Enantioselective synthesis of planar-chiral 1,11-dioxa[11]paracyclophane-derived phosphoramidites and their use as chiral ligands

Article abstract of DOI:10.1016/j.tetasy.2016.08.015

A library of bench-stable planar-chiral 1,11-dioxa[11]paracyclophane-derived phosphoramidites was synthesized by a three step procedure: enantioselective ortho-lithiation, reductive amination and coupling with phosphorochloridites. The efficacy of these phosphoramidite as chiral ligands was tested in the Pd-catalyzed allylic alkylation of dimethyl malonate and the Cu-catalyzed ethylation of chalcone under the reported conditions, with moderate enantioselectivity being obtained.

Full text of DOI:10.1016/j.tetasy.2016.08.015

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective synthesis of planar-chiral 1,11-dioxa-
[
11]paracyclophane-derived phosphoramidites and their use as
chiral ligands
a
b
a,c,
⇑
Madhurima Hazra , Kyalo Stephen Kanyiva , Takanori Shibata
a
Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Tokyo 1698555, Japan
International Center for Science and Engineering Programs (ICSEP), Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 1698555, Japan
JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
A library of bench-stable planar-chiral 1,11-dioxa[11]paracyclophane-derived phosphoramidites was
synthesized by a three step procedure: enantioselective ortho-lithiation, reductive amination and cou-
pling with phosphorochloridites. The efficacy of these phosphoramidite as chiral ligands was tested in
the Pd-catalyzed allylic alkylation of dimethyl malonate and the Cu-catalyzed ethylation of chalcone
under the reported conditions, with moderate enantioselectivity being obtained.
Received 12 July 2016
Accepted 25 August 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
1
4c
hydrogenations,14d hydroformylations,14e Heck
1
. Introduction
alkylations,
1
4f
15,16
reactions, etc.
Since enantiomerically pure compounds play crucial roles in the
areas connected to pharmaceuticals, agrochemicals, flavours and
fragrance industries, their preparation has become a major goal
In contrast, we developed a facile synthesis of planar-chiral 1,n-
dioxa[n]paracyclophanes through enantioselective ortho-lithia-
1
7
tion. Due to its unique planar chirality, paracyclophane has
potential in terms of asymmetric catalysis. Although the first rep-
resentative example of cyclophane was developed by Brown and
1
–3
for synthetic organic chemists.
In this context, efficient chiral
4
metal catalysis is an alluring field exhibiting fruitful results. The
design of chiral ligands forms the basis for enantioselectivity. Phos-
are widely used as chiral sources. Notable
achievements in this field have been reported using BINAP and
1
8
Farthing in 1949, only one example of [2.2]paracyclophane-
derived phosphoramidite ligands was recently published, as far
as we know, where they were used as a chiral ligand in the Cu-cat-
5
–7
phorus ligands
8
a
8b
8c,d
19
its derivatives, BINAPO, DIPAMP,
and a series of TunaPhos
alyzed conjugate addition. Previously we reported that planar-
8
e
ligands. In spite of the immense success with bidentate ligands,
the last decade has witnessed the development of various
monodentate chiral phosphorus ligands. Investigations in this
area have been comprehensively carried out by several research
chiral 1,n-dioxa[n]paracyclophanyl phosphines worked as chiral
ligands in Pd-catalyzed Sonogashira and Suzuki couplings of lim-
2
0
ited substrates.
Recently, we further prepared planar-chiral
phosphites possessing a 1,n-dioxa[n]paracyclophane scaffold and
groups, such as Feringa,9
a,b
Pringle,
9c
Reetz,
9d
and Chan.
9e
used them as chiral ligands in Pd-catalyzed allylic alkylations
2
1
Different classes of chiral phosphorus ligands were explored,
and Rh-catalyzed 1,4-additions.
which play excellent roles in achieving high enantioselectivity in
Herein, we describe a three-step procedure for the first synthe-
sis of phosphoramidites with planar-chirality on their nitrogen
atom via the reaction of planar-chiral 1,11-dioxa[11]paracyclo-
phanylamines and 1,11-dioxa[11]paracyclophanyl methylamines
asymmetric synthesis.1
0–12
In this regard, we turned our attention
towards the asymmetric synthesis of phosphoramidite ligands due
to their easy accessibility, high stability and rapid fine tuning of
properties with the variation of substituents at the nitrogen
0
with 2,2 -biarylene phosphorochloridites derived from chiral or
1
3
atom. A variety of asymmetric reactions have been studied with
achiral diols and phosphorus trichlorides (Scheme 1). Apart from
chiral BINOL as a backbone, there are also several reports on
these ligands and reported with significant results, including Rh-
and Cu-catalyzed conjugate additions,1
4a,b
Pd-catalyzed allylic
SPINOL and TADDOL as a backbone. From this study, a diverse
series of ligand library was synthesized bearing planar-chiral para-
cyclophane scaffold and chiral binol/biphenol as a backbone. The
cooperative effect of both planar- and axial chiralities of ligands
in inducing enantioselectivity was tested in Pd-catalyzed allylic
22
23
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetasy.2016.08.015
957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
0
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2
M. Hazra et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
(
CH
2
)
9
2 9
(CH )
O
O
NaBH(OAc)
3 equiv)
3
O
(
2
+
(1)
R
N
R1
R2
O
O
AcOH, DCE
2 -6 h, rt
(
98% ee)
NHR3
P
O
n
(1.2 equiv)
= Ph, R2 = H
= H, R2 = H
O
1
R
3
3
3
a (R3 = Bn): 79%, 98% ee
1
n = 0, 1
R
3
b (R = Me): 45%
1
2
R
= Me, R = Me
3
c (R = i-Pr): 86%
2 9
(CH )
O
(CH
2
)
9
(CH2)9
O
HO
HO
+
+
PCl
3
O
same
as above
NHR
4
O
n
+
R NH
(2)
2
NHR4
(
1.2 equiv)
R4 = Bn
i-Pr
CHO
(97% ee)
O
O
Scheme 1. Creation of a library of planar-chiral phosphoramidites.
5
5
a (R4 = Bn): 64%, 97% ee
4
4
b (R = i-Pr): 94%
alkylations of dimethyl malonate and Cu-catalyzed conjugate addi-
tions of chalcone using diethylzinc.
Scheme 3. Synthesis of planar-chiral secondary amines.
2
. Results and discussion
O
A new family of chiral monodentate phosphoramidite ligands
ClP
O
was synthesized by a three-step procedure. First, the enantioselec-
(
2 9
CH )
1
7
tive ortho-lithiation of 1,11-dioxa[11]paracyclophane 1 in the
O
n-BuLi (2.0 equiv)
presence of (+)-sparteine followed by quenching with trimethylsi-
TMEDA (2.0 equiv)
(2.0 equiv)
2
4
lylmethyl azide gave planar-chiral paracyclophanylamine 2 with
THF, -78 °C, 2 h
THF, -78 °C to rt
NHR
excellent ee (Scheme 2).
O
n
n = 0: 3a-3c
n = 1: 5a, 5b
(
CH
2
)
9
(
CH
2
)
9
2 9
(CH )
1
) sec-BuLi (2.0 equiv)
O
O
(+)-sparteine (1.0 equiv)
O
2
Et O, -78 °C, 2 h
R
N
n
O
P
O
2
) TMSCH
2 3
N (5.0 equiv)
NH
2
O
O
Et O, -78 °C - rt
2
O
1
2
: 60%, 98% ee
L1-L9
Scheme 2. Enantioselective synthesis of a planar-chiral paracyclophanylamine.
Next, the reductive amination of carbonyl compounds by pla-
nar-chiral primary amine 2 using sodium triacetoxyborohydride
gave secondary paracyclophanylamines 3a–3c (Eq. 1 in Scheme 3).
On the other hand, reductive amination of planar-chiral aldehyde
(
CH
2
)
9
2 9
(CH )
O
O
R
N
Bn
N
O
O
O
O
1
7
P
P
4
by benzyl- and isopropylamine under the same reaction condi-
tions gave secondary paracyclophanylmethylamines 5a and 5b
Eq. 2 in Scheme 3). The retention of enantiomeric excess through
O
n
O
n
(
the reductive amination was observed by compounds 3a and 5a.
(R
(R
a
a
a
a
)-L1 (n = 0, R = Bn): 41%
)-L2 (n = 1, R = Bn): 36%
)-L3 (n = 0, R = Me): 30%
)-L4 (n = 0, R = i-Pr): 20%
(S
(S
a
)-L1 (n = 0): 65%
a
)-L2 (n = 1): 45%
Finally, these obtained secondary amines were lithiated using
(R
n-butyllithium in the presence of tetramethylethylenediamine
0
(R
(
TMEDA), and subsequently treated with in situ prepared 2,2 -biar-
ylene phosphorochloridites (Scheme 4). When paracyclophany-
0
lamine 3a was reacted with axially chiral 2,2 -binaphthylene
(
CH
2
)
9
2 9
(CH )
phosphorochloridite, (R
tively, both of which have planar and axial chiralities. From para-
cyclophanylmethylamine 5a, (R )-L2 and (S )-L2 were obtained
as diastereomers. N-Methyl and N-isopropyl analogues (R )-L3
and (R )-L4 could be prepared from 3b and 3c, respectively. The
reaction of achiral 2,2 -biphenylene phosphorochloridite with 3a,
a, and 5b gave L5–L7. Tetramethyl-substituted biphenylene-
a a
)-L1 and (S )-L1 were obtained respec-
O
O
R
N
Bn
a
a
O
O
O
O
N
P
P
O
n
O
n
a
a
0
5
L5 (n = 0, R = Bn): 70%
L6 (n = 1, R = Bn): 47%
L7 (n = 1, R = i-Pr): 30%
L8 (n = 0): 55%
L9 (n = 1): 39%
derived ligands L8 and L9 were also prepared using the same pro-
tocol. All of these phosphoramidites were purified as solids by
preparative chromatography of silica gel and were stable at ambi-
ent conditions, thus, they could be easily applied to asymmetric
reactions as chiral ligands due to their ease in handling.
Scheme 4. Synthesis of planar-chiral phosphoramidites.
To test the efficacy of our originally developed planar-chiral
paracyclophane-derived phosphoramidite ligands L1–L9, we first
chose the Pd-catalyzed asymmetric allylic alkylation, and
performed the reaction under the reported literature conditions
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M. Hazra et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
without further optimization (Table 1).25 The reaction of dimethyl
Table 2
Enantioselective Cu-catalyzed conjugate addition of chalcone with diethylzinc
malonate 7 with (E)-1,3-diphenylallyl acetate 6 furnished the ally-
lated product 8 with low to excellent yield. The stereoselectivity
and the enantioselectivity varied depending on the structure of
O
Ph
Ph
a a
the ligands. The diastereomeric pair of (R )-L1 and (S )-L1 possess-
9
2 2
Cu(OAc) •H O (2.8 mol%)
ing both planar and axial chiralities gave (R)-8 as the major enan-
tiomer with moderate ee, which suggests that the stereoselectivity
was mainly controlled by the planar chirality of the paracyclo-
phane scaffold (entries 1 and 2). However, the BINOL moiety was
also significant for enantioinduction because phosphoramidite
Et
O
L1-L9 (6 mol%)
+
Ph
∗
Ph
toluene, 0 °C, time
Et
2
Zn
10
(
3 equiv)
0
Yield (%)a
Ee (%)b
ligands L5 and L8 derived from 2,2 -biphenol and tetramethyl-
Entry
Ligand
(R )-L1
(S )-L1
Time (h)
0
substituted 2,2 -biphenol resulted in low ee (entries 7 and 10). In
1
2
3
4
5
6
7
8
9
a
1.5
1.0
3.0
1.0
1.5
2.0
3.0
5.5
1.5
5.5
5.5
>99
>99
>99
>99
91
>99
>99
70
44 (R)
18 (S)
6 (S)
17 (R)
64 (R)
7 (S)
contrast, the diastereomeric pair of paracyclophanylmethy-
a
lamine-based (R
a
)-L2 and (S
a
)-L2 showed the opposite stereoselec-
(R
a
)-L2
)-L2
(S
(R
(R
a
tivity, which suggests that the stereoselectivity was mainly
controlled by the axial chirality of the BINOL moiety (entries 3
and 4). However, ligand L6 possessing only planar chirality gave
the best ee (70%) (entry 8). Other paracyclophanylmethylamine-
based ligands L7 and L9 gave poorer enantioselectivities (entries
a
)-L3
)-L4
a
L5
L6
L7
L8
L9
4 (R)
19 (R)
50 (R)
14 (R)
4 (R)
89
88
63
1
1
0
1
9
and 11). These results show that the planar-chirality of dioxa-
paracyclophane operated as an efficient chiral scaffold in phospho-
ramidite ligand, but the choice of substituent on the nitrogen atom
a
Isolated yield.
b
0
Ee was determined by HPLC analysis using Daicel Chiralcel OD-3 (eluent: 0.5%
and 2,2 -biphenylene diol moiety was also critical.
2-propanol in hexane, flow rate: 1.0 mL/min). The absolute configuration of the
major isomer was described in the parentheses.
Table 1
Enantioselective Pd-catalyzed allylic alkylation of malonate
ligands resulted in the different degree of enantioinduction by the
cooperative effect of three substituents of the nitrogen atom. When
OAc
[
Pd(allyl)Cl]
L1-L9 (8 mol%)
CH CO K (1.3 equiv)
BSA (1.3 equiv)
2
(2 mol%)
(R
a
)-L10, which is a planar chirality-free analogue of (R
a
)-L3, was
Ph
Ph
used, the enantioselectivity was dramatically decreased
6
3
2
MeO
C
CO
2
Me
2
(Scheme 5).
+
CH Cl , -60 °C, 2 d
2
2
Ph
∗
Ph
CH
2
(CO
2
Me)
2
(
1.76 equiv)
8
7
OMe
O
O
P
N
Entry
Ligand
Yield (%)a
Ee (%)b
MeO
Me
1
2
3
4
5
6
7
8
9
(R
a
)-L1
)-L1
49
76
75
74
81
36
97
82
86
23
50
48 (R)
39 (R)
62 (S)
67 (R)
12 (S)
10 (R)
6 (R)
70 (R)
51 (R)
15 (R)
8 (R)
(S
a
(R
a
)-L10 (6 mol%)
Cu(OAc) •H O (2.8 mol%)
toluene, 0 °C, 1 h
(R
a
)-L2
)-L2
2
2
1
0
(S
(R
(R
a
Et Zn
(3 equiv)
9
+
2
a
)-L3
)-L4
76%
21% ee (R)
a
L5
L6
L7
L8
L9
Scheme 5. Control experiment using (R
a
)-L10 with no planar chirality.
1
1
0
1
3
. Conclusions
A library of chiral phosphoramidite ligands with planar chirality
a
Isolated yield.
b
Ee was determined by HPLC analysis using Daicel Chiralcel OD-3 (eluent: 1% 2-
propanol in hexane, flow rate: 0.5 mL/min). The absolute configuration of the major
isomer is described in the parentheses.
on their nitrogen atom was synthesized and tested as chiral ligands
in two well-known asymmetric reactions under the literature con-
ditions. These newly synthesized ligands are highly air and mois-
ture stable and thus, stringent care is not required to handle
them. A slight tuning of the ligand structure effects a diverse
change of enantioinduction in Pd-catalyzed allylic alkylations and
Cu-catalyzed conjugate addition reactions. The applications of
these phosphoramidite ligands possessing a planar-chiral paracy-
clophane scaffold to other asymmetric reactions are ongoing in
our laboratory.
Next, we examined ligands L1–L9 for the Cu-catalyzed asym-
metric conjugate addition of chalcone (9) with diethylzinc under
the literature condition,26 and the alkylated product 10 was
obtained in moderate to quantitative yield (Table 2). In contrast
to the Pd-catalyzed allylic alkylation, the diastereomeric pair of
(
R
a
)-L1 and (S
duct 10, and the ee was different (entries 1 and 2). The diastere-
omeric pair of paracyclophanylmethylamine-based (R )-L2 and
)-L2 showed low enantioselectivity (entries 3 and 4). The choice
a
)-L1 gave the opposite enantiomers of ethylated pro-
a
(S
a
of substituent on the nitrogen atom was important; the methyl
group gave the best ee (64%) among the paracyclophanylamine-
4. Experimental
4.1. General
2
7
based ligands possessing a BINOL scaffold (entries 1, 5 and 6).
0
As for the ligand with an achiral 2,2 -biphenol scaffold, isopropyl
group on the nitrogen atom could induce moderate ee (entries
Unless otherwise noted, all materials were purchased from
commercial suppliers and used as received. Anhydrous solvents
7
–9). Thus, a slight alteration in the structure of phosphoramidite
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4
M. Hazra et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
were stocked on activated molecular sieves 4 Å under an argon
atmosphere, and degassed by argon bubbling prior to use. All reac-
tions were carried out under an argon atmosphere in oven-dried
glassware with a magnetic stirring bar.
H NMR spectra were recorded on JEOL AL-400 (400 MHz) spec-
trometers. Chemical shifts are reported in parts per million (d) rel-
1H), 6.84 (dd, J = 4.8, 3.8 Hz, 1H), 6.34–6.32 (m, 1H), 6.28–6.27
(m, 1H), 4.77 (br s, 1H), 4.34–4.12 (m, 4H), 4.06–4.04 (m, 2H),
1
3
1.61–1.47 (m, 4H), 0.95–0.74 (m, 10H); C NMR (ppm) d 155.9,
141.9, 141.1, 139.5, 128.5, 127.4, 127.1, 119.4, 107.8, 104.3, 71.6,
71.4, 47.9, 30.2, 30.1, 27.9, 26.2, 26.1, 25.8, 25.6 (two pair of peaks
1
ꢀ1
are overlapped at aromatic region); IR (cm ) 2924, 2852, 2362,
2340, 1603, 1516, 1456, 1182, 977, 697,419; HRMS(ESI) calcd for
3
ative to internal standard TMS (0 ppm) for CDCl . The peak
+
25
patterns are indicated as follows: s, singlet; d, doublet; dd, doublet
of doublet; t, triplet; q, quartet; m, multiplet, br s, broad singlet.
The coupling constants, J, are reported in Hertz (Hz). 13C NMR spec-
tra were obtained by JEOL AL-400 (100 MHz) spectrometers and
referenced to the internal solvent signals (central peak is
C
22
H
29NNaO
2
[M+Na] : 362.2090; found: 362.2091. [
D
a] = +63.2
(c 0.76, CHCl
3
, 98% ee). Ee was determined by HPLC analysis using
a chiral column (Daicel Chiralpak IA: 4 ꢁ 250 mm, 254 nm UV
detector, rt, eluent: 10% EtOAc in hexane, flow rate: 1 mL/min,
retention time: 8.3 min for minor isomer and 10.7 min for major
isomer).
7
4
7.0 ppm in CDCl
00 (200 MHz) spectrometers and H
was used as an NMR solvent. High-res-
3
). 31P NMR spectra were obtained by JEOL AL-
PO was used as an external
3
4
standard (0.00 ppm). CDCl
3
4
.3.2. 13-Methylamino-1,11-dioxa[11]paracyclophane 3b
olution mass spectra (HRMS) were measured on ESI (Electrospray
ionization) method at a JEOL GC-mate II. Preparative thin-layer
chromatography (PTLC) was performed with silica gel-precoated
glass plates (Merck 60 GF254) prepared in our laboratory. Flash
column chromatography was performed over silica gel 200–300.
Yellow viscous oil. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
1
2
1
1
2
1
1.7 mg, 45%. H NMR (ppm) d 6.90–6.87 (m, 1H), 6.40–6.35 (m,
H), 4.34 (br s, 1H), 4.26–4.15 (m, 4H), 2.88 (d, J = 2.5 Hz, 3H),
.69–1.61 (m, 4H), 1.04–0.90 (m, 10H); C NMR (ppm) d 156.1,
43.4, 141.3, 119.3, 107.3, 103.6, 71.6, 71.4, 30.5, 30.3, 30.0, 28.0,
6.1, 26.1, 25.8, 25.4; IR (cm ) 3426, 2923, 2852, 2362, 1606,
518, 1457, 1186, 981, 447, 419; HRMS(ESI) calcd for C16
1
3
ꢀ
1
4
.2. Experimental procedure for the preparation of amine 2
H26NO
2
(Scheme 2)
+
26
[
D 3
M+H] : 264.1958; found: 264.1958. [a] = +88.2 (c 1.32, CHCl ).
In a two-neck flask purged with argon, a solution of 1,11-dioxa
[
2
11]paracyclophane 1 (0.5 mmol) in Et O (0.5 ml) was added fol-
4.3.3. 13-Isopropylamino-1,11-dioxa[11]paracyclophane 3c
lowed by (+)-sparteine (1 equiv) and the resulting solution was
cooled to ꢀ78 °C. Next, sec-BuLi (0.98 M) (2 equiv) was added
dropwise and stirred at ꢀ78 °C for 2 h. A solution of trimethylsilyl-
Pale yellow viscous oil. PTLC (eluent: hexane/EtOAc = 5/). Yield:
24.8 mg, 86%. H NMR (ppm) d 6.85–6.83 (m, 1H), 6.32–6.30 (m,
1
2H), 4.24–4.10 (m, 5H), 3.57 (br s, 1H), 1.65–1.60 (m, 4H), 1.25–
1
3
methyl azide (5 equiv) in Et
2
O (0.6 mL) was added dropwise and
1.20 (m, 6H), 1.03–0.87 (m, 10H); C NMR (ppm) d 156.0, 141.3,
the reaction mixture was warmed to ambient temperature. The
reaction was quenched with a saturated aqueous solution of
141.0, 119.5, 106.8, 104.0, 71.6, 71.4, 43.6, 30.4, 30.1, 27.9, 26.1,
ꢀ
1
26.1, 25.8, 25.4, 23.0, 22.9; IR (cm ) 3419, 2924, 2853, 2363,
1605, 1516, 1458, 1187, 420; HRMS(ESI) calcd for C18H30NO2 [M
NH
4
Cl and extracted with EtOAc (10 ml ꢁ 3). The organic layer
+
25
was washed with brine and dried over Na
2
SO4. The solution
+H] : 292.2270; found: 292.2271. [
a]
D
= +98.4 (c 0.57, CHCl3).
was evaporated and purified through PTLC (eluent: hexane/
EtOAc = 5/1). Yield: 75.8 mg, 60%.
4
5
.3.4. 13-(Benzylamino)methyl-1,11-dioxa[11]paracyclophane
a
4
.2.1. 13-Amino-1,11-dioxa[11]paracyclophane 2
Yellow viscous liquid. H NMR (ppm) d 6.90–6.88 (m, 1H), 6.45–
1
Pale yellow viscous oil. PTLC (eluent: hexane/EtOAc = 3/1).
1
Yield: 21.5 mg, 64%. H NMR (ppm) d 7.35–7.30 (m, 4H), 7.26–
7.24 (m, 1H), 7.02–7.00 (m, 1H), 6.99–6.94 (m, 2H), 4.22–4.17
6
1
1
.43 (m, 2H), 4.26–4.15 (m, 4H), 3.87 (br s, 2H), 1.71–1.61 (m, 4H),
.03–0.90 (m, 10H); C NMR (ppm) d 155.7, 141.5, 140.0, 120.6,
1
3
(
m, 4H), 4.06 (d, J = 13.7 Hz, 1H), 3.83–3.74 (m, 2H), 3.63 (d,
10.0, 108.2, 71.4, 71.3, 30.2, 30.0, 27.9, 26.1, 26.1, 25.7, 25.4; IR
ꢀ1
J = 13.7 Hz, 1H), 2.02 (br s, 1H), 1.68–1.58 (m, 4H), 0.96–0.73 (m,
10H); C NMR (ppm) d 154.5, 152.6, 140.3, 133.0, 128.3, 128.1,
126.8, 121.6, 120.0, 119.7, 71.7, 71.1, 52.9, 48.5, 30.0, 29.8, 27.7,
(
cm ) 3365, 2924, 2851, 2362, 1617, 1506, 1457, 1198, 1163,
1
3
+
9
82; HRMS(ESI) calcd for C15
H24NO
2
[M+H] : 250.1802; found:
2
3
2
50.1802. [a] = +38.6 (c 0.57, CHCl , 98% ee). Ee was determined
D
3
2
6.2, 26.0, 25.8, 25.2 (two pairs of peaks are overlapped at aromatic
by HPLC analysis using a chiral column (Daicel Chiralpak IA:
ꢀ1
region); IR (cm ) 2925, 2854, 2361, 1491, 1456, 1199, 1150, 979,
4
ꢁ 250 mm, 254 nm UV detector, rt, eluent: 40% EtOAc in hexane,
+
8
24, 736, 698; HRMS(ESI) calcd for C23
H
32NO
2
[M+H] : 354.2425;
, 97% ee). Ee was
flow rate: 0.5 mL/min, retention time: 10.2 min for minor isomer
and 11.0 min for major isomer).
2
6
found: 354.2428. [
a]
D
= +13.0 (c 0.85, CHCl
3
determined by HPLC analysis using a chiral column (Daicel Chiral-
cel OD-H: 4 ꢁ 250 mm, 254 nm UV detector, rt, eluent: 10% 2-pro-
panol in hexane, flow rate: 0.5 mL/min, retention time: 16.4 min
for major isomer and 24.0 min for minor isomer).
4
.3. General experimental procedure for reductive amination
(
Eq. 1 in Scheme 3)
To a two-neck flask purged with argon, a solution of appropriate
amine (0.1 mmol) and aldehyde (1.2 equiv) in 1,2-dichloroethane
4.3.5. 13-(Isopropylamino)methyl-1,11-dioxa[11]paracycloph-
ane (5b)
(
0.3 mL) was added followed by NaBH(OAc)
0.02 mL). The reaction mixture was stirred until completion of
CO was added to
the reaction mixture and extracted with dichloromethane
10 ml ꢁ 3). The organic layer was washed with water, dried over
Na SO and evaporated to dryness. The obtained crude products
were isolated through PTLC.
3
(3 equiv) and AcOH
(
Yellow viscous oil. PTLC (eluent: Hex/EtOAc = 3/1). Yield:
1
the reaction. A saturated aqueous solution of K
2
3
32.1 mg, 94%. H NMR (ppm) d 6.97 (d, J = 2.4 Hz, 2H), 6.94–6.92
(m, 1H), 4.22–4.17 (m, 4H), 4.03 (d, J = 13.5 Hz, 1H), 3.61 (d,
J = 13.5 Hz, 1H), 2.79–2.77 (dd, J = 5.9, 2.7 Hz, 1H), 1.66–1.61 (m,
4H), 1.43 (br s, 1H), 1.07 (d, J = 5.6 Hz, 6H), 0.97–0.67 (m, 10H);
(
2
4
1
3
C NMR (ppm) d 154.5, 152.6, 133.5, 121.5, 119.9, 119.5, 71.7,
7
1.1, 47.4, 46.7, 30.1, 29.9, 27.8, 26.2, 26.0, 25.8, 25.3, 23.0, 22.7.
ꢀ1
4
.3.1. 13-Benzylamino-1,11-dioxa[11]paracyclophane 3a
IR (cm ) 3853, 3749, 3735, 3649, 2924, 2853, 2361, 1490, 1457,
1193; HRMS(ESI) calcd for C19H32NO [M+H] : 306.2425; found:
2
306.2428. [a] = +8.8 (c 0.61, CHCl ).
D 3
+
Yellow viscous oil. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
28
1
2.5 mg, 79%. H NMR (ppm) d 7.40–7.30 (m, 4H), 7.25–7.23 (m,
Please cite this article in press as: Hazra, M.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.08.015

M. Hazra et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
4
.4. General procedure for the synthesis of phosphoramidite
NMR (ppm) d 154.0, 153.3, 149.8, 149.5, 138.0, 132.8, 132.5,
ligands L1–L9 (Scheme 4)
131.4, 130.7, 130.7, 130.1, 130.0, 128.4, 128.3, 128.2, 127.0,
1
27.0, 126.9, 126.0, 125.9, 124.7, 124.5, 124.1, 124.1, 122.7,
In a Schlenk tube evacuated and purged with argon (3 times), a
solution of appropriate planar-chiral amine 3a–3c, 5a and 5b
122.4, 122.2, 121.9, 120.3, 120.1, 72.0, 71.0, 47.3, 44.8, 30.0, 29.6,
27.8, 26.2, 26.1, 26.0, 25.2; P (ppm) d 147.0. IR (cm ) 2924,
3
1
ꢀ1
(
0.1 mmol) in THF (0.5 mL) and TMEDA (2 equiv) were added and
2852, 2361, 2329, 1490, 1457, 1230, 1200, 936, 822, 420; HRMS
+
cooled to ꢀ78 °C. A hexane solution of n-BuLi (1.54 M, 2 equiv)
was added dropwise to the solution, and the reaction mixture
was stirred for 2 h at ꢀ78 °C. A THF solution (0.6 mL) of commer-
(ESI) calcd for
C
43
H
42NNaO
4
P
[M+Na] : 690.2739; found:
3
).
2
6
690.2744. [
a]
D
= ꢀ113.0 (c 1.06, CHCl
0
cially available 2,2 -binaphthalene phosphorochloridites (2 equiv)
0
4.4.4. (S
methyl)dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-
amine (S )-L2
a
)-N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl-
or in situ prepared 2,2 -biarylene phosphorochloridite [prepared
by mixing the corresponding biaryl diol (0.20 mmol) and PCl
(
and warmed to room temperature overnight. The resulting solu-
tion was filtered through filter paper using dichloromethane and
then evaporated to dryness. The crude products were purified
through PTLC to furnish the desired ligands.
0
0
3
a
0.28 mmol) at 75 °C overnight] was added dropwise at ꢀ78 °C
Foamy white solid. PTLC (eluent: hexane/EtOAc = 3/1). Yield:
1
3
3
7
2.8 mg, 45%. Mp: 114–118 °C. H NMR (ppm) d 7.98 (dd, J = 8.8,
.1 Hz, 1H), 7.93 (dd, J = 8.3, 4.2 Hz, 1H), 7.84–7.81 (m, 2H), 7.56–
.53 (m, 1H), 7.44–7.31 (m, 8H), 7.27–7.26 (m, 2H), 7.21–7.13
(
1
m, 3H), 6.86–6.77 (m, 2H), 4.62–4.55 (m, 1H), 4.35–4.28 (m,
H), 4.20–4.12 (m, 1H), 3.83–3.67 (m, 4H), 3.50–3.44 (m, 1H),
4
.4.1. (R
a
)-N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl)-
1
3
0
0
1.65–1.56 (m, 3H), 0.82–0.12 (m, 11H); C NMR (ppm) d 155.0,
52.3, 149.8, 149.7, 149.2, 138.3, 132.8, 132.5, 131.3, 130.8,
130.7, 130.2, 130.1, 128.9, 128.4, 128.2, 128.1, 127.5, 127.0,
dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-amine (R
a
)-L1
1
Foamy white solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
2
4
4
1
4
1
0
1
1
1
2
6.4 mg, 41%. Mp: 124–128 °C. H NMR (ppm) d 8.04–7.90 (m,
1
1
2
26.9, 126.1, 125.9, 124.8, 124.5, 122.5, 122.0, 121.6, 120.5,
19.6, 119.2, 71.5, 71.3, 50.6, 42.5, 30.2, 29.3, 27.3, 25.4, 25.2,
H), 7.68 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.45–7.36 (m,
H), 7.27–7.24 (m, 3H), 7.06–7.04 (m, 4H), 6.97 (d, J = 8.7 Hz,
H), 6.77 (d, J = 8.1 Hz, 1H), 6.53 (s, 1H), 4.56–4.51 (m, 1H), 4.43–
.35 (m, 2H), 4.23 (dd, J = 14.4, 3.4 Hz, 1H), 3.97–3.88 (m, 2H),
.82–1.77 (m, 2H), 1.45–1.42 (m, 2H), 0.95–0.80 (m, 8H), 0.72–
31
4.5 (a pair of peaks in the aliphatic region is overlapped);
P
ꢀ1
(
ppm) d 148.7. IR (cm ) 2929, 2362, 2343, 2328, 1507, 1489,
+
1
230, 421; HRMS(ESI) calcd for
C
43
H
42NNaO [M+Na] :
4
P
2
4
1
3
690.2740; found: 690.2744. [
a]
D
= +174.5 (c 1.10, CHCl ).
3
.71 (m, 2H); C NMR (ppm) d 154.8, 150.0, 149.2, 142.5, 139.6,
38.5, 137.9, 134.8, 132.8, 132.6, 131.5, 130.8, 130.3, 129.1,
28.3, 127.9, 127.1, 127.0, 126.8, 126.1, 124.9, 124.7, 124.2,
24.1, 122.6, 122.2, 122.1, 122.0, 121.6, 118.3, 71.4, 50.3, 30.1,
9.4, 27.6, 26.5, 25.9, 25.8, 25.3 (a pair of peaks in the aliphatic
4
.4.5. (R
a
)-N-(1,11-Dioxa[11]paracyclophan-13-yl)-N-methyl-
0
0
dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-amine (R
a
)-L3
Foamy white solid. PTLC (eluent: toluene only). Yield: 17.1 mg,
31
ꢀ1
region is overlapped); P (ppm) d 140.3. IR (cm ) 3749, 3735,
649, 2921, 2361, 2343, 1734, 1363, 1229, 420; HRMS(ESI) calcd
1
3
7
7
1
1
1
0%. Mp: 110–115 °C. H NMR (ppm) d 7.99 (dd, J = 8.8, 8.8 Hz, 2H),
3
for
.94 (dd, J = 8.1, 3.3 Hz, 2H), 7.59 (dd, J = 12.0, 8.8 Hz, 2H), 7.46–
.41 (m, 3H), 7.35 (d, J = 8.6 Hz, 1H), 7.31–7.29 (m, 1H), 7.27 (s,
H), 7.07 (d, J = 7.8 Hz, 1H), 6.90–6.87 (m, 2H), 4.46–4.41 (m,
H), 4.34–4.30 (m, 1H), 4.18–4.14 (m, 2H), 2.73 (s, 3H), 1.78–
+
C
42
H
40NNaO
4
P
[M+Na] : 676.2584; found: 676.2587.
).
2
3
[
a
]
D
= ꢀ193.7 (c 0.91, CHCl
3
4
.4.2. (S
a
)-N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl)-
13
.77 (m, 1H), 1.71–1.65 (m, 2H), 1.05–0.84 (m, 11H); C NMR
0
0
dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-amine (S
a
)-L1
(
ppm) d 155.7, 149.3, 149.1, 132.8, 132.6, 131.5, 130.7, 130.4,
Foamy white solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
1
3
30.1, 128.3, 128.3, 127.0, 126.1, 124.9, 124.7, 124.2, 124.0,
24.0, 122.7, 122.2, 119.1, 119.0, 117.8, 117.6, 71.6, 71.4, 34.9,
0.3, 29.6, 27.7, 26.3, 26.1, 26.0, 25.3 (two pairs of peaks in the aro-
1
4
1.6 mg, 65%. Mp: 126–130 °C.
H NMR (ppm) d 7.98 (d,
J = 8.5 Hz, 1H), 7.91 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 6.6 Hz, 1H),
7
7
J = 15.3 Hz, 1H), 4.39–4.21 (m, 3H), 4.13–4.03 (m, 2H), 1.76–1.50
(
1
1
1
1
.75 (d, J = 8.6 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.46–7.33 (m, 5H),
.25–7.12 (m, 7H), 6.91 (br s, 2H), 6.79 (d, J = 6.9 Hz, 1H), 4.62 (d,
31
ꢀ1
matic region are overlapped); P (ppm) d 144.0. IR (cm ) 2924,
362, 2328, 1746, 1734, 1539, 1507, 1456, 1229, 420; HRMS(ESI)
2
+
calcd for C36
H
36NNaO
4
P [M+Na] : 600.2274; found: 600.2274.
).
m, 4H), 1.00–0.79 (m, 10H); 13C NMR (ppm) d 155.1, 149.8,
28
[a
]
D
= ꢀ124.7 (c 0.43, CHCl
3
49.8, 149.7, 149.0, 138.3, 135.7, 135.5, 132.8, 132.6, 131.4,
30.6, 130.4, 129.8, 128.4, 128.3, 128.2, 127.9, 127.1, 127.0,
26.6, 126.1, 126.0, 124.9, 124.5, 122.0, 121.9, 121.0, 120.9,
4.4.6. (R
a
)-N-(1,11-Dioxa[11]paracyclophan-13-yl)-N-isopropyl-
3
1
0
0
18.1, 71.5, 70.8, 49.8, 30.3, 29.6, 27.7, 26.6, 26.3, 25.1, 25.3;
P
dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-amine (R )-L4
a
ꢀ1
(
1
+
ppm) d 140.7. IR (cm ) 2924, 2854, 2361, 1601, 1508, 1457,
223, 966, 813, 445; HRMS(ESI) calcd for C42 40NNaO P [M
= ꢀ61.9 (c 0.51, CHCl ).
Foamy white solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
H
4
12.4 mg, 20%. Mp: 116–120 °C. H NMR (ppm) d 8.0–7.89 (m,
+
23
Na] : 676.2584; found: 676.2587. [
a
]
D
3
4H), 7.67 (d, J = 8.7 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.42–7.35 (m,
4
H), 7.26–7.24 (m, 2H), 7.05 (d, J = 8.8 Hz, 1H), 6.95 (d, J = 8.1 Hz,
4
.4.3. (R
methyl)dinaphtho[2,1-d:1 ,2 -f][1,3,2]dioxaphosphepin-4-
amine (R )-L2
Foamy white solid. PTLC (eluent: hexane/EtOAc = 3/1). Yield:
a
)-N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl-
1H), 6.65 (s, 1H), 4.50–4.37 (m, 2H), 3.99 (d, J = 8.4 Hz, 1H), 3.78
(s, 1H), 3.58–3.53 (m, 1H), 1.87–1.83 (m, 1H), 1.72–1.66 (m, 1H),
1.42–1.20 (m, 2H), 0.99–0.85 (m, 8H), 0.96 (d, J = 6.3 Hz, 3H),
0
0
a
1
3
0.88 (d, J = 6.4 Hz, 3H), 0.80–0.66 (m, 2H); C NMR (ppm) d
179.8, 178.8, 154.1, 151.7, 150.1, 149.8, 132.9, 132.7, 131.4,
130.8, 130.1, 129.8, 128.9, 128.4, 128.3, 127.7, 127.1, 127.1,
126.0, 125.9, 124.7, 124.4, 122.6, 122.3, 120.4, 119.9, 71.7, 71.2,
1
2
5.2 mg, 36%. Mp: 113–117 °C.
H NMR (ppm) d 7.98 (d,
J = 8.8 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H),
7
7
.76 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.39 (dd, J = 7.7,
.7 Hz, 1H), 7.35–7.30 (m, 3H), 7.28 (d, J = 7.5 Hz, 2H), 7.25–7.18
31
53.4, 30.2, 29.7, 29.6, 27.7, 26.6, 26.0, 25.6, 22.9, 21.5; P (ppm)
ꢀ
1
(
1
m, 5H), 7.15 (d, J = 8.7 Hz, 1H), 7.10–7.03 (m, 2H), 6.92 (br s,
H), 4.51 (dd, J = 15.3, 10.3 Hz, 1H), 4.20–4.08 (m, 4H), 4.05 (dd,
J = 15.3, 4.4 Hz, 1H), 3.69 (dd, J = 18.7, 15.4 Hz, 1H), 3.38 (dd,
d 144.4. IR (cm ) 2926, 2360, 2339, 1735, 1540, 1509, 1490,
1363, 1231, 948, 517, 458, 420; HRMS(ESI) calcd for C38 40NNaO
= ꢀ142.5 (c 0.87,
H
4
-
+
30
P [M+Na] : 628.2584; found: 628.2587. [
a]
D
1
3
J = 15.3, 5.9 Hz, 1H), 1.72–1.46 (m, 4H), 0.93–0.68 (m, 10H);
C
CHCl ).
3
Please cite this article in press as: Hazra, M.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.08.015

6
M. Hazra et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
4
.4.7. N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl)dibenzo-
1065, 857, 759, 699, 593, 476, 418; HRMS(ESI) calcd for
+
[d,f][1,3,2]dioxaphosphepin-6-amine L5
C
38
H
44NNaO
= ꢀ123.3 (c 0.56, CHCl
4
P
[M+Na] :
632.2897;
found:
632.2900.
2
7
Foamy white solid. PTLC (eluent: toluene only). Yield: 38.9 mg,
[a
]
D
3
).
1
7
6
4
0
1
1
1
2
1
C
0%. Mp: 68–74 °C. H NMR (ppm) d 7.48 (m, 2H), 7.36–7.26 (m,
H), 7.11–7.05 (m, 5H), 6.97–6.93 (m, 1H), 6.78–6.72 (m, 2H),
.61–4.35 (m, 4H), 4.12–4.06 (m, 2H), 1.72–1.61 (m, 3H), 0.92–
.78 (m, 11H); C NMR (ppm) d 155.1, 151.9, 150.9, 149.9,
38.2, 135.3, 135.1, 131.3, 130.6, 129.9, 129.8, 129.5, 129.3,
29.0, 128.0, 126.8, 125.0, 124.6, 122.5, 122.2, 122.1, 121.5,
21.4, 118.1, 71.6, 71.3, 49.8, 30.4, 29.6, 27.8, 26.5, 26.1, 25.9,
4.4.11. N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-ylmethyl)-
2,4,8,10-tetramethyldibenzo[d,f][1,3,2]dioxaphosphepin-6-
amine L9
1
3
White solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield: 24.5 mg,
1
39%. Mp: 76–80 °C. H NMR (ppm) d 7.37 (d, J = 6.8 Hz, 2H), 7.31
(dd, J = 7.6, 7.6 Hz, 2H), 7.27–7.26 (m, 1H), 7.14 (s, 1H), 7.01–6.98
(m, 3H), 6.92–6.90 (m, 3H), 4.24–4.20 (m, 1H), 4.15–3.97 (m,
3
1
ꢀ1
5.4; P (ppm) d 141.0. IR (cm ) 2924, 2852, 2361, 1493, 1474,
457, 1436, 1246, 1192, 1166, 885; HRMS(ESI) calcd for
5H), 3.92 (d, J = 14.7, Hz, 2H), 2.36 (s, 3H), 2.32 (s, 3H), 2.27 (s,
+
13
34
H
36NNaO
4
P
[M+Na] :
576.2280;
found:
576.2274.
3H), 2.04 (s, 3H), 1.29–1.27 (m, 3H), 0.82–0.52 (m, 11H);
C
2
4
[a
]
D
= ꢀ90.5 (c 0.53, CHCl
3
).
NMR (ppm) d 154.8, 152.7, 149.6, 147.9, 146.7, 138.1, 133.2,
32.6, 131.3, 130.9, 130.9, 130.8, 130.0, 129.9, 129.2, 128.2,
1
4
.4.8. N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-ylmethyl)-
127.8, 127.7, 127.2, 120.3, 119.5, 99.9, 71.6, 71.4, 30.2, 29.7, 27.7,
25.9, 25.6, 25.5, 25.2, 20.8, 20.8, 16.5, 16.5. (Two pairs of peaks
dibenzo[d,f][1,3,2]dioxaphosphepin-6-amine L6
3
1
Foamy white solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
are overlapped in the aliphatic region.) P (ppm) d 143.0. IR
1
ꢀ1
2
1
7
4
3
6.5 mg, 47%. Mp: 65–70 °C. H NMR (ppm) d 7.42 (d, J = 7.5 Hz,
H), 7.39–7.36 (m, 5H), 7.34–7.24 (m, 4H), 7.22–7.16 (m, 3H),
.04 (d, J = 7.9 Hz, 1H), 6.91–6.90 (m, 2H), 4.41–4.35 (m, 1H),
.29–4.24 (m, 1H), 4.20–4.15 (m, 1H), 4.13–3.93 (m, 4H), 3.89–
.86 (m, 1H), 1.71–1.54 (m, 3H), 1.16–1.09 (m, 1H), 0.88–0.75
(cm ) 2923, 2851, 2362, 2338, 1735, 1489, 1363, 1214, 1194,
+
854, 420; HRMS(ESI) calcd for C39
H
46NNaO
4
P [M+Na] : 646.3054;
2
5
found: 646.3057. [
a
]
D
= +24.1 (c 1.27, CHCl ).
3
0
4.4.12. N-(2,5-Dimethoxyphenyl)-N-methyldinaphtho[2,1-d:1 ,
m, 3H), 0.56–0.51 (m, 7H); 13C NMR (ppm) d 154.8, 152.5, 151.9,
2 -f][1,3,2]dioxaphosphepin-4-amine L10
0
(
1
1
1
2
51.8, 138.3, 131.4, 131.4, 130.4, 130.4, 129.7, 129.5, 129.3,
29.0, 128.6, 128.3, 127.2, 124.7, 124.2, 122.2, 121.7, 120.2,
20.1, 119.5, 71.8, 71.1, 49.4, 43.3, 30.1, 29.7, 27.6, 25.8, 25.6,
5.6, 25.0 (a pair of peaks in the aromatic region is overlapped);
Foamy white solid. PTLC (eluent: toluene only). Yield: 13.9 mg,
29%. Mp: 89–92 °C. H NMR (ppm) d 7.97–7.89 (m, 4H), 7.56–7.53
(m, 2H), 7.45–7.33 (m, 4H), 7.28–7.22 (m, 2H), 6.88–6.84 (m, 2H),
1
6.72–6.69 (m, 1H), 3.89–3.87 (m, 3H), 3.75–3.73 (m, 3H), 2.59–2.57
3
1
ꢀ1
13
P (ppm) d 149.1. IR (cm ) 2927, 2361, 2341, 1734, 1541, 1489,
(m, 3H); C NMR (ppm) d 153.9, 150.2, 150.1, 149.5, 135.2, 135.0,
1
436, 1191, 884, 772, 447, 419; HRMS(ESI) calcd for C35
H
38NNaO
4
P
132.9, 131.4, 130.8, 130.2, 129.9, 128.3, 128.2, 127.0, 126.9, 126.0,
124.0, 124.0, 122.7, 122.2, 122.0, 115.0, 114.9, 113.4, 111.1, 99.9,
+
20
[
M+Na] : 590.2430; found: 590.2431. [
a
]
D
= ꢀ8.7 (c 0.61, CHCl
3
).
3
1
ꢀ1
5
6.6, 55.7, 35.0; P (ppm) d 144.7. IR (cm ) 2927, 1614, 1587,
1
for
500, 1460, 1327, 1269, 1221, 1063, 937, 820; HRMS(ESI) calcd
4
.4.9. N-(1,11-Dioxa[11]paracyclophan-13-ylmethyl)-N-iso-
+
C
29
H
25NO
4
P
[M+H] :
482.1517;
found:
482.1516.
propyldibenzo[d,f][1,3,2]dioxaphosphepin-6-amine L7
32
[a
]
D
= ꢀ72.1 (c 0.77, CHCl
3
).
Foamy white solid. PTLC (eluent: hexane/EtOAc = 5/1). Yield:
1
1
1
1
5.4 mg, 30%. Mp: 130–134 °C. H NMR (ppm) d 7.42 (dd, J = 7.6,
.6 Hz, 1H), 7.38 (dd, J = 7.6, 1.6 Hz, 1H), 7.35 (dd, J = 7.7, 1.8 Hz,
H), 7.31 (dd, J = 7.7, 1.6 Hz, 1H), 7.23–7.17 (m, 5H), 6.80 (d,
Acknowledgments
This work was supported by JST, ACT-C, Japan. We are grateful
to Tokyo Chemical Industry Co., Ltd. (TCI) for generously supplying
J = 1.6 Hz, 2H), 4.26–4.19 (m, 1H), 4.17–4.13 (m, 2H), 4.04–3.97
m, 2H), 3.85 (ddd, J = 12.0, 6.6, 3.1 Hz, 1H), 3.69–3.61 (m, 1H),
(
1
,11-dioxa[11]paracyclophane.
1
1
0
1
1
4
.65–1.58 (m, 1H), 1.56–1.48 (m, 1H), 1.43 (d, J = 6.7 Hz, 3H),
.27–1.23 (m, 1H), 1.14 (d, J = 6.7 Hz, 3H), 1.10–1.05 (m, 1H),
.81–0.74 (m, 2H), 0.52–0.39 (m, 8H); C NMR (ppm) d 154.8,
52.6, 152.6, 151.4, 133.5, 130.3, 130.3, 129.9, 129.5, 129.3,
28.9, 124.7, 124.0, 122.4, 121.7, 120.2, 119.7, 118.9, 71.7, 71.2,
13
A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.08.
3
1
9.2, 41.3, 30.2, 29.7, 27.5, 25.8, 25.6, 25.5, 25.0, 23.2, 23.0;
P
ꢀ1
0
15.
(
ppm) d 151.3. IR (cm ) 2924, 2852, 2362, 1488, 1435, 1247,
1
C
191, 1095, 1036, 888, 847, 765, 419; HRMS(ESI) calcd for
+
28
References
31
H
38NNaO
4
P [M+Na] : 542.2432; found: 542.2431. [
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D
a] = +86.9
(c 0.84, CHCl
3
1
2
.
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.4.10. N-Benzyl-N-(1,11-dioxa[11]paracyclophan-13-yl)-2,4,8,-
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Please cite this article in press as: Hazra, M.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.08.015