Perfluoroalkylation through cross-metathesis between alkenes and (perfluoroalkyl)propenes

Article abstract of DOI:10.1002/ejoc.200800230

A new approach to perfluoroalkylated compounds based on cross-metathesis between perfluoropropenes and terminal alkenes has been developed. The reaction is catalysed with high efficiency and selectivity by the Hoveyda-Grubbs second-generation catalyst under mild reaction conditions. The method is applicable to a wide range of compounds, such as vinylaromatics, isoprenoids and saccharides. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800230

FULL PAPER
DOI: 10.1002/ejoc.200800230
Perfluoroalkylation through Cross-Metathesis between Alkenes and
(Perfluoroalkyl)propenes
[b]
[a,b]
Barbara Eignerová,[a,b] Martin Dracínský, and Martin Kotora*
ˇ
Keywords: Perfluoroalkylation / Ruthenium / Cross-metathesis / Hoveyda–Grubbs catalysts / Alkenes
A new approach to perfluoroalkylated compounds based on
cross-metathesis between perfluoropropenes and terminal
alkenes has been developed. The reaction is catalysed with
high efficiency and selectivity by the Hoveyda–Grubbs sec-
ond-generation catalyst under mild reaction conditions. The
method is applicable to a wide range of compounds, such as
vinylaromatics, isoprenoids and saccharides.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
has been recently used for the synthesis of perfluoroalk-
ylated cyclodextrins.[10] Since it has been demonstrated that
the inductive effects of perfluoroalkyl groups change pro-
foundly with the distance from the reaction centre [e.g., dif-
ferent reactivities of RFCH=CH2 and RFCH2CH=CH2,[11a]
and also of RF(CH2)nCH2I[11b]], we were interested in the
reactivities and scope of (perfluoroalkyl)propenes in cross-
metathesis reactions.
Introduction
Fluorine-containing compounds are ever more popular
targets of the pharmaceutical and specialty chemicals in-
dustries.[1] This stems from the fact that the presence of
fluorine or fluorinated functional groups with their unique
properties gives the target molecules special (desirable)
properties (e.g., metabolic stability, increased lipophilicity
etc.).[2] Although there have been considerable advances in
perfluoroalkylation reactions,[3] there is still demand for de-
velopment and introduction of new methodologies in this
area of chemistry.
Results and Discussion
Since metathesis between alkenes and highly fluorinated
substrates is a rather unexplored area, and because related
compounds – (perfluoroalkyl)propenes – can be easily ac-
cessible from simple starting materials, we decided to study
their synthetic potential in cross-metathesis reactions and
their potential use in the synthesis of fluoroalkyl com-
pounds. As representatives of (perfluoroalkyl)propenes we
chose 4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoronon-1-ene [(per-
fluorohexyl)propene, 1a], 4,4,5,5,6,6,6-heptafluorohex-1-
ene [(perfluoropropyl)propene, 1b] and 4-(trifluoromethyl)-
4,5,5,5-tetrafluoropent-1-ene [(perfluoroisopropyl)propene,
1c]. Initially, compound 1a was synthesized by a two-step
procedure based on the copper-catalysed addition of per-
fluorohexyl iodide to allyl alcohol,[12] followed by elimi-
nation promoted by zinc under acidic conditions.[13] Later,
a more convenient one-step procedure based on the radical
reactions between the appropriate perfluoroalkyl iodides
and allyltributylstannane was used.[14]
We found that cross-metathesis reactions between the
prepared (perfluoroalkyl)propenes and various terminal al-
kene substrates could be conveniently carried out not only
in dichloromethane at reflux in the presence of the Hov-
eyda–Grubbs second-generation catalyst (Figure 1), but
also that a (perfluoroalkyl)propene/substrate ratio of 2:1
was sufficient to achieve reasonable yields of the desired
compounds (Scheme 1).
Alkene metathesis, which allows double bonds to be cou-
pled under mild reaction conditions, is one of the most
widely exploited methods in organic synthesis.[4] Because of
its generality it is not surprising that it has also been ap-
plied, in a few cases, in organofluorine chemistry for the
synthesis of homoallyl,[5] allyl[6] or vinyl fluorides,[7] and
also for perfluoroalkylation through the use of (perfluoro-
alkyl)ethenes.[8,9] In the report by Blechert et al.[9] it is dem-
onstrated that (perfluoroalkyl)ethenes can be used as sub-
strates in ruthenium-catalysed cross-metathesis reactions
for the synthesis of perfluoroalkylated compounds. Al-
though this is a useful method, for the successful execution
of the reaction it was necessary to use at least a tenfold
excess of the corresponding (perfluoroalkyl)ethene with re-
spect to the substrate and also to run the reaction in trifluo-
rotoluene to overcome solubility problems. This approach
[a] Department of Organic and Nuclear Chemistry and Centre for
New Antivirals and Antineoplastics, Faculty of Science, Charles
University,
Hlavova 8, 128 43 Praha 2, Czech Republic
Fax: +420-221-951 326
E-mail: kotora@natur.cuni.cz
[b] Institute of Organic Chemistry and Biochemistry, Academy of
Sciences of the Czech Republic,
Flemingovo nám. 2, 166 10 Praha 6, Czech Republic
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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FULL PAPER
Table 1. Synthesis of perfluoroalkylated compounds by cross-me-
tathesis.[a]
Figure 1. The Grubbs second-generation (G-II) and the Hoveyda–
Grubbs second-generation (H-G II) catalysts.
Scheme 1. Cross-metathesis between 1 and 2 to afford 3.
To determine the scope of the perfluoroalkylation pro-
cedure with respect to structural variation of the substrates,
we tested the metathesis reactions with a wide range of ter-
minal alkenes 2, and the results are summarized in Table 1.
All reactions were carried out until the disappearance of
the starting material 2 or until progress of the reaction was
no longer observable. With regard to homodimerization of
the starting compounds, this was not detected for substrates
2; only perfluoroalkenes 1 underwent the reaction in iso-
lable amounts.
Initially, all reactions were carried out with (perfluoro-
hexyl)propene (1a). Metathesis with 1- and 2-vinylnaphtha-
lene (2a and 2b) thus afforded rather low yields of the corre-
sponding perfluoroalkylated alkenes 3 (17%) and 4 (15%);
however, these low yields could be attributed to the propen-
sities of 2a and 2b to undergo polymerization (Entries 1 and
2). A considerably better result was obtained with vinylfer-
rocene (2c), with the product 5 being obtained in a reason-
able 48% yield (Entry 3). The metathesis reaction also pro-
ceeded very well with alkenes such as 2d,[15] with the corre-
sponding product 6 being obtained in 66% yield (Entry 4).
These positive results prompted us to shift our attention to
perfluoroalkylation of more complex compounds such as
isoprenoids. The reaction was thus carried out with alkene
2e, obtained from lithocholic acid (Entry 5), and the prod-
uct 7a was isolated in a very good 75% yield.
[a] All reactions were catalysed with the Hoveyda–Grubbs second-
generation catalyst (10 mol-%) unless noted (reaction time 3 h).
[b] Isolated yields. [c] The Grubbs second-generation catalyst
(10 mol-%) was used.
the same conditions a reaction was also performed with
Metathesis between 2e and 1a was also carried out in the compound 2h (Entry 8), to give product 10a in a good yield
presence of the Grubbs second-generation catalyst in order of 79%. Finally, the metathesis reaction was carried out
to compare the catalytic activities and selectivities of the with the 1-allylglucose derivative 2i and yielded the ex-
two catalysts. It proceeded well enough, affording the ex- pected compound 11 in 64% yield (Entry 9).
pected product 7a in 59% yield, but the formation of a
minor amount of homodimer dim-2e (10%) was also ob- presence of 5 and 2 mol-% of catalyst. In the former case
served. the conversion of the starting material was quantitative and
Metathesis with substrate 2e was also carried out in the
1
Metathesis was then also carried out with compound 2f in the latter 80% (according to H NMR analysis of the
(Entry 6), giving the expected product 8 in a good 64% reaction mixtures).
yield. Gratifyingly, the metathesis also proceeded with com-
In addition, metathesis reactions between 1b or 1c and
pound 2g, possessing a free hydroxy group (Entry 7), to selected substrates were carried out. The reaction between
yield the desired product 9a in a good 70% yield. Under 2e and 1c gave 7c in a good 63% yield (Entry 5). Also, me-
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Eur. J. Org. Chem. 2008, 4493–4499

Perfluoroalkylation by Cross-Metathesis
tathesis between 2g and 1b or 1c yielded the corresponding strates becomes a desirable issue.[16] The obtained results
products 9b and 9c in good yields of 71 and 75%, respec- showed that (perfluorohexyl)propene (1a) could undergo
tively (Entry 7). A similar result was observed in the reac- easy dimerization to dim-2a, which could also participate in
tion between 1b and 2h, which afforded the corresponding metathesis reactions. Therefore, 1a and other (perfluoro-
product 10b in 81% yield (Entry 8).
alkyl)propenes could be classified as Type I olefins. Since
In most cross-metathesis reactions E/Z selectivity can be (perfluoroalkyl)ethenes are classified as Type II olefins, it
a critical issue, especially when the double bond of the ob- is obvious that there are considerable differences in their
tained alkene is intended for further elaboration. Fortu- reactivities. These differences could be attributable to the
nately, though, we were pleased to find that in most cases presence of the methylene group as the spacer between the
the cross-metathesis proceeded with a high degree of E double bond and the perfluoroalkyl moiety, diminishing its
selectivity (Ͼ98%). In fact, we did not usually observe any inductive effect. Nonetheless, one should keep in mind that
signals that could be attributed to Z isomers in the NMR the Grubbs categorization was based on reactions carried
spectra. An exception from this general trend was the me- out with different types of catalysts (the ruthenium-based
tathesis between the protected alkene derivative 2e and (per- Grubbs first- and Grubbs second-generation catalysts and
fluoroisopropyl)propene (1c), which gave product 7c as a the molybdenum-based Schrock catalyst) from those used
mixture of E/Z isomers in 7:1 ratio. Interestingly, the reac- in our case.
tions between alkene 2g, bearing a free hydroxy group, and
Removal of the protecting TBDMS group from 7a with
1a–1c also gave the corresponding products 9a–9c as mix- Et3N·3HF[17] afforded compound 9a in 63% yield. Re-
tures of double bond isomers with unhelpful E/Z ratios moval of the THP protecting group from 10a and 10b
(1.5–2:1).
(Scheme 3) with p-TsOH in MeOH proceeded quantita-
Since the homodimer of (perfluorohexyl)propene (dimer tively, affording substances 12a and 12b in very good 91
dim-1a) was the major side product in cross-metathesis re- and 93% isolated yields, respectively. Analogously, depro-
actions involving 1a and the steroid homodimer (dim-2e) tection of the saccharide derivative 11 under basic condi-
was a side product in cross-metathesis between 1a and 2e tions (MeONa/MeOH) afforded 13 in a good 92% yield.
catalysed by the Grubbs second-generation catalyst (En-
try 5), we were interested in whether these compounds
could also participate in cross-metathesis. A larger quantity
of dim-2e was synthesized from 2e in the presence of the
Grubbs second-generation catalyst (the Hoveyda–Grubbs
second-generation catalyst did not promote the reaction).
Three cross-metathesis reactions were then investigated:
i) between dim-2e and dim-1a, ii) between 2e and dim-1a,
and iii) between dim-2e and 1a (Scheme 2). In the first case,
the reaction did not take place. In the second case, a
smooth reaction was observed, affording the desired cross-
metathesis product 7a in quantitative yield (1H NMR
yield). In the last case (i.e., the attempted reaction between
dim-2e and 1a), again no reaction was observed. Cross-me-
tathesis between dim-1a and vinylferrocene (2c) was also in-
vestigated. The reaction proceeded with full conversion of
2c and yielded 5 in 42% isolated yield (homodimerization
of 2c was not observed).
Scheme 3. Deprotection of 10 and 11.
Easy functionalization of the obtained perfluoro-
alkylated alkenes was demonstrated by catalytic dihy-
droxylation of the double bonds. Dihydroxylation of 7a
with osmium tetraoxide under standard conditions
(Scheme 4)[18] afforded the corresponding dihydroxy com-
pound 14 as a 1:1 diastereoisomeric mixture in 41% iso-
lated yield.
Scheme 2. Cross-reactions between terminal and internal alkenes.
In view of the above findings, the classification of (per-
fluoroalkyl)propenes with respect to (perfluoroalkyl)ethenes
according to the Grubbs categorization of alkenyl sub- Scheme 4. Catalytic dihydroxylation of 7a to afford 14.
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B. Eignerová, M. Dracˇínský, M. Kotora
FULL PAPER
167 (32), 153 (23). HR-MS (FAB) calcd. for C19H11F13 [M]+
486.0653; found 486.0631. Rf(hexane) = 0.53.
Conclusions
In summary, the metathesis reactions between (perfluoro-
alkyl)propenes and various terminal alkenes including ter-
penes and saccharides proceeded in all cases in good to ex-
cellent yields under mild reaction conditions (reflux in
DCM) and with favourable (perfluoroalkyl)propene/sub-
strate ratios (2:1). The reaction conditions and the known
1-[(E)-4Ј,4Ј,5Ј,5Ј,6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,9Ј-Tridecafluoronon-1Ј-enyl]-
ferrocene (5): The reaction was carried out with 2c (106 mg,
0.5 mmol) and 1a (360 mg, 1 mmol) by the General Procedure. Col-
umn chromatography on silica gel (toluene) and crystallization
(CH2Cl2/hexane) yielded compound 5 (130 mg, 48 %) as orange
1
crystals: m.p. 91–92 °C. [α]2D0 = +6.9 (c = 0.17, CHCl3). H NMR
tolerance of the catalysts used for a wide range of func- (600 MHz, CDCl3): δ = 2.87 (dt, J = 18.0, 7.3 Hz, 2 H), 4.11 (s, 5
H), 4.23 (m, 2 H), 4.35 (m, 2 H), 5.70 (dt, J = 15.6, 7.3 Hz, 1 H),
6.37 (br. d, J = 15.7 Hz, 1 H) ppm. 13C NMR (150.9 MHz, CDCl3):
δ = 35.25 (t, JC,F = 45.3 Hz, CH2), 66.85 (2 C, 2ϫCH), 68.95 (2
tional groups enabled metathesis also to be carried out with
substrates possessing unprotected hydroxy groups, thus al-
lowing direct perfluoroalkylation and avoiding often
lengthy and problematic protection/deprotection reaction
sequences. In addition, (perfluoroalkyl)propenes can be
classified as Type I olefins, unlike (perfluoroalkyl)ethenes,
which behave rather like Type II olefins (according to the
Grubbs categorization). This reaction thus provides a sim-
ple pathway for introduction of perfluoroalkyl groups into
compounds with various degrees of complexity.
C, 2 ϫCH), 69.18 (5 C, 5ϫCH), 81.74 (CH), 112.46 (t, JC,F
=
4.3 Hz, CH), 135.20 (CH) ppm. IR (CHCl ): ν = 3099, 3011, 1657,
˜
3
1412, 1347, 1243, 1145, 1106, 962 cm–1. MS (FAB): m/z = 544
[M]+ (28), 274 (17), 256 (13), 232 (12), 181 (76), 149 (22). HR-
MS (FAB) calcd. for C19H13F13Fe [M]+ 544.0159; found 544.0154.
Rf(hexane) = 0.31.
2-[6Ј-Methoxy-2Ј-((E)-4ЈЈ,4ЈЈ,5ЈЈ,5ЈЈ,6ЈЈ,6ЈЈ,7ЈЈ,7ЈЈ,8ЈЈ,8ЈЈ,9ЈЈ,9ЈЈ,9ЈЈ-
tridecafluoronon-1ЈЈ-enyl)-1Ј,2Ј,3Ј,4Ј-tetrahydronaphthalen-1Ј-yl]-1-
phenylethanone (6): The reaction was carried out with 2d (100 mg,
0.33 mmol) and 1a (238 mg, 0.66 mmol) by the General Procedure.
Column chromatography on silica gel (hexane/diethyl ether 20:1)
and on fluorinated silica gel (first elution MeOH/water 4:1, wash-
ing of the non-fluorinated starting material, second elution diethyl
ether, washing of the product) yielded compound 6 (144 mg, 66%)
as a yellowish oil: [α]2D0 = +2.0 (c = 0.30, CHCl3). 1H NMR
(600 MHz, CDCl3): δ = 1.73 (m, 1 H), 1.99 (dtd, J = 13.5, 6.7,
3.5 Hz, 1 H), 2.52 (m, 1 H), 2.73 (td, J = 18.1, 7.0 Hz, 2 H), 2.80
(t, J = 6.5 Hz, 2 H), 3.25 (dd, J = 17.7, 5.2 Hz, 1 H), 3.36 (dd, J
= 17.7, 7.0 Hz, 1 H), 3.50 (m, 1 H), 5.47 (dtd, J = 15.4, 7.1, 0.8 Hz,
1 H), 5.72 (ddt, J = 15.4, 8.2, 1.3 Hz, 1 H), 6.62 (d, J = 2.8 Hz, 1
H), 6.68 (dd, J = 8.5, 2.8 Hz, 1 H), 7.00 (d, J = 8.5 Hz, 1 H), 7.45
(m, 2 H), 7.56 (m, 1 H), 7.95 (m, 2 H) ppm. 13C NMR (150.9 MHz,
CDCl3): δ = 26.07 (CH2), 27.09 (CH2), 34.82 (t, JC,F = 22.6 Hz,
CH2), 37.35 (CH), 41.95 (CH), 45.76 (CH2), 55.14 (CH3), 112.55
(CH), 113.36 (CH), 117.07 (t, JC,F = 4.2 Hz, CH), 128.01 (2 C,
2ϫCH), 128.60 (2 C, 2ϫCH), 129.61 (CH), 130.96 (C), 133.07
(CH), 137.13 (C), 137.59 (C), 141.79 (CH), 157.61 (C), 199.11
Experimental Section
General Procedure for Cross-Metathesis between Terminal Alkenes
and (Perfluoroalkyl)propenes: The Hoveyda–Grubbs second-gener-
ation catalyst (10 mol-%) was added under argon to a mixture of
a terminal alkene (2a–2j, 1 equiv.) and a (perfluoroalkyl)propene
(1a–c, 2 equiv.) in DCM. The resulting solution was stirred at 42 °C
for 3 h. Removal of the solvent in vacuo gave a brown oil, which
could be purified by flash chromatography.
2-[(E)-4Ј,4Ј,5Ј,5Ј,6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,9Ј-Tridecafluoronon-1Ј-enyl]-
naphthalene (3): The reaction was carried out with 2a (154 mg,
1 mmol) and (perfluorohexyl)propene (1a, 720 mg, 2 mmol) by the
General Procedure. Column chromatography on silica gel (hexane/
heptane, 1:1) afforded compound 3 (81 mg, 17%) as a white foam:
[α]2D0 = +3.0 (c = 0.26, CHCl3). H NMR (600 MHz, CDCl3): δ =
1
3.07 (br. td, J = 18.1, 7.2 Hz, 2 H), 6.26 (dt, J = 15.8, 7.3 Hz, 1
H), 6.78 (br. d, J = 15.8 Hz, 1 H), 7.47 (m, 2 H), 7.60 (dd, J = 8.6,
1.8 Hz, 1 H), 7.74 (d, J = 1.7 Hz, 1 H), 7.81 (m, 3 H) ppm. 13C
NMR (150.9 MHz, CDCl3): δ = 35.27 (t, JC,F = 22.6 Hz, CH2),
116.31 (t, J = 4.4 Hz, CH), 123.29 (CH), 126.17 (CH), 126.41 (CH),
126.64 (CH), 127.68 (CH), 128.05 (CH), 128.36 (CH), 133.18 (C),
(C) ppm. IR (CHCl ): ν = 3088, 3061, 3028, 2839, 1685, 1609, 1598,
˜
3
1449, 1352, 1242, 1145, 1120, 974, 598 cm–1. MS (FAB): m/z = 639
[M + H]+ (3), 595 (2), 519 (21), 262 (8), 253 (9), 155 (22). HR-
MS (FAB) calcd. for C28H24F13O2 [M]+ 639.1569; found 639.1562.
Rf(hexane/Et2O, 20:1) = 0.25.
133.45 (C), 133.61 (C), 137.33 (CH) ppm. IR (CHCl ): ν = 3061,
˜
3
3010, 1657, 1628, 1599, 1509, 1364, 1347, 1243, 1145, 969 cm–1.
MS (FAB): m/z = 487 [M + H]+ (12), 361 (7), 312 (3), 233 (5),
207 (46), 156 (32). HR-MS (FAB) calcd. for C19H12F13 [M + H]+
487.0731; found 487.0717. Rf(hexane) = 0.53.
(1ЈЈ,1ЈЈ-Dimethylethyl)dimethyl{[(3α)-20-(6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,
10Ј,10Ј,11Ј,11Ј,11Ј-tridecafluoroundec-3Ј(E)-en-1Ј-yl)pregnan-3-
yl]oxy}silane (7a): The reaction was carried out with 2e (95 mg,
0.2 mmol) and 1a (144 mg, 0.4 mmol) by the General Procedure.
Column chromatography on silica gel (hexane/toluene, 20:1)
1-[(E)-4Ј,4Ј,5Ј,5Ј,6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,9Ј-Tridecafluoronon-1Ј-enyl]-
naphthalene (4): The reaction was carried out with 2b (154 mg,
1 mmol) and 1a (720 mg, 2 mmol) by the General Procedure. Col-
umn chromatography on silica gel (hexane/heptane, 1:1) afforded
compound 4 (75 mg, 15%) as a white foam: [α]2D0 = +10.9 (c = 0.21,
yielded compound 7a (121 mg, 75%) as a colourless oil: [α]2D0
=
+21.0 (c = 0.27, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 0.06
(s, 6 H), 0.62 (s, 3 H), 0.89 (s, 9 H), 0.90 (s, 3 H), 0.91 (d, J =
6.4 Hz, 3 H), 2.13 (m, 1 H), 2.78 (dt, J = 18.2, 6.8 Hz, 2 H), 3.58
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 3.14 (m, 2 H), 6.16 (dt, (m, 1 H), 5.38 (m, 1 H), 5.69 (m, 1 H) ppm. 13C NMR (150.9 MHz,
J = 15.6, 7.2 Hz, 1 H), 7.37 (dt, J = 15.7, 1.5 Hz, 1 H), 7.45 (m, 1
H), 7.51 (m, 2 H), 7.58 (m, 1 H), 7.81 (m, 1 H), 7.86 (m, 1 H), 8.06
(m, 1 H) ppm. 13C NMR (150.9 MHz, CDCl3): δ = 35.48 (t, JC,F
= 22.5 Hz, CH2), 119.37 (t, JC,F = 4.4 Hz, CH), 123.61 (CH),
124.24 (CH), 125.58 (CH), 125.91 (CH), 126.27 (CH), 128.49 (CH),
CDCl3): δ = –4.62 (2 C, 2ϫCH3), 11.92 (CH3), 18.36 (C), 18.38
(CH3), 20.79 (CH2), 23.38 (CH3), 24.20 (CH2), 25.97 (3 C,
3 ϫCH3), 26.40 (CH2), 27.29 (CH2), 28.29 (CH2), 29.33 (CH2),
31.01 (CH2), 34.58 (C), 34.82 (t, JC,F = 22.6 Hz, CH2), 35.13 (CH2),
35.28 (CH), 35.57 (CH2), 35.84 (CH), 36.91 (CH2), 40.15 (CH2),
128.58 (CH), 130.98 (C), 133.55 (C), 134.09 (C), 134.88 (CH) ppm. 40.18 (CH), 42.29 (CH), 42.70 (C), 56.17 (CH), 56.41 (CH), 72.85
IR (CHCl ): ν = 3064, 3050, 1592, 1510, 1344, 1344, 1267, 1243, (CH), 115.85 (t, JC,F = 4.0 Hz, CH), 139.64 (CH) ppm. IR
˜
3
1145, 969 cm–1. MS (FAB): m/z = 486 [M]+ (22), 467 (4), 196 (3), (CHCl ): ν = 2931, 2859, 1672, 1471, 1373, 1243, 1071, 972 cm–1.
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Perfluoroalkylation by Cross-Metathesis
MS (FAB): m/z = 804 [M]+ (2), 672 (4), 654 (3), 630 (1), 315 (9),
280 (20). Rf(hexane/toluene, 10:1) = 0.42.
CH2), 35.17 (CH2), 35.29 (CH), 35.36 (C), 35.88 (CH), 37.58
(CH2), 40.30 (CH2), 40.51 (CH), 42.74 (C), 43.73 (CH), 56.12
(CH), 56.20 (CH), 115.10 (CH), 137.70 (CH) ppm.
Mixture of (1ЈЈ,1ЈЈ-Dimethylethyl)dimethyl{(3α)-20-[(6Ј-trifluoro-
methyl-6Ј,7Ј,7Ј,7Ј-tetrafluorohept-3Ј(E/Z)-en-1Ј-yl)pregnan-3-yl]-
oxy}silane (7c): The reaction was carried out with 2e (80 mg,
0.17 mmol) and 1c (72 mg, 0.34 mmol) by the General Procedure.
Column chromatography on silica gel (heptane) afforded the title
compound 7c (69 mg, 63%, inseparable 7:1 mixture of E/Z iso-
mers) as a colourless oil: [α]2D0 = +31.5 (c = 0.21, CHCl3). IR
Mixture of (3α,5β)-20-(6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,10Ј,10Ј,11Ј,11Ј,11Ј-Tri-
decafluoroundec-3Ј(E/Z)-en-1Ј-yl)pregnan-3-ol (9a): The reaction
was carried out with 2g (100 mg, 0.28 mmol) and 1a (180 mg,
0.5 mmol) by the General Procedure. Column chromatography on
silica gel (toluene/diethyl ether, 20:1) and on fluorinated silica gel
(first elution 7:1 MeOH, water washing of the non-fluorinated
starting material, second elution diethyl ether, washing of the prod-
uct) afforded the title compound 9a (135 mg, 70%, inseparable 2:1
mixture of E/Z isomers) as a colourless oil: [α]2D0 = +14.0 (c = 0.19,
(CHCl ): ν = 2931, 2859, 1671, 1471, 1374, 1244, 1091, 974 cm–1.
˜
3
MS (FAB): m/z = 653 [M – H]+ (2), 521 (5), 463 (2), 413 (1), 337
(9), 236 (4). HR-MS (FAB) calcd. for C35H56OF7Si [M – H]+
653.3989; found 653.3971. Rf(heptane) = 0.45.
CHCl ). IR (CHCl ): ν = 3609, 2938, 2867, 1672, 1471, 1377, 1365,
˜
3
3
1242, 1145, 1031, 1012, 973 cm–1. MS (ESI): m/z = 690 [M]+ (1),
663 (14), 610 (3), 648 (10), 426 (100), 316 (43), 288 (98). HR-MS
(FAB) calcd. for C32H42F7 [M – OH]+ 673.3079; found 673.3089.
Rf(toluene/diethyl ether, 20:1) = 0.25.
Isomer (E)-7c: 1H NMR (600 MHz, CDCl3): δ = 0.06 (s, 6 H), 0.62
(s, 3 H), 0.89 (s, 9 H), 0.89 (d, J = 6.8 Hz, 3 H), 0.90 (s, 3 H), 2.13
(m, 1 H), 2.79 (br. dd, J = 20.0, 7.2 Hz, 2 H), 3.58 (m, 1 H), 5.36
(dm, J = 15.2 Hz, 1 H), 5.65 (dm, J = 15.2 Hz, 1 H) ppm. 13C
NMR (150.9 MHz, CDCl3): δ = –4.62 (2 C, 2ϫCH3), 11.92 (CH3), Isomer (E)-9a: 1H NMR (500 MHz, CDCl3): δ = 0.64 (s, 3 H), 0.91
18.32 (CH3), 18.36 (C), 20.79 (CH2), 23.38 (CH3), 24.21 (CH2), (d, J = 6.6 Hz, 3 H), 0.92 (s, 3 H), 2.78 (dt, J = 18.2, 6.8 Hz, 2 H),
25.97 (3 C, 3ϫCH3), 26.40 (CH2), 27.29 (CH2), 28.27 (CH2), 29.20 3.63 (m, 1 H), 5.38 (m, 1 H), 5.69 (m, 1 H) ppm. 13C NMR
(CH2), 31.00 (CH2), 34.58 (d, JC,F = 20.9 Hz, CH2), 34.58 (C), (125.7 MHz, CDCl3): δ = 11.95 (CH3), 18.39 (CH3), 20.81 (CH2),
35.07 (CH2), 35.19 (CH), 35.57 (CH2), 35.84 (CH), 36.90 (CH2), 23.36 (CH3), 24.19 (CH2), 26.41 (CH2), 27.18 (CH2), 28.26 (CH2),
40.14 (CH2), 40.17 (CH), 42.28 (CH), 42.70 (C), 56.16 (CH), 56.40 30.53 (2ϫCH2), 34.55 (C), 34.82 (t, JC,F = 22.7 Hz, CH2), 35.13
(CH), 72.85 (CH), 116.97 (d, JC,F = 5.6 Hz, CH), 138.93 (CH2), 35.26 (CH), 35.32 (CH2), 35.83 (CH), 36.44 (CH2), 40.19
(CH) ppm.
(CH2), 40.42 (CH), 42.08 (CH), 42.71 (C), 56.16 (CH), 56.51 (CH),
71.88 (CH), 115.89 (t, JC,F = 4.1 Hz, CH), 139.61 (CH) ppm.
Isomer (Z)-7c: 1H NMR (600 MHz, CDCl3): δ = 0.06 (s, 6 H), 0.63
(s, 3 H), 0.89 (s, 9 H), 0.89 (d, J = 6.8 Hz, 3 H), 0.90 (s, 3 H), 2.13
(m, 1 H), 2.86 (br. dd, J = 19.6, 7.6 Hz, 2 H), 3.58 (m, 1 H), 5.36
Isomer (Z)-9a: 1H NMR (500 MHz, CDCl3): δ = 0.65 (s, 3 H), 0.91
(d, J = 6.6 Hz, 3 H), 0.92 (s, 3 H), 2.78 (dt, J = 18.2, 6.8 Hz, 2 H),
(dm, J = 15.2 Hz, 1 H), 5.65 (dm, J = 15.2 Hz, 1 H) ppm. 13C 3.63 (m, 1 H), 5.38 (m, 1 H), 5.69 (m, 1 H) ppm. 13C NMR
NMR (150.9 MHz, CDCl3): δ = –4.62 (2 C, 2ϫCH3), 11.92 (CH3), (125.7 MHz, CDCl3): δ = 12.01 (CH3), 18.52 (CH3), 20.81 (CH2),
18.32 (CH3), 18.36 (C), 20.79 (CH2), 23.38 (CH3), 24.21 (CH2), 23.36 (CH3), 24.19 (CH2), 26.41 (CH2), 27.18 (CH2), 28.26 (CH2),
25.97 (3 C, 3ϫCH3), 26.40 (CH2), 27.29 (CH2), 28.27 (CH2), 29.20 29.31 (t, JC,F = 22.7 Hz, CH2), 30.53 (CH2), 34.55 (C), 35.13 (CH2),
(CH2), 31.00 (CH2), 34.58 (d, JC,F = 20.9 Hz, CH2), 34.58 (C), 35.26 (CH), 35.32 (CH2), 35.83 (CH), 36.44 (CH2), 39.26 (CH2),
35.07 (CH2), 35.19 (CH), 35.57 (CH2), 35.84 (CH), 36.90 (CH2), 40.19 (CH2), 40.42 (CH), 42.08 (CH), 42.71 (C), 56.16 (CH), 56.51
40.14 (CH2), 40.17 (CH), 42.28 (CH), 42.70 (C), 56.16 (CH), 56.40 (CH), 71.88 (CH), 117.49 (t, JC,F = 4.0 Hz, CH), 137.54 (CH) ppm.
(CH), 72.85 (CH), 116.05 (d, JC,F = 5.6 Hz, CH), 136.84
Mixture of (3α,5β)-20-(6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,8Ј-Heptafluorooct-3Ј(E/Z)-
(CH) ppm.
en-1Ј-yl)pregnan-3-ol (9b): The reaction was carried out with 2g
Mixture of 20-(6Ј,6Ј,7Ј,7Ј,8Ј,8Ј,9Ј,9Ј,10Ј,10Ј,11Ј,11Ј,11Ј-Tridecafluo- (80 mg, 0.22 mmol) and 1b (105 mg, 0.5 mmol) by the General Pro-
roundec-3Ј(E/Z)-en-1Ј-yl)pregnane (8): The reaction was carried out
with 2f (75 mg, 0.22 mmol) and 1a (158 mg, 0.44 mmol) by the Ge-
neral Procedure. Column chromatography on silica gel (heptane)
afforded the title compound 8 (95 mg, 64%, inseparable 4:1 mixture
of E/Z isomers) as a colourless oil: [α]2D0 = +39.6 (c = 0.11, CHCl3).
cedure. Column chromatography on silica gel (toluene) afforded
the title compound 9b (80 mg, 71%, inseparable 1.5:1 mixture of
E/Z isomers) as a white powder: m.p. 88–89 °C. [α]2D0 = +25.6 (c =
0.23, CHCl ). IR (CHCl ): ν = 3609, 2935, 2867, 1672, 1377, 1353,
˜
3
3
1276, 1031, 1012, 972 cm–1. MS (EI): m/z = 540 [M]+ (1), 522 (8),
493 (3), 301 (3), 285 (31), 257 (12), 215 (36). HR-MS (EI) calcd.
for C29H43OF7 [M]+ 540.3202; found 540.3228. Rf(toluene) = 0.29.
IR (CHCl ): ν = 2931, 2863, 1673, 1375, 1363, 1242, 1145,
˜
3
973 cm–1. MS (APCI): m/z = 674 [M]+ (1), 607 (65), 551 (52), 495
(36), 439 (9), 391 (7), 278 (4). Rf(heptane) = 0.80.
Isomer (E)-9b: 1H NMR (500 MHz, CDCl3): δ = 0.64 (s, 3 H), 0.90
(d, J = 6.6 Hz, 3 H), 0.92 (s, 3 H), 2.78 (m, 2 H), 3.63 (m, 1 H),
5.37 (m, 1 H), 5.68 (m, 1 H) ppm. 13C NMR (125.7 MHz, CDCl3):
1
Isomer (E)-8: H NMR (500 MHz, CDCl3): δ = 0.64 (s, 3 H), 0.91
(d, J = 6.5 Hz, 3 H), 0.91 (s, 3 H), 2.78 (td, J = 18.7, 7.1 Hz, 2 H),
5.38 (m, 1 H), 5.69 (dtt, J = 15.4, 6.8, 1.4 Hz, 1 H) ppm. 13C NMR δ = 11.99 (CH3), 18.38 (CH3), 20.81 (CH2), 23.36 (CH3), 24.20
(125.7 MHz, CDCl3): δ = 11.97 (CH3), 18.41 (CH3), 20.82 (CH2), (CH2), 26.41 (CH2), 27.19 (CH2), 28.27 (CH2), 30.54 (2 C,
21.33 (CH2), 24.23 (CH2), 24.27 (CH3), 27.03 (CH2), 27.25 (CH2), 2ϫCH2), 34.56 (m, CH2), 35.13 (CH2), 35.25 (CH), 35.33 (CH2),
27.52 (CH2), 28.30 (CH2), 29.32 (CH2), 34.82 (t, JC,F = 22.4 Hz, 35.84 (CH), 36.44 (CH2), 40.19 (CH2), 40.43 (CH), 42.09 (CH),
CH2), 35.17 (CH2), 35.29 (CH), 35.36 (C), 35.88 (CH), 37.58 42.71 (C), 56.17 (CH), 56.51 (CH), 71.86 (CH), 115.87 (CH),
(CH2), 40.30 (CH2), 40.51 (CH), 42.74 (C), 43.73 (CH), 56.20
(CH), 56.63 (CH), 115.85 (CH), 139.65 (CH) ppm.
139.56 (CH) ppm.
Isomer (Z)-9b: 1H NMR (500 MHz, CDCl3): δ = 0.65 (s, 3 H), 0.91
(d, J = 6.4 Hz, 3 H), 0.92 (s, 3 H), 2.78 (m, 2 H), 3.63 (m, 1 H),
5.37 (m, 1 H), 5.68 (m, 1 H) ppm. 13C NMR (125.7 MHz, CDCl3):
1
Isomer (Z)-8: H NMR (500 MHz, CDCl3): δ = 0.65 (s, 3 H), 0.91
(d, J = 6.5 Hz, 3 H), 0.91 (s, 3 H), 2.78 (td, J = 18.7, 7.1 Hz, 2 H),
5.38 (m, 1 H), 5.69 (dtt, J = 15.4, 6.8, 1.4 Hz, 1 H) ppm. 13C NMR δ = 12.04 (CH3), 18.52 (CH3), 20.81 (CH2), 23.36 (CH3), 24.20
(125.7 MHz, CDCl3): δ = 11.97 (CH3), 18.41 (CH3), 20.82 (CH2), (CH2), 26.41 (CH2), 27.19 (CH2), 28.27 (CH2), 29.31 (m, CH2),
21.33 (CH2), 24.23 (CH2), 24.27 (CH3), 27.03 (CH2), 27.25 (CH2), 30.54 (CH2), 35.13 (CH2), 35.25 (CH), 35.33 (CH2), 35.84 (CH),
27.52 (CH2), 28.30 (CH2), 29.32 (CH2), 34.82 (t, JC,F = 22.4 Hz, 36.44 (CH2), 39.34 (CH2), 40.19 (CH2), 40.43 (CH), 42.09 (CH),
Eur. J. Org. Chem. 2008, 4493–4499
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4497

B. Eignerová, M. Dracˇínský, M. Kotora
42.71 (C), 56.17 (CH), 56.45 (CH), 71.86 (CH), 117.43 (CH), (d, J = 6.6 Hz, 3 H), 2.74 (m, 2 H), 3.48 (m, 1 H), 3.53 (m, 1 H),
FULL PAPER
137.50 (CH) ppm.
3.92 (m, 1 H), 4.72 (m, 1 H), 5.30 (br. dt, J = 15.2, 7.1 Hz, 1 H),
5.34 (m, 1 H), 5.55 (ddt, J = 15.3, 8.8, 1.3 Hz, 1 H) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 12.02 (CH3), 19.36 (CH3), 20.01 (CH2),
20.10 (CH2), 20.14 (CH3), 20.98 (CH2), 24.24 (CH2), 25.46 (CH2),
27.94 (CH2), 28.24 (CH2), 29.66 (CH2), 31.24 (CH2), 31.28 (CH2),
31.84 (CH), 31.87 (CH2), 34.48 (t, JC,F = 22.6 Hz, CH2), 36.74 (C),
36.78 (C), 37.17 (CH2), 37.42 (CH2), 38.73 (CH2), 39.60 (CH2),
40.21 (2 C, CH and CH2), 42.32 (C), 50.11 (CH), 50.14 (CH), 55.35
(CH), 56.69 (CH), 62.82 (CH2), 62.94 (CH2), 75.95 (CH), 96.81
(CH), 96.98 (CH), 113.56 (CH), 121.43 (CH), 121.50 (CH), 140.86
(3α,5β)-20-[6Ј-(Trifluoromethyl)-6Ј,7Ј,7Ј,7Ј-tetrafluorohept-3Ј-en-1Ј-
yl]pregnan-3-ol (9c): The reaction was carried out with 2g (150 mg,
0.42 mmol) and 1c (168 mg, 0.80 mmol) by the General Procedure.
Column chromatography on silica gel (hexane/diethyl ether, 5:1)
afforded the title compound 9c (171 mg, 75%, inseparable 1:1 mix-
ture of E/Z isomers) as a colourless oil. [α]2D0 = +19.6 (c = 0.16,
CHCl ). IR (CHCl ): ν = 3610, 2937, 2867, 1671, 1376, 1365, 1286,
˜
3
3
1030, 1012, 974 cm–1. MS (FAB): m/z = 563 [M + Na]+ (2), 523
(5), 507 (12), 337 (8), 263 (9), 233 (4), 179 (8). Rf(hexane/diethyl
ether, 4:1) = 0.26.
(C), 141.04 (C), 145.31 (CH) ppm. IR (CHCl ): ν = 3005, 2944,
˜
3
2870, 1668, 1378, 1353, 1274, 976, 956 cm–1. MS (FAB): m/z = 617
[M + Na]+ (7), 571 (2), 529 (3), 507 (4), 309 (12), 253 (14). HR-
MS (FAB) calcd. for C32H45O2F7Na [M + Na]+ 617.3205; found
617.3189. Rf(15:1 hexane/diethyl ether) = 0.27.
Isomer (E)-9c: 1H NMR (600 MHz, CDCl3): δ = 0.63 (s, 3 H), 0.90
(d, J = 6.3 Hz, 3 H), 0.92 (s, 3 H), 2.80 (m, 2 H), 3.63 (m, 1 H),
5.36 (m, 1 H), 5.65 (m, 1 H) ppm. 13C NMR (150.9 MHz, CDCl3):
δ = 11.92 (CH3), 18.29 (CH3), 20.76 (CH2), 23.34 (CH3), 24.18
(CH2), 26.38 (CH2), 27.14 (CH2), 28.24 (CH2), 29.17 (CH2), 30.45
(CH2), 32.62 (d, JC,F = 20.9 Hz, CH2), 34.52 (C), 35.02 (CH2),
35.15 (CH), 35.28 (CH2), 35.78 (CH), 36.35 (CH2), 40.13 (CH2),
40.35 (CH), 42.01 (CH), 42.67 (C), 56.10 (CH), 56.45 (CH), 71.85
(CH), 116.95 (d, JC,F = 5.4 Hz, CH), 138.89 (CH) ppm.
Isomer (Z)-9c: 1H NMR (600 MHz, CDCl3): δ = 0.64 (s, 3 H), 0.89
(d, J = 6.3 Hz, 3 H), 0.92 (s, 3 H), 2.80 (m, 2 H), 3.63 (m, 1 H),
5.36 (m, 1 H), 5.65 (m, 1 H) ppm. 13C NMR (150.9 MHz, CDCl3):
δ = 12.00 (CH3), 18.47 (CH3), 20.76 (CH2), 23.34 (CH3), 24.18
(CH2), 26.38 (CH2), 27.14 (CH2), 28.24 (CH2), 30.45 (CH2), 32.54
(d, JC,F = 20.9 Hz, CH2), 34.52 (C), 35.02 (CH2), 35.15 (CH), 35.28
(CH2), 35.78 (CH), 36.35 (CH2), 39.12 (CH2), 40.13 (CH2), 40.35
(CH), 42.01 (CH), 42.64 (C), 55.60 (CH), 56.39 (CH), 71.85 (CH),
118.49 (d, JC,F = 5.6 Hz, CH), 136.79 (CH) ppm.
1-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-D-glucopyranosyl)-5,5,6,6,7,7,8,8,
9,9,10,10,10-tridecafluorodec-2(E)-ene (11): The reaction between 2i
(93 mg, 0.25 mmol) and 1a (180 mg, 0.5 mmol) was carried out by
the General Procedure. Column chromatography on silica gel (hex-
ane/EtOAc, 5:1) and crystallization from pentane/Et2O yielded 11
(112 mg, 64%) as white crystals: m.p. 66–67 °C. [α]2D0 = +52.8 (c =
0.17, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 2.04 (s, 6 H), 2.06
(s, 3 H), 2.08 (s, 3 H), 2.36 (dt, J = 15.8, 4.9 Hz, 1 H), 2.62 (ddd,
J = 15.8, 11.1, 7.3 Hz, 1 H), 2.83 (td, J = 18.2, 6.9 Hz, 2 H), 3.85
(ddd, J = 9.3, 5.0, 2.7 Hz, 1 H), 4.04 (dd, J = 12.3, 2.6 Hz, 1 H),
4.27 (m, 2 H), 5.00 (t, J = 9.1 Hz, 1 H), 5.10 (dd, J = 9.4, 5.7 Hz,
1 H), 5.32 (t, J = 9.1 Hz, 1 H), 5.58 (m, 1 H), 5.70 (m, 1 H) ppm.
13C NMR (125.7 MHz, CDCl3): δ = 20.60 (CH3), 20.62 (CH3),
20.65 (CH3), 20.67 (CH3), 29.29 (CH3), 34.75 (t, JC,F = 22.3 Hz,
CH2), 62.01 (CH2), 68.56 (CH), 68.94 (CH), 70.05 (CH), 70.21
(CH), 71.81 (CH), 119.86 (t, JC,F = 4.1 Hz, CH), 133.05 (CH),
Tetrahydro-2Ј-{[(3β)-25,25,26,26,27,27,28,28,29,29,30,30,30-trideca-
fluorochola-5,22(E)-dien-3-yl]oxy}-2H-pyran (10a): The reaction
was carried out with 2h (82 mg, 0.2 mmol) and 1a (144 mg,
0.4 mmol) by the General Procedure. Column chromatography on
silica gel (hexane/diethyl ether, 20:1) and crystallization from ace-
tone yielded the compound 10a (115 mg, 79%) as white crystals:
m.p. 144–145 °C. [α]2D0 = –25.2 (c = 0.20, CHCl3). 1H NMR
(600 MHz, CDCl3): δ = 0.70 (s, 3 H), 1.01 (s, 3 H), 1.04 (d, J =
6.6 Hz, 3 H), 2.75 (m, 2 H), 3.48 (m, 1 H), 3.53 (m, 1 H), 3.92 (m,
1 H), 4.72 (m, 1 H), 5.30 (br. dt, J = 15.2, 7.1 Hz, 1 H), 5.34 (m,
1 H), 5.55 (ddt, J = 15.3, 8.8, 1.3 Hz, 1 H) ppm. 13C NMR
(150.9 MHz, CDCl3): δ = 12.02 (CH3), 19.37 (CH3), 20.02 (CH2),
20.10 (CH2), 20.14 (CH3), 21.00 (CH2), 24.24 (CH2), 25.46 (CH2),
27.95 (CH2), 28.24 (CH2), 29.67 (CH2), 31.25 (CH2), 31.28 (CH2),
31.84 (CH), 31.87 (CH2), 34.74 (t, JC,F = 22.6 Hz, CH2), 36.75 (C),
36.78 (C), 37.18 (CH2), 37.42 (CH2), 38.73 (CH2), 39.60 (CH2),
40.22 (CH + CH2), 42.32 (C), 50.11 (CH), 50.15 (CH), 55.36 (CH),
56.70 (CH), 62.83 (CH2), 62.95 (CH2), 75.96 (CH), 96.81 (CH),
96.99 (CH), 113.58 (CH), 121.43 (CH), 121.51 (CH), 140.87 (C),
169.49 (C), 169.58 (C), 170.11 (C), 170.61 (C) ppm. IR (CHCl ): ν
˜
3
= 2957, 1751, 1650, 1455, 1431, 1348, 1245, 1145, 972 cm–1. MS
(ESI): m/z = 704 [M]+ (3), 667 (2), 645 (23), 525 (4), 483 (6), 314
(3), 288 (6). HR-MS (ESI) calcd. for C24H26O9F13 [M + H]+
705.1369; found 705.1395. Rf(hexane/diethyl ether, 2:1) = 0.21.
Supporting Information (see also the footnote on the first page of
this article): Experimental details, spectral characteristics of com-
pounds, copies of NMR spectroscopic data.
Acknowledgments
Financial support for the Centre for New Antivirals and Antineo-
plastics (1M0508) and from the Ministry of Education of the Czech
Republic (Project No. MSM0021620857) and from the Grant
Agency of AS CR (Project No. IAA 400 550 609) is gratefully
acknowledged.
141.04 (C), 145.36 (CH) ppm. IR (CHCl ): ν = 3005, 2944, 2870,
˜
3
1668, 1379, 1361, 1242, 975 cm–1. MS (FAB): m/z = 745 [M + H]+
(1), 663 (4), 341 (12), 207 (18). HR-MS (FAB) calcd. for
C35H46O2F13 [M++H] 745.3290; found 745.3276. Rf(hexane/diethyl
ether, 15:1) = 0.27.
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white crystals: m.p. 159–160 °C. [α]2D0 = –42.3 (c = 0.24, CHCl3).
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4498
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4493–4499

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