Synthesis of C1-symmetric chiral tripodal oxazolines through an oxazoline exchange reaction with amino alcohols

Article abstract of DOI:10.1016/j.tetlet.2004.07.107

Oxazolines undergo an exchange reaction with added amino alcohols in the presence of zinc chloride. Various C₁-symmetric chiral tripodal tris(oxazolines) with two different oxazoline units were synthesized from chiral C₃-symmetric tris(oxazolines) through an oxazoline exchange reaction with amino alcohols in the presence of zinc chloride. Evaluation of the new oxazolines as chiral molecular receptor showed that some of the receptors have chiral discrimination ability.

Full text of DOI:10.1016/j.tetlet.2004.07.107

Tetrahedron
Letters
Tetrahedron Letters45 (2004) 6835–6838
Synthesis of C1-symmetric chiral tripodal oxazolines through an
oxazoline exchange reaction with amino alcohols
Sung-Gon Kim, Hye Ran Seong, Jeongryul Kim and Kyo Han Ahn*
Department of Chemistry and Division of Molecular and Life Science, Pohang University of Science and Technology,
San 31 Hyoja-dong, Pohang 790-784, Republic of Korea
Received 16 June 2004; revised 23 July 2004; accepted 26 July 2004
Available online 10 August 2004
Abstract—Various C1-symmetric chiral tripodal tris(oxazolines) with two different oxazoline units were synthesized from chiral
C3-symmetric tris(oxazolines) through an oxazoline exchange reaction with amino alcohols in the presence of zinc chloride. Eval-
uation of the new oxazolines as chiral molecular receptor showed that some of the receptors have chiral discrimination ability.
Ó 2004 Elsevier Ltd. All rights reserved.
Oxazolines are useful metal ligands in asymmetric cata-
lysts1 and also important heterocycles found in various
natural products.2 Chiral oxazolinesare uusally pre-
pared by coupling of carboxylic acidswith amino alcoh-
olsfollowed by ring formation or by direct condensation
of nitrileswith amino alcoholsin the presence of a Lewis
acid such as zinc chloride.3 Among chiral oxazolines,
C2-symmetric bis(oxazolines) have been widely used in
metal-catalyzed asymmetric catalysis.4 Recently we
introduced C3-symmetric tripodal oxazolines, which
have several unique features as artificial receptors.5 We
also demonstrated that the C3-symmetric tripodal oxaz-
olines are potentially useful ligands for potassium eno-
To synthesize C1-symmetric benzene-based tripodal
oxazolines( C1-BTOs), several approaches are possible.
One isto introduce three oxazoline ringswith at leats
one different substituent that provide the screw-sense
chirality, depicted astype
6
I
(R 1 = R2
6
¼ R3 or
R1 ¼ R3, oxazoline substituents at C-5).
6
6
latesin an aysmmetric conjugate addition reaction.
Our tripodal oxazolinesprovide
Another approach to synthesize C1-BTOsisto introduce
one oxazoline ring, of which substituent has the oppo-
site stereochemistry to that of the other two (type II
a
C3-symmetric
Ôscrew-senseÕ chiral environment upon binding organo-
ammonium or potassium ions. During the studies, we
became interested in tripodal oxazolines of C1-symme-
try, that is, non-C3-symmetric, which would provide a
different chiral environment.7 In an effort to synthesize
C1-symmetric tripodal oxazolines, we have found that
oxazoline ringsundergo an exchange reaction with ami-
no alcoholsin the presence of zinc chloride. Herein, we
wish to report a novel synthesis of C1-symmetric tripo-
dal oxazolinesthrough the oxazoline exchange reaction.
C1-BTOs). In this case, we can use either the same oxaz-
olines(type IIa) or different ones(type IIb; R
1
6
¼ R2).
We studied the latter approach. The type II oxazolines
seem to provide a chiral environment of marked steric
difference compared to type I.
To synthesize the type II C1-BTOsin which R 1
first studied the introduction of third oxazoline part into
6
¼ R2, we
a bis(oxazoline) precursor, 1a, asshown in Scheme 1.
The bis(oxazoline) 1a wasprepared from tri(scyano-
methyl)mesitylene by treatment with L-valinol in the
presence of zinc chloride (1.2equiv) in refluxing chloro-
benzene for 60h in 15% isolated yield, together with 34%
of the corresponding tris(oxazolines) (2a).5 Treatment of
Keywords: Oxazoline exchange reaction; Chiral oxazolines; Tripodal
ligands.
*
Corresponding author. Tel.: +82 54 279 2105; fax: +82 54 279
3399; e-mail: ahn@postech.ac.kr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.107

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S.-G. Kim et al. / Tetrahedron Letters 45 (2004) 6835–6838
Scheme 1. Synthesis of C-BTO 3a from bis(oxazoline) 1a.
Scheme 2. Synthesis of C1-BTO 3c from C3-BTO 2b through oxazoline
exchange mediated by ZnCl2.
bis(oxazoline) 1a with D-alaninol under similar reaction
conditionsafforded C1-BTO 3a in 12% isolated yield, to-
gether with recovered 1a in 25% yield.
in the presence of zinc chloride (1.2equiv) in refluxing
chlorobenzene for 12h afforded C1-BTO 3c in 32% yield,
with recovered starting 2b in 18% yield (Scheme 2).
Compared to the synthetic route that starts with
bis(oxazoline) 1a (Scheme 1), thisexchange route was
much more efficient and provided various C1-BTOsin
higher yields. The results are summarized in Table 1.8
Using 1.5equiv of amino alcohols, usually Ômono-ex-
changedÕ productswere produced in 30–34% yieldswith
recovered starting oxazolines (18–43% yields) (entries
3–5). When 2.4equiv of amino alcoholswere used, Ôdi-
exchangedÕ productswere produced in 17–20% yields
along with mono-exchanged products(10–12% yield)s
(entries6 and 7). Thus, the oxazoline exchange reaction
is useful for the synthesis of tris(oxazolines) composed
of different oxazolines, which are otherwise difficult to
synthesize by known methods. Although a metal-cata-
9
lyzed trans-amidation reaction isknown, to the best
of our knowledge, thisisthe firts example of metal-
catalyzed oxazoline exchange reaction with amino
alcohols.10
Changing the amino alcohol, from D-alaninol to 2-ami-
no-2-methyl-1-propanol, provided the corresponding
C1-BTO (3b) in 26% yield, recovered starting material
(5%), and an unexpected product in 12% yield. The
unexpected product wasfound to be C1-BTO 3c. This
result indicated that an oxazoline could be converted
into another oxazoline through an exchange reaction
with an added amino alcohol under the reaction condi-
tions. Based on this finding we investigated the exchange
reaction for the tripodal oxazolines 2 to synthesize var-
ious C1-BTOs 3. The exchange reaction occurred gener-
ally for the oxazolinesexamined. For example,
treatment of tris(oxazoline) 2b with L-valinol (1.5equiv)
Considering the importance of bis- and tris(oxazoline)
ligandsin catalytic asymmetric reactionsand molecular
recognitions, this oxazoline exchange reaction may also
be potentially useful in constructing libraries of oxazo-
line ligandsfrom a variety of chiral amino alcohols
available.
We briefly evaluated C1-BTOs 3a–g aschiral molecular
receptorstoward an a-phenylethylammonium ion by the
5c
extraction method aswe reported. All the receptors
showed high percent extraction, indicating that they
a
Table 1. Synthesis of C1-BTOs 3 from bis- and tris(oxazolines) 1a and 2 mediated by ZnCl2
Entry
Reactant
Amino alcohol (equiv)b
Temp (°C)c
Time (h)
Product (yield %)d
1
2
3
4
5
6
7
1a
1a
2b
2c
2c
2c
2e
D-Alaninol (2.4)
2-Amino-2-methyl-1-propanol (3.0)
L-Valinol (1.5)
Reflux
Reflux
Reflux
80
120
72
12
12
6
3a (12), 1a (25)
3b (26), 3c (12), 1a (5)
3c (32), 2b (18)
L-Valinol (1.5)
3d (30), 3a (6), 2c (43)
3e (34), 2c (18)
3f (20), 3e (12)
L-Phenylglycinol (1.5)
L-Phenylglycinol (2.4)
L-Phenylglycinol (2.4)
100
100
24
24
100
3g (17), 2d (10)
a 1.2molarequiv of ZnCl2 are used.
b The numbers in parentheses are molar equiv used.
c Chlorobenzene asthe solvent.
d Isolated yields after column chromatography on SiO2; other minor side products are not included.

S.-G. Kim et al. / Tetrahedron Letters 45 (2004) 6835–6838
6837
(h) Bedekar, A. V.; Koroleva, E. B.; Andersson, P. G. J.
Org. Chem. 1997, 62, 2158–2526; (i) Pirrung, M. C.;
Tumey, L. N. J. Comb. Chem. 2000, 2, 675–680; (j) Wuts,
P. G. M.; Northuis, J. M.; Kwan, T. A. J. Org. Chem.
2000, 65, 9223–9225; (k) Rajaram, S.; Sigman, M. S. Org.
Lett. 2002, 4, 3399–3401.
are stronger binders toward ammonium ion. A signifi-
cant chiral discrimination was observed in the cases of
C1-BTOs 3e–g, whereaslittle enantioeslection wasob-
served in the cases of other receptors. For example, with
C1-BTO 3f 100% extraction and an enantioselection of
59(S):41(R) were obtained, and with 3g 80% extraction
and an enantioselection of 58(S):42(R) were obtained.
Thus, only those C1-BTOs that have phenyl-substituted
oxazolines show substantial enantioselection, which im-
plies that the oxazoline substituent plays an important
role in the chiral discrimination. Also, the enantioselec-
tivity observed with the C1-BTOsare lower than that
observed with the C3-symmetric PhBTO.5c These results
raise questions on the enantioselection mechanism with
the C1-BTOsin comparison with the C3-PhBTO.
4. For recent reviews, see: (a) Ghosh, A. K.; Mathivanan, P.;
Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1–45; (b)
Jørgense, K. A.; Johannsen, M.; Yao, S.; Audrain, H.;
Thurhauge, J. Acc. Chem. Res. 1999, 32, 605–613; (c)
Evans, D. A.; Rovis, T.; Johnson, J. S. Pure Appl. Chem.
1999, 71, 1407–1415; (d) Thorhauge, J.; Roberson, M.;
Hazell, R. G.; Jørgensen, K. A. Chem. Eur. J. 2002, 8,
1888–1898.
5. Generally, the formation of tris(oxazolines) are preferred
over mono- and bis(oxazolines) under the conditions,
which makes a stepwise introduction of oxazoline rings
not feasible for the synthesis of C1-symmetric tripodal
oxazolines. For our contributions to molecular recogni-
tion area with C3-symmetric tripodal oxazolines, see: (a)
Ahn, K. H.; Kim, S.-G.; Jung, J.; Kim, K.-H.; Kim, J.;
Chin, J.; Kim, K. Chem. Lett. 2000, 170–171; (b) Kim,
S.-G.; Ahn, K. H. Chem. Eur. J. 2000, 6, 3399–3403; (c)
Kim, S.-G.; Kim, K.-H.; Jung, J.; Shin, S. K.; Ahn, K. H.
J. Am. Chem. Soc. 2002, 124, 591–596; (d) Ahn, K. H.;
Ku, H.-y.; Kim, Y.; Kim, S.-G.; Kim, Y. K.; Son, H. S.;
Ku, J. K. Org. Lett. 2003, 5, 1419–1422; (e) Kim, S.-G.;
Kim, K.-H.; Kim, Y. K.; Shin, S. K.; Ahn, K. H. J. Am.
Chem. Soc. 2003, 125, 13819–13824.
In conclusion, we have synthesized various chiral tripo-
dal oxazolinesthat have C1-symmetry. The synthesis
involved a novel zinc chloride-promoted oxazoline
exchange reaction with added amino alcohols. A prelim-
inary study showed that some of the C1-BTOsalso have
chiral discrimination ability toward an a-phenylethyl-
ammonium ion. A further study on the chiral discrimi-
nation mechanism and catalytic asymmetric reactions
with the C1-BTOsare under invetsigation and will be
reported elsewhere.
6. Kim, S.-G.; Ahn, K. H. Tetrahedron Lett. 2001, 42,
4175–4177.
Acknowledgements
7. Recently a modular approach to C1- and C3-symmetric
chiral tripodal oxazoline ligands for asymmetric catalysis
wasreported: Bellemin-Laponnaz, S.; Gade, L. H. Angew.
Chem., Int. Ed. 2002, 41, 3473–3475.
Thiswork wasfinancially supported by the Center for
Integrated Molecular Systems sponsored by the Korea
Science and Engineering Foundation.
8. A typical exchange reaction procedure and characteriza-
tion data of the oxazolines: a mixture of dry ZnCl2
(491mg, 3.6mmol), tris(oxazoline) 2b (1.36g, 3.0mmol),
and L-valinol (464mg, 4.5mmol) in chlorobenzene (30mL)
wasstirred under reflux for 42h. The reaction mixture was
cooled to room temperature, and the solvent was removed
under reduced pressure. The residue was dissolved in
dichloromethane, and it was washed with saturated
aqueousammonium chloride oslution, then with brine.
The organic layer wasdried over anhydrousmagneisum
sulfate and concentrated in vacuo. The residue was
purified by silica gel chromatography (EtOAc, then 3%
MeOH/ethyl acetate) to afford tris(oxazoline) 3c (460mg,
32%) as a solid, together with the starting material 2b
(254mg, 18%). Compound 1a: Rf = 0.59 (1:9 MeOH/
References and notes
1. For reviewsof chiral oxazoline ligandsin aysmmetric
catalysis, see: (a) Gant, T. G.; Meyers, A. I. Tetrahedron
1994, 50, 2297–2360; (b) Ghosh, A. K.; Mathivanan, P.;
Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1–45; (c)
Gomez, M.; Muller, G.; Rocamora, M. Coordin. Chem.
Rev. 1999, 193–195, 769–835; (d) Pfaltz, A. Synlett 1999,
835–842; (e) Johnson, J. S.; Evans, D. A. Acc. Chem. Res.
2000, 33, 325–335; (f) Fache, F.; Schulz, E.; Lorraine
Tommasino, M.; Lemaire, M. Chem. Rev. 2000, 100,
2159–2232.
2. (a) Abbenante, G.; Fairlie, D. P.; Gahan, R.; Hanson, G.
R.; Pierens, G. K.; van den Brenk, A. L. J. Am. Chem.
Soc. 1996, 118, 10384–10388; (b) Wif, P.; Fritch, P. C.;
Geib, S. J.; Sefler, A. M. J. Am. Chem. Soc. 1998, 120,
4105–4112, and referencescited therein; (c) Deng, S.;
Taunton, J. J. Am. Chem. Soc. 2002, 124, 916–917.
3. For oxazoline synthesis, see: (a) Lowenthal, R. E.; Abiko,
A.; Masamune, S. Tetrahedron Lett. 1990, 31, 6005–6008;
20
1
EtOAc); mp 124–125°C; ½aŠ À 88:6 (c 1.00, CHCl3); H
NMR (300MHz, CDCl3) d D4.19–4.10 (m, 2H), 3.93–3.84
(m, 4H), 3.70 (s, 4H), 3.66 (s, 2H), 2.38 (s, 9H), 1.78–1.70
(m, 2H), 0.82 (d, J = 6.8Hz, 6H), 0.90 (d, J = 6.8Hz, 6H);
13C NMR (75MHz, CDCl3) d 165.4, 137.6, 135.3, 131.9,
126.3, 118.1, 72.2, 70.2, 32.7, 30.4, 19.5, 19.2, 18.1, 17.6,
17.5; MS (EI) m/z (rel intensity) 409 (M+, 76), 366 (100),
324 (33); elemental analysis calcd for C25H35N3O2: C,
73.31; H, 8.61; N, 10.26; found: C, 73.30; H, 8.52; N,
(b) Muller, D.; Umbricht, G.; Weber, B.; Pfaltz, A. Helv.
10.23. Compound 3a: Rf = 0.42 (1:9 MeOH/EtOAc); mp
¨
25
D
Chim. Acta 1991, 74, 232–240; (c) Evans, D. A.; Woerpel,
K. A.; Hinman, M. M.; Faul, M. M. J. Am. Chem. Soc.
1991, 113, 726–728; (d) Bolm, C.; Weickhardt, K.;
Zehnder, M.; Ranff, T. Chem. Ber. 1991, 124,
136–137°C; ½aŠ À 42:6 (c 1.00, CHCl3); 1H NMR
(300MHz, CDCl3) d 4.26 (dd, J = 9.2, 8.1Hz, 1H), 4.18–
4.09 (m, 3H), 3.92–3.83 (m, 4H), 3.75–3.68 (m, 7H), 2.36
(s, 9H), 1.79–1.69 (m, 2H), 1.20 (d, J = 6.6Hz, 3H), 0.83
(d, J = 6.8Hz, 6H), 0.91 (d, J = 6.8Hz, 6H); 13C NMR
(75MHz, CDCl3) d 165.9, 165.8, 136.2, 136.1, 131.1, 131.0,
74.4, 72.2, 70.1, 61.7, 30.7, 30.5, 21.9, 19.2, 18.2, 17.5, 17.4;
MS (EI) m/z (rel intensity) 467 (M+, 100), 424 (24), 382
(17); HRMS (EI) calcd for C28H41N3O3: 467.3148, found:
1173–1180; (e) Vorbruggen, H.; Krolikiewicz, K. Tetra-
¨
hedron 1993, 49, 9353–9372; (f) Denmark, S. E.; Nakaj-
ima, N.; Nicaise, O. J.-C.; Frencher, A.-M.; Edwards, J. P.
J. Org. Chem. 1995, 60, 4884–4892; (g) Wipf, P.;
Venkatraman, S. Tetrahedron Lett. 1996, 37, 4659–4662;

6838
S.-G. Kim et al. / Tetrahedron Letters 45 (2004) 6835–6838
467.3142. Compound 3b: Rf = 0.33 (1:9 MeOH/EtOAc);
CDCl3) d 167.6, 165.8, 143.0, 136.3, 136.2, 131.2, 131.1,
129.0, 127.8, 127.0, 75.3, 74.4, 69.8, 61.7, 30.5, 21.9, 17.5,
17.4; MS (EI): m/z (rel intensity) 473 (M+, 100), 442 (20),
416(15); HRMS (EI) calcd for C 29H35N3O3: 473.2678,
25
D
mp 158–159°C; ½aŠ À 77:2 (c 0.50, CHCl3); 1H NMR
(300MHz, CDCl3) d 4.17–4.09 (m, 2H), 3.91–3.82 (m,
6H), 3.70 (s, 4H), 3.67 (s, 2H), 2.35 (s, 9H), 1.76–1.68 (m,
2H), 1.22 (s, 6H), 0.82 (d, J = 6.8Hz, 6H), 0.90 (d,
J = 6.8Hz, 6H); 13C NMR (75MHz, CDCl3) d 165.9,
164.4, 136.3, 136.2, 131.2, 131.1, 79.5, 72.1, 70.1, 67.2,
32.7, 30.7, 30.5, 28.7, 19.2, 18.2, 17.5, 17.4, 17.3; MS (EI)
m/z (rel intensity) 481 (M+, 100), 467 (32), 396 (22);
HRMS (EI) calcd for C29H43N3O3: 481.3302, found:
481.3310. Compound 3c: Rf = 0.26 (0.5:9.5 MeOH/
found: 473.2672. Compound 3f: Rf = 0.62 (0.5:9.5
25
MeOH/EtOAc); mp 75–76°C;½aŠ À 20:4 (c 0.50, CHCl3);
D
1H NMR (300MHz, CDCl3) d 7.32–7.19 (m, 10H), 5.14
(dd, J = 10.1, 8.3Hz, 2H), 4.57 (dd, J = 10.1, 8.5Hz, 2H),
4.28 (dd, J = 9.3, 8.1Hz, 1H), 4.15–4.10 (m, 1H), 4.04 (dd,
J = 8.5, 8.3Hz, 2H), 3.84 (s, 4H), 3.77 (t, J = 7.6Hz, 1H),
3.72 (s, 2H), 2.48 (s, 3H), 2.43 (s, 6H), 1.20 (d, J = 6Hz,
3H); 13C NMR (75MHz, CDCl3) d 167.5, 165.8, 143.0,
136.3, 136.2, 131.3, 131.0, 129.0, 127.8, 127.0, 75.3, 74.4,
69.9, 61.7, 30.5, 21.9, 17.7, 17.6; MS (EI): m/z (rel
intensity) 535 (M+, 100), 505 (22), 414 (15); HRMS (EI)
calcd for C34H37N3O3: 535.2835, found: 535.2826. Com-
pound 3g: Rf = 0.45 (1:9 MeOH/EtOAc); mp 44–45°C;
25
1
EtOAc); mp 166–167°C; ½aŠ À 33:4 (c 0.50, CHCl3); H
NMR (300MHz, CDCl3) d D4.16–4.10 (m, 1H), 3.91–3.82
(m, 6H), 3.70 (s, 2H), 3.68 (s, 4H), 2.36 (s, 9H), 1.79–1.68
(m, 1H), 1.22 (s, 12H), 0.82 (d, J = 6.8Hz, 6H), 0.90 (d,
J = 6.8Hz, 6H); 13C NMR (75MHz, CDCl3) d 165.9,
164.4, 136.2, 131.1, 131.0, 79.5, 72.1, 70.1, 67.2, 32.7, 30.7,
30.5, 28.7, 19.2, 18.1, 17.5, 17.4; MS (EI) m/z (rel intensity)
467 (M+, 100), 453 (24), 396 (33); HRMS (EI) calcd for
25
D
1
½aŠ À 44:8 (c 0.50, CHCl3); H NMR (300MHz, CDCl3)
d 7.34–7.19 (m, 10H), 5.14 (dd, J = 10.2, 8.3Hz, 2H), 4.57
(dd, J = 10.2, 8.4Hz, 2H), 4.21 (t, J = 9.4Hz, 2H), 4.04
(dd, J = 8.4, 8.3Hz, 2H), 3.85 (s, 4H), 3.75 (t, J = 9.4Hz,
2H), 3.71 (s, 2H), 2.48 (s, 3H), 2.42 (s, 6H); 13C NMR
(75MHz, CDCl3) d 167.6, 167.1, 143.0, 136.2, 131.3, 131.0,
129.0, 127.8, 127.0, 126.3, 75.3, 69.9, 67.9, 54.7, 30.5, 30.3,
17.7, 17.6; MS (EI): m/z (rel intensity) 521 (M+, 100), 491
(20); HRMS (EI) calcd for C33H35N3O3: 521.2678, found:
521.2676.
C28H41N3O3: 467.3148, found: 467.3143. Compound 3d:
25
D
Rf = 0.24 (1:9 MeOH/EtOAc); mp 126–127°C; ½aŠ þ 15:7
1
(c 1.50, CHCl3); H NMR (300MHz, CDCl3) d 4.27 (dd,
J = 9.3, 8.1Hz, 2H), 4.16–4.07 (m, 3H), 3.93–3.86 (m, 2H),
3.76–3.64 (m, 8H), 2.36 (s, 9H), 1.80–1.69 (m, 1H), 1.20 (d,
J = 6.5Hz, 6H), 0.84 (d, J = 6.8Hz, 6H), 0.91 (d,
J = 6.8Hz, 6H); 13C NMR (75MHz, CDCl3) d 165.9,
165.8, 136.1, 136.0, 131.1, 131.0, 74.4, 72.1, 70.1, 61.7,
30.7, 30.4, 21.9, 19.2, 18.2, 17.5, 17.4; HRMS (EI) calcd
for C26H37N3O3: 439.2835, found: 439.2848. Compound
3e: Rf = 0.48 (5:95 MeOH/EtOAc); mp 89–90°C;
9. Eldred, S. E.; Stone, D.; Gellma, S. H.; Stahl, S. S. J. Am.
Chem. Soc. 2003, 125, 3422–3423.
10. A plausible mechanism for the oxazoline exchange reac-
tion may be proposed: an amino alcohol adds to the
oxazoline C@N bond that isactivated by zinc chloride
coordination, producing the corresponding tetra-
hedral intermediate, which undergoes subsequent ring
opening-ring closing sequences to kick out the other
amino alcohol.
25
1
½aŠ þ 24:4 (c 0.50, CHCl3); H NMR (300MHz, CDCl3)
D
d 7.31–7.20 (m, 5H), 5.14 (t, J = 8.7Hz, 1H), 4.58 (dd,
J = 10.2, 8.4Hz, 1H), 4.28 (dd, J = 9.3, 8.1Hz, 2H),
4.13–4.05 (m, 2H), 4.04 (dd, J = 8.4, 8.1Hz, 1H), 3.83 (s,
2H), 3.72 (t, J = 7.8Hz, 2H), 3.67 (s, 4H), 2.42 (s, 6H),
2.37 (s, 3H), 1.20 (d, J = 6.6Hz, 6H); 13C NMR (75MHz,