[2,3]-Wittig sigmatropic rearrangement of γ-allyloxy-β-enaminoesters

Article abstract of DOI:10.1055/s-2003-38362

The dianions derived from γ-allyloxy-β-enaminoesters undergo a [2,3]-Wittig sigmatropic rearrangement leading to γ-hydroxy-β-enaminoester derivatives, which can be subsequently lactonized to the corresponding 4-aminofuran-2(5H)-ones.

Full text of DOI:10.1055/s-2003-38362

LETTER
663
[2,3]-Wittig Sigmatropic Rearrangement of g-Allyloxy-b-Enaminoesters
[
2,3]-W
i
s
ttig Rearr
a
o
b
f
γ
-Allyloxy-
e
β
-Enamino
l
ester
s
le Pévet, Christophe Meyer,* Janine Cossy
Laboratoire de Chimie Organique, associé au CNRS, ESPCI, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Fax +33(1)40794660; E-mail: christophe.meyer@espci.fr
Received 22 January 2003
considered since it had previously provided the best re-
sults in the case of γ-allyloxy-β-ketoesters.6,8 However, no
reaction occurred at room temperature and the use of a
large excess of LiHMDS (8 equiv) in refluxing THF was
required in order to promote the dilithiation of 2 and its
[2,3]-Wittig rearrangement. Indeed, after quenching with
TMSCl, the surprisingly stable tris-silylated γ-hydroxy-β-
enaminoester 3 was isolated in 63% yield. This compound
was desilylated by using n-Bu4NF in THF and afforded
the γ-hydroxy-β-enaminoester 4 (86%), but no subsequent
lactonization occurred under these conditions for this sub-
strate (Scheme 2).
Abstract: The dianions derived from γ-allyloxy-β-enaminoesters
undergo a [2,3]-Wittig sigmatropic rearrangement leading to γ-hy-
droxy-β-enaminoester derivatives, which can be subsequently
lactonized to the corresponding 4-aminofuran-2(5H)-ones.
Key words: β-ketoesters, β-enaminoesters, lithiation, Wittig rear-
rangement, lactones
Tetronic acid derivatives are found in a wide variety of bi-
ologically active natural products.1 The nitrogen ana-
logues of tetronic acids [4-aminofuran-2(5H)-ones] also
constitute an important class of compounds in pharmaceu-
tical or agrochemical research.2,3 Moreover, these sub-
strates have been used as key reagents or intermediates in
the synthesis of natural products.4,5 Recently, we have
demonstrated that the dianions derived from γ-allyloxy-β-
ketoesters underwent a [2,3]-Wittig rearrangement lead-
ing to γ-hydroxy-β-ketoesters derivatives and to tetronic
acids after subsequent lactonization.6 Herein, we report
the extension of this methodology to γ-allyloxy-β-enami-
noesters of type A with the aim of synthesizing γ-hy-
droxy-β-enaminoesters derivatives of type B and 4-
aminofuran-2-(5H)-ones of type C (Scheme 1).
H
H
O
O
O
N
NH4OAc
O
O
EtO
EtO
EtOH, reflux
87%
1
2
LiHMDS (8 equiv.)
THF, reflux
O
NHLi
OLi NHLi
[2,3]
O
EtO
EtO
OLi
TMSCl (8 equiv.)
63%
O
NHR
O
NR
O
N(TMS)2
OTMS
O
NH2
O
O
EtO
EtO
n-Bu4NF
A
EtO
EtO
THF
86%
[2,3]
OH
3
4
NHR
Scheme 2
O
NHR
EtO
O
O
The feasibility of the [2,3]-Wittig rearrangement of γ-al-
lyloxy-β-enaminoesters derived from primary amines was
next examined. Thus, condensation of 1 with allylamine
and benzylamine gave the corresponding γ-allyloxy-β-
enaminoesters 5a and 5b respectively (96–100%). Unlike
the β-enaminoester 2, compounds 5a and 5b exist as equi-
librium mixtures of (Z) and (E) isomers (through the inter-
mediate imine tautomeric form) and this discrepancy was
attributed to the possibility for the amino moiety to give
rise to a hydrogen bond either with the oxygen atom of the
carbonyl group or the γ-allyloxy substituent (Scheme 3).7
Contrary to LiHMDS as a base, which proved totally inef-
ficient at promoting the dilithiation of 5a and 5b, a more
reactive alkyllithium reagent such as n-BuLi led to satis-
factory results.8 Indeed, when 5a and 5b were treated with
an excess of n-BuLi (4 equiv, THF, –78 °C),9 the forma-
tion of the dianions and their subsequent [2,3]-Wittig re-
OR'
C
B
Scheme 1
When ethyl 4-allyloxyacetoacetate 1 was treated with am-
monium acetate in ethanol, the corresponding β-enami-
noester 2 was obtained in 87% yield as a single isomer of
(Z)-configuration, due to the propensity of the amino
group to make two hydrogen bonds with the oxygen at-
oms of the carbonyl group and the allyloxy substituent.7 In
order to generate the dianion of 2 and study the feasibility
of a subsequent [2,3]-Wittig rearrangement, the use of
lithium hexamethyldisilazide (LiHMDS) as a base was
Synlett 2003, No. 5, Print: 10 04 2003.
Art Id.1437-2096,E;2003,0,05,0663,0666,ftx,en;G01503ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

664
I. Pévet et al.
LETTER
O
O
O
NHR
O
NHBn
NHBn
RNH2
1) n-BuLi (4 equiv.), THF
–78 °C to –30 °C
O
cat. AcOH
O
O
EtO
EtO
EtO
2) TMSCl
O
3) n-Bu4NF, THF
toluene, 60 °C
96-100%
1
O
9
R = Allyl
R = Benzyl
5a
5b
8
59%
R
H
R
O
R
N
O
N
Scheme 5
O
O
EtO
EtO
EtO
(Z)-isomer
of compounds 5a and 5b. Under these conditions, the
diastereomeric γ-trimethylsilyloxy-β-enaminoesters 6c
and 6′c were obtained in a ratio of 70/30.10 The mixture of
these two compounds was lactonized by treatment with n-
Bu4NF, without epimerization, to a diastereomeric mix-
ture of the corresponding 4-aminofuran-2-(5H)-ones 7c
and 7′c (75%, 70/30 ratio). These diastereomers could be
easily separated by flash chromatography or fractional
crystallization from diethyl ether and the absolute config-
uration of the major diastereomer 7c at C5 was assigned to
be (R) (Scheme 6).11
H
N
R
H
O
N
O
O
O
OEt
(E)-isomer
Scheme 3
arrangement occurred within a few hours and after
quenching with TMSCl, the corresponding γ-trimethylsi-
lyloxy-β-enaminoesters 6a and 6b were formed. Due to
their moderate stability on silica gel, low isolated yields of
these compounds were obtained (45–54%). However,
treatment of the crude 6a and 6b with n-Bu4NF in THF af-
forded the corresponding N-substituted-4-aminofuran-2-
(5H)-ones 7a (68%) and 7b (69%), resulting from desily-
lation and subsequent lactonization. Worthy of note is the
fact that compounds 7a and 7b are obtained in satisfactory
yields from the β-ketoester 1, since by comparison, direct
condensation of 5-allyltetronic acid with benzylamine un-
der different conditions (cat. TsOH or HOAc, C6H6 or tol-
uene) did not provide 7b in yields greater than 30%
(Scheme 4).
H2N
cat. AcOH
Ph
O
O
O
HN
Ph
O
O
EtO
EtO
toluene, 60 °C
1
5c
1) n-BuLi (4 equiv.)
THF, –78 °C
2) TMSCl
HN
O
HN
Ph
OTMS
Ph
Ph
Ph
EtO
EtO
O
O
O
6c
(major)
+
7c
n-Bu4NF
+
THF, r.t.
75% (2 steps)
HN
O
HN
O
NHR
O
NLiR
n-BuLi
(4 equiv.)
O
O
6'c
(minor)
7'c
OTMS
EtO
R = Allyl
R = Benzyl
EtO
THF, –78 °C
5a
5b
OLi
7c/7'c = 70/30
6c/6'c = 70/30
TMSCl
Scheme 6
NHR
O
NHR
n-Bu4NF
Since literature results concerning the enantioselective
version of the [2,3]-Wittig rearrangement based on the use
of chiral auxiliaries have highlighted the tremendous ef-
fect of the reaction conditions and particularly the choice
of the solvent,12,13 a related study was undertaken in the
case of substrate 5c. It was found that switching from THF
to a less (Et2O) or non-coordinating solvent (toluene) led
to a slight reversal or decrease of the diastereoselectivity.
A higher reaction temperature was also required in the
case of toluene, due to the poor solubility of the dilithiated
species. By contrast, the use of TMEDA, LiBr or HMPA,
which are all expected to induce deaggregation of the
dilithiated γ-allyloxy-β-enaminoester 5c resulted in an in-
crease of the diastereomeric ratio (Scheme 7).
EtO
THF, r.t.
O
O
OTMS
R = Allyl
R = Benzyl
R = Allyl
R = Benzyl
7a
68%
7b 69%
6a
6b (45-54%)
Scheme 4
Similarly, the β-enaminoester 8 having a tertiary allylic
ether moiety, was rearranged according to the same se-
quence to compound 9 (59%) bearing a trisubstituted dou-
ble bond, thereby supporting a concerted [2,3]-Wittig
sigmatropic rearrangement rather than a [1,2]-Wittig rear-
rangement (Scheme 5).
The opportunity for achieving asymmetric induction by
the use of chiral amines in the [2,3]-Wittig rearrangement
of γ-allyloxy-β-enaminoesters was next investigated. The
β-enaminoester 5c was obtained in quantitative yield by
condensation of (R)-α-methylbenzylamine with 1, and re-
arranged according to the procedure optimized in the case
We have shown that dilithiated γ-allyloxy-β-enami-
noesters underwent a [2,3]-Wittig rearrangement leading
to γ-hydroxy-β-enaminoester derivatives and/or to 5-al-
lyl-4-aminofuran-2(5H)-ones after lactonization. Encour-
Synlett 2003, No. 5, 663–666 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
[2,3]-Wittig Rearrangement of γ-Allyloxy-β-Enaminoesters
665
1705, 1630, 1620, 1605, 1585, 1170, 925, 785, 740 cm–1; 1H NMR
(300 MHz, CDCl3): δ = 7.35–7.22 (m, 5 H), 6.60 (br t, J = 5.5 Hz,
1 H, NH), 5.71 (ddt, J = 17.0, 10.3 and 7.0 Hz, 1 H), 5.18–5.08 (m,
2 H), 4.83 (dd, J = 6.2 and 4.4 Hz, 1 H), 4.50 (s, 1 H), 4.25 (d,
J = 5.5 Hz, 2 H), 2.66 (m, 1 H), 2.46 (m, 1 H). 13C NMR (75 MHz,
CDCl3): δ = 175.3 (s), 170.3 (s), 136.6 (s), 131.1 (d), 128.7 (d, 2 C),
127.7 (d), 127.3 (d, 2 C), 119.3 (t), 81.6 (d), 77.6 (d), 48.9 (t), 37.0
(t). MS (EI, 70 eV): m/z (%) = 229 (26) [M+•], 188 (20), 110 (6), 92
(9), 91 (100), 65 (8). Anal. Calcd for C14H15NO2: C, 73.34; H, 6.59;
N, 6.11. Found C, 73.18; H, 6.78; N, 5.99.
HN
1) n-BuLi (4 equiv.)
(2.5M/hexanes)
solvent (additives)
O
HN
Ph
O
Ph
5
EtO
O
O
2) n-Bu4NF, THF
5c
7c(5R)/7'c(5S)
Diastereomeric
ratio 7c/7'c
Solvent / additives
Conditions
Yield
–78 °C, 2 h
–78 °C, 6 h
THF
70/30
45/55
50/50
80/20
80/20
88/12
75%
53%
79%
52%
70%
64%
Et2O
–10 °C, 3 h
Toluene
THF/LiBr (10 equiv.)
–78 °C to –50 °C, 15 h
THF/TMEDA (16 equiv.)
THF/HMPA (4/1)
–78 °C, 3 h
–78 °C, 4 h
References
(1) (a) Effenberger, F.; Syed, J. Tetrahedron: Asymmetry 1998,
9, 817. (b) Bühler, H.; Bayer, A.; Effenberger, F. Chem.–
Eur. J. 2000, 6, 2564; and references cited therein.
(2) (a) Hiyama, T.; Oishi, H.; Saimoto, H. Tetrahedron Lett.
1985, 26, 2459. (b) Hiyama, T.; Oishi, H.; Suetsugu, Y.;
Nishide, K.; Saimoto, H. Bull. Chem. Soc. Jpn. 1987, 60,
2139. (c) Syed, J.; Förster, S.; Effenberger, F. Tetrahedron:
Asymmetry 1998, 9, 805. (d) Wang, J.; Jiang, X.; Chen, M.;
Ge, Z.; Hu, Y.; Hu, H. J. Chem. Soc., Perkin Trans. 1 2001,
66; and references cited in these articles.
Scheme 7
aging levels of asymmetric induction have been obtained
by using a chiral amine. Application of this methodology
to the synthesis of nitrogen heterocycles and/or tetronic
acids containing natural products are currently being
studied.
(3) (a) Greenhill, J. V.; Ramli, M.; Tomassini, T. J. Chem. Soc.,
Perkin Trans. 1 1975, 588. (b) Boosen, K.-J. Helv. Chim.
Acta 1977, 60, 1256. (c) Schmidt, R. R.; Talbiersky, J.
Angew. Chem., Int. Ed. Engl. 1978, 17, 204. (d) Momose,
T.; Toyooka, N.; Nishi, T.; Takeuchi, Y. Heterocycles 1988,
27, 1907. (e) Martin, M. R.; Mateo, A. I. Tetrahedron:
Asymmetry 1994, 5, 1385. (f) Veronese, A. C.; Callegari, R.;
Basato, M.; Valle, G. J. Chem. Soc., Perkin Trans. 1 1994,
1779.
(4) (a) Nishide, K.; Aramata, A.; Kamanaka, T.; Inoue, T.;
Node, M. Tetrahedron 1994, 50, 8337. (b) Schlessinger, R.
H.; Iwanowicz, E. J.; Springer, J. P. Tetrahedron Lett. 1988,
29, 1489. (c) Schlessinger, R. H.; Mjalli, A. M. M.; Adams,
A. D.; Springer, J. P.; Hoogsteen, K. J. Org. Chem. 1992, 57,
2992. (d) Schlessinger, R. H.; Pettus, T. R. R.; Springer, J.
P.; Hoogsteen, K. J. Org. Chem. 1994, 59, 3246.
Ethyl 4-(allyloxy)-3-(benzylamino)but-2-enoate (5b): Benzyl-
amine (1.5 mL, 13 mmol) and HOAc (50 µL, 0.84 mmol, 0.07
equiv) were successively added to a solution of 1 (2.5 g, 13 mmol)
in toluene (15 mL). After 5 h at 60 °C, the reaction mixture was con-
centrated under reduced pressure. The residue was taken-up in tol-
uene and concentrated under reduced pressure (this operation was
repeated until no more water remained). The crude material was
dried under vacuum (0.1 mmHg) for 2 h to give 3.8 g (100%) of 5b
as a yellow oil (70/30 mixture of Z/E isomers). IR: 3400, 3300,
1
1675, 1650, 1600, 1225, 1045, 1005, 930, 790, 730, 700 cm–1. H
NMR (300 MHz, CDCl3): major isomer: δ = 8.67 (br s, 1 H, NH),
7.38–7.21 (m, 5 H), 5.86 (ddt, J = 17.3, 10.3 and 5.5 Hz, 1 H), 5.31–
5.16 (m, 2 H), 4.71 (s, 1 H), 4.50 (d, J = 6.2 Hz, 2 H), 4.11 (q,
J = 7.2 Hz, 2 H), 4.03 (s, 2 H), 3.98 (dt, J = 5.5 and 1.5 Hz, 2 H),
1.25 (t, J = 7.0 Hz, 3 H); minor isomer: δ = 7.38–7.21 (m, 5 H), 5.95
(br s, 1 H, NH), 5.87 (ddt, J = 17.3, 10.3 and 5.5 Hz, 1 H), 5.31–5.16
(m, 2 H), 4.80 (d, J = 1.5 Hz, 2 H), 4.62 (br t, J = 1.5 Hz, 1 H), 4.20
(d, J = 5.5 Hz, 2 H), 4.14–4.01 (m, 4 H), 1.23 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): major isomer: δ = 170.4 (s), 159.1 (s),
138.9 (s), 133.8 (d), 128.6 (d, 2 C), 127.5 (d), 126.8 (d, 2 C), 117.7
(t), 84.0 (d), 71.0 (t), 68.9 (t), 58.6 (t), 46.6 (t), 14.4 (q); minor iso-
mer: δ = 168.5 (s), 159.2 (s), 136.9 (s), 133.7 (d), 128.7 (d, 2 C),
127.6 (d), 127.2 (d, 2 C), 117.7 (t), 80.3 (d), 72.0 (t), 68.0 (t), 58.4
(t), 47.1 (t), 14.5 (q). MS (EI, 70 eV): m/z (%) = 275 (8) [M+.], 246
(7), 219 (9), 175 (28), 174 (11), 146 (26), 144 (17), 104 (10), 92 (9),
91 (100). HRMS (EI): Calcd. for C16H21NO3 [M+.]: 275.1521.
Found 275.1526.
(e) Schlessinger, R. H.; Li, Y.-J. J. Am. Chem. Soc. 1996,
118, 3301. (f) Dankwardt, S. M.; Dankwardt, J. W.;
Schlessinger, R. H. Tetrahedron Lett. 1998, 39, 4971.
(g) Dankwardt, J. W.; Dankwardt, S. M.; Schlessinger, R. H.
Tetrahedron Lett. 1998, 39, 4979.
(5) (a) Paulvannan, K.; Stille, J. R. J. Org. Chem. 1994, 59,
1613. (b) Cook, G. R.; Behloz, L. G.; Stille, J. R. J. Org.
Chem. 1994, 59, 3575. (c) Hitotsuyanagi, Y.; Kobayashi,
M.; Fukuyo, M.; Takeya, K.; Itokawa, H. Tetrahedron Lett.
1997, 38, 8295.
(6) Pévet, I.; Meyer, C.; Cossy, J. Tetrahedron Lett. 2001, 42,
5215.
(7) (a) Aberhart, D. J.; Lin, H.-J. J. Org. Chem. 1981, 46, 3749.
(b) Shieh, T.-L.; Lin, C.-T.; McKenzie, A. T.; Byrn, S. R. J.
Org. Chem. 1983, 48, 3103. (c) Melillo, D. G.; Cvetovich,
R. J.; Ryan, K. M.; Sletzinger, M. J. Org. Chem. 1986, 51,
1498. (d) Hiyama, T.; Kobayashi, K.; Nishide, K. Bull.
Chem. Soc. Jpn. 1987, 60, 2127. (e) Pawlak, J. M.; Khau, V.
V.; Hutchison, D. R.; Martinelli, M. J. J. Org. Chem. 1996,
61, 9055. (f) Soloshonok, V. A.; Kukhar, V. P. Tetrahedron
1996, 52, 6953. (g) Cavé, C.; Gassama, A.; Mahuteau, J.;
d’Angelo, J.; Riche, C. Tetrahedron Lett. 1997, 38, 4773.
(8) Although the deprotonation of tertiary β-enaminoesters at
the γ-position (including N,N-disubstituted 4-aminofuran-2-
(5H)-ones)4 is well-documented, the double metalation of
primary or secondary ones has not been reported to our
5-Allyl-4-(benzylamino)furan-2(5H)-one (7b): To a solution of
5b (4.5 g, 16 mmol) in THF (70 mL) at –78 °C, was added dropwise
n-BuLi (26 mL, 2.5 M in hexanes, 65 mmol, 4 equiv). After 2 h at
–78 °C, TMSCl (8.3 mL, 65 mmol, 4 equiv) was added dropwise
and after 2 h at r.t., the reaction mixture was concentrated under re-
duced pressure. The residue was taken-up in pentane, filtered
through Celite and the insoluble lithium salts were thoroughly
washed with pentane. The filtrate was concentrated under reduced
pressure and the residual oil was dissolved in THF (25 mL). To the
resulting solution at 0 °C was added n-Bu4NF (25 mL, 1 M in THF,
25 mmol, 1.5 equiv) and after 15 h at r.t., the reaction mixture was
concentrated under reduced pressure. The residue was purified by
flash chromatography (CH2Cl2/EtOAc: 90/10, 80/20) to give 2.6 g
(69%) of 7b as a pale yellow solid; mp = 88–89 °C. IR: 3270, 3070,
Synlett 2003, No. 5, 663–666 ISSN 0936-5214 © Thieme Stuttgart · New York

666
I. Pévet et al.
LETTER
(11) The diastereomeric ratio (7c/7′c)was determined by 1H
knowledge. See: (a) Schlessinger, R. H.; Iwanowicz, E. J.;
Springer, J. P. J. Org. Chem. 1986, 51, 3073.
NMR. These two diastereomers were separated and
hydrolyzed to the corresponding enantiomeric tetronic acids
(+)-11 and (–)-11 respectively. The (5R) absolute
configuration of tetronic acid (+)-11 was assigned after
hydrogenation, by correlation with the known optically pure
(5R)-5-propyltetronic acid (+)-12 (Scheme 9).1a
(b) Schlessinger, R. H.; Li, Y.-J.; Von Langen, D. J. J. Org.
Chem. 1996, 61, 3226. (c) Schlessinger, R. H.; Gillman, K.
W. Tetrahedron Lett. 1996, 37, 1331. (d) Dankwardt, J. W.;
Dankwardt, S. M.; Schlessinger, R. H. Tetrahedron Lett.
1998, 39, 4983. (e) Schlessinger, R. H.; Pettus, L. H. J. Org.
Chem. 1998, 63, 9089. (f) Schlessinger, R. H.; Gillman, K.
W. Tetrahedron Lett. 1999, 40, 1257.
HN
OH
OH
(9) Due to their moderate stability on silica gel, the β-enamino-
esters 5a–c and 8 were conveniently engaged in the
rearrangement step without further purification and
therefore an excess of n-BuLi (4 equiv) was routinely used
in order to ensure an efficient metalation process of these
crude compounds at –78 °C. The nucleophilic addition of
n-BuLi to the ester carbonyl group of lithiated β-enamino-
esters, and/or N,O-dilithiated β-enaminoesters arising from
the [2,3]-sigmatropic rearrangement, has never been
observed as a side reaction. The fact that these species may
be considered as vinylogous lithiated carbamates probably
accounts for their low reactivity towards n-BuLi.
Ph
a
b
O
O
n-Pr
O
O
O
O
(+)-11
(+)-12
7c
20 +122(c 1.0 CHCl ) [α]D20 +23(c 1.0 CHCl ) [α]D
20
(c 0.6 EtOH)
+10.5
[α]D
3
3
[α]D20 +9.2 (c 0.6 EtOH)1a
HN
OH
Ph
a
O
O
O
O
(-)-11
–23(c 1.0 CHCl3)
7'c
20
[α]D20 +64 (c 1.0 CHCl3)
[α]D
(10) Due to the complexity of the NMR spectra of the mixture of
6c and 6′c (presence of Z/E isomers in equilibrium for each
diastereomer), the diastereomeric ratio (6c/6′c) was
evaluated by GC-MS after calibration with authentic
samples prepared by condensation of (R)-α-methyl-
benzylamine with the γ-trimethylsilyloxy-β-ketoester 10
resulting from the [2,3]-Wittig rearrangement of 1 and
subsequent silylation with TMSCl (Scheme 8).6
Scheme 9 Reagents and Conditions: a) 35% aq HCl, CCl4, reflux;
b) H2, Pd/C (cat.), EtOH.
(12) General reviews on the [2,3]-Wittig rearrangement:
(a) Nakai, T.; Mikami, K. Chem. Rev. 1986, 86, 885.
(b) Marshall, J. A. In Comprehensive Organic Chemistry,
Vol. 3; Trost, B. M.; Fleming, I., Eds.; Pergamon Press:
Oxford, 1991, 975–1014. (c) Brückner, R. In
Comprehensive Organic Chemistry, Vol. 6; Trost, B. M.;
Fleming, I., Eds.; Pergamon Press: Oxford, 1991, 873–907.
(d) Kallmerten, J. In Houben-Weyl, Methods of Organic
Chemistry, Vol. E 21d; Helmchen, G.; Hoffmann, R. W.;
Mulzer, J.; Schaumann, E., Eds.; Thieme-Verlag: Stuttgart,
1995, 3757–3809.
1) LiHMDS
(2.5 equiv.)
O
O
O
O
O
EtO
EtO
THF, r.t.
1
10
OTMS
2) TMSCl
69%
H2N
cat. AcOH
toluene, 60 °C
Ph
(13) (a) Takahashi, O.; Mikami, K.; Nakai, T. Chem. Lett. 1987,
69. (b) Sudo, A.; Hashimoto, Y.; Kimoto, H.; Hayashi, K.;
Saigo, K. Tetrahedron: Asymmetry 1994, 5, 1333.
(c) Enders, D.; Backhaus, D. Synlett 1995, 631. (d) Enders,
D.; Backhaus, D.; Runsink, J. Tetrahedron 1996, 52, 1503.
(e) Enders, D.; Bartsch, M.; Runsink, J. Synthesis 1999,
243. (f) Kress, M. H.; Yang, C.; Yasuda, N.; Grabowski, E.
J. J. Tetrahedron Lett. 1997, 38, 2633. (g) Hiersemann, M.;
Lauterbach, C.; Pollex, A. Eur. J. Org. Chem. 1999, 2713.
(h) Hiersemann, M. Tetrahedron 1999, 55, 2625.
25%
O
HN
Ph
O
HN
Ph
+
EtO
EtO
6'c
6c
OTMS
OTMS
6c/6'c = 50/50
Scheme 8
Synlett 2003, No. 5, 663–666 ISSN 0936-5214 © Thieme Stuttgart · New York