Synthesis of fluorohydrins through electrophilic fluorination of allyl silanes

Article abstract of DOI:10.1055/s-0030-1260074

A convenient method for the efficient and regioselective monofluorination of allyl silanes to afford 1-fluoro-3-silyl-2-ols in 43-62% yields via fluorohydroxylation, using Selectfluor as the eletrophilic fluorination reagent has been developed. The regios

Full text of DOI:10.1055/s-0030-1260074

SPECIAL TOPIC
2383
Synthesis of Fluorohydrins through Electrophilic Fluorination of Allyl Silanes
S
ynthesis of Fluorohydr
e
ins ibo Wang, Bo Xu,* Gerald B. Hammond*
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA
Fax +1(502)8523899; E-mail: bo.xu@louisville.edu; E-mail: gb.hammond@louisville.edu
Received 29 April 2011
Dedicated to Professor Kenji Uneyama on the occasion of his 70th birthday
silyl)propan-2-ol (2a; Table 1, entry 1) in 56%, which in-
Abstract: A convenient method for the efficient and regioselective
monofluorination of allyl silanes to afford 1-fluoro-3-silyl-2-ols in
43–62% yields via fluorohydroxylation, using Selectfluor as the
eletrophilic fluorination reagent has been developed. The regiose-
dicated that the reaction occurred independently of the
gold catalyst. Increasing the amount of water led to a
slightly increased yield (Table 1, entry 2), but a further in-
lectivity can be rationalized by considering the stabilization of the crease in the water content actually decreased the yield
b-carbocation intermediate by the silyl group.
(Table 1, entry 3). We also investigated other nucleo-
philes. No reaction was observed when ethanol was used
as both nucleophile and solvent (Table 1, entry 4), but the
fluorination of 1a in acetonitrile–ethanol (10:1) afforded
(2-ethoxy-3-fluoropropyl)triisopropylsilane (2b) in 61%
yield (Table 1, entry 5). This result indicated that the sol-
vent (MeCN) played an important role in this transforma-
tion. The reaction of 1a with other nucleophiles, such as
acetic acid, formamide and diethylamine, afforded com-
plex mixtures (Table 1, entries 6, 7). Thus, the reaction
conditions presented in Table 1, entry 2 was regarded as
optimal for further studies.
Key words: allyl silanes, fluorination, fluorohydrins, regioselectiv-
ity
Extensive research has established that the chemical reac-
tivity of fluorinated organic compounds is distinct from
other halide-containing analogues.1 Consequently, fluo-
rine substitution can effectively modify the physicochem-
ical properties of a molecule. In this regard, fluorohydrins
have been sought as intermediates and biological targets.2
Typically, fluorohydrins are synthesized through epoxide
ring opening using a fluorinating agent;3 however, in
many cases, the regioselectivity and yields are less than
satisfactory. There are other methods that rely on fluori-
nated molecular building blocks, but these building blocks
are often derived from potential atmospheric ozone-
depleting agents such as CFHCl2.4
ClAuPPh3 (5 mol%)
Selectfluor (1.5 equiv)
TIPS
HO
TIPS
1a
F
MeCN–H2O (20:1)
r.t., 24 h
2a, 50%
Scheme 1
Table 1 Screening Conditions
Selectfluor is an exceptionally stable, virtually non-
hygroscopic, crystalline, electrophilic fluorinating agent5
that has been used in several applications, such as fluoro-
hydroxylation of aryl substituted allenes.6 Recently, we
reported a versatile synthesis of fluoroketones through
gold-catalyzed fluorination of alkynes using Selectfluor.7
During our attempts to extend the scope of this reaction to
alkenes, we conducted the fluorination of allyltriisopro-
pylsilane (1a) in the presence of 5 mol% [AuClPPh3]; this
reaction afforded the fluorohydrin product 2a in around
50% yield (Scheme 1). Further investigations revealed
that no other regioisomer was formed. This reaction rep-
resented a highly regioselective intermolecular fluorohy-
droxylation of an alkene. Gouverneur and co-workers
have reported an electrophilic fluorocyclization of allyl si-
lanes,8 but, to the best of our knowledge, the synthetically
more useful intermolecular fluorohydroxylation of allyl
silanes has not been reported before.
TIPS
Selectfluor (1.5 equiv)
MeCN, r.t., 24 h
TIPS
F
nucleophile (Nu)
Nu
1a
2a
Entry
Nucleophile (ratio MeCN/Nu)
H2O (20:1)
Yield (%)
56
1
2
3
4
5
6
7
8
H2O (10:1)
60
H2O (5:1)
55
EtOH
NR
EtOH (10:1)
AcOH (10:1)
HCONH2 (10:1)
Et2NH (10:1)
61
mixture
mixture
NR
Further optimization of this transformation is shown in
Table 1. Without any gold catalyst, the fluorination of 1a
in acetonitrile–water (20:1) gave 1-fluoro-3-(triisopropyl-
With optimized reaction conditions in hand, we explored
the scope of this transformation (Table 2). The reactions
of allyltriisopropylsilane (1a) with water, ethanol, isopro-
panol, allyl alcohol, butan-1-ol and 2-cyclohexylethanol
SYNTHESIS 2011, No. 15, pp 2383–2386
Advanced online publication: 17.06.2011
DOI: 10.1055/s-0030-1260074; Art ID: C02011SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
1
1

2384
W. Wang et al.
SPECIAL TOPIC
gave good yields (Table 2, entries 1–6). Use of the relative may be due to a competing electrophilic fluorodesilyla-
more sterically hindered isopropanol substrate reduced tion reaction of allyl silane 1. Gouverneur and co-workers
the yield slightly (Table 2, entry 3). Higher temperature have developed efficient syntheses of allyl and propargyl
(60 °C) was needed for complete reaction of 1a with allyl fluorides through the fluorodesilylation of allyl and alle-
alcohol, furnishing product 2d in 61% yield (Table 2, en- nyl silanes.9 In those transformations,9 allyl silanes with a
try 4). Reaction of allyltriphenylsilane (1b) with acetoni- smaller silyl group (e.g., TMS) were used. The bulkier si-
trile–water (10:1) afforded 2g in 55% yield (Table 2, entry lyl group (e.g., TIPS) used in our examples are more resis-
7). Diallyl silanes, such as diallyldiphenylsilane (1c), tant to fluorodesilylation, but may not completely prevent
were highly reactive under the standard conditions and the fluorodesilylation process. If desired, the silyl group in
failed to give the desired fluorinated product (Table 2, en- 2 can be removed by applying literature methods.8
try 8). The reaction of allyl silane with a non-terminal
double bond, such as 1d, worked well (Table 2, entry 9).
The good, but not excellent, yields observed in Table 2
The proposed mechanism is shown in Scheme 2. It has
been well established that the silyl group has a strong sta-
Table 2 Scope of the Reaction
R3Si
Selectfluor (1.5 equiv)
MeCN–Nu (10:1), r.t., 24–36 h
R3Si
F
Nu
1
2
Entry
1
1
Nu
2
Yield (%)a
60
TIPS
F
F
TIPS
H2O
HO
O
1a
2a
TIPS
2
3
1a
1a
EtOH
61
43
2b
TIPS
OH
F
O
2c
F
O
4b
1a
61
OH
TIPS
2d
TIPS
F
5
6
1a
1a
60
62
OH
O
2e
TIPS
F
OH
O
2f
Ph3Si
7
8
H2O
H2O
55
–
Ph3Si
F
HO
1b
2g
Ph2
Si
complex mixture
1c
O
O
O
OH
9
H2O
59
TIPS
O
1d
F
TIPS
2h
a Isolated yield.
b Reaction was conducted at 60 °C.
Synthesis 2011, No. 15, 2383–2386 © Thieme Stuttgart · New York

SPECIAL TOPIC
Synthesis of Fluorohydrins
2385
bilizing effect on b-carbocations and radical cations.10
This fact is probably the key reason for the regioselectiv-
ity observed. We propose that allyl silane reacts with
Selectfluor to give b-carbocation A, and quenching of A
by a nucleophile gives the final product 2. Single-electron
transfer (SET) has been proposed in many Selectfluor-
mediated reactions;5b it is also possible that the present re-
action goes through an SET mechanism, that is, the reac-
tion of 1 with Selectfluor would give radical cation B,
which would then react with a nucleophile to give the final
product 2.
was stirred at r.t. for 24–36 h and the progress of reaction was mon-
itored by TLC. After completion of the reaction, the mixture was
quenched with sat. aq NH4Cl (10 mL), extracted with hexane or
Et2O (2 × 15 mL) and the combined organic layers were dried over
MgSO4. After evaporation, the residue was subjected to flash silica
gel column chromatography (hexane to hexane–CH2Cl2, 1:1), af-
fording 2a.
1-Fluoro-3-(triisopropylsilyl)propan-2-ol (2a)
Yield: 70 mg (60%); colorless oil.
1H NMR (500 MHz, CDCl3): d = 0.68–0.74 (m, 1 H), 0.78–0.86 (m,
1 H), 1.02–1.17 (m, 21 H), 2.17 (s, 1 H), 4.10–4.27 (m, 2 H), 4.31–
4.44 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.6, 12.2 (d, J = 4 Hz), 19.0 (d,
J = 2 Hz), 68.2 (d, J = 18 Hz), 89.2 (d, J = 170 Hz).
Cl
N
R3N-F
19F NMR (470 MHz, CDCl3): d = –220.8 to –220.5 (m).
N
F
–
R3N
F
2BF4
GC/MS (EI): m/z = 172, 103, 41.
HRMS (ESI): m/z [M + Na]+ calcd for C12H27FNaOSi+: 257.1713;
+
Selectfluor
found: 257.1712.
R3Si
R3Si
Nu
R3Si
R3N-F
(2-Ethoxy-3-fluoropropyl)triisopropylsilane (2b)
Yield: 80 mg (61%); colorless oil.
B
Nu
1
1H NMR (500 MHz, CDCl3): d = 0.73–0.77 (m, 1 H), 0.89–0.94 (m,
1 H), 1.04–1.09 (m, 21 H), 1.20 (t, J = 7 Hz, 3 H), 3.47–3.53 (m,
1 H), 3.71–3.78 (m, 2 H), 4.29–4.36 (m, 1 H), 4.39–4.46 (m, 1 H).
SET process
R3N
F
13C NMR (125 MHz, CDCl3): d = 11.7, 11.8 (d, J = 5 Hz), 15.9,
19.0, 65.5, 75.9 (d, J = 18 Hz), 87.9 (d, J = 174 Hz).
19F NMR (470 MHz, CDCl3): d = –220.3 to –220.1 (m).
R3Si
Nu
R3Si
R3Si
Nu
R3N-F
F
F
1
2
A
GC/MS (EI): m/z = 243, 202, 147, 121, 41.
HRMS (ESI): m/z [M + Na]+ calcd for C14H31FNaOSi+: 285.2026;
found: 285.2026.
two-electron process
Scheme 2 Proposed mechanism
(3-Fluoro-2-isopropoxypropyl)triisopropylsilane (2c)
Yield: 59 mg (43%); colorless oil.
In conclusion, we have developed a convenient method
for the efficient monofluorination of allyl silanes using
Selectfluor as the electrophilic fluorination reagent. The
stabilizing effect of the silyl group on the b-carbocation is
critical for the success of this reaction. The use of easy-to-
handle N–F reagents is a particularly attractive feature of
this reaction. Further research on the implications of this
transformation, including an asymmetric version, is under
way in our laboratory.
1H NMR (500 MHz, CDCl3): d = 0.76–0.83 (m, 2 H), 0.96–1.03 (m,
21 H), 1.09 (d, J = 7.5 Hz, 6 H), 3.71–3.81 (m, 2 H), 4.16–4.38 (m,
2 H).
13C NMR (125 MHz, CDCl3): d = 11.5, 12.5 (d, J = 7.5 Hz), 18.8 (d,
J = 5 Hz), 22.3, 23.2, 69.8 (d, J = 2 Hz), 72.8 (d, J = 22 Hz), 87.4
(d, J = 216 Hz).
19F NMR (470 MHz, CDCl3): d = –220.4 to –220.1.
GC/MS (EI): m/z = 216, 192, 172, 103.
HRMS (ESI+): m/z [M + Na]+ calcd for C15H33FNaOSi+: 299.2182;
found: 299.2184.
The 1H, 13C and 19F NMR spectra were recorded at 500, 126 and 470
MHz, respectively, using CDCl3 as solvent. The chemical shifts are
reported in d (ppm) values relative to CHCl3 (d = 7.26 ppm for 1H
[2-(Allyloxy)-3-fluoropropyl]triisopropylsilane (2d)
Yield: 84 mg (61%); colorless oil.
NMR and d = 77.0 ppm for 13C NMR) and CFCl3 (d = 0 ppm for 19
F
NMR), multiplicities are indicated by: s (singlet), d (doublet), t
(triplet), q (quartet), p (pentet), h (hextet), m (multiplet) and br
(broad). Coupling constants (J) are reported in hertz. All air- and/or
moisture-sensitive reactions were carried out under an argon atmo-
sphere. All reagents and solvents were employed without further
purification. The products were purified using a CombiFlash system
(Teledyne ISCO) or a regular glass column. TLC was developed on
Merck silica gel 60 F254 aluminum sheets. IR spectra were record-
ed with a Bruker IFS 25 spectrometer. High resolution ESI-MS
were obtained with a MS-FTICR-MSn system (LTQ FT, Thermo
Electron Corp.).
1H NMR (500 MHz, CDCl3): d = 0.67–0.71 (m, 2 H), 0.77–1.03 (m,
21 H), 3.70–3.78 (m, 1 H), 3.94–3.98 (m, 1 H), 4.10–4.15 (m, 1 H),
4.22–4.29 (m, 1 H), 4.34–4.30 (m, 1 H), 5.05–5.09 (m, 1 H), 5.17–
5.21 (m, 1 H), 5.80–5.89 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.4, 18.8, 71.0 (d, J = 3 Hz), 75.6
(d, J = 22 Hz), 88.7 (d, J = 217 Hz), 116.5, 135.1.
19F NMR (470 MHz, CDCl3): d = –219.5 to –219.2 (m).
GC/MS (EI): m/z = 213, 189, 171, 81.
HRMS (ESI): m/z [M + Na]+ calcd for C15H31FNaOSi+: 297.2026;
found: 297.2026.
Synthesis of 2; General Procedure
To a solution of 1a (99 mg, 0.5 mmol) in MeCN–H2O (10:1, 3 mL)
was added Selectfluor (266 mg, 0.75 mmol). The reaction mixture
(2-Butoxy-3-fluoropropyl)triisopropylsilane (2e)
Yield: 87 mg (60%); colorless oil.
Synthesis 2011, No. 15, 2383–2386 © Thieme Stuttgart · New York

2386
W. Wang et al.
SPECIAL TOPIC
1H NMR (500 MHz, CDCl3): d = 0.74–0.78 (m, 2 H), 0.90–0.95 (m,
3 H), 1.05–1.10 (m, 21 H), 1.36–1.40 (m, 2 H), 1.53–1.60 (m, 2 H),
3.43–3.47 (m, 1 H), 3.62–3.67 (m, 1 H), 3.69–3.77 (m, 1 H), 4.29–
4.36 (m, 1 H), 4.39–4.46 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.7, 11.8, 14.1, 19.1, 19.6, 32.6,
70.0, 76.0 (d, J = 17 Hz), 87.8 (d, J = 174 Hz).
References
(1) (a) Chambers, R. D. Fluorine in organic chemistry;
Blackwell Publishing Ltd./CRC Press: Boca Raton, 2004.
(b) Hiyama, T. Organofluorine compounds, chemistry and
applications; Springer-Verlag: Berlin, 2000. (c) Kirsch, P.
Modern fluoroorganic chemistry; Wiley-VCH: Weinheim,
2004. (d) Muller, K.; Faeh, C.; Diederich, F. Science 2007,
317, 1881. (e) Schlosser, M. Angew. Chem. Int. Ed. 1998,
37, 1496. (f) Soloshonok, V. A. Fluorine-containing
synthons, ACS Symposium Series 911; Oxford University
Press: Washington DC, 2005. (g) Uneyama, K.
19F NMR (470 MHz, CDCl3): d = –220.5 to –220.2 (m).
GC/MS (EI): m/z = 275, 231, 174, 100.
HRMS (ESI+): m/z [M + Na]+ calcd for C16H35FNaOSi+: 313.2339;
found: 313.2339.
Organofluorine Chemistry; Blackwell Publishing: Oxford,
2006.
[2-(2-Cyclohexylethoxy)-3-fluoropropyl]triisopropylsilane (2f)
Yield: 103 mg (60%); colorless oil.
(2) (a) Camps, F.; Fabrias, G.; Guerrero, A. Tetrahedron 1986,
42, 3623. (b) Fox, D. T.; Poulter, C. D. J. Org. Chem. 2005,
70, 1978. (c) Jie, M. S. F. L. K.; Lau, M. M. L.; Lam, C. N.
W.; Alam, M. S.; Metzger, J. O.; Biermann, U. Chem. Phys.
Lipids 2003, 125, 93. (d) Kim, H. O.; Lim, M. H.; Park, J.
G.; Moon, H. R.; Jacobson, K. A.; Kim, H.-D.; Chun, M. W.;
Jeong, L. S. Nucleosides, Nucleotides Nucleic Acids 2003,
22, 923. (e) Lan, Y.; Hammond, G. B. J. Org. Chem. 2000,
65, 4217. (f) Lan, Y.; Hammond, G. B. Org. Lett. 2002, 4,
2437. (g) Lim, M. H.; Kim, H. O.; Moon, H. R.; Lee, S. J.;
Chun, M. W.; Gao, Z.-G.; Melman, N.; Jacobson, K. A.;
Kim, J. H.; Jeong, L. S. Bioorg. Med. Chem. Lett. 2003, 13,
817. (h) Mastihubova, M.; Biely, P. Tetrahedron Lett. 2001,
42, 9065. (i) Runge, M.; Haufe, G. J. Org. Chem. 2000, 65,
8737.
(3) (a) Akiyama, Y.; Fukuhara, T.; Hara, S. Synlett 2003, 1530.
(b) Bruns, S.; Haufe, G. J. Fluorine Chem. 2000, 104, 247.
(c) Islas-Gonzalez, G.; Puigjaner, C.; Vidal-Ferran, A.;
Moyano, A.; Riera, A.; Pericas, M. A. Tetrahedron Lett.
2004, 45, 6337. (d) Mikami, K.; Ohba, S.; Ohmura, H.
J. Organomet. Chem. 2002, 662, 77. (e) Nicoletti, M.;
O’Hagan, D.; Slawin, A. M. Z. J. Am. Chem. Soc. 2005, 127,
482. (f) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.;
Tokunaga, M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307.
(g) Yoshino, H.; Nomura, K.; Matsubara, S.; Oshima, K.;
Matsumoto, K.; Hagiwara, R.; Ito, Y. J. Fluorine Chem.
2004, 125, 1127.
1H NMR (500 MHz, CDCl3): d = 0.64–0.90 (m, 2 H), 0.81–0.87 (m,
3 H), 0.92–1.04 (m, 21 H), 1.05–1.19 (m, 4 H), 1.30–1.41 (m, 2 H),
1.51–1.63 (m, 4 H), 3.34–3.40 (m, 1 H), 3.58–3.68 (m, 2 H), 4.19–
4.26 (m, 1 H), 4.33–4.38 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.7, 11.8, 18.3, 19.1 (d, J =
3 Hz), 26.7 (d, J = 37 Hz), 33.6 (d, J = 23 Hz), 34.7, 38.0, 68.1, 76.0
(d, J = 18 Hz), 87.9 (d, J = 174 Hz).
19F NMR (470 MHz, CDCl3): d = –220.0 to –219.7 (m).
GC/MS (EI): m/z = 283, 214, 172, 158, 69.
HRMS (ESI+): m/z [M + Na]+ calcd for C20H41FNaOSi+: 367.2808;
found: 367.2808.
1-Fluoro-3-(triphenylsilyl)propan-2-ol (2g)
Yield: 86 mg (55%); colorless oil.
1H NMR (500 MHz, CDCl3): d = 0.64–0.90 (m, 2 H), 0.81–0.87 (m,
3 H), 0.92–1.04 (m, 21 H), 1.05–1.19 (m, 4 H), 1.30–1.41 (m, 2 H),
1.51–1.63 (m, 4 H), 3.34–3.40 (m, 1 H), 3.58–3.68 (m, 2 H), 4.19–
4.26 (m, 1 H), 4.33–4.38 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.7, 11.8, 18.3, 19.1 (d, J =
3 Hz), 26.7 (d, J = 37 Hz), 33.6 (d, J = 23 Hz), 34.7, 38.0, 68.1, 76.0
(d, J = 18 Hz), 87.9 (d, J = 174 Hz).
19F NMR (470 MHz, CDCl3): d = –220.0 to –219.7 (m).
GC/MS (EI): m/z = 283, 214, 172, 158, 69.
(4) Xu, B.; Hammond, G. B. J. Org. Chem. 2006, 71, 3518.
(5) (a) Schueler, M. Speciality Chemicals Magazine 2006, 26,
20. (b) Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.;
Vincent, S. P.; Wong, C.-H. Angew. Chem. Int. Ed. 2005, 44,
192.
(6) Zhou, C.; Li, J.; Lu, B.; Fu, C.; Ma, S. Org. Lett. 2008, 10,
581.
(7) Wang, W.; Jasinski, J.; Hammond, G. B.; Xu, B. Angew.
Chem. Int. Ed. 2010, 49, 7247.
2-Fluoro-3-hydroxy-4-(triisopropylsilyl)butyl Acetate (2h)
Yield: 92 mg (59%); colorless oil.
1H NMR (500 MHz, CDCl3): d = 0.79–0.82 (m, 1 H), 0.91–0.96 (m,
1 H), 1.06–1.14 (m, 21 H), 1.99 (d, J = 5 Hz, 1 H), 2.11–2.13 (m,
3 H), 3.98–4.04 (m, 1 H), 4.25–4.35 (m, 1 H), 4.37–4.43 (m, 1 H),
4.48–4.51 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 11.6 (d, J = 9 Hz), 13.5, 19.0,
21.0, 63.7 (d, J = 23 Hz), 68.5 (d, J = 20 Hz), 95.8 (d, J = 175 Hz).
(8) Wilkinson, S. C.; Lozano, O.; Schuler, M.; Pacheco, M. C.;
Salmon, R.; Gouverneur, V. Angew. Chem. Int. Ed. 2009, 48,
7083.
19F NMR (470 MHz, CDCl3): d = –198.2 to –197.9 (m).
GC/MS (EI): m/z = 285, 225, 181, 112, 43.
HRMS (ESI): m/z [M + Na]+ calcd for C15H31FNaO3Si+: 329.1924;
found: 329.1924.
(9) (a) Tredwell, M.; Gouverneur, V. Org. Biomol. Chem. 2006,
4, 26. (b) Pacheco, M. C.; Gouverneur, V. Org. Lett. 2005,
7, 1267. (c) Greedy, B.; Paris, J.-M.; Vidal, T.; Gouverneur,
V. Angew. Chem. Int. Ed. 2003, 42, 3291. (d) Sawicki, M.;
Kwok, A.; Tredwell, M.; Gouverneur, V. Beilstein J. Org.
Chem. 2007, 3, 34. (e) Carroll, L.; McCullough, S.; Rees,
T.; Claridge, T. D. W.; Gouverneur, V. Org. Biomol. Chem.
2008, 6, 1731. (f) Carroll, L.; Pacheco, M. C.; Garcia, L.;
Gouverneur, V. Chem. Commun. 2006, 4113.
Acknowledgment
We are grateful to the National Science Foundation for financial
support (CHE-0809683 and CHE-1111316), and acknowledge the
support provided by the CREAM Mass Spectrometry Facility (Uni-
versity of Louisville) funded by NSF/EPSCoR (EPS-0447479).
(10) Olah, G. A.; Prakash, G. K. S. Carbocation chemistry;
Wiley-Interscience: Hoboken NJ, 2004.
Synthesis 2011, No. 15, 2383–2386 © Thieme Stuttgart · New York