Diastereoselective synthesis of a seco-taxane

Article abstract of DOI:10.1055/s-1999-2889

Ketone 9 was synthesized in 7 steps from commercially available 2- methylcyclohexane-1,3-dione in a diastereoselective fashion. Shapiro reaction of easily available trisylhydrazone 11 with benzaldehyde was used as a model for A- and C-ring coupling. Final

Full text of DOI:10.1055/s-1999-2889

LETTER
1555
Diastereoselective Synthesis of a seco-Taxane
a
a
b
a*
Damien Bourgeois, Jean-Yves Lallemand, Ange Pancrazi, Joëlle Prunet
a
Laboratoire de Synthèse Organique, associé au CNRS, Ecole Polytechnique, DCSO, 91128 Palaiseau, France
Fax: (33) 1 69 33 30 10. E-mail : Joelle.Prunet@polytechnique.fr
b
Laboratoire de Synthèse Organique Sélective et Chimie Organométallique, UCP-ESCOM, EP 1822, 5 Mail Gay Lussac, Neuville/Oise,
9
5031 Cergy-Pontoise, France
Fax (33) 1 46 83 55 89; E-mail: ange.pancrazi@cep.u-psud.fr
Received 6 July 1999
Abstract: Ketone 9 was synthesized in 7 steps from commercially
available 2-methylcyclohexane-1,3-dione in a diastereoselective
fashion. Shapiro reaction of easily available trisylhydrazone 11
with benzaldehyde was used as a model for A- and C-ring coupling.
Finally, reaction of trisylhydrazone 24 with A-ring aldehyde 4, un-
der carefully controlled conditions, gave seco-taxane 27 with high
diastereoselectivity for the diol moiety.
1
ref 7
+
Li
O
O
O
O
TMSO
CHO
O
4
5
O
6
Key words: Shapiro reaction, vinyllithium, stereoselectivity, seco-
taxane, taxol
Due to their novel mode of action and complex structure
O
O
®
2
O
as well as their low natural availability, taxol 1 and tax-
®
3
otere 2, two potent antitumor agents, remain of great
7
O
synthetic interest for organic chemists. At this time six to-
4
Scheme 2
tal syntheses of taxol and some synthetic approaches
5
have been reported in several reviews. Our convergent
synthetic approach towards taxol is based on the prepara-
tion of the seco-taxane 3 by coupling A and C-rings. B-
ring closure is envisaged from 3 through a metathesis
In order to get around the 1,4-addition at this stage of the
synthesis, we decided to prepare a C-ring moiety encom-
passing the required vinylic function (Scheme 3). Vinyl-
lithium intermediate 8 could arise from ketone 9 either
6
7
reaction or a vinyl-vinyl coupling reaction (Scheme 1).
9
directly under the Shapiro conditions or via the corre-
sponding bromide or iodide. To test the feasibility of the
R
2
O
transformation from 9 to 8, we used ketone 10 (which is
R O
OH
7
X
OPG
9
7
1
0
an intermediate in the synthesis of 4) as a readily avail-
Y
able model (Scheme 3). Trisylhydrazone 11 was obtained
in 92% yield. When treated with 4 equivalents of n-BuLi,
it furnished the vinylic anion which could be trapped with
benzaldehyde to give 12 in good yield.
1
R NH
O
B
C
5
3
1
3 A
1
2
D O
OAc
O
H
Ph
O
HO
O
OBz
OH
Taxol (paclitaxel)
Taxotere (docetaxel) R1 = t-BuOCO, R2 = H
1
2
R1 = C6H5CO, R2 = Ac
O
3 R = H, Me
OBn
OBn
Scheme 1
C
Li
O
In a first route, we synthesized compound 6 by coupling
aldehyde 4 and vinyllithium derivative 5 derived from the
corresponding vinyl bromide (Scheme 2). To our sur-
8
9
8
prise, this reaction was highly diastereoselective and de-
livered 6 as only one diastereomer (>95:5 by H NMR)
O
O
a)
O
O
b)
O
O
1
after protection of the diol system. Unfortunately, at-
tempts to introduce the vinylic chain on the C-ring via
conjugate additions of cuprates to enone derivative 6
failed to produce seco-taxane 7.
Ph
O
TrisHNN
10
11
OH 12
a) TrisNHNH , THF, HCl conc. cat., 92%. b) 4 equiv n-BuLi, THF/
2
TMEDA 9:1, -78°C, 30 min, 0°C, 1 min, 4 equiv PhCHO, -78°C,
3
0 min, 77%.
Scheme 3
Synlett 1999, No. 10, 1555–1558 ISSN 0936-5214 © Thieme Stuttgart · New York

1
556
D. Bourgeois et. al.
LETTER
Vinyl bromide 13 and vinyl iodide 14 could not be ob-
tained free of the corresponding alkene via trisylhydra-
zone 11. However, formation of the unsubstituted
O
O
O
1
0
11
hydrazone, followed by reaction with NBS or iodine,
led to 13 or 14 in good yields and very cleanly (Scheme
). Halogen-metal exchange was performed with t-BuLi
a)
b)
O
O
O
O
4
15
18
and reaction of the vinyllithium derivative with benzalde-
hyde gave 12 in 90% and 51% yields respectively from 13
and 14. In conclusion, all options to make vinyllithium de-
rivatives 8 seemed to be open.
OH
OH
H-
O
O
18
O
O
19
20
O
O
Conditions
19 : 20
a)
b)
10
12
NaBH4 /MeOH/CH2Cl2
NaBH4/CeCl3 /0°C
1 : 2
1 : 1
X
1
1
3 X = Br
4 X = I
DIBAl-H/PhMe/ -78°C–>20°C
L-Selectride/THF/0°C
cat. SmI2/i-PrOH/THF
LiAlH4/PhMe/60-70°C
1 : 5
a) i- H NNH H O, EtOH, Et N, 100°C, 12 h.; ii- NBS, Pyr, 0°C,
2
2•
2
3
4 : 96
1 : 1*
53 : 47
7
0
1
0% or I , DBU, Et O, 80%. b) 2 equiv t-BuLi, THF, -78°C, 30 min,
°C, 1 min, 3 equiv PhCHO, -78°C, 30 min, 90% from 13, 51% from
4.
2 2
Scheme 4
a) NaH, DMF, propargyl bromide, 73%.
b) HOCH CMe CH OH, BF OEt , CH Cl , 75%.
We then addressed the preparation of ketone 9. The bak-
er’s yeast mediated monoreduction of prochiral 2-methyl-
2
2
2
3•
2
2
2
*
15% conversion.
1
2
2
-propargylcyclohexan-1,3-dione 15 has been described
Scheme 5
1
3
by Brooks, yielding the hydroxyketone with the (2R,3S)
configuration required for our synthesis. This procedure
could be successfully reproduced with excellent ee (95%,
determined by GC on the Mosher ester derivative), but the
purification of the desired diastereomer proved difficult.
In a first time, a racemic synthesis was effected.
tion reaction of the acetylenic function and compound 22
was obtained in 88% yield. Acidic hydrolysis of 22 deliv-
ered the corresponding ketone 23 and partial hydrogena-
Protection of ketone 15 as the monoketal 18 was not com- tion of the triple bond afforded the expected ketone 9.
plete (60% yield, 40% starting material), but an easy sep-
aration via crystallisation of ketal 18 from the unpurified
mixture allowed practical preparation of 18 in 75% yield
after 3 turnovers. Diastereoselective reduction of the ke-
tone function was then tested under several conditions
OH
OBn
OBn
a)
b)
O
O
O
(
1
Scheme 5). Sodium borohydride reduction of 18 gave a
:2 mixture of the two alcohols 19 and 20 in a quantitative
O
O
O
yield, while Luche’s conditions led to a 1:1 mixture of di-
astereomers. Reduction with DIBAl-H gave the undesired
19 + 20 (1:1)
21
22
2
4
0 as the major diastereomer, and L-Selectride led to a
1
4
:96 ratio of 19:20. Use of catalytic SmI /i-PrOH led in
2
OBn
OBn
this case to a poor conversion and a 1:1 ratio of isomers.
15
c)
d)
The best yield was obtained with LiAlH in toluene.
4
Alcohols 19 and 20 were not separated, and we took profit
of a secondary reaction with the acetylenic group to pro-
tect selectively alcohol 19 as its benzyl derivative. Effec-
tively, treatment of a 1:1 mixture of alcohols 19 and 20
with KH/THF/BnBr/cat. TBAI furnished benzyl deriva-
tive 21 as a pure isomer with concomitant degradation of
alcohol 20 (Scheme 6). Having in hand the required pure
compound 21, treatment with t-BuOK led to an isomeriza-
O
O
2
3
9
a) KH, THF, BnBr, TBAI, 50%. b) t-BuOK, DMSO, 120°C, 88%. c)
cat. TsOH, acetone, H O, >95%. d) H , Pd Lindlar >95%.
2
2
Scheme 6
Synlett 1999, No. 10, 1555–1558 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Diastereoselective Synthesis of a seco-Taxane
1557
We then turned to the formation of the corresponding vi- In conclusion, a new synthesis of a taxol C-ring was de-
nyllithium. Ketone 9 was converted to trisylhydrazone 24 veloped. The key coupling reaction of C-ring with A-ring
in good yield, but attempts to make the unsubstituted hy- using a vinyllithium intermediate was carried out via a
drazone were unsuccessful: reduction of the terminal alk- Shapiro reaction. This reaction led to formation of seco-
ene was an unavoidable side-reaction. Under the previous taxane 27 which possesses the required stereochemistry
Shapiro conditions (4 equiv n-BuLi, 9:1 THF/TMEDA, 4 for taxol at the diol level. Preparation of an enantiopure
equiv PhCHO), 24 led to adduct 25 in 65% yield (Scheme seco-taxane is in progress, and B-ring closure using orga-
7
). But when A-ring 4 was used as the electrophile, with nometallic-catalyzed reactions will be tested in the near
only 2 equiv of n-BuLi to avoid unwanted addition of the future.
base onto the aldehyde, the reaction was not reproducible
and yielded mostly alkene 26, presumably because of a
Acknowledgement
difficult formation of the vinylic anion.
The CNRS and the Ecole Polytechnique are thanked for financial
support.
OBn
References and Notes
b)
(1) This route could lead to optically active 9 if an
enantioselective reduction of C7 ketone using baker’s yeast
was effected.
Ph
OBn
OH
25
(
2) a) Wani, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.;
McPhail, A. T. J. Am. Chem. Soc. 1971, 93, 2325. b) ACS
Symposium Series 583, Taxane Anticancer Agents : Basic
Science and Current Status; Georg, G.I.; Chen, T.T.; Ojima,
I.; Vyas, D.M., Eds.; American Chemical Society,
Washington D.C., 1995.
a)
2
diastereomers, 1:1
9
TrisHNN
OBn
24
c)
(
(
3) Lavelle F.; Guéritte-Voegelein, F.; Guénard, D. Bull. Cancer,
1993, 80, 326. Guénard, D.; Guéritte-Voegelein, F.; Potier, P.
2
6
Acc. Chem. Res. 1993, 26, 160 and references therein.
4) a) Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet,
P. G.; Guy, R. K.; Claiborne, C. F.; Renaud, J.; Couladouros,
E. A.; Paulvannan, K.; Sorensen, E. J. Nature 1994, 367, 630.
Nicolaou, K. C.; Nantermet, P. G.; Ueno, H.; Guy, R. K.;
Couladouros, E. A.; Sorensen, E. J. J. Am. Chem. Soc. 1995,
117, 624. Nicolaou, K. C.; Liu, J. J.; Yang, Z.; Ueno, H.;
Sorensen, E. J.; Claiborne, C. F.; Guy, R. K.; Hwang, C. K.;
Nakada, M.; Nantermet, P. G. J. Am. Chem. Soc. 1995, 117,
634. Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Nantermet, P. G.;
Claiborne, C. F.; Renaud, J.; Guy, R. K.; Shibayama, K.
J. Am. Chem. Soc. 1995, 117, 645. Nicolaou, K. C.; Ueno, H.;
Liu, J. J.; Nantermet, P. G.; Yang, Z.; Renaud, J.; Paulvannan,
K.; Chadha, R. J. Am. Chem. Soc. 1995, 117, 653. b) Holton,
R. A.; Somoza, C.; Kim, H. B.; Liang, F.; Biediger, R. J.;
Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S.;
a) TrisNHNH , THF, HCl conc. cat., 92%. b) 4 equiv n-BuLi, THF/
TMEDA 9:1, -78°C, 30 min, 0°C, 1 min, 4 equiv PhCHO, -78°C, 30
min, 65%. c) 2.1 equiv n-BuLi, THF, -78°C, 30 min, 0°C, 1 min, 4, -
2
7
8°C, 30 min.
Scheme 7
This problem was solved by using t-BuLi. After treatment
of 24 with 2.2 equivalents of t-BuLi and addition of alde-
hyde 4, the seco-taxane was obtained in 44% yield, after
hydrolysis of the silyl ether with TFA, as a 2:1 mixture of
diastereomers 27 and 28, but H NMR analysis and nOe
experiments showed clearly that the alkylation is totally
stereoselective and only one diastereomer was obtained
1
6
1
Nadizadeh, H.; Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang,
P.; Murthi, K. K.; Gentile, L. N.; Liu, J. H. J. Am. Chem. Soc.
1
7
for the diol moiety (Scheme 8).
1994, 116, 1597. Holton, R. A.; Kim, H. B.; Somoza, C.;
Liang, F.; Biediger, R. J.; Boatman, P. D.; Shindo, M.; Smith,
C. C.; Kim, S.; Nadizadeh, H.; Suzuki, Y.; Tao, C.; Vu, P.;
Tang, S.; Zhang, P.; Murthi, K. K.; Gentile, L. N.; Liu, J. H.
ibid. 1994, 116, 1599. c) Masters, J. J.; Link, J. T.; Snyder, L.
B.; Young, W. B.; Danishefsky, S. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1723. d) Wender, P. A.; Badham, N. F.;
Conway, S. P.; Floreancig, P. E.; Glass, T. E.; Gränicher, C.;
Houze, J. B.; Jänichen, J.; Lee, D.; Marquess, D. G.;
OBn
7
OBn
1
1
0 9
5
1
1
6
5
b)
8
3
1
2
24
1
2
1
3
14
4
HO
HO
OH
OH
McGrane, P. L.; Meng, W.; Mucciaro, T. P.; Mühlebach, M.;
Natchus, M. G.; Paulsen, H.; Rawlins, D. B.; Satkofsky, J.;
Shuker, A. J.; Sutton, J. C.; Taylor, R. E.; Tomooka, K. J. Am.
Chem. Soc. 1997, 119, 2755. Wender, P. A.; Badham, N. F.;
Conway, S. P.; Floreancig, P. E.; Glass, T. E.; Houze, J. B.;
Krauss, N. E.; Lee, D.; Marquess, D. G.; McGrane, P. L.;
Meng, W.; Natchus, M. G.; Shuker, A. J.; Sutton, J. C.;
Taylor, R. E. J. Am. Chem. Soc. 1997, 119, 2757.
2
7
2:1 ratio
28
a) i- 2.2 equiv t-BuLi, THF, -78°C, 30 min, 0°C, 1 min, 4, -78°C, 2
h, 44%; ii- TFA, CH Cl , 5 min, >95%.
2
2
Scheme 8
e) Mukaiyama, T.; Shiina, I.; Iwadare, H.; Saitoh, M.;
Nishimura, T.; Ohkawa, N.; Sakoh, H.; Nishimura, H.; Tani,
Synlett 1999, No. 10, 1555–1558 ISSN 0936-5214 © Thieme Stuttgart · New York

1
558
D. Bourgeois et. al.
LETTER
Y.-I.; Hasegawa, M.; Yamada, K.; Saito, K. Chem. Eur. J.
washed with water and brine, dried over MgSO and
4
1999, 5, 121. f) Morihara, K.; Hara, R.; Kawahara, S.;
concentrated in vacuo. The resulting crude product was
Nishimori, T.; Nakamura, N.; Kusama, H.; Kuwajima, I. J.
Am. Chem. Soc. 1998, 120, 12980.
5) See Ref. 1b); Nicolaou, K. C.; Dai, W.-M.; Guy, R. K. Angew.
diluted with 3 mL of CH Cl , treated with 10 drops of TFA
and stirred at 20°C for 5 min. The reaction mixture was then
concentrated in vacuo and the resulting crude product purified
2
2
(
Chem., Int. Ed. Engl. 1994, 33, 15. Boa, A. N.; Jenkins, P. R.;
Lawrence, N. J. Contemp. Org. Synth. 1994, 1, 47. Kingston,
D. G. I.; Molinero, A. A.; Rimoldi, J. M. Prog. Chem. Org.
Nat. Prod. 1993, 61, 1. Swindell, C. S. Stud. Nat. Prod. Chem.
by flash chromatography on silica gel (eluant Et O/EP 20:80)
to give 26 mg (30%) of 27 and 13 mg (14%) of 28 as colorless
oils, along with 17 mg (34%) of recovered aldehyde 4 and
2
10 mg (22%) of alkene 26.
1
1993, 12, 179. Paquette, L. A. Stud. Nat. Prod. Chem. 1992,
27: H NMR (CDCl , 400 MHz) d (ppm) 7.37-7.25 (m, 5H,
3
11, 3. Kingston, D. G. I. Pharmac. Ther. 1991, 52 , 1.
Ar), 6.20 (t, 1H, J = 3.8 Hz, H-4), 6.16 (brdd, 1H, J = 17.7,
11.2 Hz, H-10), 5.51 (dq, 1H, J = 12.2, 7.4 Hz, CH-9), 5.28
(dd, 1H, J = 11.1, 2.6 Hz, CH 10cis), 5.15 (dm, 1H,
Swindell, C. S. Org. Prep. Proced. Int. 1991, 23, 465.
(
(
6) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995,
2-
2
8, 446.
J = 12.2 Hz, H-9), 4.93 (dd, 1H, J = 17.6, 2.7 Hz,
7) A vinyltin-vinyltin palladium-catalyzed reaction could be
envisaged. For a significant example, see : Borzilleri, R. M.;
Weinreb, S. M.; Danilova, N. A.; Vel’der, Ya. L.; Spirikhin, L.
V. Synthesis 1989, 633.
CH 10trans), 4.64 (d, 1H, J = 12.0 Hz, O-CH Ar), 4.55 (d,
2-
2-
1H, J = 12.0 Hz, O-CH Ar), 4.27 (d, 1H, J = 5.6 Hz, H-2),
2-
3.56 (dd, 1H, J = 11.3, 3.4 Hz, H-7), 2.77 (s, 1H, HO-1),
2.24-2.17 (m, 4H, CH ), 2.03 (d, 1H, J = 5.8 Hz, HO-2),
2
(
(
8) Muller, B.; Delaloge, F.; den Hartog, M.; Férézou, J.-P.;
Pancrazi, A.; Prunet, J.; Lallemand, J.-Y. Tetrahedron Lett.
1.94-1.86 (m, 2H, CH ), 1.78 (dd, 3H, J = 7.5, 1.6 Hz,
2
CH CH-9), 1.69 (s, 3H, CH 12), 1.72-1.47 (m, 2H, CH ),
3
-
3-
2
13
1996, 37, 3313.
1.51, 1.21, 1.06 (3s, 9H, CH 8, CH 15); C NMR (CDCl3,
3- 3-
9) Chamberlin, A. R.; Bloom, S. H. Org. React. 1990, 39, 1.
Adlington, R. M.; Barrett, A. G. Acc. Chem. Res. 1983, 16, 55.
Chamberlain, A. R.; Stemke, J. E.; Bond, F. T. J. Org. Chem.
100.6 MHz) d (ppm) 147.1 (Ar), 139.0 (3), 137.2 (11), 137.1,
135.9 (9, 10), 127.9, 127.2, 127.1, 126.0, 125.1 (Ar, 4, CH-9),
127.3 (12), 118.7 (CH 10), 82.2 (7), 76.2 (1), 71.8 (2), 71.4
2-
1978, 43, 147. Shapiro, R. H.; Hornamoan, E. C. J. Org.
(O-CH Ar), 47.8 (8), 43.6 (15), 28.4, 27.6, 24.1, 22.5 (5, 6,
2-
Chem. 1974, 39, 2302.
13, 14), 25.4, 22.4, 21.2, 14.6 (CH 8, CH C-9, CH 12, 2
3-
3-
3-
(
(
10) Mori, H.; Tsuneda, K. Chem. Pharm. Bull. 1963, 11, 1413.
11) Barton, D. H. R.; O'Brien, R. E.; Sternhell, S. J. J. Chem. Soc.
CH 15).
3-
1
28: H NMR (CDCl , 400 MHz) d (ppm) 7.36-7.30 (m, 5H,
3
1962, 470.
Ar), 6.29 (dd, 1H, J = 5.4, 2.3 Hz, H-4), 6.18 (brdd, 1H,
J = 17.4, 11.0 Hz, H-10), 5.53 (dq, 1H, J = 11.7, 7.1 Hz,
CH-9), 5.46 (dm, 1H, J = 11.8 Hz, H-9), 5.28 (dd, 1H,
J = 11.1, 2.7 Hz, CH 10cis), 4.93 (dd, 1H, J = 17.6, 2.7 Hz,
(
12) Prepared from commercial 2-methylcyclohexane-1,3-dione
according to the procedure described by Dauben, W. G.; Hart,
D. J. J. Org. Chem. 1977, 42, 3787.
2
-
(
(
(
(
13) Brooks, D. W.; Mazdiyasni, H.; Grothaus, P. G. J. Org. Chem.
CH 10trans), 4.62 (d, 1H, J = 12.0 Hz, O-CH Ar), 4.53 (d,
1H, J = 12.0 Hz, O-CH Ar), 4.19 (d, 1H, J = 4.5 Hz, H-2),
2-
3.73 (dd, 1H, J = 11.7, 3.3 Hz, H-7), 2.90 (s, 1H, HO-1),
2
-
2
-
1
987, 52, 3223.
14) Collin, J.; Namy, J.-L.; Kagan, H. B. Nouv. J. Chim. 1986, 10,
29-232.
2
2.35-2.20 (m, 2H, CH ), 2.10 (dddd, 1H, J = 18.4, 11.1, 5.6,
2
15) Férézou, J.-P.; Julia, M.; Li, Y.; Liu, L. W.; Pancrazi, A. Bull.
Soc. Chim. Fr. 1995, 132, 428-452.
16) Typical procedure 9–>27: To a solution of 9 (100 mg,
2.5 Hz, CH ), 1.98 (d, 1H, J = 4.4 Hz, HO-2), 1.95-1.80 (m,
2
3H, CH ), 1.70 (s, 3H, CH 12), 1.67 (d, 3H, J = 6.8 Hz,
2
3-
CH CH-9), 1.65-1.50 (m, 2H, CH ), 1.22, 1.20, 1.10 (3s, 9H,
3
-
2
13
1
86 mmol) in 1.5 ml THF at -78°C was added dropwise over 3
CH 8, 2 CH 15); C NMR (CDCl , 100.6 MHz) d (ppm)
3- 3- 3
min 260 ml (470 mmol, 2.5 equiv) of a 1.7 M t-BuLi solution
in hexanes. The resulting red solution was stirred at -78°C for
145.6 (Ar), 138.9 (3), 138.0, 135.9 (9, 10), 137.2 (11), 128.0,
127.4, 127.1, 126.2, 125.9 (Ar, 4, CH-9), 127.5 (12), 118.8
(CH 10), 81.1 (7), 78.7 (1), 71.6 (O-CH Ar), 71.4 (2), 45.7
30 min, during which time it turned to dark red. Temperature
2-
2-
was then quickly raised to 0°C for 1 min, causing intense
bubbling and decoloration to light yellow, then set back down
to -78°C. A solution of aldehyde 4 (50 mg, 185 mmol) in
(8), 43.6 (15), 28.4, 27.6, 24.4, 23.6 (5, 6, 13, 14), 25.5, 22.3,
22.0, 21.1, 14.7 (CH 8, CH C-9, CH 12, CH 15).
(17) A detailed analysis of diastereoselective additions of C-ring
nucleophiles to A-ring aldehydes will be reported shortly.
3-
3-
3-
3-
0.5 ml THF was then added via cannula to the vinyl anion
solution prepared above, and the resulting mixture was stirred
at -78°C for 2 h. The reaction mixture was quenched at -78°C
by 2 ml of sat. aq. NaHCO and allowed to warm to room
Article Identifier:
3
temperature. The layers were separated, the aqueous layer was
extracted with ether, and the combined organic layers were
1437-2096,E;1999,0,10,1555,1558,ftx,en;G17799ST.pdf
Synlett 1999, No. 10, 1555–1558 ISSN 0936-5214 © Thieme Stuttgart · New York