (entry 5).
Both copper salts were further examined in experiments with
other ligands and on other substrates under optimized conditions
(Table 3). In agreement with our previous observations, the reac-
tions with copper(II) triflate gave the best results in general. Re-
sults with copper(II) acetate are given when its use resulted in
higher yields and/or ee of the corresponding product. The use of
copper(II) acetate was found to be beneficial only in combination
with the dimethylamino ligand (R)-4a.
**
(S,R,R) configuration were calculated at the B3LYP/6-31G level
and compared with experimental spectra (Fig. 3). A similar confor-
mational analysis was carried out for (R,S,S), (R,S,R), and (R,R,R)-4a.
This revealed two conformers, both with (S,S) configuration at the
naphthyl–phenyl stereogenic axes, differing in the orientation of
the lone electron pair at the nitrogen atom, with relative popula-
tions of 85% (Fig. 2b) and 15%. Again, the other configurations were
either energetically unfavorable or sterically impossible. The IR
absorption and VCD spectra of two abundant conformers of 4a
with (R,S,S) configuration were calculated at the B3LYP/6-31G** le-
vel, weight-averaged and compared with experimental spectra
(Fig. 4). An excellent agreement between the calculated and exper-
imental spectra for both the phosphoramidites 4a and 5a confirms
the exclusive (R,S,S) and (S,R,R) configurations of 4a and 5a,
respectively.16
Reasonable levels of enantioselectivity in the copper-catalyzed
diethylzinc addition to chalcone and benzalacetone were observed
when the dimethylamino ligand (S)-5a was used (70% and 74% ee).
Since phosphoramidites have been successfully used as ligands
in the stereoselective catalysis of copper-mediated conjugate addi-
tion,4 we tested phosphoramidites 4 and 5 as ligands in conjugate
additions of diethylzinc to enones and a nitroalkene. Optimization
Table 2
Optimization of the reaction conditions in the conjugate addition catalyzed by the
copper complex of phosphoramidite (S)-5aa
c
Entry
Copper source (mol %)
T (°C)
Yieldb (%)
ee %
1
2
3
4
5
Cu(OTf)2 (0.5)
Cu(OTf)2 (1)
Cu(OTf)2 (2)
ꢀ10
ꢀ10
ꢀ10
ꢀ10
ꢀ30
27
69
77
27
10
52 (ꢀ)
65 (ꢀ)
70 (ꢀ)
10 (ꢀ)
49 (ꢀ)
Cu(OAc)2ꢁH2O (2)
Cu(OTf)2 (2)
a
b
c
Reagents and conditions: Et2Zn (1.7 equiv), CuX2, (S)-5a, toluene, 16 h.
1H NMR yield with ferrocene as the internal standard.
Determined by HPLC on Chiralcel Daicel OD-H.
Table 3
Conjugate additions catalyzed by the copper complexes of phosphoramidites (R)-4
and (S)-5a
c
Entry
R
Y
X
L*
Yieldb (%)
ee %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
H
H
H
H
H
H
Cl
Cl
COPh
COPh
COPh
COPh
COPh
COPh
COMe
COMe
COMe
COMe
COMe
COMe
COMe
COMe
COMe
COMe
NO2
OAc
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OAc
OTf
OTf
OTf
OAc
OAc
4a
4a
4b
4c
5a
5b
4a
4b
5a
4a
4b
5a
4a
4a
4b
5a
4a
5a
62
15
99
92
77
66
55
62
63
47
58
77
60
89
55
66
65
34
39 (+)
18 (+)
69 (+)
57 (+)
70 (ꢀ)
74 (ꢀ)
18d (+)
14d (+)
15d (ꢀ)
33d (+)
17d (+)
21d (ꢀ)
28 (+)
19 (+)
39 (+)
74 (ꢀ)
30e (+)
24e (ꢀ)
Cl
MeO
MeO
MeO
H
H
H
H
H
H
NO2
a
Reagents and conditions: Et2Zn (1.7 equiv), CuX2 (2 mol %), L* (4 mol %), tolu-
ene, ꢀ10 °C, 16 h.
b
1H NMR yield with ferrocene as the internal standard.
Determined by HPLC on Chiralcel Daicel OD-H.
Determined by HPLC on Chiralcel Daicel AD-H.
Determined by GC on Chiralsil b-Dex.
c
d
**
Figure 4. B3LYP/6-31G IR and VCD spectra of (R,S,S)-4a and the experimental IR
e
and VCD spectra measured in CDCl3 (0.13 mol Lꢀ1).

N. Miklášová et al. / Tetrahedron Letters 51 (2010) 1966–1970
1969
(S)-7: Yield 100% (0.94 g), off white solid, mp 120–128 °C with decomp., ½a D20
ꢃ
The latter value is higher than those previously reported with other
simple binaphthyl-based phosphoramidites (such as 1, up to 60%
ee),6,17 although application of chiral amine-based phosphorami-
dites leads to higher levels of stereoselectivity (e.g., 93% ee in the
case of 2).5a Diethylzinc additions to substituted benzalacetones
and nitrostyrene occurred with low enantioselectivity, but slightly
higher with the dimethylamino ligand (R)-4a (18–33% ee).
In conclusion, bis-ortho- and bis-meta-phenylene homologues
of BINOL-based phosphoramidites were prepared and their stereo-
chemistry was determined by VCD spectroscopy. Preliminary test-
ing of the prepared ligands in copper-catalyzed conjugate addition
of diethylzinc to acyclic enones and nitrostyrene gave the corre-
sponding products in low to moderate ee (up to 74% ee). The design
of this group of ligands and their application in enantioselective
catalytic transformations are under further investigation.
ꢀ2.70 (c 1; CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.94 (d, J = 8.1 Hz, 2H),
d = 7.89 (d, J = 8.4 Hz, 2H), 7.49 (ddd, J = 7.8, 6.3, 1.5 Hz, 2H), 7.41–7.29 (m, 6H),
6.74 (dd, J = 8.1, 7.8 Hz, 2H), 6.54 (dd, J = 7.2, 1.8 Hz, 2H), 6.07 (d, J = 7.8 Hz, 2H),
5.90 (dd, J = 2.1, 1.8 Hz, 2H), 4.63 (br s, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d = 154.3 (2C), 142.9 (2C), 139.1 (2C), 134.4 (2C), 134.1 (2C), 132.3 (2C), 128.3
(2C), 128.2 (2C), 128.1 (2C), 128.0 (2C), 127.4 (2C), 126.6 (2C), 125.6 (2C), 121.7
(2C), 116.4 (2C), 113.2 (2C) ppm. IR (KBr):
m = 3305, 2923, 1684, 1653, 1559,
1465, 1338, 1191, 810, 782, 677 cmꢀ1. Anal. Calcd for C32H22O2 (438.52): C,
87.65; H, 5.06. Found: C, 87.15; H, 5.32.
10. (a) Gergely, I.; Hegedüs, C.; Gulyás, H.; Szöllösy, A.; Monsees, A.; Riermeier, T.;
Bakos, J. Tetrahedron: Asymmetry 2003, 14, 1087–1090; (b) Nozaki, K.; Sakai, N.;
Nanno, T.; Higashijima, T.; Mano, S.; Horiuchi, T.; Takaya, H. J. Am. Chem. Soc.
1997, 119, 4413–4423; (c) Scherer, J.; Huttner, G.; Büchner, M.; Bakos, J. J.
Organomet. Chem. 1996, 520, 45–58.
11. Hust, R.; de Vries, N. K.; Feringa, B. L. Tetrahedron: Asymmetry 1994, 5, 699–708.
12. To a solution of (R)-6 or (S)-7 (1.14 mmol, 0.50 g) in benzene (10 mL) were
added NH4Cl (0.028 mmol, 1.5 mg) and HMPT (1.42 mmol, 0.23 g). The
reaction mixture was heated to reflux for 4 h, then the solvent was removed
and the pure phosphoramidites (R)-4a and (S)-5a were isolated as white
powders by chromatography, using short silica gel columns, neutralized with
Et3N (eluent CH2Cl2/hexanes, 5:1).
Acknowledgments
(R)-4a: Yield 64% (0.37 g), white solid, mp 97–107 °C with decomp., ½a D20
ꢃ
+1.99
(c 1.00; CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.75–7.88 (m, 4H), 7.41–7.48
(m, 3H), 7.29–7.36 (m, 5H), 6.87–6.99 (m, 2H), 7.10–7.20 (m, 2H), 6.74–6.80
(m, 2H), 6.67 (ddd, J = 7.5, 7.5, 0.8 Hz, 1H), 6.50 (ddd, J = 7.5, 7.5, 0.8 Hz, 1H),
2.52 (s, 3H), 2.49 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3): d = 150.37, 149.7,
137.2, 135.7, 135.3, 134.4, 134.1, 133.0 (2C), 132.8, 132.2, 131.2 (2C), 130.1,
129.3 (2C), 128.3 (2C), 127.9 (2C), 127.5 (2C), 127.1 (2C), 125.8 (2C), 125.4 (2C),
121.8, 121.4, 117.4, 117.2, 35.2, 34.9 ppm. 31P NMR (121.5 MHz, CDCl3):
The authors thank Professor Kenneth Ruud and Dr. Maxime
Guillaume (University of Tromsø, Norway) for helping with the
project and for valuable discussions. We also acknowledge the
CTCC (University of Tromsø, Norway) and Computer Center (ICT
Prague, Czech Republic) for providing access to computational re-
sources. This work was supported by the Slovak Research and
Development Agency (Grant LPP-0210-06), the Slovak Grant
Agency for Science (Grant No. 1/0265/09) and the Ministry of Edu-
cation, Youth, and Sports of the Czech Republic (Research grant
MSM6046137307).
d = 126.0 ppm. IR (CDCl3):
m = 3055, 2840, 2803, 1578, 1488, 1233, 1195, 1079,
820, 752, 710 cmꢀ1. HRMS: no molecular peak observable; calcd for C32H21O2P
[MꢀN(CH3)CH2]+ 468.1279, found 468.2003.
(S)-5a: Yield 37% (0.22 g), white solid, mp 95–105 °C with decomp., ½a D20
ꢀ6.23
ꢃ
(c 1.00, CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.84–7.96 (m, 4 H), 7.40–7.51
(m, 3H), 7.28–7.32 (m, 5H), 6.79 (dd, J = 8.1, 0.9 Hz, 1H), 6.73 (dd, J = 8.0, 1.0 Hz,
1H), 6.62 (q, J = 7.3 Hz, 2H), 6.20 (s, 1H), 6.13 (dd, J = 7.6, 1.2 Hz, 1H), 6.00 (d,
J = 7.3 Hz, 1H), 5.61 (br s, 1H), 2.90 (s, 3H), 2.86 (s, 3H) ppm. 13C NMR (75 MHz,
CDCl3): d = 154.3, 142.8, 142.5, 139.7, 138.9, 134.5, 134.4, 134.2, 132.3, 132.2,
128.2 (2C), 128.0 (2C), 127.4 (2C), 127.3, 127.2, 127.1, 126.7, 126.6 (2C), 126.5
(2C), 125.5 (2C), 123.1, 122.7, 119.4, 119.2, 118.1 (2C), 35.2, 34.9 ppm. 31P NMR
Supplementary data
(121.5 MHz, CDCl3): d = 146.2 ppm. IR (CDCl3):
m = 3050, 2929, 2843, 1578,
General procedures, methods for molecular modelling and char-
acterization data for the products of diethylzinc addition, and NMR
spectra of compounds (R)-4, (S)-5, (R)-6, and (S)-7 are available.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.02.041.
1487, 1258, 1182, 1065, 819, 788, 714 cmꢀ1. HRMS: calcd for C34H26NO2PH
[M+H]+ 512.1780, found 512.2352; calcd for C32H21O2P [MꢀN(CH3)CH2]+
468.1279, found 468.2641.
13. (a) Pena, D.; Minnaard, A. J.; de Vries, J. G.; Feringa, B. L. J. Am. Chem. Soc. 2002,
124, 14552–14553; (b) Albert, J.; Bosque, R.; Cadena, J. M.; Delgado, S.; Granell,
J. J. Organomet. Chem. 2001, 634, 83–89; (c) Chow, C. P.; Berkman, C. E.
Tetrahedron Lett. 1998, 39, 7471–7474.
14. General procedure: (R)-4a or (S)-5a (0.49 mmol, 0.25 g) dissolved in toluene
(12.5 mL) was treated with 2 equiv of the corresponding amine (0.98 mmol), in
the presence of 1.5 equiv of 5-phenyl-1H-tetrazole (0.71 mmol, 0.10 g). The
reaction was carried out under reflux for 6–9 h. Then the solvent was removed
and the products were isolated by chromatography on short silica gel columns,
neutralized with Et3N (eluent CH2Cl2/hexanes, 5:1).
References and notes
1. (a) Nájera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584–4671; (b) Tang, W.;
Zhang, X. Chem. Rev. 2003, 103, 3029–3069.
2. RajanBabu, T. V. Chem. Rev. 2003, 103, 2845–2860.
(R)-4b: Yield 29% (0.07 g), white solid, mp 97–99 °C, ½a D20
ꢃ
+2.44 (c 0.50, CHCl3).
3. Yamada, K.; Tomioka, K. Chem. Rev. 2008, 108, 2874–2886.
1H NMR (300 MHz, CDCl3): d = 7.75–7.88 (m, 4H), 7.40–7.49 (m, 4H), 7.28–7.34
(m, 2H), 7.09–7.19 (m, 2H), 6.88–6.98 (m, 4H), 6.84 (d, J = 7.1 Hz, 2H), 6.70 (dd,
J = 7.4, 1.2 Hz, 1H), 6.48 (dd, J = 7.1, 1.2 Hz, 1H), 2.88 (m, 2H), 1.54 (m, 6H), 1.25
(m, 2H) ppm. 13C NMR (75 MHz, CDCl3): d = 150.2, 150.1, 137.4, 135.5, 132.4,
134.8, 133.3 (2C), 132.3, 130.2, 129.6 (2C), 128.1 (2C), 128.0 (2C), 127.9 (2C),
127.8 (2C), 127.6 (2C), 127.3 (2C), 126.0 (2C), 125.6 (2C), 122.0, 121.8, 121.6,
117.6, 44.9, 44.6, 27.0, 26.9, 25.2 ppm. 31P NMR (121.5 MHz, CDCl3):
4. (a) Jerphangon, T.; Pizutti, M. G.; Minaard, A. J. Chem. Soc. Rev. 2009, 38, 1039–
1075; (b) Alexakis, A.; Bäckvall, J. E.; Krause, N.; Pàmies, O.; Diéguez, M. Chem.
Rev. 2008, 108, 2796–2823.
5. (a) Alexakis, A.; Benhaim, C.; Rosset, S.; Humam, M. J. Am. Chem. Soc. 2002, 124,
5262–5263; (b) Feringa, B. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries, A.
H. M. Angew. Chem., Int. Ed. 1997, 36, 2620–2623; (c) de Vries, A. H. M.;
Meetsma, A.; Feringa, B. L. Angew. Chem., Int. Ed. 1996, 35, 2374–2376.
6. Arnold, L. A.; Imbos, R.; Mandoli, A.; de Vries, A. H. M.; Naasz, R.; Feringa, B. L.
Tetrahedron 2000, 56, 2865–2878.
7. (a) van der Berg, M.; Minnaard, A. J.; Haak, R. M.; Leeman, M.; Schudde, E. P.;
Meetsma, A.; Feringa, B. L.; de Vries, A. H. M.; Maljaars, C. E. P.; Willans, C. E.;
Hyett, D.; Boogers, J. A. F.; Hendrickx, H. J. W.; de Vries, J. G. Adv. Synth. Catal.
2003, 345, 308–323; (b) Toselli, N.; Martin, D.; Achard, M.; Tenaglia, A.; Bürgi,
T.; Buono, G. Adv. Synth. Catal. 2008, 350, 280–286.
d = 122.2 ppm. IR (CDCl3):
m = 3058, 2933, 2844, 1577, 1488, 1439, 1275,
1194, 1056, 819, 751, 710 cmꢀ1
552.2092, found 552.2599.
.
HRMS: calcd for C37H30NO2PH [M+H]+
(R)-4c: Yield 50% (0.13 g), white solid, mp 97–100 °C, ½a D20
ꢃ
+2.0 (c 0.010, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.75–7.89 (m, 4H), 7.42–7.49 (m, 3H), 7.28–7.36
(m, 3H), 7.10–7.20 (m, 2H), 6.90–7.00 (m, 4H), 6.85 (d, J = 7.9 Hz, 2H), 6.71 (dd,
J = 7.4, 1.3 Hz, 1H), 6.51 (dd, J = 7.4, 1.3 Hz, 1H), 3.46 (t, J = 4.6 Hz, 4H), 2.95 (m,
4H) ppm. 13C NMR (75 MHz, CDCl3): d = 150.1, 149.5, 136.9, 135.8, 135.2,
134.5, 133.2 (2C), 132.1, 131.2, 129.9, 129.1 (2C), 128.0, 127.8 (2C), 127.6 (2C),
127.1 (2C), 127.0 (2C), 125.9 (2C), 125.6 (2C), 125.5 (2C), 122.2, 121.6, 117.1,
116.8, 67.7 (2C), 44.0, 43.8 ppm. 31P NMR (121.5 MHz, CDCl3): d = 120.7 ppm.
8. Krascsenicsová, K.; Walla, P.; Kasák, P.; Uray, G.; Kappe, O. C.; Putala, M. Chem.
Commun. 2004, 2606–2608.
9. To a stirred solution of (R)-9 or (S)-10 (2.28 mmol, 1 g) in CH2Cl2 (30 ml) was
added dropwise BBr3 (22.8 mmol, 22.8 ml, 1 M solution in CH2Cl2) at 0 °C. After
being stirred at r.t. for 4 h, the reaction mixture was poured into ice-water. The
product was extracted with CH2Cl2 (3 ꢂ 50 ml), washed with brine, and dried
over Na2SO4. Evaporation of the solvent afforded pure (R)-6 or (S)-7.
IR (CDCl3):
m = 3062, 2945, 2892, 1579, 1488, 1439, 1245, 1204, 1190, 1112,
1078, 958, 818, 751 cmꢀ1. HRMS: calcd for C36H28NO3PH [M+H]+ 554.1885,
found 554.2612.
(R)-6: Yield 96% (0.90 g), off white solid, mp 96–100 °C with decomp., ½a D20
ꢃ
(S)-5b: Yield 51% (0.13 g), white solid, mp 99–101 °C, ½a D20
ꢀ8.0 (c 0.010,
ꢃ
+1.44 (c 1; CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.96 (dd, J = 7.5, 8.4 Hz, 4H),
7.54 (ddd, J = 7.8, 5.7, 2.1 Hz, 2H), 7.46–7.34 (m, 6H), 7.03 (dd, J = 8.4, 8.4 Hz,
2H), 6.90–6.72 (m, 2H), 6.43–6.28 (m, 4H), 3.57 (br s, 2H) ppm. 13C NMR
(75 MHz, CDCl3): d = 152.9 (2C), 132.6 (2C), 129.7 (2C), 129.6 (2C), 129.5 (2C),
128.8 (2C), 128.7 (2C), 128.6 (2C), 128.4 (2C), 128.0 (2C), 127.8 (2C), 127.2 (2C),
CHCl3). 1H NMR (300 MHz, CDCl3): d = 7.83–8.08 (m, 4H), 7.28–7.53 (m, 9H),
7.17 (d, J = 7.4 Hz, 2H), 6.63–6.90 (m, 2H), 6.53 (m, 1H), 6.28 (dd, J = 7.6, 1.4 Hz,
1H), 6.06 (d, J = 7.4 Hz, 1H), 2.35 (m, 2H), 1.66 (m, 4H), 1.25 (m, 4H) ppm. 13C
NMR (75 MHz, CDCl3): d = 154.7, 154.4, 142.8, 142.5, 139.7, 138.9, 134.5, 134.4,
134.2, 132.2 (2C), 128.2 (2C), 128.0 (2C), 127.4 (2C), 127.2 (2C), 127.1 (2C),
126.5 (2C), 125.5 (2C), 123.1, 122.9, 122.7, 119.4, 119.3, 118.2 (2C), 45.0, 44.7,
27.0, 26.9, 24.9 ppm. 31P NMR (121.5 MHz, CDCl3): d = 143.1 ppm. IR (CDCl3):
127.0 (2C), 126.2 (2C), 119.7 (2C), 116.9 (2C) ppm. IR (KBr):
m = 3446, 2922,
1684, 1653, 1558, 1464, 1395, 1067, 875, 763, 668 cmꢀ1. Anal. Calcd for
C32H22O2 (438.52): C, 87.65; H, 5.06. Found: C, 87.24; H, 5.27.
m
= 3050, 2924, 2851, 1579, 1487, 1464, 1258, 1192, 1065, 937, 819, 780,

1970
N. Miklášová et al. / Tetrahedron Letters 51 (2010) 1966–1970
703 cmꢀ1. HRMS: calcd for C37H30NO2PH [M+H]+ 552.2092, found 552.2426.
(121.5 MHz, CDCl3): d = 142.8 ppm. IR (CDCl3): m = 3051, 2924, 2852, 1580,
(S)-5c: Yield 25% (0.06 g), white solid, mp 96–100 °C, ½a D20
ꢃ
ꢀ14.0 (c 0.010;
1487, 1464, 1259, 1194, 1069, 962, 822, 788, 703 cmꢀ1. HRMS: calcd for
C36H28NO3PH [M+H]+ 554.1885, found 554.2698.
CHCl3). 1H NMR (300 MHz, CDCl3): d = 8.05–8.08 (m, 2H), 7.80–7.97 (m, 2H),
7.40–7.52 (m, 5H), 7.27–7.36 (m, 7H), 6.53–6.82 (m, 1H), 5.99 (m, 3H), 3.93 (t,
J = 4.9 Hz, 4H), 3.18 (t, J = 4.9 Hz, 4H) ppm. 13C NMR (75 MHz, CDCl3): d = 153.2,
149.2, 137.9, 137.5, 137.4, 137.0, 136.8 (2C), 134.3, 133.6, 133.2, 133.1, 131.1,
130.6, 129.6 (2C), 129.2 (2C), 128.3 (2C), 127.9 (2C), 127.5 (2C), 126.3 (2C),
125.7 (2C), 120.5, 120.4, 118.2, 117.1, 67.8 (2C), 44.5, 43.9 ppm. 31P NMR
15. (a) Stephens, P. J.; Devlin, F. J.; Pan, J. J. Chirality 2008, 20, 643–663; (b)
Stephens, P. J.; Devlin, F. J. Chirality 2000, 12, 172–179.
ˇ
16. Julínek, O.; Setnicka, V.; Miklášová, N.; Putala, M.; Ruud, K.; Urbanová, M. J.
Phys. Chem. A 2009, 113, 10717–10725.
17. Cramer, N.; Laschat, S.; Baro, A. Organometallics 2006, 25, 2284–2291.