Highly enantioselective Pd(II)-catalyzed Wacker-type cyclization of 2-allylphenols by use of bisoxazoline ligands with axis-unfixed biphenyl backbone

Article abstract of DOI:10.1016/j.tetlet.2007.04.064

A series of axis-unfixed bisoxazoline ligands with different steric and electronic properties has been synthesized. Due to the different steric interactions, the ligands afforded only one of the two possible diastereomeric Pd(II)-complexes upon metal coor

Full text of DOI:10.1016/j.tetlet.2007.04.064

Tetrahedron Letters 48 (2007) 4179–4182
Highly enantioselective Pd(II)-catalyzed Wacker-type
cyclization of 2-allylphenols by use of bisoxazoline ligands
with axis-unfixed biphenyl backbone
Feijun Wang, Yong Jian Zhang, Guoqiang Yang and Wanbin Zhang*
Department of Chemistry, School of Chemistry and Chemical Technology, Shanghai Jiao Tong University,
800 Dongchuan Road, Shanghai 200240, PR China
Received 31 January 2007; revised 16 April 2007; accepted 17 April 2007
Available online 19 April 2007
Abstract—A series of axis-unfixed bisoxazoline ligands with different steric and electronic properties has been synthesized. Due to
the different steric interactions, the ligands afforded only one of the two possible diastereomeric Pd(II)-complexes upon metal co-
ordination. The palladium complex (S,aS)-8c showed excellent catalytic activities and enantioselectivities in Wacker-type cyclization
of allylphenols with up to 98% ee.
Ó 2007 Elsevier Ltd. All rights reserved.
Pd(II)-catalyzed intramolecular Wacker-type cycliza-
tions have emerged as a versatile strategy in the construc-
tion of a range of heterocycles.1 However, in striking
contrast to the well-defined Pd(0)-catalyzed asymmetric
reactions,2 asymmetric oxidative cyclizations with
Pd(II)-complexes have received relatively little attention.
Previous attempts at asymmetric version of this oxidative
cyclizations were reported by Hosokawa and Mura-
hashi,3 nevertheless, the Wacker-type cyclization of 2-
allylphenols by use of a chiral p-allylpalladium complex
afforded dihydrobenzofurans with only 29% ee. Re-
cently, Hayashi and co-workers reported an important
breakthrough on the Pd(II)-catalyzed enantioselective
Wacker-type cyclization of 2-allylphenols with chiral
bisoxazoline ligands based on binaphthyl backbone
(boxax).4,5 In the cyclization of 1a, 96% ee was obtained
in the presence of p-benzoquinone in methanol by using
boxax.4a Sasai and co-workers reported asymmetric oxi-
dative tandom cyclization of alkenyl alcohols with spiro
bisoxazoline ligands (SPRIXs) which gave a bicyclic
product with a high enantiomeric excess (up to 95%).6
Enantioselective aerobic cyclization was also reported
with Pd(II)/sparteine as a catalyst system, however, the
enantioselectivities are not sufficiently high.7
These ligands exist as an equilibrium mixture of diaste-
reomers in solution as a result of the rotation around
axis of biphenyl backbone, but only one of the two pos-
sible diastereomers was observed on complexation of
ligands 3a with copper(I) salts. In view of atom economy,
traditional axis-fixed oxazoline ligands9 require inconve-
nient diastereomeric separation in their synthetic pro-
cesses, and generally, only one diastereomeric pure
form of the ligands works effectively in catalytic asym-
metric reactions due to their configurational matching–
mismatching effect. Whereas the axial flexible ligands
can afford completely a single diastereomeric metal cat-
alyst on complexing process without any ligand wasting
caused by configurational mismatching. Therefore, here-
in we report the development of highly enantioselective
Pd(II)-catalyzed Wacker-type cyclization of 2-allylphe-
nols with our axial flexible bisoxazoline 3 as chiral
ligands.
Pd(II), chiral ligand
reoxidant
O
OH
1a
2a
Ph
Recently, we reported C2-symmetric bisoxazoline
ligands 3a bearing an axis-unfixed biphenyl backbone.8
O
N
N
O
Ph
*
Corresponding author. Tel./fax: +86 21 5474 3265; e-mail:
wanbin@sjtu.edu.cn
3a
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.064

4180
F. Wang et al. / Tetrahedron Letters 48 (2007) 4179–4182
Table 1. The complexation behavior of ligands 3
In order to evaluate the influence of steric and electronic
properties of ligands on the enantioselective transforma-
tion, a series of axis-unfixed oxazoline ligands 3b–e has
been synthesized. Bisoxazoline ligand, 2,20-bis[(40S)-iso-
propyl oxazolin-20-yl]-5,50-dichloro-1,10-biphenyl (3b)10
was synthesized in three steps in 63% overall yield start-
ing from 5,50-dichloro-1,10-biphenyl-2,20-dicarboxylic
acid (4)8c according to the well-known procedures of
oxazoline ring formation11 (Scheme 1). 5,50-Dimethoxyl-
ated bisoxazolines 3c–e were synthesized starting from
3-bromoanisole as depicted in Scheme 2. Friedel–Crafts
acylation of 3-bromoanisole gave acylated compound 5
in 59% yield.12 Bromoform reaction of compound 5, fol-
lowed by esterification of carboxylic acid in methanol,
afforded 2-bromo-4-methoxybenzoate (6) in 87% yield.13
Ullman coupling of compound 6 with activated copper
powder followed by hydrolysis furnished biphenyl ske-
leton 7 in 58% yield. Diacid 7 was subjected to oxazoline
ring formation as the same way for synthesis of 3b to
afford 5,50-dimethoxylated bisoxazoline 3c–e14 in 54%,
50%, and 60% overall yields, respectively. The two
diastereomers of axis-unfixed bisoxazolines 3 can be
Y
N
Y
N
R
R
O
O
N
Y
N
Y
O
O
R
R
(
S
,a
R
)-3
(S,aS)-3
-M
M
M
-M
Y
N
Y
N
R
R
O
O
M
M
N
Y
N
Y
O
O
R
R
M = PdCl2
(S R)-8
,a
(S,aS)-8
(not observed)
a
b
c
d
e
(S,aR)-3: (S,aS)-3a
(S,aR)-8: (S,aS)-8a
1:1.4
0:100
1:1.4
0:100
1:2.2
0:100
1:2.5
1:1.3
0:100
0:100
a The ratios of the two diastereomers of 3 and 8 were determined by 1H
NMR (400 MHz) in CD3CN at 16 °C.
1
observed in solution at room temperature by H NMR
spectroscopy. Due to the different steric interactions,
one diastereomer dominated over the other one. Thus,
the ratios of the two diastereomers of 3 were within
afforded only one set of peaks in 1H NMR spectro-
scopy.15 This observation obviously suggested that only
one diastereomer quantitatively formed through the
coordinating process of ligands 3 with palladium ion
(Table 1). The axial configurations of the obtained com-
plexes 8 were assigned as S by comparison with our pre-
vious report on this type of metal complexes.8
1
1.3:1 to 2.5:1 by examination of H NMR spectroscopy
(Table 1). It was also shown that the two diastereomers
of all ligands 3 are in equilibrium in solution because the
ratios changed as the temperature was varied.
To evaluate the coordinating behavior of axis-unfixed
bisoxazolines 3, the reactions of 3 with 1 equiv of PdCl2
in acetonitrile-d3 at 16 °C were monitored by H NMR
spectroscopy. As expected, all of the resultant solutions
With the complexation behavior in hand, the Pd(II)-
complexes of axis-unfixed bisoxazoline ligands 3 were
used in Pd(II)-catalyzed intramolecular Wacker-type
cyclization. Typically, 2-(2,3-dimethyl-2-butenyl)phenol
(1a) was used as a model substrate for the oxidative
cyclization. The reactions were catalyzed by 10 mol %
of the Pd(II)–3 complexes generated in situ by mixing
Pd(CF3COO)2 with bisoxazolines 3 in a 1:2 molar ratio
in the presence of p-benzoquinone as reoxidant in meth-
anol at 60 °C. It was found that the catalytic efficiencies
in the cyclization reaction largely depended on the elec-
tronic properties of the 5 and 50-substituents of the
ligand as well as bulkiness of substituents on the
oxazoline rings. As shown in Table 2, with the standard
axis-unfixed bisoxazoline 3a as ligand, allylphenol 1a
was cyclized with 92% ee in high isolated yield (entry
1). However, the catalytic activity and enantioselectivity
in the cyclization were markedly decreased with 5,50-
dichlorinated bisoxazoline 3b as ligand (entry 2).
Whereas using ligand 3c, which has electronic donating
methoxy groups in ligand backbone, the reactivity and
enantioselectivity were dramatically improved (entry
3). However, when the substituents on the oxazoline
rings of ligands changed to isopropyl or benzyl groups
(3d or 3e), the cyclization afforded product 2a with
remarkably lower enantioselectivity (entries 4–5).
1
Cl
Cl
N
Ph
1) SOCl2, DMF(cat)
O
COOH
Cl
2) (S)-Phenylglycinol
HOOC
N
O
Ph
3) MsCl, Et3N, CH2Cl2
Cl
3b
4
Scheme 1.
O
COOMe
Br
Br
Br
AlCl3
CH3COCl
1) Br2, NaOH
1) Cu
2) SOCl2, MeOH
2) NaOH aq
OMe
OMe
OMe
MeO
6
5
OMe
R'
1) SOCl2, DMF(cat)
O
COOH
N
O
2) (S)-amino alcohol
HOOC
N
R'
3) MsCl, Et3N, CH2Cl2
OMe
MeO
7
3
The generality of the chelation-induced axially chiral
Pd-catalyst, 3c–Pd(CF3COO)2, has been successfully
demonstrated through the Wacker-type cyclization of
a series of o-allylphenols 1b–h and o-allylnaphthols 1i,
3c: R' = Ph
3d: R' = -Pr
3e: R' = Bn
i
Scheme 2.

F. Wang et al. / Tetrahedron Letters 48 (2007) 4179–4182
4181
Table 2. Pd(II)-catalyzed asymmetric Wacker-type cyclization of 1a
electronic and steric properties of the ligand on enantio-
selectivity have been observed, and excellent catalytic
activities and enantioselectivities with up to 98% ee were
obtained by using Pd(II)–3c complex as catalyst.
Pd(CF3COO)2 (10 mol %)
3 (20 mol %)
R
R
O
benzoquinone (4 equiv)
MeOH, 60 oC, 24 h
OH
2
1
Entry Ligand Substrate
R
Yieldb (%) eec (%)
Acknowledgment
1
2
3
4
5
6
7
8
9
10
11
12
13
3a
3b
3c
3d
3e
3c
3c
3c
3c
3c
3c
3c
3c
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
H
H
H
H
86
67
92
81
89
92
83
74
80
79
65
73
92
84
94
53
80
90
93
98
90
98
94
91d
92e
This work was supported by the National Natural
Science Foundation of China (grant nos. 20572070
and 20502015), and the Ministry of Education of China
(EYTP and SRFDP).
H
4-Me
5-Me
6-Me
4-OMe
6-OMe
4-F
References and notes
1. For a recent review, see: (a) Tsuji, J. Palladium Reagents
and Catalysts; John & Sons: Chichester, 2004; pp 27–103;
Selected examples: (b) Ro¨nn, M.; Ba¨ckvall, J. E.; Anders-
son, P. G. Tetrahedron Lett. 1995, 36, 7749; (c) Hirai, Y.;
Watanabe, J.; Nozakim, T.; Yokoyama, H.; Yamaguchi,
S. J. Org. Chem. 1997, 62, 776; (d) Pei, T.; Wang, X.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125, 648; (e)
1g
1h
1i
4-Ph
1-Naphthol 75
a All reactions were catalyzed by 10 mol % of the Pd(II)–3 complex
generated in situ by mixing Pd(CF3COO)2 with bisoxazolines 3 (Pd/
ligand 1:2) in the presence of 4 equiv of p-benzoquinone in methanol
at 60 °C for 24 h.
Muniz, K. Adv. Synth. Catal. 2004, 346, 1425.
˜
b Isolated yield by column chromatography.
2. (a) Ojima, I. Catalytic Asymmetric Synthesis; Wiley-VCH:
Weinheim, 2000; (b) Jacobsen, E. N.; Pfaltz, A.; Yama-
moto, H. In Comprehensive Asymmetric Catalysis;
Springer: Berlin, 1999; Vol. I–III.
3. (a) Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J.
Am. Chem. Soc. 1981, 103, 2318; (b) Hosokawa, T.;
Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282.
4. (a) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem. Soc.
1997, 119, 5063; (b) Uozumi, Y.; Kato, K.; Hayashi, T. J.
Org. Chem. 1998, 63, 5071; (c) Uozumi, Y.; Kyota, H.;
Kato, K.; Ogasawara, M.; Hayashi, T. J. Org. Chem.
1999, 64, 1620.
c The enantiomeric excesses were determined by chiral GC on a CP-
Chirasil-Dex CB column. The absolute configurations were deter-
mined by comparing the sign of the optical rotation with that
reported in Ref. 4
d The enantiomeric excess was determined by HPLC on a Chiracel
OD-H column.
e The enantiomeric excess was determined by HPLC on a Chirapak
AD-H column.
providing corresponding chiral 2,3-dihydrobenzofurans
2b–h and dihydronaphtho[1,2-b]furan 1i with excellent
enantioselectivities (90–98% ee). As exemplified by the
substrates with methyl groups in 4-, 5- and 6-positions
of allylphenol, the steric properties of the substrates
certainly affected the reactivity and enantioselectivity.
Thus, the Wacker-type cyclization of sterically more
hindered 6-methyl-2-allylphenol 1d showed significantly
higher enantioselectivity than that of 1b and 1c, but the
isolated yield of 2d was lower than that of 2b and 2c
(entries 6–8). Similar trends in enantioselecitivity were
observed in the cyclization of 4- and 6-methoxylate
substrates, 1e and 1f (entries 9–10). The cyclization of
1g and 1h with fluoro and phenyl group at the 4-position
of 2-allylphenol, respectively, also afforded good yields
and excellent enantioselectivities (entries 11–12).
Furthermore, for 2-(2,3-dimethyl-2-butenyl)-1-naphthol
(1i), the cyclization gave the corresponding dihydro-
naphtho[1,2-b]furan 2i with good isolated yield and high
enantioselectivity (92% ee, entry 13).
5. For an investigation of mechanistic details, see: Hayashi,
T.; Yamasaki, K.; Mimura, M.; Uozumi, Y. J. Am. Chem.
Soc. 2004, 126, 3036.
6. Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am.
Chem. Soc. 2001, 123, 2907.
7. (a) Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.;
Stoltz, B. M. Angew. Chem., Int. Ed. 2003, 42, 2892; (b)
Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am.
Chem. Soc. 2005, 127, 17778.
8. (a) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron Lett. 1997, 38, 2681; (b) Imai, Y.; Zhang, W.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. J. Org. Chem. 2000, 65,
3326; (c) Zhang, W.; Xie, F.; Matsuo, S.; Imahori, M.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron: Asymmetry
2006, 17, 767.
9. For recent review, see: (a) McManus, H. A.; Guiry, P. J.
Chem. Rev. 2004, 104, 4151; (b) Gant, T. G.; Noe, M. C.;
Corey, E. J. Tetrahedron Lett. 1995, 36, 8745; (c) Uozumi,
Y.; Kyota, H.; Kishi, E.; Kitayama, K.; Hayashi, T.
Tetrahedron: Asymmetry 1996, 7, 1603; (d) Andrus, M. B.;
Asgari, D.; Sclafani, J. A. J. Org. Chem. 1997, 62, 9365; (e)
Pippert, A. J. Helv. Chim. Acta 1998, 81, 676.
25
1
10. Compound 3b: ½aꢀD ꢁ144.76 (c 1.20, CHCl3); H NMR
(400 M, CDCl3) major: d 7.91 (d, J = 8.0 Hz, 2H, ArH),
7.20–7.45 (m, 10H, ArH), 7.12–7.18 (m, 4H, ArH), 5.15–
5.25 (m, 2H, NCH), 4.43–4.53 (m, 2H, OCH2), 3.92 (t,
J = 8.0 Hz, 2H, OCH2); minor: d 7.95 (d, J = 8.4 Hz, 2H,
ArH), 7.20–7.45 (m, 10H, ArH), 7.03–7.08 (m, 4H, ArH),
5.15–5.25 (m, 2H, NCH), 4.43–4.53 (m, 2H, OCH2), 3.98
(t, J = 8.4 Hz, 2H, OCH2); 13C NMR (100 M, CDCl3) d
70.0, 70.1, 74.6, 75.3, 126.5, 126.7, 127.4, 127.6, 127.7,
In summary, a series of axis-unfixed bisoxazoline ligands
3 with different steric and electronic properties was syn-
thesized. These ligands were proven to exist as a mixture
of two diastereomers in equilibrium in solution. Signifi-
cantly, upon coordination with a Pd(II) ion, ligands 3
afforded only one of the two possible diastereomeric
Pd(II)-complexes. In their application in Wacker-type
cyclization of allylphenols, pronounced effects of the

4182
F. Wang et al. / Tetrahedron Letters 48 (2007) 4179–4182
128.0, 128.7, 128.8, 130.1, 130.2, 131.2, 136.6, 141.8, 142.1,
2H, ArH), 4.26–4.38 (m, 2H, NCH), 4.05 (t, J = 8.8 Hz,
2H, OCH2), 3.86 (s, 6H, OCH3), 3.70–3.90 (m, 2H,
OCH2), 2.98 (dd, J = 4.8, 13.6 Hz, 2H, CH2), 2.51–2.60
(m, 2H, CH2); minor: d 7.82 (d, J = 8.4 Hz, 2H, ArH),
7.06–7.30 (m, 10H, ArH), 6.85–6.89 (m, 2H, ArH), 6.78 (d,
J = 2.8 Hz, 2H, ArH), 4.26–4.38 (m, 2H, NCH), 3.97 (t,
J = 8.8 Hz, 2H, OCH2), 3.81 (s, 6H, OCH3), 3.70–3.90 (m,
2H, OCH2), 3.07 (dd, J = 4.8, 13.6 Hz, 2H, CH2), 2.51–
2.60 (m, 2H, CH2); 13C NMR (100 M, CDCl3) d 41.7,
41.8, 55.6, 68.1, 72.1, 112.7, 113.0, 115.5, 115.8, 126.4,
126.5, 128.6, 128.7, 129.3, 129.5, 131.1, 131.5, 138.6, 143.5,
161.1, 164.6; HRMS (Micromass LCT) Calcd. for
C34H33N2O4: 533.2440. Found: 533.2434.
164.8, 162.1; HRMS (Micromass LCT) Calcd. for
C30H22N2O2Cl2: 512.1058. Found: 512.1075.
11. Zhang, W.; Adachi, Y.; Hirao, T.; Ikeda, I. Tetrahedron:
Asymmetry 1996, 7, 451.
12. Takano, D.; Fukunaga, Y.; Doe, M.; Yoshihara, K.;
Kinoshita, T. J. Heterocycl. Chem. 1997, 34, 1111.
13. Hartmann, R. W.; Vom, O. H.-D.; Schoenenberger, H.
Archiv der Pharmazie 1990, 323, 73.
25
14. Compound 3c: ½aꢀD ꢁ187.48 (c 0.88, CHCl3); 1H NMR
(400 M, CDCl3) major: d 7.91 (d, J = 8.4 Hz, 2H, ArH),
7.15–7.35 (m, 10H, ArH), 7.08–7.13 (m, 2H, ArH), 6.90–
6.96 (m, 2H, ArH), 5.15–5.24 (m, 2H, NCH), 4.48 (dd,
J = 10.0, 8.8 Hz, 2H, OCH2), 3.89 (t, J = 8.0 Hz, 2H,
OCH2), 3.85 (s, 6H, OCH3); minor: d 7.95 (d, J = 8.4 Hz,
2H, ArH), 7.15–7.35 (m, 10H, ArH), 6.90–6.96 (m, 2H,
ArH), 6.80 (d, J = 2.0 Hz, 2H, ArH), 5.15–5.24 (m, 2H,
NCH), 4.42 (dd, J = 10.0, 8.8 Hz, 2H, OCH2), 3.98 (t,
J = 8.0 Hz, 2H, OCH2), 3.82 (s, 6H, OCH3); 13C NMR
(100 M, CDCl3) d 55.5, 69.8, 69.9, 74.5, 75.2, 112.9, 115.5,
120.4, 126.7, 126.8, 127.3, 127.5, 128.5, 128.7, 131.5, 142.8,
142.9, 143.2, 143.9, 161.1, 166.0; HRMS (Micromass
LCT) Calcd. for C32H29N2O4: 505.2127. Found:
1
15. Compound (S,aS)-8a: H NMR (400 M, CD3CN): d 9.11
(dd, J = 1.6, 7.2 Hz, 2H, ArH), 8.25 (dd, J = 1.2, 7.6 Hz,
2H, ArH), 7.50–7.90 (m, 14H, ArH), 5.44 (t, J = 10.8 Hz,
2H, NCH), 4.81 (dd, J = 8.8, 9.6 Hz, 2H, OCH2), 3.81
(dd, J = 8.8, 11.2 Hz, 2H, OCH2). Compound (S,aS)-8b:
1H NMR (400 M, CD3CN): d 9.04 (d, J = 8.4 Hz, 2H,
ArH), 8.43 (d, J = 2.0 Hz, 2H, ArH), 7.50–7.70 (m, 12H,
ArH), 5.45 (t, J = 11.2 Hz, 2H, NCH), 4.85 (dd, J = 8.8,
9.6 Hz, 2H, OCH2), 3.94 (t, J = 8.4 Hz, 2H, OCH2).
1
Compound (S,aS)-8c: H NMR (400 M, CD3CN): d 9.06
25
505.2135. Compound 3d: ½aꢀD ꢁ92.31 (c 1.75, CHCl3);
(d, J = 8.4 Hz, 2H, ArH), 7.75 (d, J = 2.8 Hz, 2H, ArH),
7.51–7.64 (m, 10H, ArH), 7.35 (dd, J = 2.8, 8.8 Hz, 2H,
ArH), 5.39 (t, J = 11.2 Hz, 2H, NCH), 4.78 (t, J = 9.2 Hz,
2H, OCH2), 4.02 (s, 6H, OCH3), 3.85 (dd, J = 9.2,
11.2 Hz, 2H, OCH2). Compound (S,aS)-8d: 1H NMR
(400 M, CD3CN): d 9.02 (d, J = 8.8 Hz, 2H, ArH), 7.68
(d, J = 2.4 Hz, 2H, ArH), 7.43 (dd, J = 2.4, 8.8 Hz, 2H,
ArH), 4.56 (m, 2H, NCH), 4.25 (dd, J = 9.6, 11.2 Hz,
2H, OCH2), 4.03 (s, 6H, OCH3), 3.84 (t, J = 9.2, 11.2 Hz,
2H, OCH2), 1.24 (d, J = 6.4 Hz, 6H, CH3), 1.11–1.25 (m,
2H, CH), 0.51 (d, J = 6.4 Hz, 6H, CH3). Compound
(S,aS)-8e: 1H NMR (400 M, CD3CN): d 9.01 (d, J =
8.8 Hz, 2H, ArH), 7.56 (d, J = 2.4 Hz, 2H, ArH), 7.27–
7.40 (m, 12H, ArH), 4.47–4.56 (m, 2H, NCH), 4.38 (dd,
J = 4.4, 13.6 Hz, 2H, OCH2), 4.30 (t, J = 9.2 Hz, 2H,
OCH2), 4.00 (s, 6H, OCH3), 3.64 (dd, J = 8.8, 10.4 Hz,
2H, PhCH2), 2.88 (dd, J = 10.0, 14.0 Hz, 2H, PhCH2).
1H NMR (400 M, CDCl3) major: d 7.74 (d, J = 8.8 Hz,
2H, ArH), 6.82–6.86 (m, 2H, ArH), 6.79 (br, 2H, ArH),
4.05 (t, J = 8.0 Hz, 2H, OCH2), 3.65–3.85 (m, 10H, OCH2,
OCH3 and NCH), 1.50–1.70 (m, 2H, CH), 0.65–0.82 (m,
12H, CH); minor: d 7.79 (d, J = 8.8 Hz, 2H, ArH), 6.82–
6.86 (m, 2H, ArH), 6.70 (br, 2H, ArH), 4.04 (t,
J = 12.0 Hz, 2H, OCH2), 3.65–3.85 (m, 10H, OCH2,
OCH3 and NCH), 1.50–1.70 (m, 2H, CH), 0.65–0.82 (m,
12H, CH); 13C NMR (100 M, CDCl3) d 18.1, 18.4, 18.9,
19.0, 32.6, 32.9, 55.3, 70.2, 72.4, 72.5, 112.6, 112.8, 115.0,
115.4, 120.0, 120.5, 130.9, 131.1, 143.1, 143.5, 160.4, 160.6,
163.7, 164.0; HRMS (Micromass LCT) Calcd. for
C26H32N2O4: 436.2362. Found: 436.2358. Compound 3e:
25
1
½aꢀD ꢁ147.86 (c 1.71, CHCl3); H NMR (400 M, CDCl3)
major: d 7.74 (d, J = 8.4 Hz, 2H, ArH), 7.06–7.30 (m,
10H, ArH), 6.90 (d, J = 2.8 Hz, 2H, ArH), 6.85–6.89 (m,