A ruthenium-mediated asymmetric hydrogenation approach to the synthesis of discodermolide subunits

Article abstract of DOI:10.1055/s-0028-1087917

The C1-C7 and C9-C14 subunits of (+)-discodermolide have been synthesized using ruthenium-SYNPHOS-mediated asymmetric hydrogenation reactions of β-keto esters to set the C3, C5 and C11 hydroxy-bearing stereocenters with very high levels of diastereoselect

Full text of DOI:10.1055/s-0028-1087917

LETTER
573
A Ruthenium-Mediated Asymmetric Hydrogenation Approach to the
Synthesis of Discodermolide Subunits
Synthesis of
D
isc
h
odermolide
Subunitsistophe Roche, Rémi Le Roux, Mansour Haddad, Phannarath Phansavath,* Jean-Pierre Genêt*
Laboratoire de Synthèse Sélective Organique et Produits Naturels UMR 7573 CNRS, Ecole Nationale Supérieure de Chimie de Paris,
11 Rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Fax +33(1)44071062; E-mail: phannarath-phansavath@enscp.fr; E-mail: jean-pierre-genet@enscp.fr
Received 14 October 2008
Suzuki coupling
Stork–Wittig
Abstract: The C1–C7 and C9–C14 subunits of (+)-discodermolide
have been synthesized using ruthenium-SYNPHOS-mediated
asymmetric hydrogenation reactions of b-keto esters to set the C3,
C5 and C11 hydroxy-bearing stereocenters with very high levels of
diastereoselectivity.
24
Nozaki–Kishi
HO
8
21
15
7
O
O
OH
O
O
14
1
OH
NH2
Key words: asymmetric catalysis, hydrogenation, ruthenium, total
synthesis, natural products
OH
(+)-discodermolide
H2, [Ru*]
The polypropionate-derived marine metabolite discoder-
molide was first isolated by Gunasekera and co-workers1
in 1990 from the Caribbean deep-sea sponge Discodermia
dissoluta. Preliminary biological evaluations showed this
compound to possess potent immunosuppressive activi-
ty.2 It was later demonstrated that discodermolide exhibit-
ed excellent microtubule-stabilizing capabilities3 as well
as synergism with taxol.4 This promising biological pro-
file and the potential as chemotherapeutic agent5 have
prompted considerable synthetic efforts toward the total
synthesis of discodermolide.6
O
H
24
7
t-BuO
O
O
O
I
9
1
5
14
11
18
3
20
15
I
OP1 OP2
OTIPS
OTIPS
1
2
3
TIPSO
O
O
BnO
Ot-Bu
HO
OMe
As part of our ongoing projects involving the synthesis of
biologically relevant natural products via ruthenium-
promoted asymmetric hydrogenation,7 we were particu-
larly interested in the linear polypropionate backbone of
discodermolide, because the C2–C4, C10–C12, and C18–
C20 motifs appeared ideally suited for construction
through hydrogenation reactions. From a retrosynthetic
point of view, all of the reported total syntheses discon-
nect discodermolide into three major fragments of equal
complexity, each subunit possessing a syn,anti methyl–
hydroxy–methyl stereotriad. On this basis, we chose to
disconnect discodermolide into compounds 1, 2, and 3,
corresponding to C1–C7,8 C9–C14 and C15–C24 frag-
ments of the natural product, as depicted in Scheme 1.
Formation of the C14–C15 bond would result from a Su-
zuki coupling reaction between (Z)-alkenyl iodide 2 and
compound 3. The C7–C8 bond would be created by a
Nozaki–Kishi reaction between aldehyde 1 and a (Z)-
vinyl iodide derived from an ester at C9.
H2, [Ru*]
common precursor 4
Roche ester 5
Scheme 1 Retrosynthetic analysis for (+)-discodermolide
which in turn would be derived from methyl (S)-3-
hydroxy-2-methylpropionate (Roche ester) 5. Among the
seven stereocenters of the target subunits, three would
be created via ruthenium-mediated asymmetric hydro-
genation9 of b-keto esters using the atropisomeric ligand
SYNPHOS10 as the chiral diphosphine.
The common precursor 4 was readily prepared in five
steps starting from commercially available Roche ester 5.
After protection of the hydroxy function as a benzyl ether,
subsequent chain extension with lithio tert-butyl acetate11
delivered the b-keto ester 6 required for the asymmetric
hydrogenation reaction (Scheme 2).
The stereoselective reduction of the ketone function was
accomplished using 2 mol% of the chiral complex
{Ru[(R)-SYNPHOS]Br2} prepared in situ from commer-
cially available [Ru(cod)(2-methylallyl)2]12 and afforded
b-hydroxy ester 7 in high yield and with excellent diaste-
reoselectivity (99% de, as determined by HPLC analysis).
Subsequent diastereoselective methylation of 7 using the
Fráter–Seebach conditions13 (>95% de, only one diastereo-
Herein we report the preparation of key discodermolide
intermediates 1 and 2. In our retrosynthetic plan, both
fragments would be prepared from a common precursor 4
SYNLETT 2009, No. 4, pp 0573–0576
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.02.2009
DOI: 10.1055/s-0028-1087917; Art ID: G30708ST
© Georg Thieme Verlag Stuttgart · New York
1
mer detected by H NMR) followed by protection of the

574
C. Roche et al.
LETTER
Miyashita.20 Thus, treatment of 10 with an excess amount
of Me2CuLi (4.5 equiv) generated stereoselectively a (Z)-
vinyl copper species which was trapped with iodine to af-
ford 2 in 72% yield along with 14% of the E-isomer. It
should be noted that this particular reaction required ex-
tensive investigation of the experimental parameters be-
fore achieving a satisfactory result. Indeed, variations in
reaction time, temperature, or Me2CuLi amount resulted
invariably in lower yields of 2. Not only lower conver-
sions were usually observed but the corresponding 1,1-
dimethylalkene as well as the (Z)-alkenyl bromide were
also formed in addition to the (E)-alkenyl iodide. Starting
from the common precursor 4, the C9–C14 (2) subunit of
discodermolide was thereby generated in four steps in
40% overall yield.
O
O
O
a, b
c
HO
OMe
BnO
d, e
Ot-Bu
5
6
OH
O
TIPSO
O
BnO
Ot-Bu
BnO
Ot-Bu
7
4
Scheme 2 Synthesis of the common precursor (4). Reagents and
conditions: (a) BnOC(=NH)CCl3, TfOH, CH2Cl2, r.t., 3.5 h, 85%; (b)
LDA, t-BuOAc, THF, –40 °C, 3 h, 80%; (c) H2 (75 bar), 2 mol%
{Ru[(R)-SYNPHOS]Br2}, t-BuOH–MeOH (4:1), 50 °C, 24 h, 96%,
99% de; (d) LDA, THF, –40 °C to 0 °C, 1 h; then HMPA, MeI, THF,
–10 °C to r.t., 3 h, 73%, 95% de; (e) TIPSOTf, 2,6-lutidine, CH2Cl2,
–30 to –15 °C, 4 h, quant.
Preparation of the C1–C7 subunit (1) began with a four-
step sequence from 4 to afford the b-keto ester 12 required
for the diastereoselective hydrogenation reaction to install
the C5 hydroxy-bearing stereocenter (Scheme 4).
hydroxy function then furnished the common precursor 4
which was thereby obtained in 48% overall yield from 5.
With compound 4 in hand, we could address the prepara-
tion of the C1–C7 (1) and C9–C14 (2) fragments of disco-
dermolide. Thus, compound 2 was obtained in three steps
from 4 after deprotection of the primary hydroxy function,
followed by oxidation to the aldehyde and (Z)-alkenyl
iodide introduction under Zhao conditions14 (Scheme 3).
TIPSO
O
TIPSO
O
a, b
BnO
Ot-Bu
BnO
H
4
11
TIPSO
O
O
c, d
e
BnO
Ot-Bu
TIPSO
O
TIPSO
O
a
BnO
Ot-Bu
HO
Ot-Bu
12
TIPS MOM
O
4
8
TIPSO
OH
O
O
OAc
f–h
TIPSO
O
TIPSO
O
BnO
Ot-Bu
BnO
b
c
Ot-Bu
Ot-Bu
O
13
14
I
9
2
TIPS
O
TIPS
MOM
MOM
TIPSO
O
l
O
O
O
O
O
OAc
OH
i–k
e
d
Br
Ot-Bu
MeO
MeO
Br
10
15
16
Scheme 3 Synthesis of the C9–C14 (2) subunit of discodermolide.
Reagents and conditions: (a) H2 (1 atm), Pd/C (5%), THF, r.t., 105
min, 79%; (b) Dess–Martin periodinane, CH2Cl2, 0 °C to r.t., 4 h,
83%; (c) Ph3PEtI, n-BuLi, THF, I2, –78 °C to –20 °C, 20 min; then
NaHMDS, THF, 2 min; then 9, THF, –78 °C to r.t., 4.5 h, 12%; (d)
CBr4, PPh3, Et3N, CH2Cl2, r.t., 30 min, 84%; (e) MeLi, CuI, Et2O,
0 °C then r.t., 30 min, then 10, Et2O, –90 to –70 °C, 1 h, then I2, THF,
r.t., 45 min, 72%.
O
O
m
O
n
O
TIPSO
OH
TIPSO
O
17
1
Scheme 4 Synthesis of the C1–C7 (1) subunit of discodermolide.
Reagents and conditions: (a) DBAL-H, toluene, –78 °C to –60 °C, 2
h, 78%; (b) Dess–Martin periodinane, CH2Cl2, 0 °C to r.t., 3.5 h, 95%;
This Zhao olefination reaction has been employed by
Smith,15 Marshall,16 and the Novartis group17 on related (c) LDA, t-BuOAc, THF, –78 °C, 15 min, 99%; (d) Dess–Martin per-
iodinane, CH2Cl2, 0 °C to r.t., 1.5 h, quant.; (e) H2 (80 bar), 4 mol%
[{RuCl[(R)-SYNPHOS]}(m-Cl)3][Me2NH2], MeOH, r.t., 22 h, 94%,
99% de; (f) MOMCl, DIPEA, CH2Cl2, 0 °C to r.t., 22 h, 82%; (g)
LiAlH4, Et2O, r.t., 3.5 h, 97%; (h) Ac2O, DMAP, pyridine, CH2Cl2,
r.t., 30 min, 99%; (i) H2 (1 atm), Pd/C (5%), THF, r.t., 25 min, quant.;
substrates in their syntheses of discodermolide, delivering
the corresponding (Z)-vinyl iodides in modest yields. In
our hands, however, the reaction proved even more trou-
blesome and provided 218 in only 12% yield. To circum-
vent this restrictive step, aldehyde 9 was converted into
dibromoolefin 1019 in order to install the critical (Z)-alke-
nyl iodide using the procedure reported by Tanino and
(j) NaIO4, RuCl3, MeCN–CCl4–H2O, r.t., 2 h; (k) MeI, K2CO3, DMF,
r.t., overnight, 76% (2 steps); (l) K2CO3, MeOH, r.t., 30 min, 84%;
(m) PPTS, t-BuOH, 80 °C, overnight, 58%; (n) Dess–Martin periodi-
nane, CH2Cl2, 0 °C to r.t., 6 h, 69%.
Synlett 2009, No. 4, 573–576 © Thieme Stuttgart · New York

LETTER
Synthesis of Discodermolide Subunits
575
First, conversion of 4 into aldehyde 11 was performed us-
ing a hydride reduction–Dess–Martin oxidation sequence.
Addition of lithio tert-butyl acetate to 11 afforded the cor-
responding b-hydroxy ester as a mixture of diastereomers
(7:3 in favor of the undesired Felkin syn-product) which
was directly subjected to Dess–Martin oxidation, leading
to compound 12 in quantitative yield. The following hydro-
genation reaction was initially performed in methanol at
80 °C under 80 bar of hydrogen, using 2 mol% of the
chiral complex {Ru[(R)-SYNPHOS]Br2}. However, un-
der these conditions, the expected b-hydroxy ester 13 was
obtained in only 52% yield along with recovered starting
material as well as some transesterified hydrogenated
product. Variation of the reaction conditions (tempera-
ture, hydrogen pressure, reaction time, solvent, and/or cat-
alyst loading) did not allow any improvement. As the use
of {Ru[(R)-SYNPHOS]Br2} in the hydrogenation reac-
tion failed to afford reasonable yields of 13, we tried an
Ikariya-type complex21 bearing (R)-SYNPHOS as a
ligand.22 The reaction was conducted in methanol at room
temperature under 80 bar of hydrogen using 1 mol% of
the complex [{RuCl[(R)-SYNPHOS]}(m-Cl)3][Me2NH2].
Under these conditions, the corresponding b-hydroxy
ester was obtained in 68% yield with no transesterification
product observed. Finally, using 4 mol% of the ruthenium
complex under the otherwise aforementioned conditions,
the hydrogenation reaction proceeded in a satisfactory
94% yield and with a high level of diastereoselectivity
(99% de, as determined by HPLC analysis). Having com-
pound 13 in hand, a few functional transformation steps
remained in order to obtain aldehyde 1. Thus, after MOM
protection, the ester function was reduced to the corre-
sponding alcohol which was acylated to furnish com-
pound 14. The benzyl ether was then converted into ester
15 by deprotection of the primary alcohol, RuCl3/NaIO4
oxidation and methylation of the resulting carboxylic
acid. After hydrolysis of the acetate function, access to
compound 1 required a lactonization step. To this end, 16
was treated with a catalytic amount of PPTS in refluxing
tert-butanol, which resulted in cleavage of the MOM ether
and subsequent lactonization at the C5 position. Finally,
Dess–Martin oxidation of 17 completed the synthesis of
the C1–C7 fragment (1)23 of discodermolide which was
thereby prepared in 14 steps from 4 in 14% overall yield.
References and Notes
(1) (a) Gunasekera, S. P.; Gunasekera, M.; Longley, R. E.;
Schulte, G. K. J. Org. Chem. 1990, 55, 4912; correction:
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G. K.; Longley, R. E.; Isbruker, R. A.; Pomponi, S. A. J. Nat.
Prod. 2002, 65, 1643.
(2) (a) Longley, R. E.; Caddigan, D.; Harmony, D.; Gunasekera,
M.; Gunasekera, S. P. Transplantation 1991, 52, 650.
(b) Longley, R. E.; Caddigan, D.; Harmony, D.; Gunasekera,
M.; Gunasekera, S. P. Transplantation 1991, 52, 656.
(3) (a) Hung, D. T.; Chen, J.; Schreiber, S. L. Chem. Biol. 1996,
3, 287. (b) ter Haar, E.; Kowalski, R. J.; Hamel, E.; Lin,
C. M.; Longley, R. E.; Gunasekera, S. P.; Rosenkranz, H. S.;
Day, B. W. Biochemistry 1996, 35, 243. (c) Klein, L. E.;
Freeze, B. S.; Smith, A. B. III.; Horwitz, S. B. Cell Cycle
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A. B. III.; Goldberg, G. L.; Horwitz, S. B.; McDaid, H. M.
Clin. Cancer Res. 2006, 12, 298. (b) Honore, S.; Kamath,
K.; Braguer, D.; Horwitz, S. B.; Wilson, L.; Briand, C.;
Jordan, M. A. Cancer Res. 2004, 64, 4957. (c) Martello,
L. A.; McDaid, H. M.; Regl, D. L.; Yang, C.-P. H.; Meng,
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Cancer Res. 2000, 6, 1978. (d) Kowalsky, R. J.;
Giannakakou, P.; Gunasekera, S. P.; Longley, R. E.; Day,
B. W.; Hamel, E. Mol. Pharmacol. 1997, 52, 613.
(5) Smith, A. B. III.; Freeze, B. S.; LaMarche, M. J.; Sager, J.;
Kinzler, K. W.; Vogelstein, B. Bioorg. Med. Chem. Lett.
2005, 15, 3623.
(6) (a) For a review of the total syntheses prior to 2003:
Paterson, I.; Florence, G. J. Eur. J. Org. Chem. 2003, 2193.
(b) For a recent review on syntheses, construction and
biological evaluation of analogues: Smith, A. B. III.; Freeze,
B. S. Tetrahedron 2008, 64, 261. (c) For a recent review on
total syntheses of discodermolide and dictyostatin: Florence,
G. J.; Gardner, N. M.; Paterson, I. Nat. Prod. Rep. 2008, 25,
342. (d) For references to synthetic approaches to
discodermolide, see ref. 6b.
(7) (a) Labeeuw, O.; Blanc, D.; Phansavath, P.;
Ratovelomanana-Vidal, V.; Genet, J.-P. Eur. J. Org. Chem.
2004, 2352. (b) Le Roux, R.; Desroy, N.; Phansavath, P.;
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3911.
(8) Synthetic approaches to discodermolide involving C1–C7
lactone subunit: (a) Miyazawa, M.; Oonuma, S.; Maruyama,
K.; Miyashita, M. Chem. Lett. 1997, 26, 1191. (b) Misske,
A. M.; Hoffman, H. M. R. Tetrahedron 1999, 55, 4315.
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Sankar, A. R.; Kunwar, A. C. Tetrahedron Lett. 2001, 42,
4713. (d) Day, B. W.; Kangani, C. O.; Avor, K. S.
Tetrahedron: Asymmetry 2002, 13, 1161.
(9) For reviews on Ru-catalyzed asymmetric hydrogenation,
see: (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH:
New York, 2000, 1. (b) Noyori, R. Angew. Chem. Int. Ed.
2002, 41, 2008. (c) Kitamura, M.; Noyori, R. In Ruthenium
in Organic Synthesis; Murahashi, S.-i., Ed.; Wiley-VCH:
Weinheim, 2004, 3. (d) Genet, J.-P. Acc. Chem. Res. 2003,
36, 908.
In conclusion, discodermolide subunits 1 and 2 have been
efficiently prepared from a common precursor 4, possess-
ing a syn,anti methyl–hydroxy–methyl stereotriad. The
C3, C5, and C11 hydroxy-bearing stereocenters have been
set through ruthenium-promoted asymmetric hydrogena-
tion reactions using SYNPHOS as a ligand. This route
provides good yields and high levels of diastereoselectiv-
ity. Efforts are currently under way to complete the C15–
C24 subunit of discodermolide as well.
(10) (a) Duprat de Paule, S.; Champion, N.; Ratovelomanana-
Vidal, V.; Genet, J.-P.; Dellis, P. . (b) Duprat de Paule, S.;
Jeulin, S.; Ratovelomanana-Vidal, V.; Genet, J.-P.;
Champion, N.; Dellis, P. Tetrahedron Lett. 2003, 44, 823.
(c) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal,
V.; Genet, J.-P.; Champion, N.; Dellis, P. Eur. J. Org. Chem.
Acknowledgment
R.L.R. and C.R. are grateful to the Ministère de l’Education Natio-
nale et de la Recherche for a grant (2004-2006 and 2006-2008,
respectively).
Synlett 2009, No. 4, 573–576 © Thieme Stuttgart · New York

576
C. Roche et al.
LETTER
2003, 1931. (d) Duprat de Paule, S.; Jeulin, S.;
Ratovelomanana-Vidal, V.; Genet, J.-P.; Champion, N.;
Deschaux, G.; Dellis, P. Org. Process Res. Dev. 2003, 7,
399.
3 H). 13C NMR (75 MHz, CDCl3): d = 173.0, 137.6, 100.3,
80.2, 75.7, 47.1, 45.3, 33.7, 28.1, 18.3, 16.1, 13.1, 10.9.
IR (film): 1732, 1640, 1257, 883 cm–1. MS (DCI/NH3):
m/z = 551 [M + H]+, 472 [M + NH4t-Bu]+.
(11) (a) Rathke, M. W.; Lindert, A. J. Am. Chem. Soc. 1971, 93,
2318. (b) Wolberg, M.; Ji, A.; Hummel, W.; Müller, M.
Synthesis 2001, 937.
(12) Genet, J.-P.; Pinel, C.; Ratovelomanana-Vidal, V.; Mallart,
S.; Cano de Andrade, M. C.; Laffitte, J. A. Tetrahedron:
Asymmetry 1994, 5, 665.
(13) (a) Fráter, G. Helv. Chim. Acta 1979, 62, 2825.
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197.
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2827.
(15) (a) Smith, A. B. III.; Beauchamp, T. J.; LaMarche, M. J.;
Kaufman, M. D.; Qiu, Y. P.; Arimoto, H.; Jones, D. R.;
Kobayashi, K. J. Am. Chem. Soc. 2000, 122, 8654. (b) For
an investigation of the mechanism of this transformation,
see: Harimoto, H.; Kaufman, M. D.; Kobayashi, K.; Qiu, Y.;
Smith, A. B. III. Synlett 1998, 765.
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Schaer, K.; Gamboni, R.; Bach, A.; Chaudhary, A.; Chen, S.;
Chen, W.; Hu, B.; Jagoe, C. T.; Kim, H.-Y.; Kinder, F. R.;
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L. Org. Process Res. Dev. 2004, 8, 101.
(19) Spectroscopic Data for Compound 10
[a]D25 +5.5 (c 1.05, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 6.23 (d, J = 9.8 Hz, 1 H), 4.28 (dd, J = 6.8, 4.1 Hz, 1 H),
2.52–2.67 (m, 2 H), 1.47 (s, 9 H), 1.13 (d, J = 7.2 Hz, 3 H),
1.10 (s, 18 H), 1.04–1.13 (s, 3 H), 1.07 (d, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.7, 140.8, 88.8, 80.7,
75.1, 46.9, 42.0, 28.2, 18.2, 15.5, 13.1, 9.4. IR (film): 1733,
1460, 1255, 882 cm–1. MS (DCI/NH3): m/z = 529 [M + H]+.
Anal. Calcd for C21H40Br2O3Si: C, 47.73; H, 7.63. Found: C,
47.81; H, 7.51.
(20) Tanino, K.; Arakawa, K.; Satoh, M.; Iwata, Y.; Miyashita,
M. Tetrahedron Lett. 2006, 47, 861.
(21) (a) Ikariya, T.; Ishii, Y.; Kawano, H.; Arai, T.; Saburi, M.;
Yoshikawa, S.; Akutagawa, S. J. Chem. Soc., Chem.
Commun. 1985, 922. (b) Ohta, T.; Tonomura, Y.; Nozaki,
K.; Takaya, H.; Mashima, K. Organometallics 1996, 15,
1521. (c) Mashima, K.; Nakamura, T.; Matsuo, Y.; Tani, K.
J. Organomet. Chem. 2000, 607, 51.
(22) Jeulin, S.; Champion, N.; Dellis, P.; Ratovelomanana-Vidal,
V.; Genet, J.-P. Synthesis 2005, 3666.
(23) Spectroscopic Data for Compound 1
[a]D25 –2.5 (c 0.8, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 9.85 (dd, J = 2.5, 1.3 Hz, 1 H), 4.91 (ddd, J = 10.5, 7.4,
4.0 Hz, 1 H), 3.87 (t, J = 2.3 Hz, 1 H), 2.80 (td, J = 7.5, 2.3
Hz, 1 H), 2.78 (td, J = 16.7, 4.0, 1.3 Hz, 1 H), 2.68 (ddd,
J = 16.7, 7.4, 2.5 Hz, 1 H), 2.04–2.15 (m, 1 H), 1.28 (d,
J = 7.5 Hz, 3 H), 0.98–1.10 (m, 24 H). 13C NMR (75 MHz,
CDCl3): d = 199.5, 173.1, 76.3, 75.0, 46.5, 44.4, 33.6, 18.1,
16.7, 13.9, 12.7. IR (film): 2731, 1735, 1223, 883 cm–1.
MS (DCI/NH3): m/z = 360 [M + NH4]+, 343 [M + H]+.
(18) Spectroscopic Data for Compound 2
[a]D25 +3.6 (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3):
d = 5.22 (dq, J = 9.1, 1.1 Hz, 1 H), 4.32 (dd, J = 7.0, 4.1 Hz,
1 H), 2.64 (qd, J = 7.1, 4.1 Hz, 1 H), 2.43–2.50 (m, 1 H), 2.42
(d, J = 1.1 Hz, 3 H), 1.45 (s, 9 H), 1.19 (d, J = 7.1 Hz, 3 H),
1.10 (br s, 18 H), 0.98–1.15 (m, 3 H), 1.01 (d, J = 7.0 Hz,
Synlett 2009, No. 4, 573–576 © Thieme Stuttgart · New York

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