Synthesis of vinyllactones via allylic oxidation of alkenoic acids

Article abstract of DOI:10.1055/s-0031-1289549

A one-step access to vinyllactones is described utilizing the Pd-catalyzed allylic oxidation of alkenoic acids. The influence of ring size as well as the olefin configuration is investigated culminating in the synthesis of goniothalamin analogues. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289549

LETTER
2689
Synthesis of Vinyllactones via Allylic Oxidation of Alkenoic Acids
Vinyllactones via
Allya
rn
tina Bischop, Jörg Pietruszka*
Institut für Bioorganische Chemie der Heinrich-Heine-Universität Düsseldorf im Forschungszentrum Jülich,
Stetternicher Forst, Geb. 15.8, 52426 Jülich, Germany
Fax +49(2461)616196; E-mail: j.pietruszka@fz-juelich.de
Received 19 August 2011
medium-sized rings can be readily rationalized by the
proposed3c intermediate 8 (Scheme 3): ring strain will dis-
favor the formation of compound 8 for n = 2–5. However,
the observation would also imply that additional substitu-
ents at the w-position of heptenoic acid 95 should probably
slow down the lactonization, but nevertheless give d-lac-
tones 10, only. While an acid with two substituents (9a:
R1 = R2 = Me) was expected to be a difficult substrate, we
were surprised to find that E-configured acid 9b did not
react, but all Z-substrates 9c–e resulted in the formation of
the expected lactones 10c–e albeit in poor yield (27–
43%). Since the actual coordination sphere on the palladi-
um intermediates is not completely understood in the
present transformation, the stereochemical rationalization
is still under investigation.
Abstract: A one-step access to vinyllactones is described utilizing
the Pd-catalyzed allylic oxidation of alkenoic acids. The influence
of ring size as well as the olefin configuration is investigated culmi-
nating in the synthesis of goniothalamin analogues.
Key words: allyl complexes, catalysis, lactones, oxidation, palladi-
um
Vinyllactone 1 has regularly attracted considerable inter-
est of organic chemists, both as a key intermediate in syn-
thesis as well as a model compound proving the efficiency
of developed synthetic methodology.1 While enantio-
selective access is arguably most efficiently achieved via
a chemoenzymatic approach,1d obviously the shortest
route is the one-step Pd-catalyzed allylic C–H activation
of alkenoic acids or esters 2 directly leading to the title
compound 1 (Scheme 1). Elegant oxidative cyclization
processes have been reported to yield five- and six-mem-
bered lactones,1e,f albeit long reaction times (5–7 d) and
byproducts preventing the isolation of pure product 1 need
to be considered when utilizing acid 2.1f Tailor-made con-
ditions for the synthesis of macrolactones have more re-
cently been established by the White group.2 In view of
our ongoing efforts towards the syntheses of lactone-
containing natural products,3 we intended to investigate
the scope of this alternative catalytic system.
A drawback of the standard conditions is obviously the
prolonged reaction time. Microwave-assisted conversions
are a common alternative for accelerating reactions.6 A
O
Pd(OAc)2⋅3 (10 mol%),
benzoquinone (1 equiv), EtOAc
O
CO2H
4 Å MS, r.t., 4 d
2
1 (79%)
O
O
O
O
O
O
n
O
Pd-catalyzed
H
4 (96%)
5 (n = 2–5: no product)
6 (82%)
C–H activation
O
CO2H
CO2H
Ph
S
S
Ph
1
2
O
O
3
7
Scheme 1 One-step retrosynthesis of vinyllactone 1
Scheme 2 Synthesis of vinyllactones from w-alkenoic acids
We were pleased to find that, upon applying the White
conditions utilizing catalyst 3 (albeit at room tempera-
ture), on heptenoic acid (2), formation of lactone 1 was
immediately possible in good yield (79%, Scheme 2) not
observing any difficulties during purification. While the
corresponding butyrolactone 4 could also be readily syn-
thesized (96%), medium-ring lactones 5 could not be iso-
lated. Additional substituents did not hamper the reaction:
lactone 6 (from the known4 acid 7) was formed in 82%
yield. The difficulties observed for the transformation to
O
R2
Pd(OAc)2⋅3 (10 mol%),
benzoquinone (2 equiv)
R2
O
CO2H
R1
EtOAc, 4 Å MS,
r.t., 4 d
R1
9
10
R1
Me
Me
H
H
H
R2
Me
H
Me
Et
i-Pr
Entry
a
b
c
d
e
Yield
–
–
33%
27%
43%
O
Pd O
n = 0, 1: favored
n = 2–5: disfavored
n
SYNLETT 2011, No. 18, pp 2689–2692
x
x
.x
x
.2
0
1
1
8
Advanced online publication: 19.10.2011
DOI: 10.1055/s-0031-1289549; Art ID: D26711ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 3 Synthesis of substituted vinyllactones 10

2690
M. Bischop, J. Pietruszka
LETTER
O
brief survey of different solvents (ethylene glycol, 2-
PrOH, EtOH, DMSO, CH2Cl2, DCE, EtOAc) indicated
that lactone formation was best achieved in EtOAc. Side-
product formation was observed at temperatures above
80 °C (at 150 W), and best results were obtained at 40 °C.
A yield of 77% of lactone 1 was isolated after 135 minutes
representing a dramatic decrease in reaction time. Unfor-
tunately, the conditions do not generally give better re-
sults as can been seen for butyrolactone 4 (62%,
Scheme 4).
O
O
a) n-BuLi (1.2 equiv), THF,
–78 °C, 30 min
O
NH
O
N
b) 2 (1.2 equiv), Et3N,
PivCl (1.3 equiv),
0 °C to r.t., 2 h
18 (91%)
17
1. NaHMDS (1.2 equiv), 19 (1.5 equiv),
THF, –78 °C, 30 min (65%)
2. Mg(OMe)2, MeOH, 0 °C, 1 h (78%)
O
N
CO2Me
O2SPh
Ph
19
OH
O
Pd(OAc)2⋅3 (10 mol%),
20
benzoquinone (1 equiv), EtOAc
1. Cl3CC(=NH)OPMB (2 equiv), CSA (0.1 equiv),
CH2Cl2, r.t., 12 h (76%)
2. 20% NaOH, MeOH, reflux, 2 h (98%)
O
2
MW: 40 °C, 150 W, 135 min
1 (77%)
O
Pd(OAc)2⋅3 (10 mol%),
benzoquinone (1 equiv)
OPMB
Scheme 4 Microwave-assisted synthesis of lactones 1 and 4
CO2H
OPMB
O
EtOAc, 4 Å MS,
r.t., 4 d
22
(18%; syn/anti 39:61)
21
Next, we investigated stereoselective approaches, but all
attempts to apply enantioselective, catalytic variants7
failed. Furthermore, we noted that, while kinetic enzymat-
ic resolutions worked in principal, the overall efficiency
was low since the background (unselective) hydrolysis
was too high. Hence we focused on diastereoselectivity:
Starting from the known8 b-hydroxy ester 11, acid 12 was
readily available (85%, Scheme 5). However, allylic oxi-
dation to furnish lactone 13 failed. When introducing a p-
methoxybenzyl (PMB) protecting group9 first (yield of
ether 14: 77%), the liberated acid 15 (66%) was shown to
be a suitable substrate furnishing the separable d-lactone
16 in reasonable yield (50%, syn/anti = 40:60).10
Scheme 6 Induced diastereoselectivity of lactonization
1. a) NaHMDS (1.3 equiv),
THF, –78 °C, 1 h
b) MeI (2.6 equiv), THF, –78 °C (83%)
CO2H
18
2. 30% H2O2, LiOH (2.1 equiv),
THF–H2O, 0 °C, 3 h (87%)
23
Pd(OAc)2⋅3 (10 mol%),
benzoquinone (1 equiv), EtOAc,
4 Å MS, r.t., 4 d
N
N
O
Mes
Mes
Cl
Ru
O
20% NaOH,
MeOH, reflux, 3 h
Cl
OH
OH
CO2H
CO2Me
O
24
(78%; syn/anti 36:64)
i-Pr
11
12 (85%)
25
Cl3CC(=NH)OPMB (2 equiv),
CSA (0.1 equiv), CH2Cl2,
r.t., 12 h
Pd(OAc)2⋅3 (10 mol%),
styrene (7.5 equiv), 25 (5 mol%),
CH2Cl2, 40 °C, 36 h (55%)
benzoquinone (1 equiv), EtOAc,
4 Å MS, r.t., 4 d
OPMB
O
O
O
O
CO2Me
O
O
14 (77%)
+
OH
Ph
Ph
13
20% NaOH,
MeOH, reflux, 2 h
25a
25b
O
O
OPMB
Pd(OAc)2⋅3 (10 mol%),
benzoquinone (1 equiv)
i-Pr2NH (1.2 equiv), n-BuLi
(1.1 equiv), PhS(=Nt-Bu)Cl
(1.2 equiv), –78 °C, 1.5 h
O
CO2H
O
EtOAc, 4 Å MS,
r.t., 4 d
OPMB
16
(50%; syn/anti 40:60)
Ph
O
O
15 (66%)
(S)-goniothalamin (27)
O
O
Scheme 5 Simple diastereoselectivity of lactonization
Ph
Ph
26 (46%)
ent-26 (69%)
However, the diastereoselectivity was low with the sub-
stituent in b-position, and hence we next investigated a-
substituted acids.
Scheme 7 Synthesis of goniothalamin analogues 26
Following a procedure of Guerlavais et al.,11 Evans auxil-
iary 17 was acylated yielding amide 18 (91%, Scheme 6);
selective oxidation with oxaziridine 19 and solvolysis
yielded a-hydroxy ester 20.12 Protection9 and
Synlett 2011, No. 18, 2689–2692 © Thieme Stuttgart · New York

LETTER
Vinyllactones via Allylic Oxidation
2006, 128, 9032.
2691
saponification4 led to the desired acid 21. Allylic oxida-
tion provided the separable lactones 22 in low yield and
selectivity (18%, syn/anti = 39:61). Omitting protecting
groups that can be cleaved under oxidative conditions, we
finally focused on the methyl-substituted acid 23 that was
conveniently synthesized from amide 18 (Scheme 7).11,13
Oxidative cyclization was straightforward (78%); howev-
er, the diastereomers were not separable at this stage (syn/
anti = 36:64). Nevertheless, after successful cross met-
athesis,14 the lactones 25a and 25b were readily isolated
(55%). Introduction of the Michael system was achieved
utilizing the protocol by Matsuo and Aizawa.15 The go-
niothalamin analogues 26 and ent-26 were obtained, and
the assignment of configuration of the stereogenic center
formed during allylic oxidation was further confirmed by
comparison of the specific rotation with goniothalamin
(27): while both S-enantiomers do have a negative value
[(S)-27: –170 (c 1.7, CHCl3); (S)-26: –153 (c 1.5,
CHCl3)], the R-enantiomers show positive values.16,17 It is
interesting to note that a number of structural features
have been included in structure–activity relationship stud-
ies,18 but additional substituents at the Michael system are
still elusive in such investigations. On the basis of the
present findings, the gap should be closed in due course.
(3) (a) Korpak, M.; Pietruszka, J. Adv. Synth. Catal. 2011, 353,
1420. (b) Bischop, M.; Doum, V.; Nordschild née Rieche,
A. C. M.; Pietruszka, J.; Sandkuhl, D. Synthesis 2010, 527.
(c) Pietruszka, J.; Rieche, A. C. M. Adv. Synth. Catal. 2008,
350, 1407. (d) Pietruszka, J.; Rieche, A. C. M.; Schöne, N.
Synlett 2007, 2525. (e) Pietruszka, J.; Wilhelm, T. Synlett
2003, 1698.
(4) Walborsky, H. M.; Topolski, M.; Hamdouchi, C.;
Pankowski, J. J. Org. Chem. 1992, 57, 6188.
(5) (a) For compound 9a, see: DeMartino, M. P.; Chen, K.;
Baran, P. S. J. Am. Chem. Soc. 2008, 130, 11546. (b) For
compounds 9b–e, see: Kaga, H.; Miura, M.; Orito, K. J. Org.
Chem. 1989, 54, 3477.
(6) For a recent review, see: Caddick, S.; Fitzmaurice, R.
Tetrahedron 2009, 65, 3325.
(7) Covell Dustin, J.; White, M. C. Angew. Chem. Int. Ed. 2008,
47, 6448.
(8) Hiebel, M.-A.; Pelotier, B.; Goekjian, P.; Piva, O. Eur. J.
Org. Chem. 2008, 713.
(9) Wang, Y.-G.; Kobayashi, Y. Org. Lett. 2002, 4, 4615.
(10) The syn isomer was recently utilized for the synthesis of the
lyngbouillodide macrolactone core: Webb, D.; van den
Heuvel, A.; Koegl, M.; Ley, S. V. Synlett 2009, 2320.
(11) Guerlavais, V.; Carroll, P. J.; Joullié, M. M. Tetrahedron:
Asymmetry 2002, 13, 675.
(12) (a) Fürstner, A.; Radkowski, K.; Wirtz, C.; Goddard, R.;
Lehmann, C. W.; Mynott, R. J. Am. Chem. Soc. 2002, 124,
7061. (b) Evans, D. A.; Weber, A. E. J. Am. Chem. Soc.
1987, 109, 7151. (c) Macritchie, J. A.; Silcock, A.; Willis,
C. L. Tetrahedron: Asymmetry 1997, 8, 3895.
(13) Nagai, K.; Doi, T.; Sekiguchi, T.; Namatame, I.; Sunazuka,
T.; Tomoda, H.; Omura, S.; Takahashi, T. J. Comb. Chem.
2005, 8, 103.
(14) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hovedya,
A. H. J. Am. Chem. Soc. 2000, 122, 8168. (b) Gessler, S.;
Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41, 9973.
(15) Matsuo, J.-i.; Aizawa, Y. Tetrahedron Lett. 2005, 46, 407.
(16) (a) Hlubucek, J. R.; Robertson, A. V. Aust. J. Chem. 1967,
20, 2199. (b) Bose, D. S.; Reddy, A. V. N.; Srikanth, B.
Synthesis 2008, 2323.
In summary, the present work demonstrates the scope of
the White catalyst for the synthesis of g- and d-lactones.
Substituent effects were investigated and culminated in
the first synthesis of new goniothalamin analogues 26 that
also allowed the confirmation of the absolute configura-
tion.
Acknowledgment
We gratefully acknowledge the Jürgen Manchot Stiftung (scholar-
ship for M.B.), the Deutsche Forschungsgemeinschaft, the Ministry
of Innovation, Science and Research of the German federal state of
North Rhine-Westphalia, the Heinrich Heine University Düssel-
dorf, and the Forschungszentrum Jülich GmbH for the generous
support of our projects. Donations from BASF AG, Chemetall
GmbH, and Wacker AG were greatly appreciated. We thank Birgit
Henßen, Christoph Lorenz, Vera Ophoven, Bea Paschold, and Truc
Pham for supporting experiments.
(17) Selected Data for Acid 23
[a]D20 +17.2 (c 0.96, CHCl3). IR (film): nmax = 3073, 2977,
2935, 2861, 2648, 1702, 1642, 1465, 1417, 1381, 1290,
1236, 1191, 996, 910, 812, 742 cm–1. 1H NMR (600 MHz,
CDCl3): d = 1.19 (d, 3JMe,2 = 7.0 Hz, 3 H, CH3), 1.41–1.49
(m, 3 H, 3-Ha, 4-H), 1.66–1.73 (m, 1 H, 3-Hb), 2.05–2.09 (m,
2 H, 5-H), 2.47 (mc, 1 H, 2-H), 4.96 (ddt, 3J7E,6 = 10.2 Hz,
2J7E,7Z = 2.0 Hz, 4J7E,5 = 1.2 Hz, 1 H, 7–HE), 5.01 (ddd,
3J7Z,6 = 17.1 Hz, 2J7Z,7E = 2.0 Hz, 4J7Z,5 = 1.6 Hz, 1 H, 7–HZ),
5.80 (ddt, 3J6,7Z = 17.1 Hz, 3J6,7E = 10.2 Hz, 3J6,5 = 6.7 Hz, 1
H, 6-H), 11.5 (br s, 1 H, COOH) ppm. 13C NMR (151 MHz,
CDCl3): d = 16.9 (CH3), 26.4 (C-4), 32.9 (C-3), 33.6 (C-5),
39.2 (C-2), 114.8 (C-7), 138.4 (C-6), 183.0 (C-1) ppm.
MS (EI, 70 eV): m/z (%) = 124 (2) [M – OH]+, 101 (3)
[C5H8O2]+, 96 (6) [C7H13]+, 87 (13) [C4H6O2]+, 74 (100)
[C3H5O2]+, 69 (90) [C4H6O]+, 55 (38) [C3H4O]+. Anal. Calcd
for C8H14O2 (142.20): C, 67.57; H, 9.92. Found: C, 67.52; H,
10.02.
References and Notes
(1) Selected examples: (a) Corey, E. J.; Guzman-Perez, A.;
Lazerwith, S. E. J. Am. Chem. Soc. 1997, 119, 11769.
(b) Jacobo, S. H.; Chang, C.-T.; Lee, G.-J.; Lawson, J. A.;
Powell, W. S.; Pratico, D.; FitzGerald, G. A.; Rokach, J.
J. Org. Chem. 2006, 71, 1370. (c) Mac, D. H.; Samineni, R.;
Petrignet, J.; Srihari, P.; Chandrasekhar, S.; Yadav, J. S.;
Grée, R. Chem Commun. 2009, 4717. (d) Fischer, T.;
Pietruszka, J. Adv. Synth. Catal. 2007, 348, 4388.
(e) Larock, R. C.; Hightower, T. R. J. Org. Chem. 1993, 58,
5298. (f) Annby, U.; Stenkula, M.; Andersson, C.-M.
Tetrahedron Lett. 1993, 34, 8545. (g) For a recent review on
Pd-catalyzed allylic C–H bond activation, see: Liu, G.; Wu,
Y. Top. Curr. Chem. 2010, 292, 195.
Selected Data for Vinyllactone 2519
IR (film): nmax = 3027, 2967, 2935, 2875, 1729, 1599, 1578,
1495, 1450, 1376, 1363, 1239, 1184, 1100, 1073, 1011, 969,
933, 749, 694 cm–1. MS (EI, 70 eV): m/z (%) = 216 (73)
[M]+, 187 (5) [C13H16O]+, 160 (7) [C11H12O]+, 146 (37)
[C10H10O]+, 129 (77) [C10H10]+, 115 (54) [C9H8]+, 104 (100)
[C8H7]+, 91 (61) [C7H6]+, 77 (30) [C6H5]+, 56 (80) [C4H8]+.
Anal. Calcd for C14H16O2 (216.28): C, 77.75; H, 7.46.
(2) Leading references: (a) Stang, E. M.; White, M. C. Angew.
Chem. Int. Ed. 2011, 50, 547. (b) Stang, E. M.; White, M. C.
Nat. Chem. 2009, 1, 2094. (c) Fraunhoffer, K. J.;
Prabagaran, N.; Sirois, L. E.; White, M. C. J. Am. Chem. Soc.
Synlett 2011, No. 18, 2689–2692 © Thieme Stuttgart · New York

2692
M. Bischop, J. Pietruszka
LETTER
Found: C, 77.52; H, 7.35.
Isomer 25a
(C-6), 126.4 (arom. CH), 126.6 (C-1¢), 128.1 (arom. 4-CH),
128.7 (arom. CH), 132.1 (C-2¢), 136.0 (arom. Cipso), 175.4
(C-2) ppm.
[a]D20 +18.2 (c 0.60, CHCl3). 1H NMR (600 MHz, CDCl3):
d = 1.35 (d, 3JMe,3 = 7.1 Hz, 3 H, CH3), 1.63–1.70 (m, 1 H, 4-
Ha), 1.78–1.85 (m, 1 H, 5-Ha), 2.08–2.12 (m, 2 H, 4-Hb, 5-
Hb), 2.53 (ddq, 3J3,4a = 8.8 Hz, 3J3,4b = 7.0 Hz, 3J3,Me = 7.0
Hz, 1 H, 3-H), 4.97 (dddd, 3J6,5a = 10.9 Hz, 3J6,1¢ = 6.2 Hz,
3J6,5b = 3.4 Hz, 4J6,2¢ = 1.4 Hz, 1 H, 6-H), 6.21 (dd,
3J1¢,2¢ = 16.0 Hz, 3J1¢,6 = 6.2 Hz, 1 H, 1¢-H), 6.66 (dd,
3J2¢,1¢ = 16.0 Hz, 4J2¢,6 = 1.4 Hz, 1 H, 2¢-H), 7.25–7.28 (m, 1
H, arom. 4-CH), 7.31–7.34 (m, 2 H, arom. CH), 7.37–7.39
(m, 2 H, arom. CH) ppm. 13C NMR (151 MHz, CDCl3):
d = 14.3 (CH3), 28.2 (C-4), 29.5 (C-5), 36.0 (C-3), 81.5 (C-
6), 126.6 (arom. CH), 127.5 (C-1¢), 128.1 (arom. 4-CH),
128.7 (arom. CH), 131.9 (C-2¢), 136.0 (arom. Cipso), 174.0
(C-2) ppm.
Selected Data for Goniothalamin Analogue 26
[a]D20 –152.5 (c 1.5, CHCl3). IR (film): nmax = 3028, 2926,
1710, 1599, 1578, 1495, 1450, 1362, 1338, 1230, 1144,
1109, 1081, 1042, 1014, 968, 918, 861, 753, 731, 693 cm–1.
1H NMR (600 MHz, CDCl3): d = 1.95 (dt, 4JMe,4 = 2.2 Hz,
5JMe,5 = 1.5 Hz, 3 H, CH3), 2.48–2.52 (m, 2 H, 5-H), 5.05
(mc, 1 H, 6-H), 6.27 (dd, 3J1¢,2¢ = 15.9 Hz, 3J1¢,6 = 6.3 Hz, 1 H,
1¢-H), 6.61 (mc, 1 H, 4-H), 6.71 (dd, 3J2¢,1¢ = 15.9 Hz,
4J2¢,6 = 1.4 Hz, 1 H, 2¢-H), 7.26–7.29 (m, 1 H, arom. 4-CH),
7.32–7.34 (m, 2 H, arom. CH), 7.38–7.40 (m, 2 H, arom.
CH) ppm. 13C NMR (151 MHz, CDCl3): d = 17.1 (CH3),
30.3 (C-5), 78.0 (C-6), 126.0 (C-1¢), 126.9, 128.3, 128.8
(arom. CH), 128.9 (C-3), 132.8 (C-2¢), 135.9 (arom. Cipso),
138.5 (C-4), 165.5 (C-2) ppm. MS (EI, 70 eV): m/z
(%) = 214 (36) [M]+, 186 (10) [C12H11O2]+, 171 (4)
[C13H14]+, 129 (12) [C10H10]+, 115 (11) [C9H8]+, 104 (21)
[C8H7]+, 89 (29) [C7H6]+, 82 (100) [C5H6O]+, 54 (24)
[C4H6]+.
Isomer 25b
[a]D20 +29.2 (c 1.35, CHCl3). 1H NMR (600 MHz, CDCl3):
d = 1.27 (d, 3JMe,3 = 6.8 Hz, 3 H, CH3), 1.58–1.64 (m, 1 H, 4-
Ha), 1.82–1.89 (m, 1 H, 5-Ha), 2.05–2.16 (m, 2 H, 4-Hb, 5-
Hb), 2.66 (ddq, 3J3,4a = 10.5 Hz, 3J3,4b = 7.8 Hz, 3J3,Me = 6.8
Hz, 1 H, 3-H), 5.00 (dddd, 3J6,5a = 9.9 Hz, 3J6,1¢ = 6.0 Hz,
3J6,5b = 4.0 Hz, 4J6,2¢ = 1.4 Hz, 1 H, 6-H), 6.20 (dd,
3J1¢,2¢ = 16.0 Hz, 3J1¢,6 = 6.0 Hz, 1 H, 1¢-H), 6.67 (dd,
3J2¢,1¢ = 16.0 Hz, 4J2¢,6 = 1.4 Hz, 1 H, 2¢-H), 7.25–7.28 (m, 1
H, arom. 4-CH), 7.31–7.34 (m, 2 H, arom. CH), 7.37–7.39
(m, 2 H, arom. CH) ppm. 13C NMR (151 MHz, CDCl3):
d = 16.4 (CH3), 25.4 (C-4), 27.5 (C-5), 33.7 (C-3), 78.3
(18) For a recent SAR study, see: de Fatima, A.; Modolo, L. V.;
Conegero, L. S.; Pilli, R. A.; Ferreira, C. V.; Kohn, L. K.;
de Carvalho, J. E. Curr. Med. Chem. 2006, 13, 3371.
(19) The synthesis of isomers of compound 25 was recently
reported: Diba, A. K.; Noll, C.; Richter, M.; Gieseler, M. T.;
Kalesse, M. Angew. Chem. 2010, 122, 8545.
Synlett 2011, No. 18, 2689–2692 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.