Synthesis of perfluoroalkyl-substituted γ-lactones and 4,5-dihydropyridazin-3(2H)-ones via donor-acceptor cyclopropanes

Article abstract of DOI:10.1002/hlca.201200413

Rh₂(OAc)₄-Catalyzed decomposition of diazo esters in the presence of perfluoroalkyl- or perfluoroaryl-substituted silyl enol ethers smoothly provided the corresponding alkyl 2-siloxycyclopropanecarboxylates in very good yields. The generated donor-acceptor cyclopropanes are equivalents of γ-oxo esters, which we demonstrated by their one-pot transformations to yield fluorine-containing heterocycles. A reductive procedure selectively afforded perfluoroalkyl-substituted γ-hydroxy esters or γ-lactones. The treatment of the donor-acceptor cyclopropanes with hydrazine or phenylhydrazine afforded a series of perfluoroalkyl- and perfluoroaryl- substituted 4,5-dihydropyridazin-3(2H)-ones. Copyright

Full text of DOI:10.1002/hlca.201200413

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Helvetica Chimica Acta – Vol. 95 (2012)
Synthesis of Perfluoroalkyl-Substituted g-Lactones and 4,5-Dihydropyridazin-
3(2H)-ones via DonorꢀAcceptor Cyclopropanes
by Daniel Gladow and Hans-Ulrich Reissig*
Institut fꢀr Chemie und Biochemie, Freie Universitꢁt Berlin, Takustrasse 3, DE-14195 Berlin
(fax: þ 49(30)83855367; e-mail: hans.reissig@chemie.fu-berlin.de)
Dedicated to Prof. Dieter Seebach on the occasion of his 75th birthday
Rh2(OAc)4-Catalyzed decomposition of diazo esters in the presence of perfluoroalkyl- or
perfluoroaryl-substituted silyl enol ethers smoothly provided the corresponding alkyl 2-siloxycyclopro-
panecarboxylates in very good yields. The generated donorꢀacceptor cyclopropanes are equivalents of g-
oxo esters, which we demonstrated by their one-pot transformations to yield fluorine-containing
heterocycles. A reductive procedure selectively afforded perfluoroalkyl-substituted g-hydroxy esters or
g-lactones. The treatment of the donorꢀacceptor cyclopropanes with hydrazine or phenylhydrazine
afforded a series of perfluoroalkyl- and perfluoroaryl-substituted 4,5-dihydropyridazin-3(2H)-ones.
1. Introduction. – The use of small-ring compounds in organic synthesis started to
flourish in the 1970s [1]. Based on first results of Wenkert [2], our group introduced the
concept of donorꢀacceptor cyclopropanes in 1980 [3] and subsequently published
many examples of valuable synthetic transformations of this class of small-ring
compounds1). More recently, a boost of new methods involving donorꢀacceptor
cyclopropanes, in particular [3 þ 2] and [3 þ 3] cycloadditions, could be recorded, and
many applications to the synthesis of natural products were reported [5].
We are currently interested in rarely explored perfluoroalkyl- and perfluoroaryl-
substituted donorꢀacceptor cyclopropanes2) in order to explore their synthetic
usefulness for the preparation of fluorine-containing products, in particular of
heterocyclic compounds. Owing to the strong electron-withdrawing and hydrophobic
properties of fluorine-containing substituents, their incorporation into organic mole-
cules often leads to remarkable changes in their biological activity, degradability, and
bioavailability. In detail, fluorinated compounds show different lipophilicity, volatility,
acidity, and increased metabolic stability. As a consequence, ca. 20% of all presently
used drugs and 30% of all agrochemicals on the market contain fluorine and the
number is steadily increasing [7].
As first target product class, we were aiming to g-lactones, since ca. 10% of all
natural products with a biological profile, including antibiotic, antitumor, and
1
)
For reviews on donorꢀacceptor cyclopropanes, see [4a – 4e]. For an interesting theoretical study on
donorꢀacceptor cyclopropanes, see [4f].
2
)
For an excellent review on CF3-substituted cyclopropanes, see [6a]. For recent original reports, see
[6b – 6g].
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢀrich

Helvetica Chimica Acta – Vol. 95 (2012)
1819
antifungal activities, contain this substructure [8]. The properties of their fluorinated
analogs should, therefore, be of interest3). We also wanted to prepare pyridazin-3(2H)-
ones, since they constitute an important class of N-containing heterocycles possessing
various biological activities [10]. As early as 1886, Fischer set a common route towards
these compounds by condensation of 4-oxoalkanoic acid derivatives with hydrazine
and its derivatives, respectively [11]. In earlier publications, we reported that g-lactones
[12] and pyridazin-3(2H)-ones [13] are directly available from alkyl 2-silyloxycyclo-
propanecarboxylates A which are ring-opened in protic solvents, liberating the
corresponding g-oxo esters B (Scheme 1)4). These intermediates then rapidly undergo
subsequent reactions either providing the g-lactones C or pyridazin-3(2H)-ones D. We
were curious to learn how perfluoroalkyl and perfluoroaryl substituents will influence
these transformations. Recently, Wan et al. [15] investigated the reaction of various w-
fluoroalkylated keto esters (obtained by other methods) with hydrazine and phenyl-
hydrazine, yielding fluoroalkyl-substituted heterocyclic 1,2-diaza 3-ones of different
ring size.
Scheme 1. One-Pot Transformations of DonorꢀAcceptor Cyclopropanes A to g-Lactones C and 4,5-
Dihydropyridazin-3(2H)-ones D. TMS: Me3Si.
2. Results and Discussion. – 2.1. Synthesis of Silyloxycyclopropanes. The perfluoro-
alkyl- and perfluoroaryl-substituted silyl enol ethers 1a – 1c were prepared starting
from the corresponding methyl ketones by standard methods. Their reactivity towards
carbenium ions was recently studied in collaboration with the group of Mayr, and a
dramatic decrease of rates was found; e.g., perfluoroalkyl-substituted silyl enol ether 1b
is less reactive by eight orders of magnitude compared to its non-fluorinated
counterpart [16]. We were very pleased to experience that this dramatically reduced
nucleophilicity does not prevent cyclopropanations with diazo esters in the presence of
suitable catalysts. Hence, addition by syringe pump of methyl diazoacetate 2a to a soln.
of silyl enol ethers 1a – 1c in CH2Cl2 in the presence of catalytic amounts of dirhodium
tetraacetate (Rh2(OAc)4) at room temperature provided, after chromatographic
purification, the desired silyloxycyclopropanes 3a – 3c in excellent yields (Table 1,
3
)
)
Trifluoromethyl-substituted lactones and functionalized alcohols are described in [9a – 9i]. For the
preparation of a-trifluoromethyl g-lactones, see [9j] and references cited therein.
For other one-pot transformations of silyloxycyclopropanes, see [14].
4

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 1. Conversion of Silyl Enol Ethers 1 to Perfluoroalkyl- and Perfluoroaryl-Substituted
2-Silyloxycyclopropanes 3. TMS: Me3Si.
Entry
1
2
R1
R2
R3
3
Yield [%]
dr
1
2
3
4
5
6
1a
1b
1c
1a
1b
1d
2a
2a
2a
2b
2b
2b
C5F11
CF3
C6F5
C5F11
CF3
H
H
H
H
CF3
CF3
CF3
Me
Me
Me
Et
Et
Et
3a
3b
3c
3d
3e
3f
92
84
90
86
85
76
50 : 50
25 : 75
43 : 57
83 : 17
77: 23a)
63 : 37
a) Compound trans-3e was found to be the major diastereoisomer as determined by NOE experiments.
Entries 1 – 3). We observed no or rather low cis/trans selectivity in these reactions and
did not assign the configuration of the slightly preferred isomer of compound 3b. Ethyl
3,3,3-trifluoro-2-diazopropanoate (2b) was employed to introduce a CF3 group at C(1)
of the silyloxycyclopropanes. The carbenoid addition was similarly performed as for 2a
and silyl enol ethers 1a and 1b were smoothly converted to cyclopropane derivatives 3d
and 3e, respectively, bearing perfluoroalkyl groups at C(1) and C(2) (Entries 4 and 5).
The diastereoselectivity of the reaction was moderate. For product 3e, we could assign
trans-configuration to the major isomer by NOE measurements. For comparison, we
also prepared cyclopropane 3f starting from the non-fluorinated silyl enol ether 1d and
diazo alkanoate 2b. The compilation of Table 1 illustrates that all cyclopropanations
proceeded in excellent-to-good yields and with moderate-to-low diastereoselectivity.
The missing diastereoselectivity is of no consequence for the subsequent trans-
formations reported in this study, since the ring opening to intermediates of type B
converts C(2) to a C¼O group.
2.2. Synthesis of g-Lactones. Perfluoroalkyl-substituted 2-silyloxycyclopropanes
were then converted to g-hydroxy esters 4 or g-lactones 5. Reaction of 3a, 3b, 3e, and 3f
either with NaBH4 or with KBH4 in MeOH (Methods A and B, resp.) afforded the
corresponding g-hydroxy esters 4a – 4d in good yields (Table 2). These conditions
induce desilylation of compounds 3 and their subsequent ring opening. The resulting g-
oxo esters are smoothly reduced by the hydride reagent to provide the alcohols 4.
Compared to their non-fluorinated analogs, these g-hydroxy esters do not undergo
spontaneous cyclization to the corresponding g-lactones. Switching to Method C, which
involves treatment with para-toluenesulfonic acid (TsOH) after the reduction step
allowed the preparation of the desired perfluoroalkyl-substituted g-lactones 5a – 5d in
good yields. As expected, compounds 4c and 5c containing CF3 groups at two
stereogenic centers were formed as mixture of diastereoisomers.
2.3. Synthesis of Pyridazin-3(2H)-ones. The reactions of perfluoroalkyl- and
perfluoroaryl-substituted 2-silyloxycyclopropanes 3a – 3c, 3e, and 3f with NH2NH2 ·
H2O in the presence of TsOH required heating to 658 for 24 to 48 h to provide the

Helvetica Chimica Acta – Vol. 95 (2012)
1821
Table 2. Conversion of 2-Silyloxycyclopropanes 3 to g-Hydroxy Esters 4 and g-Lactones 5
Entry
3
R1
R2
R3
4
Methoda)
Yield [%]
5
Methoda)
Yield [%]
1
2
3
4
3a
3b
3e
3f
C5F11
CF3
CF3
H
H
H
CF3
CF3
Me
Me
Et
4a
4b
4c
4d
A
A
B
B
89
85
5a
5b
5c
5d
C
C
C
C
75
57
67b)
69
63c)
56
Et
a) Method A: NaBH4, MeOH, 08 to room temperature, 12 h; Method B: KBH4, MeOH, 08, 1 h; Method
c
C: 1. KBH4, MeOH, 08, 10 min to 1 h, r.t., 0 to 16 h; 2. TsOH · H2O, CH2Cl2, 12 to 72 h. b) dr 56 : 44. ) dr
59 : 41
expected pyridazin-3(2H)-ones 6a – 6e in very good-to-moderate yields (Table 3,
Entries 1 – 5). Again, the reaction conditions for the formation of the heterocyclic
system are slightly harsher than for compounds without fluorinated substituents [13]. It
is assumed that the transformation starts with a ring opening of the 2-silyloxycyclo-
propanes, followed by formation of the hydrazone of the produced g-oxo esters.
Cyclization by attack of the NHR4 group to the alkoxycarbonyl group furnishes the
heterocycle. This final step is apparently slower for products such as 6d requiring higher
reaction temperatures (Entry 4).
Table 3. Conversion of 2-Silyloxycyclopropanes 3 to Pyridazin-3(2H)-ones 6 and 7
Entry
3
R1
R2
R3
R4
6 or 7
Methoda)
Yield [%]
1
2
3a
3b
3c
3e
3f
3a
3b
3c
3e
3f
C5F11
CF3
C6F5
CF3
H
C5F11
CF3
C6F5
CF3
H
H
H
H
CF3
CF3
H
H
H
Me
Me
Me
Et
H
H
H
H
6a
6b
6c
6d
6e
7a
7b
7c
7d
7e
A
A
B
B
A
C
C
C
C
C
72
87
75
90
41
70
83
90
88
25d)
3b)
4c)
5
Et
H
6
7
8c)
9
Me
Me
Me
Et
Ph
Ph
Ph
Ph
Ph
CF3
CF3
10
Et
a) Method A: TsOH · H2O, MeOH, 658, 24 to 48 h; Method B: TsOH · H2O, toluene, 1108, 60 h; Method
c
C: TsOH · H2O, toluene, 908, 60 h. b) 2 Equiv. of NH2NH2 were used. ) 5 Equiv. of NH2NH2 were used.
d) Indole 10 was formed as a by-product.

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Helvetica Chimica Acta – Vol. 95 (2012)
The reactions of the 2-silyloxycyclopropanes with PhNHNH2 generally proceeded
more sluggishly, but also afforded the desired Ph-substituted pyridazin-3(2H)-ones
7a – 7d in good-to-excellent yields (Table 3, Entries 6 – 9). Cyclopropane derivative 3f
with a CF3 substituent at C(2) gave a unique result, as the expected pyridazin-3(2H)-
one 7e was formed in only 25% yield, and indole derivative 10 was isolated in similar
quantities (21%). Obviously, the intermediate hydrazone derived from 3f undergoes
the expected intramolecular substitution to provide 7e, but a Fischer indole synthesis
competes under these acidic conditions furnishing 10 as second product (Scheme 2).
Scheme 2. Competitive Cyclization and Indole Formation
Conclusions. – In this work, we demonstrated that, despite of the low nucleophi-
licity of perfluoroalkyl- and perfluoroaryl-substituted silyl enol ethers, their dirhodium
tetraacetate-catalyzed cyclopropanation with diazo esters provides the desired
donorꢀacceptor cyclopropanes in excellent yields. These products undergo smooth
ring-opening reactions to g-oxo esters under mild conditions which was exploited for
one-pot conversions into perfluoroalkyl-substituted g-lactones, as well as perfluoro-
alkyl- and perfluoroaryl-substituted pyridazin-3(2H)-ones. Although rates of cycliza-
tion seem to be decreased by the fluorine-containing substituents the product yields
were generally very good. The developed methods should also be applicable to the
preparation of other fluorine-containing heterocycles with potential biological activity
using fluorine-containing donorꢀacceptor cyclopropanes as key intermediates.
Experimental Part
General. Reactions were generally performed under Ar in flame-dried flasks. Solvents and reagents
were added by syringes. Diazo esters were added with an infusion pump (Precidor Type 8003). Solvents
were dried by standard procedures. Methyl 2-diazoacetate (2a) [17] and ethyl 3,3,3-trifluoro-2-
diazopropanoate (2b) [18] were prepared according to literature procedures. Reagents were purchased
and were used as received without further purification unless otherwise stated. Bulb-to-bulb distillations
were performed with a BꢀCHI glass oven (B-585). Column chromatography (CC): SiO2 (230 – 400 mesh,
Merck or Fluka) or Al2O3 (70 – 230 mesh, Merck or Fluka). Yields refer to anal. pure samples. M.p.:
Reichert apparatus Thermovar; uncorrected. IR Spectra: JASCO FT/IR-4100 spectrometer. NMR
Spectra: Bruker (AVIII 700) and JEOL (ECS 500, ECX 400, and Eclipse 500) instruments; chemical
shifts are reported relative to Me4Si (d(H) 0.00), CDCl3 (d(H) 7.26, d(C) 77.2; d(F), frequency calibrated
lock with ꢁ 1 ppm deviation) or CD3OD (d(H) 4.87, 3.31); all 13C-NMR spectra are 1H- or 19F-
decoupled; mc, centered multiplet; coupling constants in Hz. HR-MS: Agilent 6210 (ESI-TOF)
instrument. Elemental analyses: Perkin Elmer CHN-Analyzer 2400 and Vario EL Elemental Analyzer.
General Procedure (GP) for the Cyclopropanations. The silyl enol ether 1 was dissolved in CH2Cl2,
and Rh2(OAc)4 was added. A soln. of the corresponding diazo ester 2 in CH2Cl2 was added to the mixture
over 4 h using an infusion pump. After 30 min, the gas evolution decreased and the mixture was
concentrated under reduced pressure. The residue was suspended in hexane to precipitate the catalyst,

Helvetica Chimica Acta – Vol. 95 (2012)
1823
and the supernatant soln. was concentrated under reduced pressure. The crude product was purified
either by CC or distillation through a short Vigreux column (10 cm).
Methyl 2-[(Trimethylsilyl)oxy]-2-(undecafluoropentyl)cyclopropanecarboxylate (3a). According to
GP, 1a (2.99 g, 7.78 mmol), Rh2(OAc)4 (340 mg, 0.78 mmol), and 2a (3.11 g, 31.1 mmol) gave, after CC
(SiO2; 0 – 5% AcOEt in hexane), 3a (3.26 g, 92%, dr 50 :50). Colorless liquid. IR (ATR): 3090 – 2760
(CꢀH), 1750 (C¼O), 1235, 1200, 1140 (CꢀF). HR-ESI-TOF-MS: 479.0514 ([M þ Na]þ,
C13H15F11NaO3Siþ; calc. 479.0513). Anal. calc. for C13H15F11O3Si (456.32): C 34.22, H 3.31; found: C
34.18, H 3.11.
1
Data of Diastereoisomer a. H-NMR (700 MHz, CDCl3): 3.73 (s, COOMe); 2.17 (dd, J ¼ 10.2, 8.9,
HꢀC(1)); 1.81 (ddd, J ¼ 8.9, 7.2, J(H,F) ¼ 1.7, 1 H of CH2(3)); 1.42 (ddd, J ¼ 10.2, 7.2, J(H,F) ¼ 3.9, 1 H of
CH2(3)); 0.19 (s, Me3Si). 13C-NMR (176 MHz, CDCl3): 168.1 (d, J(C,F) ¼ 1.4, COOMe); 117.6 (tq, J ¼
33.0, 288, (CF2)4CF3); 114.6, 111.7, 110.7, 108.7 (4mc, (CF2)4CF3); 60.9 (t, J(C,F) ¼ 30.5, C(2)); 52.5 (q,
COOMe); 27.9 (mc, C(1)); 15.9 (td, J(C,F) ¼ 5.0, C(3)); 0.80 (q, Me3Si). 19F-NMR (470 MHz, CDCl3):
ꢀ 80.8 (t, J ¼ 9.6, (CF2)4CF3); ꢀ 114.5 to ꢀ 127.3 (4m, (CF2)4CF3).
1
Data of Diastereoisomer b. H-NMR (700 MHz, CDCl3): 3.71 (s, COOMe); 2.14 (ddt, J ¼ 9.5, 7.2,
J(H,F) ¼ 2.1, HꢀC(1)); 1.72 (td, J(H,F) ¼ 2.9, J ¼ 7.2, 1 H of CH2(3)); 1.51 (dd, J ¼ 7.2, 9.5, 1 H of
CH2(3)); 0.18 (s, Me3Si). 13C-NMR (176 MHz, CDCl3): 167.6 (s, COOMe); 117.6 (tq, J(C,F) ¼ 33.0, 288,
(CF2)4CF3); 115.5, 111.7, 110.7, 108.7 (4mc, (CF2)4CF3); 60.5 (t, J(C,F) ¼ 30.5, C(2)); 52.4 (q, COOMe);
24.2 (td, J(C,F) ¼ 6.2, C(1)); 14.6 (td, J(C,F) ¼ 3.4, C(3)); 0.75 (qq, J(C,F) ¼ 1.8, Me3Si). 19F-NMR
(470 MHz, CDCl3): ꢀ 80.8 (t, J ¼ 9.6, (CF2)4CF3); ꢀ 114.5 to ꢀ 127.3 (4m, (CF2)4CF3).
Methyl 2-(Trifluoromethyl)-2-[(trimethylsilyl)oxy]cyclopropanecarboxylate (3b). According to GP,
1b (4.00 g, 21.7 mmol), Rh2(OAc)4 (480 mg, 1.09 mmol), and 2a (8.69 g, 87.0 mmol) gave, after CC (SiO2,
20% Et2O in pentane), 3b (4.67 g, 84%, dr 75 :25). Colorless liquid. IR (ATR): 3020 – 2810 (CꢀH), 1745
(C¼O), 1330, 1280, 1250, 1170 (CꢀF). HR-ESI-TOF-MS: 279.0620 ([M þ Na]þ, C9H15F3NaO3Siþ; calc.
279.0635).
Data of the Major Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 3.72 (s, COOMe); 2.14 (dd, J ¼ 7.1,
9.7, HꢀC(1)); 1.74 (qdd, J(H,F) ¼ 1.8, J ¼ 6.9, 7.1, 1 H of CH2(3)); 1.47 (dd, J ¼ 6.9, 9.7, 1 H of CH2(3));
0.18 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 167.7 (s, COOMe); 123.8 (q, J(C,F) ¼ 277, CF3); 60.3 (q,
J(C,F) ¼ 38.3, C(2)); 52.2 (q, COOMe); 23.5 – 23.2 (m, C(1)); 16.2 – 16.0 (m, C(3)); 0.5 (qq, J(C,F) ¼ 0.8,
Me3Si). 19F-NMR (376 MHz, CDCl3): ꢀ 76.5 (s, CF3).
Data of the Minor Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 3.71 (s, COOMe); 2.14 (dd, J ¼ 8.6,
10.0, HꢀC(1)); 1.76 (dd, J ¼ 6.9, 8.6, 1 H of CH2(3)); 1.37 (qdd, J(H,F) ¼ 2.1, J ¼ 6.9, 10.0, 1 H of CH2(3));
0.20 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 168.1 (s, COOMe); 124.0 (q, J(C,F) ¼ 277, CF3); 60.4 (q,
J(C,F) ¼ 38.6, C(2)); 52.5 (q, COOMe); 27.9 – 27.6 (m, C(1)); 16.2 – 16.0 (m, C(3)); 0.6 (qq, J(C,F) ¼ 0.8,
Me3Si). 19F-NMR (376 MHz, CDCl3): ꢀ 71.8 (s, CF3).
Methyl 2-(Pentafluorophenyl)-2-[(trimethylsilyl)oxy]cyclopropanecarboxylate (3c). According to
GP, 1c (10.3 g, 36.5 mmol), Rh2(OAc)4 (161 mg, 0.365 mmol), and 2a (14.6 g, 146 mmol) gave, after flash
chromatography (SiO2; 15% Et2O in pentane), 3c (11.6 g, 90%, dr 57:43). Colorless liquid. IR (ATR):
3120 – 2730 (CꢀH), 1735 (C¼O), 1655 (C¼C); 1380, 1340, 1255, 1195, 1100 (CꢀF). HR-ESI-TOF-MS:
377.0591 ([M þ Na]þ, C14H15F5NaO3Siþ; calc. 377.0608). Anal. calc. for C14H15F5O3Si (354.34): C 47.45, H
4.27; found: C 46.66, H 4.30.
Data of the Major Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 3.62 (s, COOMe); 2.32 (tdd,
J(H,F) ¼ 1.1, J ¼ 7.5, 9.6, HꢀC(1)); 1.76 (dd, J ¼ 6.4, 9.6, 1 H of CH2(3)); 1.71 (tdd, J(H,F) ¼ 1.1, J ¼ 6.4,
7.5, 1 H of CH2(3)); 0.03 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 171.6 (s, COOMe); 146.1, 141.6, 137.6,
112.8 (4mc, Ar); 55.2 (mc, C(2)); 52.1 (q, COOMe); 27.7 (mc, C(1)); 21.8 (mc, C(3)); 0.4 (q, Me3Si). 19F-
NMR (376 MHz, CDCl3): ꢀ 140.7, ꢀ 140.9 (2m, 2 o-F); ꢀ 153.6 (m, 1 p-F); ꢀ 162.3 (m, 2 m-F).
Data of the Minor Diastereoisomer: 1H-NMR (400 MHz, CDCl3): 3.77 (s, COOMe); 2.04 (tdd,
J(H,F) ¼ 0.8, J ¼ 6.5, 7.3, 1 H of CH2(3)); 1.97 (dd, J ¼ 7.3, 9.0, 1 H of CH2(3)); 1.49 (tdd, J(H,F) ¼ 1.0,
J ¼ 6.5, 9.0, HꢀC(1)); 0.04 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 169.1 (s, COOMe); 145.7, 141.6, 137.7,
115.7 (4mc, Ar); 53.7 (mc, C(2)); 52.1 (q, COOMe); 27.6 (d, C(1)); 19.6 (mc, C(3)); 0.3 (q, Me3Si). 19F-
NMR (376 MHz, CDCl3): ꢀ 139.7 (mc, 2 o-F); ꢀ 153.1 (mc, 1 p-F); ꢀ 161.3 (mc, 2 m-F).
Ethyl 1-(Trifluoromethyl)-2-[(trimethylsilyl)oxy]-2-(undecafluoropentyl)cyclopropanecarboxylate
(3d). According to GP, 1a (12.7 g, 32.9 mmol), Rh2(OAc)4 (97 mg, 0.22 mmol), and 2b (4.00 g,

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Helvetica Chimica Acta – Vol. 95 (2012)
22.0 mmol) gave, after distillation (41 – 438/12 mbar), 3d (10.2 g, 86%, dr 83 :17). Colorless liquid. IR
(ATR): 3070 – 2830 (CꢀH), 1750 (C¼O), 1330, 1240, 1200, 1160 (CꢀF). HR-ESI-TOF-MS: 561.0547
([M þ Na]þ, C15H16F14NaO3Siþ; calc. 561.0543). Anal. calc. for C15H16F14O3Si (538.35): C 33.47, H 3.00;
found: C 33.45, H 3.04.
Data of the Major Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.25, 4.17 (AB of ABX3, J(A,X) ¼
J(B,X) ¼ 7.2, J(A,B) ¼ 10.9, COOCH2Me); 2.14 (dt, J(H,F) ¼ 1.9, J ¼ 8.3, 1 H of CH2(3)); 1.86 (ddd,
J(H,F) ¼ 0.5, 1.5, J ¼ 8.3, 1 H of CH2(3)); 1.27 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.2, COOCH2Me); 0.19 (s,
Me3Si). 13C-NMR (176 MHz, CDCl3): 162.8 (s, COOCH2Me); 123.0 (dq, J(C,F) ¼ 1.3, 276, CF3); 117.5
(tq, J(C,F) ¼ 32.8, 288, (CF2)4CF3); 115.0, 111.4, 110.7, 108.7 (4mc, (CF2)4CF3); 62.9 (t, J(C,F) ¼ 32.2,
C(2)); 63.0 (t, COOCH2Me); 38.4 (dq, J(C,F) ¼ 7.7, 33.3, C(1)); 16.8 (t, C(3)); 13.5 (q, COOCH2Me); 0.7
(q, Me3Si). 19F-NMR (376 MHz, CDCl3): ꢀ 61.6 (s, CF3); ꢀ 80.7 (tdd, J ¼ 2.5, 8.6, 11.2, (CF2)4CF3); ꢀ
106.6 to ꢀ 128.2 (m, (CF2)4CF3).
Data of the Minor Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.35 (q, J ¼ 7.1, COOCH2Me); 1.96
(dd, J(H,F) ¼ 1.7, J ¼ 8.2, 1 H of CH2(3)); 1.51 – 1.48 (m, 1 H of CH2(3)); 1.32 (t, J ¼ 7.1, COOCH2Me);
0.16 (s, Me3Si). 13C-NMR (176 MHz, CDCl3): 163.3 (s, COOCH2Me); 122.8 (q, J(C,F) ¼ 276, CF3); 117.5
(mc, (CF2)4CF3); 115.0, 111.4, 110.7, 108.8 (4mc, (CF2)4CF3); 62.9 (t, J(C,F) ¼ 30.9, C(2)); 62.9 (t,
COOCH2Me); 41.4 (dq, J(C,F) ¼ 6.8, 37.0, C(1)); 17.1 (t, C(3)); 14.1 (q, COOCH2Me); 0.7 (q, Me3Si).
(CF2)4CF3 not resolved due to overlap with major diastereoisomer. 19F-NMR (376 MHz, CDCl3): ꢀ 58.9
(dd, J ¼ 17.0, 29.3, CF3); ꢀ 80.7 (overlapping with major diastereoisomer, (CF2)4CF3); ꢀ 106.6 to
ꢀ 128.2 (m, (CF2)4CF3).
Ethyl 1,2-Bis(trifluoromethyl)-2-[(trimethylsilyl)oxy]cyclopropanecarboxylate (3e). According to
GP, 1b (22.5 g, 122 mmol), Rh2(OAc)4 (359 mg, 0.813 mmol), and 2b (14.8 g, 81.0 mmol) gave, after
distillation (82 – 848/12 mbar), 3e (23.5 g, 85%, dr 77:23). Colorless liquid. IR (ATR): 3015 – 2925
(CꢀH), 1750 (C¼O), 1335, 1300, 1260, 1165 (CꢀF). HR-ESI-TOF-MS: 377.0422 ([M þ K]þ,
C11H16F6KO3Siþ; calc. 377.0410).
Data of cis-3e. 1H-NMR (400 MHz, CDCl3): 4.28, 4.24 (AB of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1,
J(A,B) ¼ 10.8, COOCH2Me); 2.06, 1.83 (2qd, J(H,F) ¼ 1.7, J ¼ 8.2, CH2(3)); 1.28 (X of ABX3, J(A,X) ¼
J(B,X) ¼ 7.1, COOCH2Me); 0.16 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 163.1 (q, J(C,F) ¼ 2.2,
COOCH2Me); 123.0, 122.8 (2q, J(C,F) ¼ 278 each, 2 CF3); 65.5 (t, COOCH2Me); 61.6 (q, J(C,F) ¼ 40.6,
C(1)); 40.0 (q, J(C,F) ¼ 37.2, C(2)); 18.9 (mc, C(3)); 14.1 (q, COOCH2Me); 0.41 (q, Me3Si). 19F-NMR
(376 MHz, CDCl3): ꢀ 61.9 (d, J(F,H) ¼ 1.5, CF3); ꢀ 73.3 (s, CF3).
Data of trans-3e. 1H-NMR (400 MHz, CDCl3): 4.30, 4.23 (AB of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1,
J(A,B) ¼ 3.5, COOCH2Me); 2.16 (qd, J(H,F) ¼ 1.7, J ¼ 8.0, 1 H of CH2(3)); 1.96 (d, J ¼ 8.0, 1 H of
CH2(3)); 1.33 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1, COOCH2Me); 0.20 (s, Me3Si). 13C-NMR (101 MHz,
CDCl3): 163.0 (q, J(C,F) ¼ 1.4, COOCH2Me); 122.9, 122.7 (2q, J(C,F) ¼ 276, 275, 2 CF3); 63.0 (t,
COOCH2Me); 61.4 (q, J(C,F) ¼ 39.0, C(1)); 37.2 (q, J(C,F) ¼ 33.7, C(2)); 18.2 (mc, C(3)); 13.8 (q,
COOCH2Me); 0.41 (q, Me3Si). 19F-NMR (376 MHz, CDCl3): ꢀ 71.9 (q, J ¼ 11.3, CF3); ꢀ 59.5 (qd,
J(F,H) ¼ 1.7, J ¼ 11.3, CF3).
Ethyl 1-(Trifluoromethyl)-2-[(trimethylsilyl)oxy]cyclopropanecarboxylate (3f). According to GP, 1d
(19.1 g, 156 mmol), Rh2(OAc)4 (485 mg, 1.10 mmol), and 2b (20.0 g, 110 mmol) gave, after distillation
(80 – 828/12 mbar), 3f (22.5 g, 76%, dr 63 :37). Colorless liquid. IR (ATR): 3010 – 2920 (CꢀH), 1740
(C¼O), 1365, 1260, 1140, 1100 (CꢀF). HR-ESI-TOF-MS: 309.0544 ([M þ K]þ, C10H17F3KO3Siþ; calc.
309.0531).
Data of the Major Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.25, 4.21 (AB of ABX3, J(A,X) ¼
J(B,X) ¼ 7.1, J(A,B) ¼ 10.6, COOCH2Me); 3.87 (mc, HꢀC(2)); 1.96 (qdd, J(H,F) ¼ 1.6, J ¼ 5.3, 7.0, 1 H of
CH2(3)); 1.48 (t, J ¼ 7.0, 1 H of CH2(3)); 1.27 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1, COOCH2Me); 0.14 (s,
Me3Si). 13C-NMR (101 MHz, CDCl3): 164.5 (q, J(C,F) ¼ 1.4, COOCH2Me); 124.0 (q, J(C,F) ¼ 274, CF3);
61.8 (t, COOCH2Me); 55.4 (tq, J(C,F) ¼ 2.5, C(2)); 31.9 (q, J(C,F) ¼ 32.7, C(1)); 18.4 (dq, J(C,F) ¼ 1.9,
C(3)); 14.2 (q, COOCH2Me); ꢀ 0.5 (q, Me3Si). 19F-NMR (376 MHz, CDCl3): ꢀ 65.2 (s, CF3).
Data of the Minor Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.24, 4.20 (AB of ABX3, J(A,X) ¼
J(B,X) ¼ 7.1, J(A,B) ¼ 10.6, COOCH2Me); 3.87 (mc, HꢀC(2)); 1.76 – 1.62 (m, CH2(3)); 1.28 (X of ABX3,
J(A,X) ¼ J(B,X) ¼ 7.1, COOCH2Me); 0.16 (s, Me3Si). 13C-NMR (101 MHz, CDCl3): 167.7 (q, J(C,F) ¼
1.2, COOCH2Me); 124.1 (q, J(C,F) ¼ 273, CF3); 61.9 (t, COOCH2Me); 58.9 (t, C(2)); 34.0 (q,

Helvetica Chimica Acta – Vol. 95 (2012)
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J(C,F) ¼ 33.4, C(1)); 19.6 (dq, J(C,F) ¼ 1.8, C(3)); 14.2 (q, COOCH2Me); ꢀ 0.5 (q, Me3Si). 19F-NMR
(376 MHz, CDCl3): ꢀ 60.3 (s, CF3).
Methyl 5,5,6,6,7,7,8,8,9,9,9-Undecafluoro-4-hydroxynonanoate (4a). NaBH4 (45 mg, 1.20 mmol) was
added at 08 to a soln. of 3a (500 mg, 1.10 mmol) in MeOH (2 ml). After stirring at r.t. for 12 h, the
mixture was diluted with Et2O (20 ml) and washed with sat. NaHCO3 soln. (20 ml). The org. layer was
washed with brine, dried (Na2SO4), and concentrated under reduced pressure. Bulb-to-bulb distillation
(808/0.5 mbar) afforded alcohol 4a (378 mg, 89%). Colorless liquid. IR (ATR): 3880 – 3050 (OꢀH),
3050 – 2660 (CꢀH), 1725 (C¼O), 1350, 1235, 1200, 1140, 1105 (CꢀF). 1H-NMR (400 MHz, CDCl3):
4.34 – 4.11 (m, HꢀC(4)); 3.71 (s, COOMe); 3.01 (d, J ¼ 7.3, HOꢀC(4)); 2.65 (ddd, J ¼ 5.9, 8.0, 17.5, 1 H of
CH2(2)); 2.57 (ddd, J ¼ 6.0, 7.3, 17.5, 1 H of CH2(2)); 2.10 (tddd, J(H,F) ¼ 2.6, J ¼ 5.4, 8.0, 13.4, 1 H of
CH2(3)); 2.07 – 1.91 (m, 1 H of CH2(3)). 13C-NMR (126 MHz, CDCl3): 174.7 (d, J(C,F) ¼ 0.8, C(1));
117.4 (tq, J(C,F) ¼ 33.5, 288, C(9)); 116.4 – 106.0 (4m, C(5), C(6), C(7), C(8)); 69.4 (ddd, J(C,F) ¼ 23.0,
27.1, C(4)); 52.0 (q, COOMe); 29.6 (t, C(3)); 24.3 (t, C(2)). 19F-NMR (376 MHz, CDCl3): ꢀ 80.7 (tt, J ¼
2.5, 10.0, CF3(9)); ꢀ 127.4 to ꢀ 120.5 (m, CF2(5), CF2(6), CF2(7), CF2(8)). HR-ESI-TOF-MS: 409.0290
([M þ Na]þ, C10H9NaF11Oþ3 ; calc. 409.0274). Anal. calc. for C10H9F11O3 (386.16): C 31.10, H 2.35; found:
C 31.34, H 2.39.
Methyl 5,5,5-Trifluoro-4-hydroxypentanoate (4b). NaBH4 (49 mg, 2.1 mmol) was added at 08 to a
soln. of 3b (500 mg, 1.95 mmol) in MeOH (2 ml). After stirring at r.t. for 12 h the mixture was diluted
with Et2O (20 ml) and washed with sat. NaHCO3 soln. (20 ml). The org. layer was washed with brine,
dried (Na2SO4), and concentrated under reduced pressure. Bulb-to-bulb distillation (1458/15 – 20 mbar)
afforded 4b (308 mg, 85%). Colorless liquid. 1H-NMR (400 MHz, CDCl3): 4.07 – 3.92 (m, HꢀC(4)); 3.68
(s, COOMe); 3.67 – 3.58 (m, HOꢀC(4)); 2.59 – 2.49 (m, CH2(2)); 2.03 (dtd, J ¼ 3.2, 7.3, 14.5, 1 H of
CH2(3)); 1.90 (dtd, J ¼ 6.7, 10.0, 14.5, 1 H of CH2(3)). 13C-NMR (101 MHz, CDCl3): 174.4 (s, C(1)); 125.1
(q, J(C,F) ¼ 282, C(5)); 69.7 (dq, J(C,F) ¼ 31.3, C(4)); 52.2 (q, COOMe); 29.5 (t, C(2)); 24.7 (tq, J(C,F) ¼
1.7, C(3)). 19F-NMR (376 MHz, CDCl3): ꢀ 80.0 (d, J(F,H) ¼ 6.3, FꢀC(5)). HR-ESI-TOF-MS: 209.0398
([M þ Na]þ, C6H9F3NaOþ3 ; calc. 209.0396). Enantiomerically pure (R)-ethyl 5,5,5-trifluoro-4-hydroxy-
pentanoate was reported in [8], however, 13C- and 19F-NMR spectra have not been described.
Ethyl 5,5,5-Trifluoro-4-hydroxy-2-(trifluoromethyl)pentanoate (4c). KBH4 (80 mg, 1.5 mmol) was
added at 08 to a soln. of 3e (500 mg, 1.48 mmol) in MeOH (5 ml). After stirring for 1 h, the mixture was
diluted with CH2Cl2 (30 ml) and washed with 1m HCl soln. (20 ml). The org. layer was washed with brine,
dried (Na2SO4), and concentrated under reduced pressure. CC (SiO2; 50% Et2O in pentane) afforded 4c
(266 mg, 67%, dr 56 :44). Colorless oil. IR (ATR): 3705 – 3050 (OꢀH), 3050 – 2720 (CꢀH), 1730 (C¼O),
1270, 1165, 1105 (CꢀF). HR-ESI-TOF-MS: 291.0419 ([M þ Na]þ, C8H10F6NaO3þ ; calc. 291.0432). Anal.
calc. for C8H10F6O3 (268.15): C 35.83, H 3.76; found: C 35.74, H 3.76.
Data of the Major Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.30, 4.25 (AB of ABX3, J(A,X) ¼
J(B,X) ¼ 7.1, J(A,B) ¼ 10.9, COOCH2Me); 4.17 – 3.97 (m, HꢀC(4)); 3.59 – 3.27 (m, CH2(2)); 2.83 – 2.61
(m, HOꢀC(5)); 2.37 – 2.01 (m, CH2(3)); 1.30 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1, COOCH2Me).
13C-NMR (101 MHz, CDCl3): 167.6 (q, J(C,F) ¼ 2.7, C(1)); 124.7, 124.5 (2q, J(C,F) ¼ 280, 282, CF3ꢀC(2),
CF3ꢀC(4)); 68.9 (dq, J(C,F) ¼ 32.0, C(4)); 62.7 (t, COOCH2Me); 47.2 (dq, J(C,F) ¼ 28.2, C(2)); 26.6 –
26.4 (m, C(3)); 14.0 (q, COOCH2Me). 19F-NMR (376 MHz, CDCl3): ꢀ 68.3 (d, J(F,H) ¼ 8.6, CF3ꢀC(2));
ꢀ 80.3 (d, J(F,H) ¼ 6.3, CF3(5)).
Data of the Minor Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.32, 4.24 (AB of ABX3, J(A,X) ¼
J(B,X) ¼ 7.1, J(A,B) ¼ 10.7, COOCH2Me); 4.17 – 3.97 (m, HꢀC(4)); 3.59 – 3.43 (m, 1 H of CH2(2));
3.43 – 3.27 (m, 1 H of CH2(2)); 2.83 – 2.61 (m, HOꢀC(5)); 2.37 – 2.01 (m, CH2(3)); 1.31 (X of ABX3,
J(A,X) ¼ J(B,X) ¼ 7.1, COOCH2Me). 13C-NMR (101 MHz, CDCl3): 167.1 (q, J(C,F) ¼ 3.4, C(1)); 124.6,
124.50 (2q, J(C,F) ¼ 282, 280, CF3ꢀC(2), CF3ꢀC(4)); 67.5 (dq, J(C,F) ¼ 32.1, C(4)); 62.6 (t,
COOCH2Me); 46.1 (dq, J(C,F) ¼ 28.5, C(2)); 26.2 – 26.0 (m, C(3)); 13.9 (q, COOCH2Me). 19F-NMR
(376 MHz, CDCl3): ꢀ 68.1 (d, J(F,H) ¼ 8.2, CF3ꢀC(2)); ꢀ 80.4 (d, J(F,H) ¼ 6.3, CF3(5)).
Ethyl 4-Hydroxy-2-(trifluoromethyl)butanoate (4d). KBH4 (100 mg, 1.85 mmol) was added at 08 to a
soln. of 3f (500 mg, 1.85 mmol) in MeOH (5 ml). After stirring for 1 h, the mixture was diluted with
CH2Cl2 (30 ml) and washed with 1m HCl soln. (20 ml). The org. layer was washed with brine, dried
(Na2SO4), and concentrated under reduced pressure. CC (SiO2, 20% AcOEt in hexane) afforded 4d
(256 mg, 69%). Colorless liquid. IR (ATR): 3715 – 3065 (OꢀH), 3060 – 2670 (CꢀH), 1740 (C¼O), 1320,

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Helvetica Chimica Acta – Vol. 95 (2012)
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1265, 1160, 1110 (CꢀF). H-NMR (400 MHz, CDCl3): 4.24, 4.21 (AB of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1,
J(A,B) ¼ 10.8, COOCH2Me); 3.78 – 3.71 (m, 1 H of CH2(4)); 3.70 – 3.63 (m, 1 H of CH2(4)); 3.44 – 3.26
(m, HꢀC(2)); 2.22 – 1.95 (m, CH2(3)); 1.85 (s, HOꢀC(4)); 1.28 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1,
COOCH2Me). 13C-NMR (101 MHz, CDCl3): 167.9 (q, J(C,F) ¼ 3.2, C(1)); 124.9 (q, J(C,F) ¼ 280, CF3);
62.0 (t, COOCH2Me); 59.3 (t, C(4)); 47.3 (dq, J(C,F) ¼ 27.8, C(2)); 29.0 (tq, J(C,F) ¼ 2.0, C(3)); 13.9 (q,
COOCH2Me). 19F-NMR (376 MHz, CDCl3): ꢀ 68.3 (d, J(F,H) ¼ 8.4, CF3). HR-ESI-TOF-MS: 223.0558
([M þ Na]þ, C7H11F3NaO3þ ; calc. 223.0558). Anal. calc. for C7H11F3O3 (200.16): C 42.00, H 5.54; found:
C 41.88, H 5.20.
4,5-Dihydro-5-(undecafluoropentyl)furan-2(3H)-one (5a). KBH4 (59 mg, 1.10 mmol) was added at
08 to a soln. of 3a (500 mg, 1.10 mmol) in MeOH (2 ml). After stirring for 1 h at 08 and 16 h at r.t., MeOH
was removed under reduced pressure. The residue was dissolved in CH2Cl2 (10 ml), and TsOH · H2O
(140 mg, 0.736 mmol) was added. The mixture was heated under reflux for 48 h, in doing so every 12 h
CH2Cl2 was evaporated and replaced. CH2Cl2 was removed under reduced pressure and CC (SiO2; 50%
Et2O in pentane) of the crude material afforded g-lactone 5a (290 mg, 75%). Colorless liquid. IR (ATR):
1
3060 – 2690 (CꢀH), 1795 (C¼O), 1230, 1195, 1140 (CꢀF). H-NMR (400 MHz, CDCl3): 5.09 – 4.84 (m,
HꢀC(5)); 2.76 – 2.18 (m, CH2(3), CH2(4)). 13C-NMR (101 MHz, CDCl3): 174.9 (s, C(2)); 117.3 (tq,
J(C,F) ¼ 33.1, 288, (CF2)4CF3); 114.8, 111.1, 110.5, 108.6 (4mc, (CF2)4CF3); 74.3 (ddd, J(C,F) ¼ 22.2, 33.4,
C(5)); 26.3 (t, C(3)); 20.9 (t, C(4)). 19F-NMR (376 MHz, CDCl3): ꢀ 80.7 (t, J ¼ 9.9, (CF2)4CF3); ꢀ 120.9
to ꢀ 128.4 (m, (CF2)4CF3). HR-ESI-TOF-MS: 377.0005 ([M þ Na]þ, C9H5F11NaO2þ ; calc. 377.0012).
Anal. calc. for C9H5F11O2 (354.12): C 30.53, H 1.42; found: C 30.49, H 1.30.
4,5-Dihydro-5-(trifluoromethyl)furan-2(3H)-one (5b). KBH4 (105 mg, 1.95 mmol) was added at 08
to a soln. of 3b (500 mg, 1.95 mmol) in MeOH (2 ml). After stirring for 1 h at 08 and 16 h at r.t., MeOH
was removed under reduced pressure. The residue was dissolved in CH2Cl2 (10 ml), and TsOH · H2O
(175 mg, 0.920 mmol) was added. The mixture was heated under reflux for 48 h, in doing so every 12 h
CH2Cl2 was evaporated and replaced. CH2Cl2 was removed under reduced pressure and CC (SiO2; 50%
Et2O in pentane) of the crude material afforded 5b (171 mg, 57%). Colorless liquid. IR (ATR): 3060 –
2690 (CꢀH), 1795 (C¼O), 1280, 1145, 1120 (CꢀF). 1H-NMR (400 MHz, CDCl3): 4.77 (ddq, J ¼ 4.5, 8.3,
J(H,F) ¼ 6.5, HꢀC(5)); 2.80 – 2.20 (m, CH2(3), CH2(4)). 13C-NMR (101 MHz, CDCl3): 175.1 (s, C(2));
123.7 (q, J(C,F) ¼ 280, CF3ꢀC(5)); 75.0 (dq, J(C,F) ¼ 34.4, C(5)); 26.2 (t, C(3)); 21.2 (tq, J(C,F) ¼ 1.6,
C(4)). 19F-NMR (376 MHz, CDCl3): ꢀ 79.4 (d, J(F,H) ¼ 6.5, CF3ꢀC(5)). HR-ESI-TOF-MS: 155.0313
([M þ H]þ, C5H6F3Oþ2 ; calc. 155.0320). Known compound: 5b has been prepared previously; however,
NMR and MS data were not reported [15][19].
4,5-Dihydro-3,5-bis(trifluoromethyl)furan-2(3H)-one (5c). KBH4 (160 mg, 2.96 mmol) was added at
08 to a soln. of 3e (1.02 g, 2.96 mmol) in MeOH (10 ml). After stirring for 10 min at 08, the mixture was
diluted with CH2Cl2 (30 ml) and washed with 1m HCl soln. (20 ml). The org. layer was washed with brine,
dried (Na2SO4), and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (20 ml),
and TsOH · H2O (175 mg, 0.920 mmol) was added. The mixture was heated under reflux for 72 h, in doing
so every 12 h CH2Cl2 was evaporated and replaced. After removing CH2Cl2 under reduced pressure,
Na2CO3 (160 mg) was added to the crude product. Bulb-to-bulb distillation (55 – 608/0.1 mbar) afforded
5c (414 mg, 63%, dr 59 :41). Colorless liquid.
Data of the Major Diastereoisomer. IR (ATR): 3050 – 2680 (CꢀH), 1805 (C¼O), 1290, 1260, 1165,
1120 (CꢀF). 1H-NMR (400 MHz, CDCl3): 4.80 (qdd, J(H,F) ¼ 5.5, J ¼ 7.6, 8.8, HꢀC(5)); 3.61 (qd,
J(H,F) ¼ 8.3, J ¼ 10.6, HꢀC(3)); 2.82 (ddd, J ¼ 7.6, 10.4, 13.9, 1 H of CH2(4)); 2.48 (ddd, J ¼ 8.8, 10.8, 13.9,
1 H of CH2(4)). 13C-NMR (101 MHz, CDCl3): 167.0 (q, J(C,F) ¼ 3.0, C(2)); 123.2, 122.6 (2q, J(C,F) ¼
280, 279, CF3ꢀC(3), CF3ꢀC(5)); 73.1 (dq, J(C,F) ¼ 36.2, C(5)); 42.9 (dq, J(C,F) ¼ 31.2, C(3)); 22.7 (t,
C(4)). 19F-NMR (376 MHz, CDCl3): ꢀ 68.8 (mc, CF3ꢀC(3)); ꢀ 79.1 (qd, J ¼ 1.1, J(F,H) ¼ 5.5,
CF3ꢀC(5)). HR-ESI-TOF-MS: 245.0011 ([M þ Na]þ, C6H4F6NaO2þ ; calc. 245.0013). Anal. calc. for
C6H4F6O2 (222.09): C 32.45, H 1.82; found: C 32.07, H 2.26.
Data of the Minor Diastereoisomer. 1H-NMR (400 MHz, CDCl3): 4.87 (mc, HꢀC(5)); 3.64 – 3.47 (m,
HꢀC(3)); 2.82, 2.71 (2mc, CH2(4)). 13C-NMR (101 MHz, CDCl3): 167.5 (q, J(C,F) ¼ 3.1, C(2)); 123.5,
123.3 (2q, J(C,F) ¼ 278 each, CF3ꢀC(3), CF3ꢀC(5)); 73.4 (dq, J(C,F) ¼ 35.0, C(5)); 43.9 (dq, J(C,F) ¼
31.5, C(3)); 23.1 (t, C(4)). 19F-NMR (376 MHz, CDCl3): ꢀ 69.0 (d, J(F,H) ¼ 8.5, CF3ꢀC(3)); ꢀ 79.3
(d, J(F,H) ¼ 6.4, CF3ꢀC(5)).

Helvetica Chimica Acta – Vol. 95 (2012)
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4,5-Dihydro-3-(trifluoromethyl)furan-2(3H)-one (5d). KBH4 (200 mg, 3.70 mmol) was added at 08
to a soln. of 3f (1.00 g, 3.70 mmol) in MeOH (10 ml). After stirring for 30 min at 08, the mixture was
diluted with CH2Cl2 (30 ml) and washed with 1m HCl soln. (20 ml). The org. layer was washed with brine,
dried (Na2SO4) and concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (20 ml),
and TsOH · H2O (352 mg, 1.85 mmol) was added. The mixture was heated under reflux for 12 h, in doing
so every 12 h CH2Cl2 was evaporated and replaced. CH2Cl2 was removed under reduced pressure and CC
(SiO2, 10 – 50% Et2O in pentane) of the crude material afforded 5d (320 mg, 56%). Colorless liquid. IR
1
(ATR): 3070 – 2740 (CꢀH), 1780 (C¼O), 1260, 1170, 1120 (CꢀF). H-NMR (500 MHz, CDCl3): 4.49 –
4.29 (m, CH2(5)); 3.44 – 3.28 (m, HꢀC(3)); 2.63 – 2.44 (m, CH2(4)). 13C-NMR (101 MHz, CDCl3):
169.8 (q, J(C,F) ¼ 3.5, C(2)); 124.1 (q, J(C,F) ¼ 278, CF3ꢀC(3)); 66.5 (t, C(5)); 44.0 (dq, J(C,F) ¼ 30.4,
C(3)); 23.5 (tq, J(C,F) ¼ 2.0, C(4)). 19F-NMR (470 MHz, CDCl3): ꢀ 68.6 (s, CF3ꢀC(3)). HR-ESI-TOF-
MS: 177.0149 (C5H5F3NaOþ2 ; [M þ Na]þ, calc. 177.0139). Anal. calc. for C5H5F3O2 (154.09): C 38.97,
H 3.27; found: C 38.97, H 3.31.
4,5-Dihydro-6-(undecafluoropentyl)pyridazin-3(2H)-one (6a). A soln. of 3a (500 mg, 1.10 mmol),
TsOH · H2O (42 mg, 0.20 mmol), and NH2NH2 · H2O (55 mg, 1.1 mmol) in MeOH (5 ml) was heated
under reflux for 24 h. All volatiles were removed under reduced pressure and the crude product was
purified by CC (SiO2; 30% AcOEt in hexane) to afford 6a (288 mg, 72%). Colorless crystals. M.p. 110 –
1128. IR (ATR): 3770 – 3040 (NꢀH), 3040 – 2675 (CꢀH), 1655 (C¼O), 1450, 1410 (C¼N), 1240, 1205,
1110 (CꢀF). 1H-NMR (400 MHz, CDCl3): 10.48 (s, NH); 5.81 (t, J ¼ 8.4, CH2(4)); 5.63 (t, J ¼ 8.4,
CH2(5)). 13C-NMR (101 MHz, CDCl3): 167.0 (s, C(3)); 140.8 (t, J(C,F) ¼ 26.8, C(6)); 117.3 (tq, J(C,F) ¼
32.9, 289, (CF2)4CF3); 112.8, 111.2, 110.6, 108.8 (4mc, (CF2)4CF3); 25.2 (t, C(4)); 20.4 (t, C(5)). 19F-NMR
(376 MHz, CD3OD): ꢀ 82.4 (t, J ¼ 10.1, (CF2)4CF3); ꢀ 115.8 (tt, J(F,H) ¼ 2.7, J ¼ 13.5, 2 F of
(CF2)4CF3); ꢀ 122.9 to ꢀ 127.6 (m, 6 F of (CF2)4CF3). HR-ESI-TOF-MS: 389.0093 ([M þ Na]þ,
C9H5F11N2NaOþ; calc. 389.0124). Anal. calc. for C9H5F11N2O (366.13): C 29.52, H 1.38, N 7.65; found: C
29.50, H 1.60, N 7.69.
4,5-Dihydro-6-(trifluoromethyl)pyridazin-3(2H)-one (6b). A soln. of 3b (500 mg, 1.95 mmol),
TsOH · H2O (74 mg, 0.390 mmol), and NH2NH2 · H2O (98 mg, 2.00 mmol) in MeOH (5 ml) was heated
under reflux for 48 h. All volatiles were removed under reduced pressure, and the crude product was
purified by CC (neutral Al2O3, 20% AcOEt in hexane) to give 6b (282 mg, 87%). Colorless crystals. M.p.
89 – 918.1H-NMR (400 MHz, CDCl3): 9.23 (s, NH); 2.76, 2.62 (2t, J ¼ 8.3, CH2(4), CH2(5)). Known
compound: NMR data are consistent with reported values; m.p. 75 – 778 [15].
4,5-Dihydro-6-(pentafluorophenyl)pyridazin-3(2H)-one (6c). A soln. of 3c (500 mg, 1.41 mmol),
TsOH · H2O (1.34 g, 7.06 mmol), and NH2NH2 · H2O (353 mg, 7.06 mmol) in toluene (30 ml) was heated
under reflux for 60 h. All volatiles were removed under reduced pressure, and the crude product was
purified by flash chromatography (FC; SiO2; 40% AcOEt in hexane) to afford 6c (278 mg, 75%).
Colorless crystals. M.p. 158 – 1608. IR (ATR): 3730 – 3170 (NꢀH), 3170 – 2740 (CꢀH), 1690 (C¼O), 1525,
1495 (C¼N), 1340, 1295, 1215, 1130 (CꢀF). 1H-NMR (400 MHz, CDCl3): 9.72 (s, NH); 2.86, 2.64 (2t, J ¼
8.2, CH2(4), CH2(5)). 13C-NMR (101 MHz, CDCl3): 167.2 (s, C(3)); 141.7 (s, C(6)); 144.6, 141.7, 137.9,
112.3 (s, 3d, Ar); 26.2 (t, C(4)); 26.0 (m, C(5)). 19F-NMR (376 MHz, CDCl3): ꢀ 141.2 (mc, 2 F); ꢀ 152.2
(mc, 1 F); ꢀ 161.0 (mc, 2 F). HR-ESI-TOF-MS: 265.0387 ([M þ H]þ, C10H6F5N2Oþ; calc. 265.0400).
Anal. calc. for C10H5F5N2O (264.15): C 45.47, H 1.91, N 10.61; found: C 45.48, H 1.95, N 10.61.
4,5-Dihydro-4,6-bis(trifluoromethyl)pyridazin-3(2H)-one (6d). A soln. of 3e (500 mg, 1.48 mmol),
TsOH · H2O (562 mg, 2.96 mmol), and NH2NH2 · H2O (148 mg, 2.96 mmol) in toluene (7 ml) was heated
under reflux for 60 h. All volatiles were removed under reduced pressure, and the crude product was
purified by FC (SiO2; AcOEt) to give 6d (310 mg, 90%). Colorless crystals. M.p. 72 – 748. IR (ATR):
3620 – 3055 (NꢀH), 3055 – 2750 (CꢀH), 1660 (C¼O), 1480, 1440 (C¼N), 1300, 1250, 1200, 1180, 1140,
1
1120 (CꢀF). H-NMR (500 MHz, CDCl3): 9.11 (s, NH); 3.40 (X of ABX, HꢀC(4)); 3.16 – 2.87 (AB of
ABX, J(A,B) ¼ 18.4, CH2(5)). 13C-NMR (101 MHz, CDCl3): 160.3 (q, J(C,F) ¼ 2.2, C(3)); 139.7 (q,
J(C,F) ¼ 37.3, C(6)); 123.9, 112.0 (2q, J(C,F) ¼ 280, 273, CF3ꢀC(6), CF3ꢀC(3)); 40.3 (dq, J(C,F) ¼ 28.9,
C(4)); 20.5 (tq, J(C,F) ¼ 2.5, C(5)). 19F-NMR (471 MHz, CDCl3): ꢀ 68.9 (d, J(F,H) ¼ 8.4, CF3ꢀC(4));
ꢀ 71.3 (s, CF3ꢀC(6)). HR-ESI-TOF-MS: 257.0136 ([M þ Na]þ, C6H4F6N2NaOþ; calc. 257.0126). Anal.
calc. for C6H4F6N2O (234.10): C 30.78, H 1.72, N 11.97; found: C 31.05, H 1.96, N 12.37.

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Helvetica Chimica Acta – Vol. 95 (2012)
4,5-Dihydro-4-(trifluoromethyl)pyridazin-3(2H)-one (6e). A soln. of 3f (500 mg, 1.85 mmol),
TsOH · H2O (70 mg, 0.37 mmol), and NH2NH2 · H2O (93 mg, 1.85 mmol) in MeOH (5 ml) was heated
under reflux for 48 h. All volatiles were removed under reduced pressure, and the crude product was
purified by FC (neutral Al2O3; 20% AcOEt in hexane) to furnish 6e (127 mg, 41%). Colorless crystals.
M.p. 82 – 848. IR (ATR): 3745 – 3035 (NꢀH), 3035 – 2710 (CꢀH), 1670 (C¼O), 1430, 1400 (C¼N), 1310,
1260, 1190, 1155, 1120 (CꢀF). 1H-NMR (500 MHz, CDCl3): 9.51 (s, NH); 7.19 (s, HꢀC(6)); 3.36 – 3.14 (m,
HꢀC(4)); 2.91 – 2.62 (m, CH2(5)). 13C-NMR (126 MHz, CDCl3): 160.5 (q, J(C,F) ¼ 1.9, C(3)); 142.7 (d,
C(6)); 124.3 (q, J(C,F) ¼ 280, CF3); 40.6 (dq, J(C,F) ¼ 28.4, C(4)); 22.9 (tq, J(C,F) ¼ 2.7, C(5)). 19F-NMR
(471 MHz, CDCl3): ꢀ 68.7 (d, J(F,H) ¼ 8.2, CF3). HR-ESI-TOF-MS: 189.0258 ([M þ Na]þ,
C5H5F3N2NaOþ; calc. 189.0246). Anal. calc. for C5H5F3N2O (166.10): C 36.15, H 3.03, N 16.87; found:
C 36.24, H 3.04, N 16.87. The 1H-NMR data are consistent with reported values; however, additional anal.
data were not reported [20].
4,5-Dihydro-2-phenyl-6-(undecafluoropentyl)pyridazin-3(2H)-one (7a). A soln. of 3a (200 mg,
0.438 mmol), TsOH · H2O (83 mg, 0.440 mmol), and PhNHNH2 (47 mg, 0.440 mmol) in toluene (15 ml)
was stirred at 908 for 60 h. A colorless precipitate was filtered off, and all volatiles were removed under
reduced pressure. The crude product was purified by CC (SiO2; 15% AcOEt in hexane) to afford 7a
(136 mg, 70%). Yellow wax. IR (ATR): 3765 – 3185 (C¼CꢀH), 3185 – 2725 (CꢀH), 1715 (C¼O), 1495,
1430 (C¼N), 1375, 1360, 1305, 1230, 1195, 1140, 1105 (CꢀF). 1H-NMR (400 MHz, CDCl3): 7.52 – 7.25 (m,
5 arom. H); 2.96 – 2.74 (m, CH2(4), CH2(5)). 13C-NMR (101 MHz, CDCl3): 164.3 (s, C(2)); 141.7 (t,
J(C,F) ¼ 27.2, C(6)); 140.2, 128.8, 127.5, 124.7 (s, 3d, Ph); 117.4 (tq, J(C,F) ¼ 33.1, 288, (CF2)4CF3); 115.3 –
107.5 (4m, (CF2)4CF3); 27.2 (t, C(4)); 21.3 (t, C(5)). 19F-NMR (376 MHz, CDCl3): ꢀ 80.6 (tt, J ¼ 2.5, 9.9,
(CF2)4CF3); ꢀ 114.7 (tt, J ¼ 3.1, 13.6, 2 F of (CF2)4CF3); ꢀ 126.4 to ꢀ 121.3 (3m, 6 F of (CF2)4CF3). HR-
ESI-TOF-MS: 465.0443 ([M þ Na]þ, C15H9F11N2NaOþ; calc. 465.0437). Anal. calc. for C15H9F11N2O
(442.23): C 40.74, H 2.05, N 6.33; found: C 40.62, H 2.22, N 6.34.
4,5-Dihydro-2-phenyl-6-(trifluoromethyl)pyridazin-3(2H)-one (7b). A soln. of 3b (200 mg,
0.780 mmol), TsOH · H2O (148 mg, 0.780 mmol), and PhNHNH2 (84 mg, 0.78 mmol) in toluene
(15 ml) was stirred at 908 for 60 h. A colorless precipitate was filtered off, and all volatiles were
removed under reduced pressure. The crude product was purified by CC (SiO2, 15% AcOEt in hexane)
to give 7b (157 mg, 83%). Yellow oil. 1H-NMR (400 MHz, CDCl3): 7.51 – 7.36 (m, 4 arom. H); 7.33 – 7.27
(m, 1 arom. H); 2.93 – 2.73 (m, CH2(4), CH2(5)). The compound was reported as a chocolate brown solid,
and NMR data are consistent with reported values [15].
4,5-Dihydro-6-(pentafluorophenyl)-2-phenylpyridazin-3(2H)-one (7c). A soln. of 3c (500 mg,
1.41 mmol), TsOH · H2O (1.34 g, 7.06 mmol), and PhNHNH2 (763 mg, 7.06 mmol) in toluene (15 ml)
was stirred at 908 for 60 h. A colorless precipitate was filtered off, and all volatiles were removed under
reduced pressure. The crude product was purified by CC (SiO2; 30% AcOEt in hexane) to furnish 7c
(430 mg, 90%). Colorless crystals. M.p. 164 – 1668. IR (ATR): 3725 – 3125 (C¼CꢀH), 3125 – 2745 (CꢀH),
1690 (C¼O), 1525, 1490 (C¼N), 1330, 1295, 1230, 1150, 1120 (CꢀF). 1H-NMR (400 MHz, CDCl3): 7.53 –
7.23 (m, 5 arom. H); 3.07 – 2.96, 2.93 – 2.81 (2m, CH2(4), CH2(5)). 13C-NMR (101 MHz, CDCl3): 164.6 (s,
C(3)); 142.6 (mc, C(6)); 140.5, 128.7, 127.1, 124.8 (s, 3d, Ph); 144.6, 141.7, 137.9, 112.3 (4mc, Ar); 27.7 (t,
C(4)); 26.5 (mc, C(5)). 19F-NMR (376 MHz, CDCl3): ꢀ 140.9 (mc, 2 F); ꢀ 151.7 (mc, 1 F); ꢀ 160.6 (mc,
2 F). HR-ESI-TOF-MS: 363.0551 ([M þ Na]þ, C16H9F5N2NaOþ; calc. 363.0527). Anal. calc. for
C16H9F5N2O (340.25): C 56.48, H 2.67, N 8.23; found: C 56.50, H 2.71, N 8.47.
4,5-Dihydro-2-phenyl-4,6-bis(trifluoromethyl)pyridazin-3(2H)-one (7d). A soln. of 3e (500 mg,
1.48 mmol), TsOH · H2O (287 mg, 1.48 mmol), and PhNHNH2 (160 mg, 1.48 mmol) in toluene (50 ml)
was stirred at 908 for 60 h. A colorless precipitate was filtered off, and all volatiles were removed under
reduced pressure. The crude product was purified by CC (SiO2; 20% AcOEt in hexane) to yield 7d
(404 mg, 88%). Colorless crystals. M.p. 88 – 908. IR (ATR): 3735 – 3150 (C¼CꢀH), 3050 – 2785 (CꢀH),
1710 (C¼O), 1495, 1430 (C¼N), 1290, 1260, 1210, 1170, 1120 (CꢀF). 1H-NMR (500 MHz, CDCl3): 7.53 –
7.31 (m, 5 arom. H); 3.56 (m, HꢀC(4)); 3.23 – 3.06 (m, CH2(5)). 13C-NMR (101 MHz, CDCl3): 157.8 (q,
J(C,F) ¼ 2.1, C(3)); 139.2 (q, J(C,F) ¼ 37.3, C(6)); 139.6, 129.0, 128.2, 125.0 (s, 3d, Ph); 124.0, 119.9 (2q,
J(C,F) ¼ 281, 274, CF3ꢀC(6), CF3ꢀC(4)); 41.5 (dq, J(C,F) ¼ 28.6, C(4)); 21.1 (t, C(5)). 19F-NMR
(471 MHz, CDCl3): ꢀ 68.9 (d, J(F,H) ¼ 8.2, CF3ꢀC(6)); ꢀ 71.0 (s, CF3ꢀC(4)). HR-ESI-TOF-MS:

Helvetica Chimica Acta – Vol. 95 (2012)
1829
333.0437 ([M þ Na]þ, C12H8F6N2NaOþ; calc. 333.0439). Anal. calc. for C12H8F6N2O (310.20): C 46.46, H
2.60, N 9.03; found: C 46.37, H 2.53, N 8.96.
4,5-Dihydro-2-phenyl-4-(trifluoromethyl)pyridazin-3(2H)-one (7e).
A soln. of 3f (1.00 g,
3.70 mmol), TsOH · H2O (704 mg, 3.70 mmol), and PhNHNH2 (400 mg, 3.70 mmol) in toluene (50 ml)
was stirred at 908 for 60 h. A colorless precipitate was filtered off, and all volatiles were removed under
reduced pressure. The crude product was purified by CC (SiO2; 20% AcOEt in hexane) to afford 7e
(222 mg, 25%). Orange oil. IR (ATR): 3735 – 3160 (C¼CꢀH), 3160 – 2735 (CꢀH), 1690 (C¼O), 1495,
1430 (C¼N), 1350, 1290, 1260, 1190, 1140 (CꢀF). 1H-NMR (400 MHz, CDCl3): 7.50 – 7.00 (m, HꢀC(6), 5
arom. H); 3.47 – 2.94 (m, HꢀC(4), CH2(5)). 13C-NMR (101 MHz, CDCl3): 158.4 (q, J(C,F) ¼ 2.1, C(3));
140.3 (d, C(6)); 124.5 (q, J(C,F) ¼ 280, CF3ꢀC(4)); 143.1, 128.8, 127.5, 125.1 (s, 3d, Ph); 41.8 (dq, J(C,F) ¼
28.2, C(4)); 23.5 (tq, J(C,F) ¼ 2.5, C(5)). 19F-NMR (376 MHz, CDCl3): ꢀ 68.5 (d, J(F,H) ¼ 8.7,
CF3ꢀC(4)). HR-ESI-TOF-MS: 265.0568 ([M þ Na]þ, C11H9F3N2NaOþ; calc. 265.0565). Anal. calc. for
C11H9F3N2O (242.20): C 54.55, H 3.75, N 11.57; found: C 54.52, H 3.82, N 11.40.
Ethyl 3,3,3-Trifluoro-2-(1H-indol-3-yl)propanoate (10). During the preparation of 7e, 10 was
isolated (207 mg, 21%). Brown solid. M.p. 82 – 848. IR (ATR): 3645 – 3150 (NꢀH), 3150 – 2780 (CꢀH),
1745, 1720 (C¼O), 1340, 1265, 1240, 1150, 1110 (CꢀF). 1H-NMR (400 MHz, CDCl3): 8.31 (s, NH); 7.67
(d, J ¼ 7.8, HꢀC(2’)); 7.44 – 7.15 (m, 4 arom. H); 4.67 (q, J ¼ 8.5, HꢀC(2)); 4.25, 4.22 (AB of ABX3,
J(A,X) ¼ J(B,X) ¼ 7.1, J(A,B) ¼ 10.8, COOCH2Me); 1.26 (X of ABX3, J(A,X) ¼ J(B,X) ¼ 7.1,
COOCH2Me). 13C-NMR (101 MHz, CDCl3): 167.2 (q, J(C,F) ¼ 2.5, C(1)); 124.4 (q, J(C,F) ¼ 280,
CF3); 135.9, 126.5, 124.9, 122.8, 120.5, 118.7 (2s, 4d, Ph); 111.7 (d, C(2’)); 104.0 (q, J(C,F) ¼ 2.0, C(3’));
62.2 (t, COOCH2Me); 47.7 (dq, J(C,F) ¼ 30.1, C(2)); 13.9 (q, COOCH2Me). 19F-NMR (376 MHz,
CDCl3): ꢀ 67.9 (d, J(F,H) ¼ 8.3, CF3). HR-ESI-TOF-MS: 294.0720 ([M þ Na]þ, C13H14F3NNaO2þ ; calc.
294.0718).
We gratefully acknowledge support by the Deutsche Forschungsgemeinschaft (GRK 1582 ꢃFluorine
as Key Elementꢄ) and Bayer HealthCare. Dr. Reinhold Zimmer is thanked for his assistance during
preparation of this manuscript, and Anette Semisch for preliminary experiments dealing with the
cyclopropanations employing ethyl 3,3,3-trifluoro-2-diazopropanoate.
REFERENCES
[1] D. Seebach, Angew. Chem. 1979, 91, 259; D. Seebach, Angew. Chem., Int. Ed. 1979, 18, 239; D.
Wendisch, ꢃCarbocyclic Three-Membered Ring Compoundsꢄ, in ꢃMethods in Organic Chemistry
(Houben-Weyl)ꢄ, Vol. 4/3, 4th edn., Ed. E. Mꢀller, Thieme, Stuttgart, 1971, p. 879; D. Seebach, S.
Beckmann, H. Geiger, ꢃIsocyclic Four-Membered Ring Compoundsꢄ, in ꢃMethods in Organic
Chemistry (Houben-Weyl)ꢄ, Vol. 4/4, 4th edn., Ed. E. Mꢀller, Thieme, 1971, p. 567; S. Danishefsky,
Acc. Chem. Res. 1979, 12, 66; H.-U. Reissig, ꢃThe Chemistry of the Cyclopropyl Groupꢄ, in ꢃOrganic
Synthesis via Cyclopropanes – Principles and Applicationsꢄ, Ed. Z. Rappoport, John Wiley and Sons,
London, 1987, pp. 375 – 443; H. N. C. Wong, M. Y. Hon, C. W. Tse, Y. C. Yip, J. Tanko, T. Hudlicky,
Chem. Rev. 1989, 89, 165; A. de Meijere, ꢃCarbocyclic Three- and Four-Membered Ring
Compoundsꢄ, in ꢃMethods in Organic Chemistry (Houben-Weyl)ꢄ, Vol. E17a – d, Thieme, Stuttgart,
1997; A. de Meijere, S. I. Kozhushkov, ꢃProduct Class 2: Cyclopropanesꢄ, in ꢃAlkanesꢄ, ꢃScience of
Synthesisꢄ, Vol. 48, Ed. I. Fleming, Thieme, Stuttgart, 2009, pp. 477 – 613; R. Kostikov, M. S. Baird, in
ꢃProduct Class 3: Cyclobutanesꢄ, in ꢃAlkanesꢄ, ꢃScience of Synthesisꢄ, Vol. 48, Ed. I. Fleming, Thieme,
Stuttgart, 2009, pp. 615 – 646.
[2] E. Wenkert, Acc. Chem. Res. 1980, 13, 27.
[3] H.-U. Reissig, E. Hirsch, Angew. Chem. 1980, 92, 839; H.-U. Reissig, E. Hirsch, Angew. Chem., Int.
Ed. 1980, 19, 813.
[4] a) H.-U. Reissig, Top. Curr. Chem. 1988, 144, 73; b) H.-U. Reissig, R. Zimmer, Chem. Rev. 2003, 103,
1151; c) F. Gnad, O. Reiser, Chem. Rev. 2003, 103, 1603; d) M. Yu, B. L. Pagenkopf, Tetrahedron
2005, 61, 321; e) F. De Simone, J. Waser, Synthesis 2009, 3353; f) T. F. Schneider, D. B. Werz, Org.
Lett. 2011, 13, 1848; g) M. Y. Melꢄnikov, E. M. Budynina, O. A. Ivanova, I. V. Trushkov, Mendeleev
Commun. 2011, 21, 293.

1830
Helvetica Chimica Acta – Vol. 95 (2012)
[5] C. A. Carson, M. A. Kerr, Chem. Soc. Rev. 2009, 38, 3051; M. J. Campbell, J. S. Johnson, A. T.
Parsons, P. D. Pohlhaus, S. D. Sanders, J. Org. Chem. 2010, 75, 6317; T. F. Schneider, J. Kaschel, S. I.
Awan, B. Dittrich, D. B. Werz, Chem. – Eur. J. 2010, 16, 11276; T. P. Lebold, M. A. Kerr, Pure Appl.
Chem. 2010, 82, 1797.
[6] a) O. O. Grygorenko, O. S. Artamonov, I. V. Komarov, P. K. Mykhailiuk, Tetrahedron 2011, 67, 803;
b) B. Morandi, E. M. Carreira, Angew. Chem. 2010, 122, 950; c) B. Morandi, E. M. Carreira, Angew.
Chem., Int. Ed. 2010, 49, 938; d) B. Morandi, E. M. Carreira, Angew. Chem. 2010, 122, 4390; e) B.
Morandi, E. M. Carreira, Angew. Chem., Int. Ed. 2010, 49, 4294; f) B. Morandi, J. Cheang, E. M.
Carreira, Org. Lett. 2011, 13, 3080; g) V. R. Petrov, W. Marshall, J. Fluorine Chem. 2012, 133, 61.
[7] T. Hiyama, ꢃOrganofluorine Compounds: Chemistry and Applicationsꢄ, Springer, Berlin Heidelberg,
2000; P. Kirsch, ꢃModern Fluoroorganic Chemistryꢄ, Wiley-VCH, Weinheim, 2005; K. Mꢀller, C.
Fꢁh, F. Diederich, Science 2007, 317, 1881; D. Oꢄ Hagan, Chem. Soc. Rev. 2008, 37, 308; T. Yamazaki,
T. Taguchi, I. Ojima, in ꢃFluorine in Medicinal Chemistry and Chemical Biologyꢄ, Ed. I. Ojima,
Wiley-Blackwell, Chichester, 2009, pp. 3 – 46; A. A. Gakh, L. K. Kirk, ꢃFluorinated Heterocyclesꢄ,
American Chemical Society, Washington, 2009; V. A. Petrov, ꢃFluorinated Heterocyclic Com-
pounds: Synthesis, Chemistry, and Applicationsꢄ, John Wiley & Sons, Hoboken, 2009.
[8] S. Gil, M. Parra, P. Rodriguez, J. Segura, Mini-Rev. Org. Chem. 2009, 6, 345; M. Seitz, O. Reiser,
Curr. Opin. Chem. Biol. 2005, 9, 285; E. M. Maier, in ꢃThree Carbon-Heteroatom Bonds: Esters and
Lactones; Peroxyacids and R(CO)OX Compounds; R(CO)X, X ¼ S, Se, Teꢄ, ꢃScience of Synthesis,
Houben-Weyl Methods of Molecular Transformationsꢄ, Eds. J. S. Panek, E. N. Jacobsen, Thieme,
Stuttgart, 2006, Vol. 20b, pp. 1421 – 1551.
[9] a) W. Adam, J.-C. Liu, O. Rodriguez, J. Org. Chem. 1973, 38, 2269; b) T. Kitazume, N. Ishikawa,
Chem. Lett. 1984, 13, 1815; c) D. Seebach, P. Renaud, W. B. Schweizer, M. F. Zꢀger, M.-J. Brienne,
Helv. Chim. Acta 1984, 67, 1843; d) D. Seebach, P. Renaud, Helv. Chim. Acta 1985, 68, 2342; e) M.
Acs, C. von dem Bussche, D. Seebach, Chimia 1990, 44, 90; f) C. von dem Bussche-Hꢀnnefeld, C.
Cescato, D. Seebach, Chem. Ber. 1992, 125, 2795; g) M. Gautschi, W. B. Schweizer, D. Seebach,
Chem. Ber. 1994, 127, 565; h) A. R. Sting, D. Seebach, Tetrahedron 1996, 52, 279; i) H. Angert, R.
Czerwonka, H.-U. Reissig, Liebigs Ann. 1997, 2215; j) F.-L. Qing, Z.-X. Jiang, Tetrahedron Lett.
2001, 42, 5933.
ˇ
[10] M. Tisler, B. Stanovnik, Adv. Heterocycl. Chem. 1968, 9, 211; F. R. Rittig, R. Becker, H. Bleiholder,
´
F. Feichtmayr, E. Haedicke, J. B. S. John, Pestic. Sci. 1983, 14, 299; P. Maatyus, J. Heterocycl. Chem.
1998, 35, 1075; S.-G. Lee, J.-J. Kim, H.-K. Kim, D.-H. Kweon, Y.-J. Kang, S.-D. Cho, S.-K. Kim, Y.-J.
Yoon, Curr. Org. Chem. 2004, 8, 1463.
[11] E. Fischer, Justus Liebigs Ann. Chem. 1886, 236, 126.
[12] E. L. Grimm, H.-U. Reissig, J. Org. Chem. 1985, 50, 242.
[13] I. Reichelt, H.-U. Reissig, Synthesis 1984, 786.
[14] E. L. Grimm, R. Zschiesche, H.-U. Reissig, J. Org. Chem. 1985, 50, 5543; A. Ullmann, J. Schnaubelt,
H.-U. Reissig, Synthesis 1998, 1052; R. Zimmer, A. Ziemer, M. Gruner, I. Brꢀdgam, H. Hartl, H.-U.
Reissig, Synthesis 2001, 1649; P. K. Patra, H.-U. Reissig, Eur. J. Org. Chem. 2001, 4195; I. Veljkovic,
R. Zimmer, H.-U. Reissig, I. Brꢀdgam, H. Hartl, Synthesis 2006, 2677; H. ꢅzbek, I. S. Veljkovic, H.-
U. Reissig, Synlett 2008, 3145.
[15] W. Wan, J. Hou, H. Jiang, Y. Wang, S. Zhu, H. Deng, J. Hao, Tetrahedron 2009, 65, 4212.
[16] H. A. Laub, D. Gladow, H.-U. Reissig, H. Mayr, Org. Lett. 2012, 14, 3990.
[17] E. B. Womack, A. B. Nelson, Org. Synth., Coll. Vol. 1955, 3, 392; E. B. Womack, A. B. Nelson, Org.
Synth. 1944, 24, 56.
[18] G. Shi, Y. Xu, J. Chem. Soc., Chem. Commun. 1989, 607.
[19] R. H. Groth, J. Org. Chem. 1959, 24, 1709; M. Hanack, H. Meyer, Justus Liebigs Ann. Chem. 1968,
720, 81.
[20] R. E. Brown, F. Burkamp, V. A. Doughty, S. R. Fletcher, G. J. Hollingworth, B. A. Jones, T. J. Sparey,
WO2004074290A1, 2004.
Received August 3, 2012