BF3·Et2O catalyzed diastereoselective nucleophilic reactions of 3-silyloxypiperidine N,O-acetal with silyl enol ether and application to the asymmetric synthesis of (+)-febrifugine

Article abstract of DOI:10.1016/j.tetlet.2009.04.097

The asymmetric BF₃·Et₂O catalyzed nucleophilic reactions of 3-silyloxypiperidine N,O-acetal 10 with silyl enol ethers derived from ketones are described. (+)-Febrifugine 1, an antimalarial alkaloid, was successfully synthesized based

Full text of DOI:10.1016/j.tetlet.2009.04.097

Tetrahedron Letters 50 (2009) 4046–4049
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Tetrahedron Letters
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BF3ꢀEt2O catalyzed diastereoselective nucleophilic reactions
of 3-silyloxypiperidine N,O-acetal with silyl enol ether and application
to the asymmetric synthesis of (+)-febrifugine
a,b,
Ru-Cheng Liu a, Wei Huang b, Jing-Yi Ma a, Bang-Guo Wei a, , Guo-Qiang Lin
*
*
a Department of Chemistry, Fudan University 220 Handan Road, Shanghai 200433, China
b Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric BF3ꢀEt2O catalyzed nucleophilic reactions of 3-silyloxypiperidine N,O-acetal 10 with silyl
enol ethers derived from ketones are described. (+)-Febrifugine 1, an antimalarial alkaloid, was success-
fully synthesized based on this nucleophilic substitution. In addition, N,O-acetal 10 was synthesized from
Received 9 March 2009
Revised 14 April 2009
Accepted 23 April 2009
Available online 3 May 2009
L
-benzyl glutamate in 11 steps.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Nucleophilic substitution
Piperidine
Alkaloid
N,O-Acetal
Asymmetric synthesis
1. Introduction
oxycarbonylpiperidine derivatives with the silyl enol ether of
acetone gave moderate diastereoselectivity.7a Correia group re-
ported that 3-acetoxy-N-ethoxycarbonyl-2-methoxypiperidine re-
acted with trimethylsilyl cyanide (TMSCN) in the presence of
BF3ꢀOEt2 to afford the corresponding adduct as a 1:1.3 mixture of
cis/trans diastereomers.7b Later on, Kobayashi’s group5k reported
the Sc(OTf)3-catalyzed nucleophilic substitution reaction of 3-acy-
loxypiperidines and 3-(4-methoxybenzyloxy)piperidines with
moderate diastereoselectivities. Johnson7c and Blaauw7d,e showed
that the reaction of multifunctionalized N-Cbz-piperidine system
provided only the trans product. Craig’s group studied the alkyl-
ation reactions of multifunctionalized N-tosylpiperidine system.7f
Recently, Huang5m and Chang7g have independently investigated
the allylation of 3-silyloxy and 3-methoxy 2-piperidinone with
allyltrimethylsilane reagents, the major products are in 2,3-cis-dia-
stereomers, although in moderate diastereoselectivities.
Very recently, we have reported an asymmetric synthesis of 3-
hydroxy 2,6-disubstituted piperidines.8 On pursuing our efforts on
developing efficient asymmetric methods for synthesis of 2-substi-
tuted 3-hydroxy piperidine alkaloids, we now report a highly dia-
stereoselective (up to 96:4) method for the nucleophilic
substitution of 3-silyloxy-2-acyloxypiperidine with silyl enol ether
in the presence of BF3ꢀOEt2. The total synthesis of (+)-febrifugine 1
using the key step is described.
Alkaloids containing 3-hydroxy 2-substituted piperidine rings
exist abundantly in nature. Most of them show interesting biolog-
ical activities.1 Among them, febrifugine 1 and isofebrifugine 2
(Fig. 1) are antimalarial alkaloids isolated from Chinese medicinal
plants Dichroa febrifuga Lour (Chang Shan)2 and related hydrangea
plants.3 Febrifugine 1 is approximately 100 times as effective as
quinine against Plamodia lophurae in ducks.2a The absolute config-
urations of these alkaloids were elucidated by Kobayashi et al.4
During the past ten years or so, the synthesis of these two alkaloids
and their analogues has attracted considerable attention.4,5 Halofu-
ginone 3, a pharmaceutical candidate developed from febrifugine,
is currently under phase II clinical trials for treatment of sclero-
derma in human.6
Among the reported asymmetric approaches to febrifugine, one
of the most straightforward approaches to construct the 2-substi-
tuted 3-hydroxy piperidine is the stereoselective reaction of 3-hy-
droxy-piperidine N-acyliminium ions with the nucleophiles.5k,m
While there are some reports on the diastereoselective C-2
functionalization onto the six-membered system, the control of
diastereoselectivity between the 2- and 3-positions has been far
from satisfactory.5k,m,7 For example the TiCl4-catalyzed nucleo-
philic substitution reaction of 3-acetoxy-2-methoxy-N-meth-
As shown in Scheme 1, the nucleophilic substitution reaction of
N,O-acetal 10 with silyl enol ether derived from acetone in high
stereoselectivity would be a desirable goal for the synthesis of
* Corresponding authors. Tel./fax: +86 21 54237757 (B.-G.W).
E-mail address: bgwei1974@fudan.edu.cn (B.-G. Wei).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.04.097

R.-C. Liu et al. / Tetrahedron Letters 50 (2009) 4046–4049
4047
OH
N
O
N
O
OH
N
O
Br
Cl
O
O
O
OH
N
N
N
N
H
N
H
N
H
.HBr
1 febrifugine
3 halofuginone hydrobromide
2 isofebrifugine
Figure 1.
OTBS
OTBS
.
OTBS
BF3 Et2O, CH2Cl2
SiMe3
+
1
-78 oC, 4h, 92%
L-Glutamic acid
N
OAc
N
N
OR
Cbz
10
Cbz
Cbz
N-acyliminium N,O-acetal
OH
OTBS
OTBS
Scheme 1. Synthetic strategy of (+)-febrifugine 1.
TBAF
+
THF,2h
86%
N
N
N
(+)-febrifugine 1. For this purpose, a reliable method for the prep-
aration of 3-silyloxy-2-acyloxypiperidine 10 from L-glutamic acid
is required.
Cbz
Cbz
Cbz
trans-11
cis-12
cis-11
In order to find a general method to prepare N,O-acetals such as
10, we selected -Glu(OBn)-OH 4 as a starting material. Thus, treat-
ment of -Glu(OBn)-OH 4 with an aqueous solution of NaNO2 under
Scheme 3. Structure determination of 11.
L
L
acid conditions9 followed by in situ methanolysis (MeI, DMF) affor-
ded ester 5 in 63% overall yield. Protection of the secondary alcohol
of 5 as its TBS ether (TBSCl, imidazole) and reductive removal of
the benzyl ester (Pd/C, MeOH) gave acid 6 in 71% overall yield.
Upon reduction (BH3ꢀSMe2) and tosylation, the resulting ester
was directly treated with sodium azide in the presence of pyridine
to generate azide 7 in 68% overall yield. Upon hydrogenation
(5%Pd/C, MeOH) of the azide group in 7, spontaneous cyclization
occurred to afford the known lactam10 8 in 75% yield. Lactam 8
was treated successively with n-butyllithium and benzyl carbo-
nochloridate to afford imide 9 in high yield. Reduction (NaBH4,
MeOH) of the imide carbonyl and subsequent reaction with acetic
anhydride gave N,O-acetal 10 in 58% overall yield from 8 (Scheme
2).
ble in this stage by chromatography on silica gel, we were de-
lighted to find that the two diastereoisomers were easily
separated after removal of silyl-protecting group with TBAF yield-
ing the known (2S,3S)-12 as the major diastereomers {½a D25
ꢂ
+77.2 (c
0.4, EtOH); lit5f
½
a 2D4
ꢂ
+76.2 (c 1.0, EtOH); lit5m
½
a 2D0
+77.1 (c 1.0,
ꢂ
EtOH)} in 86 % yield (Scheme 3). It is worth mentioning that when
TMSOTf was used as catalysts, a disappointing 82:18 mixture of
cis-11/trans-11 was obtained in 83% combined yield.
Encouraged by the highly cis-diastereoselective reaction of N,O-
acetal 10 with allyltrimethylsilane, we then investigated the reac-
tion of 10 with various silyl enol ethers derived from ketones as
carbon nucleophiles. The results are summarized in Table 1. To
our delight when 10 was treated with silyl enol ether in the pres-
ence of 2.0 equiv of BF3ꢀEt2O in dichloromethane at ꢁ78 °C for 4 h,
13a was generated with excellent cis-selectivity (96:4) in 78 %
yield.11 On the other hand, the reaction induced by a catalytic
amount of TMSOTf or stoichiometric amount of TiCl4 in dichloro-
methane afforded product 13a in moderate yield with diastereo-
meric ratios of 76:24 and 55:45, respectively. The silyl enol ether
derived from cyclopentanone also reacted with N,O-acetal 10 to
give a single product 13b in 71% yield, although the stereostructure
Treatment of N,O-acetal 10 with 2.0 equiv of BF3ꢀEt2O in the
presence of allyltrimethylsilane at ꢁ78 °C gave a mixture of cis-
11 and trans-11, with the ratio determined by HPLC to be 90:10.
Although the allylated product 11 and its isomer were not separa-
O
O
O
O
NH2
O
b
a
BnO
N3
OMe
OMe
BnO
OH
Table 1
OH
Nucleophilic substitution reaction of 3-silyoxy N,O-acetal
5
4
Entry
Nu
Lewis acid
Product
Yielda (cis/trans)b (%)
O
O
c
d
1
2
3
4
6
7
8
9
10
11
12
13
14
15
16
A
A
A
B
C
C
D
D
E
BF3ꢀEt2O
TBSOTf
TiCl4
13a
13a
13a
13b
13c
13c
13d
13d
13e
13f
13g
11
78 (96:4)
63 (76:24)
53 (55:45)
71
HO
OMe
OTBS
OTBS
BF3ꢀEt2O
BF3ꢀEt2O
TMSOTf
BF3ꢀEt2O
TMSOTf
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
TMSOTf
TiCl4
6
7
NR
53 (52:48)
85 (83:17)
73 (73:24)
74 (74:26)
81 (63:37)
70 (66:34)
92 (90:10)
83 (82:18)
67 (57:43)
89 (91:9)
OTBS
O
OTBS
OAc
OTBS
e
f
N
N
N
O
H
Cbz
F
Cbz
G
H
H
H
I
10
8
9
11
11
11
Scheme 2. Reagents and conditions: (a) (i) NaNO2 AcOH/H2O (V/V = 2:8), 0 °C, 3 h;
(ii) NaHCO3, MeI, DMF, rt, 18 h, two steps 63%; (b) (i) TBSCl, imid, DMAP, DMF, rt
overnight, 85%; (ii) 10% Pd/C H2, rt, 12 h, 83%; (c) (i) BH3ꢀSMe2, THF, 0 °C–rt, 16 h;
(ii) TsCl, Py, DMAP,CH2Cl2, rt, 36 h; (iii) NaN3 DMF, rt, 12 h, three steps 68%; (d)5%
Pd/C, H2, CH3OH, rt, 36 h, 75%; (e) n-BuLi, CbzCl, THF,ꢁ78 °C, 1 h, 81%; (f) (i) NaBH4,
CH3OH, 0 °C, 40 min; (ii) Ac2O, TEA, DMAP, CH2Cl2, rt, overnight, two steps 71%.
BF3ꢀEt2O
a
Isolated yields after column chromatography.
b
The cis/trans ratio was determined from the HPLC data of crude reaction
mixture.

4048
R.-C. Liu et al. / Tetrahedron Letters 50 (2009) 4046–4049
OTBS
OTBS
OTBDPS
OTBDPS
OTBS
OTBS
Nu
Lewis acid
-78 oC
O
O
b
O
a
+
Nu
OAc
+
Nu
N
N
N
N
N
N
Cbz
Cbz
13a
Cbz
14
Boc
15
Cbz
Cbz
10
13 (a~i)
OTPDPS
N
OTBDPS
O
OTMS
N
O
d
c
OTMS
OTMS
N
Br
N
N
N
Boc
O
Boc
O
C
A
B
17
16
OTMS
OTMS
OTMS
Scheme 5. Structure determination of 13a. Reagents and conditions: (a) (i)TBAF,
THF, rt, 2 h; (ii) TBDPSCl, imidazole, DMF, rt, 12 h, two steps 67%; (b) 10%Pd/C,
MeOH, Boc2O, triethylamine, rt, overnight, 87%. (c) (i) LiHMDS, THF, TMSCl; (ii) NBS,
NaHCO3, two steps 75%; (d) 4-hydroxyquinazoline, KOH, EtOH, refluxed, 83%.
Ph
C6H4-p-OMe
C6H4-o-Cl
F
D
E
OTMS
SnMe3
SiMe3
Nu
C6H4-p-Cl
disfavored attack
H
H
H
I
G
N
N
Si
O
O
O
O
Scheme 4. Lewis acid catalyzed nucleophilic substitution reaction.
TBS
OBn
favored attack
Nu
OBn
19
18
was not determined at this stage. To our disappointment, the reac-
tion of 10 with the quinazolinone-containing silyl enol ether12 did
not occur under the same conditions, even at room temperature.
Other conditions such as using acetonitrite as polar solvent to sta-
bilize the iminium ion intermediate13 and to promote the coupling
reaction, and BF3ꢀEt2O used as Lewis acid, the reaction still did not
take place. However, it was found that 2.0 equiv of TMSOTf at
ꢁ30 °C to rt led to 13c with 52:48 dr in 53% yield (entry 7). We
then investigated the reactions of 10 with other silyl enol ethers
derived from acetophenones, all reactions proceeded smoothly to
give the coupling products 13d–g in moderate diastereoselectivi-
ties (entries 8–12) (Scheme 4).
Scheme 6.
of the nucleophile to 19 would happen from the same face as that
of 3-silyloxy group, to generate a chair conformation having the
cis-stereochemistry (cis-13). This is in agreement with the results
of the six-membered-ring oxocarbenium ions reported by
Woerpel.18
Although (+)-febrifugine 1 can be easily synthesized from com-
pound 17 in one step, this route is inefficient due to the require-
ment of the two times change of protective groups. Therefore, we
then turned our attention to study the direct synthesis of 1 from
13a. Treatment of 13a with TMSOTf in the presence of N,N-diiso-
propylethylamine (DIPEA) followed by NBS afforded brominated
compound 20 in 72% yield. The reaction of 20 with 4-hydroxyqui-
nazoline in the presence of potassium hydroxide gave protected
2-epi-febrifugine 21 derivative in 85% yield. Finally, treatment of
21 in 6 N HCl solution under reflux for 4 h afforded the crude dihy-
drochloride salt of (+)-isofebrifugine 2, which is stable under acidic
conditions.5f,5i After basification of the crude dihydrochloride salt 2
with potassium carbonate, the crude was refluxed in MeOH for
4 h,5i,19 and the product was recrystallized in ethanol to give (+)-
febrifugine 1 {colorless solid, mp 139–141 °C (EtOH); lit.2b 138–
In most cases, the alkylation products are mixtures of rotamers
at room temperature, and unseparable by chromatography on sil-
ica gel. So it is hard to determine their stereochemistry by NOE
or by the known rules of this reaction system. Considering that
both cis and trans 13a could be converted to the (+)-febrifugine
1 and (+)-isofebrifugine 2, and there is a equilibrium between
these alkaloids,14 it would be difficult to determine the stereo-
chemistry of 13a according to the reported total synthesis of (+)-
febrifugine. However, the cis-13a was reported to be convertible
to the known 2-epi-febrifugine 17 derivative.5i This is a helpful
information for the determination of the stereochemistry of cis/
trans 13. Thus, reaction of 13a in the presence of TBAF in tetrahy-
drofuran followed by in situ protection (TBDPSCl, imidazole) affor-
ded ether 14 in 67% overall yield. Upon palladium-catalyzed
hydrogenation (10%Pd/C, MeOH) of ether 14, the resulting amine
was simultaneously reacted with di-tert-butyldicarbonate in the
presence of triethylamine to give 15 in one-pot with 87% yield. Fol-
lowing a routine work15 15 was converted into brominated com-
pound 16, and treatment of 16 with 4-hydroxyquinazoline in the
presence of potassium hydroxide gave 2-epi-febrifugine 17 deriva-
140 °C; ½a 2D5
ꢂ
+27.9 (c 0.52, EtOH); lit.2b
68% yield. The spectroscopic and physical data of the synthetic
½
a 2D9
+28 (c 0.5, EtOH)} in
ꢂ
OTBS
O
OTBS
O
a
b
Br
N
N
tive {½a 2D5
ꢂ
+12.8 (c 0.4,CHCl3); lit5i
½
a 2D5
+13.7 (c 0.38, CHCl3)} in 62
ꢂ
Cbz
Cbz
13a
20
% yield (Scheme 5). Thus, 13a was unambiguously established as
cis isomer. Base on this result, the configurations of 13e–h were
determined by HPLC analysis in comparison with the results of
13a and 11.
OTBS
O
N
c
(+)-febrifugine
N
N
The cis selectivity in forming 13a can be rationalized by consid-
ering the two competitive conformations of 18 and 19 in the tran-
sition state (Scheme 6). Due to the 1,3-interaction16 of the Cbz
group with the steric bulky 3-silyloxy group, the more stable tran-
sition state 19 should be the favored conformation. Axial attack17
Cbz
O
21
Scheme 7. Total synthesis of (+)-febrifugine. Reagents and conditions: (a) TMSOTf,
DIPEA, CH2Cl2,1 h, then NaHCO3, NBS, 2 h, 72%; (b) 4-hydroxyquinazoline, KOH,
EtOH, refluxed, 85%; (c) 6 N HCl, refluxed, 4 h, then EtOH, refluxed, 68%.

R.-C. Liu et al. / Tetrahedron Letters 50 (2009) 4046–4049
4049
(+)-febrifugine 1 were identical with the reported data.5 Thus, an
efficient method for the synthesis of (+)-febrifugine was estab-
lished via high diastereoselective nucleophilic substitution reac-
tion of 3-silyloxy-2-acyloxypiperidine with silyl enol ether
(Scheme 7).
(g) Taniguchi, T.; Ogasawara, K. Org. Lett. 2000, 2, 3193; (h) Takeuchi, Y.;
Azuma, K.; Takakura, K.; Abe, H.; Kim, H. S.; Wataya, Y.; Harayama, T.
Tetrahedron 2001, 57, 1213; (i) Ooi, H.; Urushibara, A.; Esumi, T.; Iwabuchi, Y.;
Hatakeyama, S. Org. Lett. 2001, 3, 953; (j) Sugiura, M.; Kobayashi, S. Org. Lett.
2001, 3, 477; (k) Sugiura, M.; Hagio, H.; Hirabayashi, R.; Kobayashi, S. J. Org.
Chem. 2001, 66, 809; (l) Sugiura, M.; Hagio, H.; Hirabayashi, R.; Kobayashi, S. J.
Am. Chem. Soc 2001, 123, 12510; (m) Huang, P. Q.; Wei, B. G.; Ruan, Y. P. Synlett
2003, 1663; (n) Katoh, M.; Matsune, R.; Nagase, H.; Honda, T. Tetrahedron Lett.
2004, 45, 6221; (o) Ashoorzadeh, A.; Caprio, V. Synlett 2005, 346; (p) Takeuchi,
Y.; Oshige, M.; Azuma, K.; Abe, H.; Harayama, T. Chem. Pharm. Bull. 2005, 53,
868; (q) Bora, S.; Oscar, L. V.; Veronique, B.; Cossy, J. Synlett 2008, 1216; (r)
Sudhakar, N.; Srinivasulu, G.; Rao, G. S.; Rao, B. V. Tetrahedron: Asymmetry 2008,
19, 2153.
2. Conclusion
In summary, nucleophilic reactions of 3-silyloxy-2-acyloxypi-
peridine with silyl enol ethers in the presence of BF3ꢀEt2O as a cat-
alyst were demonstrated to give high cis-diastereoselectivity. The
structure was determined by comparing the two known com-
pounds 12 and 17. Using this method, a highly diastereoselective
approach for the asymmetric synthesis of the antimalarial alkaloid
(+)-febrifugine 1 was developed. In addition, a new route for the
6. Elkin, M.; Reich, R.; Nagler, A.; Aingorn, E.; Pines, M.; De Groot, N.; Hochberg,
A.; Vlodavsky, I. Clin. Cancer Res. 1999, 5, 1982.
7. (a) Plehiers, M.; Hootele, C. Can. J. Chem. 1996, 74, 2444; (b) Sugisaki, C. H.;
Carroll, P. J.; Correia, C. R. D. Tetrahedron Lett. 1998, 39, 3413; (c) Johnson, C. R.;
Golebiowski, A.; Sundram, H.; Miller, M. W.; Dwaihy, R. L. Tetrahedron Lett.
1995, 36, 653; (d) Botman, P. N. M.; Dommerholt, F. J.; Gelder, R. D.;
Broxterman, Q. B.; Schoemaker, H. E.; Rutjes, F. P. J. T.; Blaauw, R. H. Org. Lett.
2004, 6, 4941; (e) Wijdeven, M. A.; Botman, P. N. M.; Wijtmans, R.; Schoemaker,
H. E.; Rutjes, F. P. J. T.; Blaauw, R. H. Org. Lett. 2005, 7, 4005; (f) Adelbrecht, J -C.;
Craig, D.; Dymock, B. W.; Thorimbert, S. Synlett 2000, 467; (g) Chen, B.-F.; Tasi,
M.-R.; Yang, C.-Y.; Chang, J.-K.; Chang, N.-C. Tetrahedron 2004, 60, 10223.
8. Liu, R.-C.; Wei, J.-H.; Wei, B.-G.; Lin, G.-Q. Tetrahedron: Asymmetry 2008, 19,
2731.
synthesis of N,O-acetal 10 from the cheap L-glutamic acid deriva-
tives was also described.
Acknowledgments
9. Deechongkit, S.; You, S. L.; Kelly, J. W. Org. Lett. 2004, 6, 479.
The authors are grateful to the National Natural Science Foun-
dation of China (20832005, 20702007) and Fudan University for
financial support.
10. Huang, P.-Q.; Feng, C.-G.; Zheng, X. J. Heterocycl. Chem. 2007, 44, 499.
11. General procedure for the synthesis of 13a–h from 10: To a solution of 10
(1.40 mmol) and silyl enol ether (4.20 mmol) in dichloromethane (10 mL)
cooled to ꢁ78 °C under argon atmosphere, a solution of BF3ꢀEt2O (2.80 mmol)
was added dropwise. After being stirred for 3.5 h at the same temperature, the
reaction was quenched with a solution of NaHCO3 aqueous and warmed to
room temperature. The mixture was extracted with CH2Cl2 (15 mL ꢃ 3) and the
combined organic layers were dried over anhydrous Na2SO4. Filtered and
concentrated, the residue was purified by chromatography on silica gel to a
mixture of two diastereoisomers 13a–h. 13a (78%, >96%, HPLC) as a colorless
References and notes
1. For reviews on piperidine alkaloids, see: (a) Fodor, G. B.; Colasanti, B. The
Pyridine and Piperidine Alkaloids: Chemistry and Pharmacology. In Alkaloids:
Chemical and Biological Perspectives; Pelletier, S. W., Ed.; Wiley-Interscience:
New York, 1985; Vol. 3, pp 1–90; (b) Schneider, M. J. Pyridine and Piperidine
Alkaloids: An Update. In Alkaloids: Chemical and Biological Perspectives;
Pelletier, S. W., Ed.; Pergamon: Oxford, 1996; Vol. 10, pp 155–299; (c)
Ciufolini, M. A.; Hermann, C. Y. W.; Dong, Q.; Shimizu, T.; Swaminathan, S.;
Xi, N. Synlett 1998, 105; (d) Zhou, W. S.; Lu, Z. H.; Xu, Y. M.; Liao, L. X.; Wang, Z.
M. Tetrahedron 1999, 55, 11959; (e) Laschat, S.; Dickner, T. Synthesis 2000,
1781; (f) Toyooka, N.; Nemoto, H. Drugs Future 2002, 27, 143; (g) Weintraub, P.
M.; Sabol, J. S.; Kane, J. M.; Borcherding, D. R. Tetrahedron 2003, 59, 2953; (h)
Bates, R. W.; Sa-Ei, K. Tetrahedron 2002, 58, 5957.
oil. ½a 2D5
ꢂ
ꢁ42.31 (c 1.31, CHCl3); IR (film): mmax 2953, 2933, 1704, 1423, 1254,
1101 cmꢁ1
;
1H NMR (400 MHz, CDCl3, rotamers): d 7.37–7.28 (m, 5H), 5.15 (br
s, 2H), 4.90–4.85 (m, 1H), 4.04–4.01 (m, 1/2H), 3.92–3.89 (m, 1/2H), 3.78–
3.71(m, 1H), 2.87–2.71 (m, 2H), 2.48–2.46 (m, 1H), 2.21 (br s, 3/2H), 2.06 (m, 3/
2H), 1.71–1.68 (m, 2H), 1.64–1.45 (m, 2H), 0.94 (s, 9H), ꢁ0.18 (s, 3H), ꢁ1.20 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): d 207.8, 155.4, 136.5, 128.4, 127.9, 127.8,
69.2, 67.2, 53.0, 39.5, 38.2, 30.1, 28.5, 25.7, 23.7, 18.0, ꢁ0.05, ꢁ5.01 ppm; MS
(ESI): 428.2 (M+Na+); HRMS (MALDI/DHB) calcd for (C22H35NO4Si+Na+):
428.2233, found: 428.2256.
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