Stereoselective synthesis of chiral hydrocarbazoles via the catalytic Diels-Alder reaction of siloxyvinylindole and cyclic Z-olefin

Article abstract of DOI:10.1016/j.tetlet.2014.10.106

The catalytic Diels-Alder reaction of siloxyvinylindole and cyclic Z-olefin derived from pyroglutamic acid gave optically active substituted hydrocarbazoles. The exo/endo selectivity of this reaction could be controlled by using an appropriate Lewis acid. Scandium triflate gave high exo-selectivity and copper triflate gave moderate endo-selectivity. Subsequent stereoselective alkylation of the cycloadduct led to the synthesis of highly substituted hydrocarbazoles with five continuous chiral centers including a quaternary carbon.

Full text of DOI:10.1016/j.tetlet.2014.10.106

Tetrahedron Letters 55 (2014) 6907–6910
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Tetrahedron Letters
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Stereoselective synthesis of chiral hydrocarbazoles via the catalytic
Diels–Alder reaction of siloxyvinylindole and cyclic Z-olefin
⇑
Keisuke Yoshida, Takahiro Morikawa, Naoto Yokozuka, Shinji Harada, Atsushi Nishida
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic Diels–Alder reaction of siloxyvinylindole and cyclic Z-olefin derived from pyroglutamic acid
gave optically active substituted hydrocarbazoles. The exo/endo selectivity of this reaction could be con-
trolled by using an appropriate Lewis acid. Scandium triflate gave high exo-selectivity and copper triflate
gave moderate endo-selectivity. Subsequent stereoselective alkylation of the cycloadduct led to the syn-
thesis of highly substituted hydrocarbazoles with five continuous chiral centers including a quaternary
carbon.
Received 13 September 2014
Revised 9 October 2014
Accepted 17 October 2014
Available online 24 October 2014
Keywords:
Catalytic Diels–Alder reaction
Scandium triflate
Ó 2014 Elsevier Ltd. All rights reserved.
Chiral hydrocarbazole
Silyl enol ether
Stereoselective alkylation
Introduction
N
N
OH
Hydrocarbazoles are important moieties in biologically active
compounds, such as strychnine (1)1 and opiate analog 22 (Fig. 1).
Due to their biological properties, methods for the stereoselective
synthesis of optically active and highly substituted hydrocarbaz-
oles are valuable in the fields of organic and medicinal chemistry.
The Diels–Alder reaction using indole derivatives is one of the most
powerful synthetic tools for the construction of a hydrocarbazole
scaffold.3 Recently, we reported the enantioselective synthesis of
substituted hydrocarbazoles by a chiral holmium complex-cata-
lyzed Diels–Alder reaction of siloxyvinylindoles 3 with acyclic E-
olefins 4 (Scheme 1, Eq. 1).4 This reaction proceeded exo-selectively
to afford optically active substituted hydrocarbazoles 5 possessing
an anti-configuration depending on the configuration of the dieno-
phile. In the total synthesis of strychnine, a syn-oriented hydrocar-
bazole would be required as a synthetic intermediate. Therefore,
we designed cyclic Z-olefin 6 derived from pyroglutamic acid as
a dienophile to obtain hydrocarbazole 7 possessing a syn-configu-
ration (Scheme 1, Eq. 2).5 To the best of our knowledge, Diels–Alder
reactions using pyroglutamic acid-derived lactam as a dienophile
under thermal conditions only gave endo-adducts.6 To obtain 7,
this Diels–Alder reaction should proceed in an exo-selective
manner.
H
H
N
H
N
H
O
O
HO
H
H
strychnine (1)
opiate analog 2
Figure 1. Selected examples of biologically active compounds that contain
hydrocarbazole.
We report here (1) the synthesis of optically active substituted
hydrocarbazoles by a catalytic Diels–Alder reaction of siloxyviny-
lindole with cyclic Z-olefin, (2) the control of exo/endo selectivity
in this reaction through the use of an appropriate Lewis acid, and
(3) the construction of a quaternary carbon by stereoselective
alkylation of the cycloadduct.
Result and discussion
Designed cyclic Z-olefin was prepared as shown in Scheme 2.
Starting from D-pyroglutamic acid 8, alcohol 9 was obtained by
esterification, protection of nitrogen, and reduction. Benzylation
of 9 and exchange of the N-protecting group yielded methyl carba-
mate 11. Introduction of an olefin moiety into 11 was accom-
plished by syn-b-elimination of sulfoxide to give cyclic Z-olefin 12.
We treated 12 with siloxyvinylindole 3 (1.5 equiv) under ther-
mal conditions (toluene, 110 °C, 8 h) as an initial trial. However,
cycloadducts were not obtained at all (Table 1, entry 1).7
⇑
Corresponding author. Tel./fax: +81 43 226 2942.
E-mail address: anishida@faculty.chiba-u.jp (A. Nishida).
http://dx.doi.org/10.1016/j.tetlet.2014.10.106
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

6908
K. Yoshida et al. / Tetrahedron Letters 55 (2014) 6907–6910
Table 1
OTIPS
O
O
4
Screening of Lewis acid for the Diels–Alder reaction
O
N
R1
Previous work
up to 99% yield
up to 94% ee
exo only
OTIPS
OBn
O
1)
N
Mbs
R1
H
O
chiral holmium
N
complex
N
O
N
Mbs
OTIPS
5
O
O
O
anti-configuration
12
3
(Mbs: 4-MeOC6H4SO2-)
N
catalyst (25 mol %)
CH2Cl2, rt, 3 days
syn-configuration
Mbs
3
OTIPS
OTIPS
OTIPS
(Mbs: 4-MeOC6H4SO2-)
H
H
OR2
This work
H
H
OBn
H
H
OBn
2)
N
Mbs
N
Mbs
N
Mbs
H
H
H
OR2
N
O
N
O
N
O
N
O
O
O
O
O
PG
13
14
PG
7 (exo-adduct)
(exo-adduct)
(endo-adduct)
6
Entry
Catalyst
Yield (13+14, %)
Ratio (13:14)b
Scheme 1. Diels–Alder reaction of siloxyvinylindole 3 with acyclic E-olefin 4 or
cyclic Z-olefin 6.
1a
2
—
No reaction
—
Al(OTf)3
Cu(OTf)2
Zn(OTf)2
Sc(OTf)3
Yb(OTf)3
Tm(OTf)3
Er(OTf)3
Ho(OTf)3
12
91
41
70
62
89
77
69
10:90
23:77
52:48
88:12
79:21
83:17
80:20
79:21
3c
4
5
6
7
8
O
OH
PMB
OBn
NH
OH
NH
a - c
d, e
N
9
O
O
O
a
b
c
Thermal conditions: toluene, 110 °C, 8 h.
Determined by 1H NMR.
Reaction time was 1 day.
8
9
10
(
D
-Pyr)
OBn
OBn
O
O
f
g - i
N
N
O
O
O
O
OTIPS
H
OTIPS
11
12
H
H
H
OBn
H
H
OBn
Scheme 2. Reagents and conditions (a) SOCl2, MeOH; (b) PMBCl, KI, NaH, THF, 0–
50 °C; (c) NaBH4, EtOH/THF, 68% for 3 steps; (d) BnBr, NaH, THF; (e) CAN, aq MeCN,
84% for 2 steps; (f) ClCO2Me, NaH, THF, 93%; (g) PhSSPh, LiHMDS, THF, À78 °C, 85%;
(h) mCPBA, CH2Cl2, 0 °C; (i) PPh3, toluene, 110 °C, 81%, for 2 steps.
N
Mbs
N
Mbs
H
H
H
H
O
N
O
N
O
O
O
O
exo-adduct
endo-adduct
Next, several metal triflates were tested to promote this Diels–
Alder reaction. First, we investigated the catalytic conditions
(25 mol % of catalyst, rt, 3 days) by using Lewis acids such as alumi-
num, copper, zinc, and scandium triflates, which are known to pro-
mote Diels–Alder reactions.8 As a result, the expected Diels–Alder
reaction proceeded in the presence of a catalytic amount of Lewis
acid to afford a separable mixture of exo-adduct 13 and endo-
adduct 14. The reactions with aluminum triflate and copper triflate
showed endo-selectivity (entries 2 and 3). When zinc triflate was
used, exo-adduct 13 and endo-adduct 14 were obtained in similar
amounts (entry 4). On the other hand, the reactions with scandium
triflate exhibited moderate exo-selectivity (entry 5). Next, we
investigated the catalytic effects of lanthanide triflates because of
their unique properties due to the specific coordination numbers
(entries 6–9).9 As a result, exo-adduct 13 was obtained in the high-
est yield with the use of thulium triflate.
The stereochemistry of both cycloadducts was determined by
NMR experiments, as shown in Figure 2. The regioselectivity of this
Diels–Alder reaction was identical to that in our previous report4
and no regioisomer was observed.
With thulium triflate and scandium triflate, the effects of the
solvent were tested, as shown in Table 2. Higher exo-selectivity
was observed when carbon tetrachloride or THF was used as a sol-
vent (entries 2 and 6). However, the yield of cycloadducts was dra-
matically decreased with the use of THF. No improvement was
: HMBC
: nOe
Figure 2. Key HMBC and NOE correlations of cycloadducts.
Table 2
Effects of solvent and reaction time in the Diels–Alder reaction
catalyst (25 mol %)
13
14
3
12
(exo-adduct)
(endo-adduct)
solvent
rt, reaction time
Entry Catalyst
Solvent
Time (d) Yield (13+14, %) Ratio (13:14)a
1
2
3
4
5
6
7
8
Tm(OTf)3 CHCl3
Tm(OTf)3 CCl4
Tm(OTf)3 1,2-DCE
Tm(OTf)3 PhCl
Tm(OTf)3 Toluene
Tm(OTf)3 THF
3
3
3
3
3
3
6
6
64
69
75
76
48
23
95
90
85:15
92:8
78:22
81:19
85:15
91:9
Tm(OTf)3 CH2Cl2
Tm(OTf)3 CCl4
84:16
93:7
9
10
11
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
CCl4
CH2Cl2
CCl4
3
6
6
70
95
98
94:6
88:12
95:5
Determined by 1H NMR.
a

K. Yoshida et al. / Tetrahedron Letters 55 (2014) 6907–6910
6909
TIPSO
OTIPS
H
H
N
Mbs
OBn
O
H
H OBn
N
N
Mbs
OTIPS
O
H
O
N
O
O
LA
O
H
OBn
O
exo-adduct
OBn
O
N
Mbs
Ln
N
Lewis acid
O
exo-transition state
O
N
LA
O
H
O
OTIPS
Mbs
Ln
N
OTIPS
H
OBn
coordinated complex
L: dienophie, solvent or product
H
H
OBn
N
O
O
N
H
O
Mbs
N
O
LA
O
O
endo-adduct
Ln
endo-transition state
Figure 3. Plausible transition states for the exo- and endo-adducts.
observed with the use of other solvents instead of dichlorometh-
ane (entries 1, 3–5). The yield of cycloadducts increased with an
increase in the reaction time from 3 days to 6 days (entries 7 and
8).
The combination of scandium triflate with carbon tetrachloride
showed higher exo-selectivity (entry 9). The yield of cycloadducts
also increased with an increase in the reaction time when scan-
dium triflate was used as a catalyst (entries 10 and 11). Although
this Diels–Alder reaction required rigorous dried conditions and a
long reaction time, as shown in the Experimental section, exo-
adduct 13 could be obtained selectively in high yields.
The plausible transition states for this Diels–Alder reaction are
shown in Figure 3. Lewis acid activated a dienophile by forming
a coordinated complex to promote the Diels–Alder reaction. The
face selectivity of this Diels–Alder reaction could be perfectly con-
trolled by the chiral center of the dienophile and both cycloadducts
were obtained via the exo- or endo-transition states, respectively.
Generally, the endo-transition state is preferred to the exo-transi-
tion state due to the secondary orbital interaction, and endo-
adducts will be obtained predominantly.
Aluminum and copper triflates promoted this Diels–Alder reac-
tion and showed good to moderate endo-selectivity. However, the
endo-transition state would be destabilized by the steric repulsion
between diene and the coordinated complex. The difference in
energy between the endo-transition state and the exo-transition
state may not be large enough because of the steric repulsion in
the endo-transition state, and a more bulky complex would be
most likely to promote this reaction exo-selectively. On the other
hand, thulium and scandium triflates showed high exo-selectivity.
These metals are capable of coordinating with the dienophile,
solvent, or product due to their high coordination numbers. The
resulting coordinated complex became more bulky, and high exo-
selectivity was observed as a result of retarding the secondary
orbital interaction.10
The high exo-selectivity with THF was also explained by the for-
mation of a more bulky coordinated complex. However, the Lewis
basicity of THF decreased the reactivity of Lewis acid and the yield
of cycloadducts was dramatically decreased. On the other hand,
carbon tetrachloride gave good results with respect to exo-selectiv-
ity without a decrease in the yield. In general, the dipole moment
of the endo-transition state is greater than that of the exo-transi-
tion state. García and Mayoral co-workers reported that a polar
solvent stabilizes the endo-transition state to increase endo-selec-
tivity.11 In our case, the endo-transition state could not be stabi-
lized with the use of carbon tetrachloride as a nonpolar solvent
and the Diels–Alder reaction proceeded exo-selectively.
Interestingly, an increase in the reaction time slightly increased
exo-selectivity. The carbonyl moieties of cycloadducts are likely to
coordinate with a Lewis acid such as scandium or thulium triflate
and a more bulky complex would be formed. This complex could
increase exo-selectivity due to its bulkiness, although reactivity
seemed to be lower.12
A chiral quaternary carbon center was constructed by stereose-
lective alkylation of the silyl enol ether moiety, as shown in
Scheme 3. When exo-adduct 13 was treated with several alkyl
halides and tetrabutylammonium fluoride at À78 °C for 10 min,
the corresponding alkylated products were obtained as a single
diastereomer in good yields. Especially, cyanomethylated com-
pound 15d could be a potential synthetic intermediate of strych-
nine.13 Sequential reactions including the Diels–Alder reaction
and stereoselective alkylation represent an effective method for
constructing a hydrocarbazole bearing five continuous chiral ste-
reocenters including a quaternary carbon.14,15
OTIPS
O
H
R
RX (2.0 equiv.)
TBAF (1.5 equiv.)
H
H
OBn
H
OBn
N
Mbs
N
Mbs
H
H
THF
N
O
N
O
—
78 ºC, 10 min
O
O
Conclusion
O
O
RX = MeI
AllylBr
13
We have synthesized optically active and highly substituted
hydrocarbazoles by the catalytic Diels–Alder reaction of siloxyv-
inylindole with cyclic Z-olefin. Exo/endo selectivity could be con-
trolled by using an appropriate Lewis acid. In particular,
scandium triflate affords exo-adduct 13 and copper triflate pro-
vides endo-adduct 14. Moreover, both enantiomers of cycloadducts
15a (R = Me): 90%
15b (R = Allyl): 86%
15c (R = Bn): 91%
BnBr
(exo-adduct)
ICH2CN
15d (R = CH2CN): 95%
Scheme 3. Stereoselective alkylation for the construction of a chiral quaternary
carbon.

6910
K. Yoshida et al. / Tetrahedron Letters 55 (2014) 6907–6910
could be easily obtained by using a dienophile derived from
D- or
Acknowledgments
L-pyroglutamic acid. Therefore, according to our method, all of
the enantiomers and diastereomers of the Diels–Alder adducts
could be stereoselectively synthesized with the use of a suitable
dienophile and Lewis acids. Alkylation of the silyl enol ether
moiety of exo-adduct 13 proceeded smoothly at À78 °C. In all
cases, the alkylated products were obtained as a single diastereo-
mer with a quaternary chiral carbon center in high yields. The
further transformation of cyanomethylated compound 15d to
strychnine is in progress.
This work was supported by JSPS KAKENHI (Grant Numbers
26ꢀ3297 (TM), 25460006 (SH), and 25293001 (AN)) and the Take-
da Science Foundation – Japan (SH).
References and notes
1. Hendrickson, J. B. In The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New
York, 1960; Vol. VI, pp 179–195.
2. Welsh, W. J.; Yu, S. J.; Nair, A. WO Patent 2004026819, 2004.
3. For 3-vinylindoles (a) Saroja, B.; Srinivasan, P. C. Synthesis 1986, 748; (b)
Murase, M.; Hosaka, T.; Koike, T.; Tobinaga, S. Chem. Pharm. Bull. 1989, 37,
1999; (c) Pindur, U.; Lutz, G.; Fischer, G.; Schollmeyer, D.; Massa, W.; Schröder,
L. Tetrahedron 1993, 49, 2863; (d) Bleile, M.; Wagner, T.; Otto, H.-H. Helv. Chim.
Acta 2005, 88, 2879; (e) Gioia, C.; Hauville, A.; Bernardi, L.; Fini, F.; Ricci, A.
Angew. Chem., Int. Ed. 2008, 47, 9236; (f) Tan, B.; Hernández-Torres, G.; Barbas,
C. F., III J. Am. Chem. Soc. 2011, 133, 12354; For 2-vinylindoles: (g) Eitel, M.;
Pindur, U. J. Org. Chem. 1990, 55, 5368; (h) Jones, S. B.; Simmons, B.; MacMillan,
D. W. C. J. Am. Chem. Soc. 2009, 131, 13606; (i) Cao, Y.-J.; Cheng, H.-G.; Lu, L.-Q.;
Zhang, J.-J.; Cheng, Y.; Chen, J.-R.; Xiao, W.-J. Adv. Synth. Catal. 2011, 353, 617;
(j) Jones, S. B.; Simmons, B.; Mastracchio, A.; MacMillan, D. W. C. Nature 2012,
475, 183; For other recent strategies: (k) Liu, Y.; Nappi, M.; Arceo, E.; Vera, S.;
Melchiorre, P. J. Am. Chem. Soc. 2011, 133, 15212; (l) Liu, Y.; Nappi, M.;
Escudero-Adán, E. C.; Melchiorre, P. Org. Lett. 2012, 14, 1310; (m) Xiao, Y.-C.;
Zhou, Q.-Q.; Dong, L.; Liu, T.-Y.; Chen, Y.-C. Org. Lett. 2012, 14, 5940; (n)
Kawano, M.; Kiuchi, T.; Negishi, S.; Tanaka, H.; Hoshikawa, T.; Matsuo, J.-I.;
Ishibashi, H. Angew. Chem., Int. Ed. 2013, 52, 906; (o) Xiao, Y.-C.; Yue, C.-Z.;
Chen, P.-Q.; Chen, Y.-C. Org. Lett. 2014, 16, 3208.
Experimental
General procedure
Sc(OTf)3 (75 lmol) in a test tube with a stirring bar was heated
at 90 °C under reduced pressure (<0.1 mmHg) for 30 min. After
being allowed to cool to room temperature, the test tube was
charged with dry argon and CCl4 (distd from CaCl2, 0.5 mL) was
added. The reaction vessel was cooled to 0 °C and a solution of 12
(300 lmol) and 3 (450 lmol) in CCl4 (distd from CaCl2,
0.6 mL + 0.4 mL to rinse) was added. Next, the mixture was warmed
to room temperature and stirred for 6 days. The reaction mixture
was quenched by the addition of H2O. The water layer was
extracted three times with CH2Cl2 and the combined organic layers
were dried over Na2SO4. The volatile materials were removed under
reduced pressure and the resulting residue was purified by column
chromatography (SiO2, hexane/AcOEt = 4/1 to 2/1) to give a mixture
of exo-adduct 13 and endo-adduct 14 as a white foam. Their ratio
was confirmed by 1H NMR (Table 2, entry 11).
4. Harada, S.; Morikawa, T.; Nishida, A. Org. Lett. 2013, 15, 5314.
5. Isomerization of acyclic Z-olefin 16 was observed under Lewis acid-catalyzed
Diels–Alder conditions (unpublished result).
O
O
Me
O
N
16
6. (a) Ohfune, Y.; Tomita, M. J. Am. Chem. Soc. 1982, 104, 3511; (b) Bailey, J. H.;
Cherry, D. Y.; Crapnell, K. M.; Moloney, M. G.; Shim, S. B.; Bamford, M. J.;
Lamont, R. B. Tetrahedron 1997, 53, 11731; (c) Oba, M.; Nishiyama, N.;
Nishiyama, K. Chem. Commun. 2003, 776; (d) Dransfield, P. J.; Dilley, A. S.;
Wang, S.; Romo, D. Tetrahedron 2006, 62, 5223.
This mixture could be separated by silica gel column chroma-
tography (CHROMATOREXÒ-DIOL (Fuji Silysia Chemical Ltd.), hex-
ane/AcOEt = 4/1) to give exo-adduct 13 and endo-adduct 14.
exo-Adduct 13: 1H NMR (400 MHz, CDCl3) d 1.06–1.08 (m, 18H),
1.14–1.24 (m, 3H), 2.03–2.11 (m, 1H), 2.23 (d, J = 4.0, 15.6 Hz, 1H),
2.58–2.64 (m, 1H), 3.28–3.78 (m, 2H), 3.79 (s, 3H), 3.90 (s, 3H), 4.00
(d, J = 3.2, 6.4 Hz, 1H), 4.38 (d, J = 8.0 Hz, 1H), 4.58 (s, 2H), 4.73 (t,
J = 2.4 Hz, 1H), 6.93–6.99 (m, 3H), 7.14 (t, J = 7.6 Hz, 1H), 7.28–
7.38 (m, 5H), 7.55 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 8.25
(d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 13.58, 17.85,
17.87, 33.89, 34.89, 47.98, 53.78, 55.41, 60.40, 61.15, 68.73,
73.43, 110.76, 114.01, 114.68, 123.49, 123.54, 127.08, 127.27,
127.52, 127.69, 127.74, 128.45, 131.17, 137.50, 141.63, 143.73,
152.29, 163.41, 173.51; IR (neat) 2943, 1787, 1720, 1593, 1354,
7. The Diels–Alder reaction of siloxyvinylindole
3 with 17 proceeded under
thermal conditions to give exo-adduct 18 and endo-adduct 19 (unpublished
result).
OTIPS
OTIPS
3
+
+
N
Mbs
CO2Me
N
Mbs
CO2Me
CH2Cl2
reflux
20h
H
O
H
O
O
O
N
N
O
N
CO2Me
O
O
O
O
17
18 (exo-adduct)
19 (endo-adduct)
y. 23%
y. 32%
8. (a) Carmona, D.; Lamata, M. P.; Oro, L. A. Coord. Chem. Rev. 2000, 717, 200–202;
(b) Reymond, S.; Cossy, J. Chem. Rev. 2008, 108, 5359. and, references cited
therein.
9. (a) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W.-L. Chem. Rev. 2002, 102,
2227; (b) Ladziata, U. ARKIVOC 2014, 307.
10. Exo selective Diels–Alder reaction could be also explained by the substitution
pattern of the reactants (a) Lam, Y.-H.; Cheong, P. H.-Y.; Mata, J. M. B.; Stanway,
S. J.; Gouverneur, V.; Houk, K. N. J. Am. Chem. Soc. 2009, 131, 1947; It was also
reported that certain metals with less coordination numbers promoted the
exo-selective Diels–Alder reaction. For example, (b) Takadoi, M.; Katoh, T.;
Ishiwata, A.; Terashima, S. Tetrahedron 2002, 58, 9903. See also references in
10(a).
11. Cativiela, C.; García, J. I.; Gil, J.; Martínez, R. M.; Mayoral, J. A.; Salvatella, L.;
Urieta, J. S.; Mainar, A. M.; Abraham, M. H. J. Chem. Soc., Perkin Trans. 2 1997,
653.
12. As control experiments, a mixture of exo-adduct 13 and endo-adduct 14 was
treated under catalytic conditions. The ratio of 13 and 14 in the resulting
solution did not change at all. When pure 13 was also treated under the same
conditions, no 14 was observed from the resulting solution. According to these
experiments, isomerization between exo and endo isomers should be excluded.
13. Beemelmanns, C.; Reissig, H.-U. Angew. Chem., Int. Ed. 2010, 49, 8021.
14. The one-pot synthesis of 15d from 12 was achieved in 53% yield.
15. Thulium triflate can be recycled and reused. (1st: yield 89%, exo/endo = 83:17,
2nd: yield 77%, exo/endo = 81:19.)
1261, 1164, 1090, 1013 cmÀ1; HRMS (ESI) m/z calcd for C40H50N2
O8SSiNa [M+Na]+ 769.2955, found 769.2957; [
CHCl3).
a
]
+5.86 (c 1.00,
20
D
endo-Adduct 14: 1H NMR (400 MHz, CDCl3) d 1.03–1.08 (m,
18H), 1.11–1.22 (m, 3H), 2.20 (d, J = 17.2 Hz, 1H), 2.67–2.82 (m,
2H), 3.61 (d, J = 6.0, 9.6 Hz, 1H), 3.68 (d, J = 3.2, 9.6 Hz, 1H), 3.71
(s, 3H), 3.80 (s, 3H), 3.97 (d, J = 2.4, 10.0 Hz, 1H), 4.01 (d, J = 4.4,
8.0 Hz, 1H), 4.55–4.59 (m, 3H), 6.88–6.95 (m, 3H), 7.06 (t,
J = 7.6 Hz, 1H), 7.29–7.36 (m, 5H), 4.44 (d, J = 7.6 Hz, 1H), 7.48 (d,
J = 7.6 Hz, 1H), 7.84 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 13.61, 17.79, 17.91, 31.07, 35.85, 45.29, 53.33, 55.48, 62.12,
64.55, 69.77, 73.44, 112.40, 114.19, 114.57, 123.05, 123.39,
127.30, 127.70, 127.81, 127.83, 128.49, 129.36, 129.59, 137.58,
141.51, 143.26, 151.82, 163.21, 170.08; IR (neat) 2943, 1752,
1714, 1594, 1346, 1258, 1159, 1090, 1011 cmÀ1; HRMS (ESI) m/z
calcd for C40H50N2O8SSiNa [M+Na]+ 769.2955, found 769.2936;
20
[a
]
À8.69 (c 1.02, CHCl3).
D