From C2- to D2-symmetry: atropos phosphoramidites with a D2-symmetric backbone as highly efficient ligands in Cu-catalyzed conjugate additions

Article abstract of DOI:10.1016/j.tetlet.2010.04.033

Atropos phosphoramidites with the D₂-symmetric biphenyl backbone were diastereoselectively prepared with ease from achiral tetrahydroxy biphenyls. This type of ligands is proved to be highly efficient in the Cu-catalyzed conjugate additions of

Full text of DOI:10.1016/j.tetlet.2010.04.033

Tetrahedron Letters 51 (2010) 3119–3122
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From C2- to D2-symmetry: atropos phosphoramidites with a D2-symmetric
backbone as highly efficient ligands in Cu-catalyzed conjugate additions
*
Hui Zhang, Fang Fang, Fang Xie, Han Yu, Guoqiang Yang, Wanbin Zhang
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Atropos phosphoramidites with the D2-symmetric biphenyl backbone were diastereoselectively prepared
Received 1 March 2010
Revised 6 April 2010
Accepted 9 April 2010
Available online 13 April 2010
with ease from achiral tetrahydroxy biphenyls. This type of ligands is proved to be highly efficient in the
Cu-catalyzed conjugate additions of diethylzinc to
a,b-unsaturated ketones and nitroalkenes. The unique
D2-symmetric backbone endows the ligands with an excellent chiral environment.
Ó 2010 Elsevier Ltd. All rights reserved.
Axial chirality is considered to be the fundamental basis for
useful reagents and catalysts in asymmetric synthesis because
of its excellent chirality transfer property.1 Chiral ligands based
on the C2-symmetric biaryl backbone are the most widely used
axially chiral compounds,2 and some of them have been success-
fully applied in industry.3 In particular, phosphoramidites with a
C2-symmetric biaryl backbone have become a very important
class of ligands in the last decade and are frequently employed
in many catalytic asymmetric transformations.4 Alexakis reported
an efficient phosphoramidite ligand 1 with induced atropoisomer-
ism on a flexible biphenol unit (Fig. 1).5 The prominent role
played by well-defined atropoisomerism of a binaphthol moiety6
or a biphenol moiety7 in efficient catalysis has been reported as
well (compounds 2 and 3 in Fig. 1). However, for the latter cases,
particularly in the case of compound 3, it is often necessary to
introduce resolution steps with limited yields to prepare the de-
sired key intermediate enantiomers, atropos binaphthols, or
biphenols, and the undesired enantiomers could not be used effi-
ciently.8 In addition, these ligands with different biaryl backbones
do not always show high enantioselectivity in different catalyses
and substrates.5–7
best of our knowledge, this form of D2-symmetric atropos scaffold
remains unexplored in the design of chiral ligands.
Inspired by the axially chiral molecules mentioned above, we
designed a new type of dibridged biphenyl phosphoramidites 5
with a D2-symmetric backbone that can be prepared with ease
from achiral tetrahydroxybiphenyls 4 (Scheme 1). For this new
type of ligands 5, four isomers with the configuration of aR/aS
and trans/cis, respectively, are possible. We expected that one of
the four isomers should dominate the others during the prepara-
tion due to the induction of the chiral amine segment, and the
undesired isomers could be degraded to achiral tetrahydroxybi-
phenyls 4 with ease for recycle.10 Furthermore, it was expected
that a ligand that is based on the D2-symmetric backbone with
more coordination sites and different chiral environments might
provide higher enantioselectivities than those based on the C2-
symmetric backbone.
Ph
N
Ph
N
Ph
N
O
O
O
O
O
O
P
P
P
In order to develop efficient and widely applicable ligands pos-
sessing the characteristic features of both inherent and induced
atropoisomerism,5–7 and to make sufficient use of the key interme-
diate enantiomers of the ligands, we searched for an alternative ap-
proach in the development of efficient phosphoramidite ligands
with a novel design concept.
Ph
Ph
Ph
1
2
3
Figure 1. Phosphoramidites with C2-symmetric backbone.
Recently, a family of axially achiral biaryls having four constitu-
tionally identical substituents at the ortho positions of the biphe-
nyl axis caught our attention (Fig. 2). When the four identical
substituents are linked pairwise by two bridges, a pair of D2-sym-
metric enantiomers is formed with stable axial chirality.9 To the
A
A
A
A
A
A
A
A
A
A
A
A
+
achiral compound
aS
aR
* Corresponding author. Tel./fax: +86 21 5474 3265.
E-mail address: wanbin@sjtu.edu.cn (W. Zhang).
Figure 2. D2-symmetric dibridged molecules.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.033

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H. Zhang et al. / Tetrahedron Letters 51 (2010) 3119–3122
R1
HO
R1
First, we attempted to synthesize ligand 5a from achiral
2,20,6,60-tetrahydroxybiphenyl 4a and (S,S)-dichlorophosphino-
(bis(1-phenylethyl))amine (Scheme 1). As expected, a mixture con-
taining one major isomer, one minor isomer, and two trace isomers
was obtained in 45% yield and the ratio of the major isomer to the
minor ones was determined to be 3.8:1 by 31P NMR.11 The major
and minor isomers were isolated by preparative HPLC. The config-
uration of the major isomer was assigned as (aR)-trans by X-ray
analysis12 (Fig. 3, (aR)-trans-5a), and that of the minor isomer
was assigned as (aR)-cis by 31P NMR determination.13 This result
shows that one of the two possible axial chiralities was induced
by the chiral amine segment during the ligand preparation. Simi-
larly, ligands 5b–d were prepared from 4b–d14 as a mixture of four
isomers with one isomer dominating the others. It was found that
the major isomers of 5b–d could be easily separated by crystalliza-
tion directly from the mixture in up to 35% yield.15 The (aR)-trans
configuration of the major isomers could be further proved by the
X-ray analysis of 5b and 5c12 (Fig. 3, (aR)-trans-5b, (aR)-trans-5c).
Furthermore, no racemization of these isomers was observed after
refluxing in toluene under nitrogen atmosphere for 12 h, showing
the high stability of the axial chirality of the ligands. In addition,
as expected, all the ligands 5a–d could be readily degraded to achi-
ral tetrahydroxybiphenyls 4 in 85–90% yields in one-pot on treat-
ment with H2O2, followed by ring opening with LiAlH4.10 This
result indicates that key intermediates 4 of the undesired isomers
can be recovered.
OH
HO
R1
OH
R1
4a~d
Ph
N PCl2
Ph
R1
R1
O
R1
O
R1
O
Ph
Ph
Ph
Ph
N
O
P
P
N
N
P
N
P
O
O
O
O
Ph
Ph
Ph
Ph
R1
R1
5a~d
R1
R1
5a~d
(aR)-trans-
(aS)-trans-
major
trace
R1
R1
O
R1
O
R1
O
Ph
Ph
Ph
Ph
O
P
O
P
N
P
N
N
N
P
O
O
O
Ph
Ph
Ph
Ph
R1
R1
R1
(aR)-cis-
R1
5a~d
5a~d
(aS)-cis-
minor
trace
The asymmetric Cu-catalyzed conjugate addition of dialkylzinc
a R1 = H, b R1 = Me, c R1 = Et, d R1 = Allyl
reagents to
a,b-unsaturated ketones has become a powerful car-
bon-carbon bond-forming method, and axially chiral phospho-
ramidite was found to be one of the most useful ligands for this
reaction.16 Thus, our axially chiral dibridged biphenyl phospho-
ramidite ligands 5 were preliminarily applied to the Cu-catalyzed
asymmetric 1,4-addition reaction with substrates 6a–c (Table 1).
First, we tested both (aR)-trans-5a and (aR)-cis-5a to see how the
cis and trans configurations influence the catalysis. As a result, both
Scheme 1. Preparation of dibridged phosphoramidites with D2-symmetric
backbone.
Table 1
Cu-catalyzed conjugate addition reactions of enones with dibridged phosphorami-
dites
Cu(OAc)2•H2O (1.0 mol%)
L (2.0 mol%), 1.2 eq ZnEt2
Et
∗
EWG
O
EWG
Toluene, -30 ºC
1~15 h
6a~c
7a~c
(aR)-trans-5a
O
O
Ph
Ph
Ph
6a
6b
6c
Entry
Substrate
Ligand
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
6a
6b
6c
6a
6b
6c
6a
6b
6c
6a
6b
6c
6a
6b
6c
(aR)-cis-5a
(aR)-cis-5a
(aR)-cis-5a
85
80
79
82
85
76
86
90
84
78
90
82
74
91
77
96 (R)
83 (S)
82 (R)
97 (R)
86 (S)
87 (R)
98 (R)
97 (S)
96 (R)
94 (R)
93 (S)
99 (R)
91 (R)
87 (S)
93 (R)
(aR)-trans-5b
(aR)-trans-5a
(aR)-trans-5a
(aR)-trans-5a
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5c
(aR)-trans-5c
(aR)-trans-5c
(aR)-trans-5d
(aR)-trans-5d
(aR)-trans-5d
(aR)-trans-5c
a
Isolated yields.
Determined by HPLC and GC analyses.
b
Figure 3. Crystal structures of the dibridged ligands.

H. Zhang et al. / Tetrahedron Letters 51 (2010) 3119–3122
3121
Table 3
cis and trans isomers gave excellent enantioselectivities for 2-
cyclohexenone (6a) with 96% and 97% ee, respectively (entries 1
and 4). For other substrates 6b–c, (aR)-trans-5a afforded good
enantioselectivities, while (aR)-cis-5a afforded slightly lower
enantioselectivities (entries 2, 3, 5, and 6). The substituents on
the ligands apparently had an influence on the catalysis. Methyl-
substituted (aR)-trans-5b was the best choice among these ligands.
It is noteworthy that all substrates 6a–c afforded enantioselectivi-
ties that were equal to or higher than 96% ee when (aR)-trans-5b
was used (entries 7–9). Ethyl-substituted (aR)-trans-5c and allyl-
substituted (aR)-trans-5d also provided good to excellent enanti-
oselectivities (entries 10–15).
Comparison of 5b with reported biaryl phosphoramidites in Cu-catalyzed conjugate
additions
Entry
Substrate
ee (%)
14c
24c,16j
38,18a
(aR)-trans-5b
1
2
3
4
6a
6b
6c
8a
96
82
—
97
93
92
82
99
—
—
98
97
96
96
66
94
Nitroalkenes are very important substrates for the asymmetric
Cu-catalyzed conjugate addition reaction with dialkylzinc re-
agents to prepare chiral amines.17 Several ligands have shown
good to excellent enantioselectivities for this kind of sub-
strate.17f,g,18b But for the axially chiral ligands, no good enantiose-
lectivity was reported with a wide scope of substrates. It was
reported that the catalysis with phosphoramidite ligands was
strongly affected by the steric and electronic elements of the sub-
strate.18 Therefore, we also applied our ligands 5 to this impor-
tant reaction (Table 2). First, we used 8a as the substrate to
examine the effect of the ligands. It was found that (aR)-trans-
5b afforded the highest enantioselectivity (96%) (entries 1–5).
Then, we applied (aR)-trans-5b to several other typical nitroalk-
ene substrates. To our delight, the ligand was widely applicable;
most of the substrates reacted in excellent enantioselectivities
(entries 6–13). In particular, for meta- and ortho-substituted sub-
strates 8c and 8d, much higher enantioselectivity was obtained
with (aR)-trans-5b than the reported ones with ligand 3 (entries
7 and 8). This ligand was effective also for the reactions of hetero-
aromatic nitroalkenes (8h and 8i) to give the addition products
with 96% ee and 99% ee, respectively (entries 12 and 13). For ali-
phatic nitroalkene (8j), however, only moderate enantioselectivity
was obtained (entry 14).
Figure 4. Plausible chiral environment in catalysis.
Comparing the results of (aR)-trans-5b with those of the re-
ported biaryl phosphoramidites 1–3 (Table 3), it can be seen that
ligand (aR)-trans-5b is a highly efficient and widely applicable li-
gand in Cu-catalyzed conjugate additions for the above-mentioned
three types of enones and nitroalkene.
crystal structure (Fig. 4). From the top view of the crystal structure
of (aR)-trans-5b, it is reasonable to speculate that when the Cu ion
was coordinated to one phosphine atom of the ligand, the benzyl
amine group attached to the other phosphine atom of the ligand
might provide a strong steric hindrance with the reaction field of
the catalytic transition states (Fig. 4, the left). However, the steric
hindrance for ligands 1–3 between the binaphthyl or biphenyl
backbone and the reaction field might be weaker than that for
(aR)-trans-5b (Fig. 4, the right for ligand 2). This might give a pos-
sible explanation for the apparent enantioselectivity increase and
wide applicability of (aR)-trans-5b compared with the reported li-
gands 1–3.
In conclusion, we have developed a novel class of atropos
dibridged biphenyl phosphoramidite ligands with the D2-sym-
metric backbone, which can be diastereoselectively prepared
from achiral tetrahydroxy biphenyls. Preliminary application of
this type of ligands shows that (aR)-trans-5b is a highly efficient
and widely applicable ligand in the Cu-catalyzed conjugate addi-
A reaction model was proposed for rationalizing the high effi-
ciency and wide applicability of ligand (aR)-trans-5b based on its
Table 2
Cu-catalyzed conjugate addition of nitroalkenes
Cu(OAc)2•H2O (1.0 mol%)
Et
L (2.0 mol%), 1.2 eq ZnEt2
NO2
NO2
R
Toluene, -45 ºC
1~6 h
R
8a~i
9a~i
Entry
Substrate (R)
Ligand
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
8a (Ph)
8a (Ph)
8a (Ph)
8a (Ph)
(aR)-cis-5a
92
92
89
83
90
87
88
77
80
89
86
86
91
77
61
74
96
83
90
97
92
85
94
92
85
96
99
62
(aR)-trans-5a
(aR)-trans-5b
(aR)-trans-5c
(aR)-trans-5d
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
(aR)-trans-5b
tion of diethylzinc to several kinds of
a,b-unsaturated ketones
and disubstituted nitroalkenes, the enantioselectivities being
comparable or superior to those obtained with reported corre-
sponding C2-symmetric ligands. The unique D2-symmetric back-
bone endows the ligands with an excellent chiral environment
and the advantage of sufficient reusability of their key intermedi-
ates 2,20,6,60-tetrahydroxybiphenyls. Further applications of the
phosphoramidite ligands are in progress in our laboratory.
8a (Ph)
8b (p-MeOC6H4)
8c (m-MeOC6H4)
8d (o-MeOC6H4)
8e (p-MeC6H4)
8f (p-ClC6H4)
8g (2-Naphthyl)
8h (2-Furyl)
8i (2-Thienyl)
8j (Cyclohexanyl)
Acknowledgments
a
We thank Professor Tsuneo Imamoto for helpful discussion.
This work was partially supported by the National Natural Science
Isolated yields.
Determined by HPLC and GC analyses.
b

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H. Zhang et al. / Tetrahedron Letters 51 (2010) 3119–3122
independent reflections (Rint = 0.0822), Final R indices [I > 2
wR2 = 0.1130. (aR)-trans-5c: C52H58N2O4P2, Mr = 836.94, T = 293(2) K,
orthorhombic, P2(1)2(1)2(1), a = 11.3264(9) Å, b = 12.6123(11) Å,
c = 33.148(3) Å, b = 90.00, V = 4735.26(70) Å3, Z = 4, calcd = 1.174 Mg mꢀ3
= 0.137 mmꢀ1, 25,989 reflections collected, 9272 independent reflections
(Rint = 0.0647), Final indices [I > 2 (I)]: R1 = 0.0640, wR2 = 0.1531. CCDC
750221 (aR)-trans-5a, 753649 (aR)-trans-5b, and 750222 (aR)-trans-5c
contain the supplementary crystallographic data for this Letter. These data
can be obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
r(I)]: R1 = 0.0551,
Foundation of China (20972095) and Science and Technology Com-
mission of Shanghai Municipality (09JC1407800), and Nippon
Chemical Industrial Co., Ltd.
q
,
l
R
r
References and notes
1. For selected reviews of axial chirality on asymmetric catalysis, see: (a) Noyori,
R. Asymmetric Catalysis in Organic Synthesis; New York: Wiley-Interscience,
1994; (b)Comprehensive Asymmetric Catalysis I–III; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999; (c) Ojima, I. Catalytic Asymmetric
Synthesis, 2nd Ed.; Wiley-VCH: New York, 2000. pp 429–463; (d) Hargaden, G.
C.; Guiry, P. J. Chem. Rev. 2009, 109, 2505–2550.
2. For recent reviews, see: (a) Chen, Y.; Yekta, S.; Yudin, A. K. Chem. Rev. 2003, 103,
3155–3212; (b) Telfer, S. G.; Kuroda, R. Coord. Chem. Rev. 2003, 242, 33–46; (c)
Berthod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev. 2005, 105,
1801–1836.
3. (a) Miyashita, A.; Yasuda, H.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori,
R. J. Am. Chem. Soc. 1980, 102, 7932–7934; (b) Noyori, R.; Takaya, H. Acc. Chem.
Res. 1990, 23, 345–350; (c) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo,
N.; Miura, T.; Kumobayashi, H. Adv. Synth. Catal. 2001, 343, 264–267; (d)
Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008–2022.
4. For selected references on the application of phosphoramidite in asymmetric
catalysis, see: (a) Franci, G.; Faraone, F.; Leitner, W. J. Am. Chem. Soc. 2002, 124,
736–737; (b) Jensen, J. F.; Svendsen, B.; la Cour, T.; Pedersen, H. L.; Johannsen,
M. J. Am. Chem. Soc. 2002, 124, 4558–4559; (c) Alexakis, A.; Benhaim, C.; Rosset,
S.; Humam, M. J. Am. Chem. Soc. 2002, 124, 5262–5263; (d) Biswas, K.; Prieto,
O.; Goldsmith, P. J.; Woodward, S. Angew. Chem., Int. Ed. 2005, 44, 2232–2234;
(e) Najera, C.; de Gracia Retamosa, M.; Sansano, J. M. Angew. Chem., Int. Ed.
2008, 47, 6055–6058.
13. (a) Hua, Z.; Ojima, I. Stony Brook University, PhD dissertation: ‘Design,
Synthesis and Application of Phosphorous Ligands in Catalytic Asymmetric
Transformations’, 2004, pp 83–86; (b) Due to the Refs. 6 and 13a, related
biphenyl phosphoramidites ligands (aS,R,R)-1 and (aR,S,S)-3 were at lower field
compared with their corresponding diastereomers (aR,S,S)-1 and (aS,R,R)-3 in
31P NMR, respectively. (aS)-5a should be at lower field than (aR)-trans-5a at
149.2 ppm in 31P NMR. However, the minor isomer at 148.1 ppm was at higher
field than (aR)-trans-5a. Therefore, this minor isomer was suggested to be (aR)-
cis-5a.
14. Fang, F.; Xie, F.; Yu, H.; Zhang, H.; Zhang, W. Tetrahedron Lett. 2009, 50, 6672–
6675.
15. (S,S,aR,S,S)-trans-3,30,5,50-Tetramethyl-dibridged biphenyl phosphoramidite
((aR)-trans-5b) 1H NMR (400 MHz, CDCl3): d = 7.20–7.07 (m, 22H, ArH), 4.85–
4.52 (m, 4H, CH), 2.49 (s, 6H, CH3), 2.14 (s, 6H, CH3), 1.79 (m, 12H, CH3); 13C
NMR (100 MHz, CDCl3): d = 148.8, 148.7, 147.37, 147.35, 132.1, 131.9, 128. 2,
128.16, 128.13, 127.96, 127.86, 126.7, 126.24, 126.22, 124.2, 52.2, 52.1, 17.7,
16.23, 16.22; 31P NMR (162 MHz, CDCl3, 85% H3PO4): d = 143.7; HRMS (ES)
calcd for C48H50N2O4P2 [M+H]+ 781.3324, found: 781.3318; mp 106–109 °C,
½ ꢁ ꢀ137 (c 0.10, CHCl3).
a 2D7
(S,S,aR,S,S)-trans-3,30,5,50-Tetraethyl dibridged biphenyl phosphoramidite
((aR)-trans-5c) 1H NMR (400 MHz, CDCl3): d = 7.04–7.26 (m, 22H, ArH), 4.52–
4.73 (m, 4H, CH), 3.16–3.25 (m, 2H, CH2), 2.67–2.76 (m, 2H, CH2), 2.43–2.57 (m,
4H, CH2), 1.49–1.95 (m, 12H, CH3), 1.19–1.24 (m, 6H, CH3), 1.06–1.13 (m, 6H,
CH3); 13C NMR (100 MHz, CDCl3): d = 148.04, 147.96, 146.9, 132.7, 132.6, 130.9,
129.8, 128.4, 128.1, 127.9, 126.7, 52.3, 52.2, 24.9, 23.6, 15,50, 15.47, 15.1; 31P
NMR (162 MHz, CDCl3, 85% H3PO4): d = 145.9; HRMS (ES) calcd for
5. Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim, C. Synlett
2001, 9, 1375–1378.
6. Feringa, B. L.; Pineschi, M.; Arnold, L. A.; de Vries, R. Angew. Chem., Int. Ed. 1997,
36, 2620–2623.
7. Hua, Z.; Vassar, V. C.; Choi, H.; Ojima, I. Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
C52H58N2O4P2 [M+H]+ 837.3950, found: 837.3944; mp 101–103 °C, ½a 2D7
ꢁ
264
5411–5416.
8. For selected references on the resolutions of related C2-symmetric axially chiral
compounds, see: (a) Brunel, J. M.; Buono, G. J. Org. Chem. 1993, 58, 7313–7314;
(b) Alexander, J. B.; Schrock, R. R.; Davis, W. M.; Hultzsch, K. C.; Hoveyda, A. H.;
Houser, J. H. Organometallics 2000, 19, 3700–3715; (c) Love, B. Curr. Org. Synth.
2006, 3, 169–185.
9. (a) Mislow, K.; Simon, E.; Glass, M. A. W.; Wahl, G. H.; Hopps, H. B. J. Am. Chem.
Soc. 1964, 86, 1710–1733; (b) Harada, T.; Tuyet, T.; Mai, T.; Oku, A. Org. Lett.
2000, 2, 1319–1322.
(c 0.10, CHCl3).
(S,S,aR,S,S)-trans-3,30,5,50-Tetraallylic dibridged biphenyl phosphoramidite
((aR)-trans-5d) 1H NMR (400 MHz, CDCl3): d = 7.04–7.14 (m, 22H, ArH), 5.81–
6.02 (m, 4H), 4.86–5.04 (m, 8H), 4.62–4.66 (m, 4H), 3.91–3.97 (m, 2H), 3.43–
3.48 (m, 2H), 3.14–3.28 (m, 4H), 1.39–2.06 (m, 12H, CH3); 13C NMR (100 MHz,
CDCl3): d = 148.8, 148.7, 147.4, 137.02, 137.00, 136.9, 131.4, 130.4, 128.7,
128.4, 128.24, 128.19, 128.17, 127.9, 127.8, 127.2, 126.9, 126.7, 115.9, 115.8,
52.3, 52.2, 35.7, 34.4, 34.3; 31P NMR (162 MHz, CDCl3, 85% H3PO4): d = 146.3;
HRMS (ES) calcd for C56H58N2O4P2 [M+H]+ 885.3933, found: 885.3949; mp
10. Wang, M.; Liu, S.; Liu, J.; Hu, B. J. Org. Chem. 1995, 60, 7364–7365.
11. 31P NMR (162 MHz, CDCl3, 85% H3PO4): 149.2 ppm as a major isomer and
148.1 ppm as a minor isomer, and 152.8 ppm and 154.1 ppm as isomers in
trace.
108–110 °C, ½a 2D7
ꢀ234 (c 0.10, CHCl3).
ꢁ
16. For selected references on Cu-catalyzed conjugate additions, see: (a) Feringa, B.
L. Acc. Chem. Res. 2000, 33, 346–353; (b) Alexakis, A.; Bckvall, J. E.; Krause, N.;
Pmies, O.; Diguez, M. Chem. Rev. 2008, 108, 2796–2823; (c) Harutyunyan, S.;
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(S,S,aR,S,S)-trans-Dibridged biphenyl phosphoramidite ((aR)-trans-5a) 1H NMR
(400 MHz, CDCl3): d = 7.34–7.39 (m, 2H, ArH), 7.22–7.15 (m, 22H, ArH), 7.04–
7.06 (m, 2H, ArH), 4.85–4.89 (m, 4H, CH), 1.79 (d, J = 7.2 Hz, 12H, CH3); 13C
NMR (100 MHz, CDCl3): d = 153.08, 153.96, 151.5, 143.0, 129.9, 128.8, 128.19,
128.17, 128.1, 126.9, 119.3, 117.5, 52.50, 52.38; 31P NMR (162 MHz, CDCl3, 85%
H3PO4): d = 148.1; HRMS (EI) calcd for C44H42N2O4P2 [MꢀH]+ 723.2551, found:
723.2545; mp 133–135 °C; ½a D27
ꢀ113 (c 0.10, CHCl3).
ꢁ
(S,S,aR,S,S)-cis-Dibridged biphenyl phosphoramidite ((aR)-cis-5a) 1H NMR
(400 MHz, CDCl3): d = 7.37–7.41 (m, 2H, ArH), 7.03–7.14 (m, 22H, ArH), 7.01–
7.03 (m, 2H, ArH), 4.60–4.82 (m, 4H, CH), 1.82 (d, J = 7.2 Hz, 12H, CH3); 13C
NMR (100 MHz, CDCl3): d = 152.94, 152.92, 152.84, 152.82, 151.6, 143.0, 129.5,
128.23, 128.18, 128.16, 128.13, 128.11, 128.10, 128.07, 127.03, 126.97, 118.6,
118.0, 52.6, 52,5; 31P NMR (162 MHz, CDCl3, 85% H3PO4): d = 146.7; HRMS (EI)
calcd for C44H42N2O4P2 [MꢀH]+ 723.2551, found: 723.2545; mp 113–116 °C;
½ ꢁ ꢀ171 (c 0.10, CHCl3).
a 2D7
12. Crystallographic data for (aR)-trans-5a: C44H42N2O4P2, Mr = 724.74,
T = 293(2) K, Orthorhombic, P2(1)2(1)2(1), a = 12.4525(8) Å, b = 12.8410(9) Å,
c = 24.4382(16) Å, b = 90.00(2), V = 3907.7(5) Å3, Z = 4,
l
q ,
calcd = 1.232 Mg mꢀ3
= 0.156 mmꢀ1, 21,675 reflections collected, 7684 independent reflections
(Rint = 0.0767), Final R indices [I > 2r(I)]: R1 = 0.0487, wR2 = 0.0702. (aR)-trans-
5b: C48H49N2O4P2, Mr = 779.83, T = 293(2) K, Orthorhombic, P2(1)2(1)2(1),
18. (a) Choi, H.; Hua, Z.; Ojima, I. Org. Lett. 2004, 6, 2689–2691; (b) Wakabayashi,
K.; Aikawa, K.; Kawauchi, S.; Mikami, K. J. Am. Chem. Soc. 2008, 130, 5012–5013.
a = 11.227(4) Å, b = 14.464(5) Å, c = 26.709(9) Å, b = 90, V = 4337(2) Å3, Z = 4,
q
calcd = 1.194 Mg mꢀ3 = 0.145 mmꢀ1
, l , 21,174 reflections collected, 9387