α-Fluorohydrazones as useful precursors in nucleophilic substitutions

Article abstract of DOI:10.1016/j.tetlet.2013.05.110

C-F bonds on α-fluorohydrazones can be substituted with a wide range of nucleophiles with the aid of mild bases. The present reaction shows that α-fluorohydrazones can be useful building blocks in synthetic chemistry.

Full text of DOI:10.1016/j.tetlet.2013.05.110

Tetrahedron Letters 54 (2013) 4102–4105
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Tetrahedron Letters
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a
-Fluorohydrazones as useful precursors in nucleophilic
substitutions
⇑
Ryota Yunoki, Atsushi Yajima, Tsuyoshi Taniguchi , Hiroyuki Ishibashi
School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
CÀF bonds on
a-fluorohydrazones can be substituted with a wide range of nucleophiles with the aid of
Received 17 April 2013
Revised 21 May 2013
Accepted 24 May 2013
Available online 4 June 2013
mild bases. The present reaction shows that
a-fluorohydrazones can be useful building blocks in syn-
thetic chemistry.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Alkyl halides
Cleavage
Fluorine
Hydrazones
Nucleophiles
EWG
NH
EWG
N
EWG
NH
Introducing fluorine atoms to organic molecules often causes
dramatic changes in the physical and biological properties, and
the benefit is maximally utilized in medicinal chemistry.1 Strong
CÀF bonds (BDE: 109.9 kcal molÀ1 for CH3F) contribute to the sta-
bility of fluorine organic compounds, implying, on the other hand,
that decomposition of fluorine compounds is difficult.2 Tradition-
ally, CÀF bonds have been recognized to be useless for chemical
transformation due to their extremely high bond energy, except
for a few examples such as aromatic nucleophilic substitution reac-
tions (SNAr reactions).3 Recently, however, development of meth-
ods for activation of unreactive CÀF bonds is a hot topic in
organic chemistry.4,5 Although these reactions often require transi-
tion metal catalysts, Lewis acids, or harsh conditions, compounds
bearing CÀF bonds can now work as sufficiently useful synthetic
precursors.
Base
NuH
N
N
N
F
Nu
R
R
R
Scheme 1. Elimination of a fluorine atom followed by the addition of nucleophiles.
tion, CÀF bond cleavage is likely to be triggered by electron-push-
ing from a nitrogen atom of the hydrazone moiety to form the
corresponding azoalkene intermediate. Since this intermediate
works as an excellent Michael acceptor, substituted products are
formally provided by addition reactions of nucleophiles (Scheme 1).
Such a formal nucleophilic substitution of
synthetically useful method as with the usual SN2 reaction of
halocarbonyl compounds, though these two reactions cannot be
bracketed together due to the difference in the mechanism (elim-
ination-addition process versus stereospecific substitution) and
reaction conditions. For instance, efficient C–C bond formation
a-halohydrazones is a
a
-
a
-Haloketones (halogen: chloro, bromo, and iodo) are impor-
tant building blocks to install ketone moieties in organic molecules
in synthetic chemistry because they are highly reactive electro-
philes in the SN2 substitution reaction.6 On the other hand,
a
-flu-
reactions of
a-chloro- or bromo hydrazones using this methodol-
ogy are known.8 In addition, CÀF cleavage reactions of
a,a-di-
oroketones are seldom used for this purpose owing to the poor
reactivity of CÀF bonds, though
a,a,a-trifluorocarbonyl com-
fluoro- and
a,a,a-trifluorohydrazones based on the similar
pounds can be activated by electroreduction.4c They are usually
useful precursors for the synthesis of fluorine compounds.7
mechanism have been reported.9 However, there are not many
practical applications of this concept involving the CÀF cleavage
to general synthetic methods. We herein demonstrate synthetic
In this Letter, we report that CÀF bonds on
a-fluorohydrazones,
which are derivatives of -fluoroketones, are readily substituted
a
usefulness of
with a variety of nucleophiles.
-Fluorohydrazone 1 (mixture of two isomers; ca. 85:15),
which was easily prepared by condensation of the corresponding
-fluoroketone10 with methyl hydrazinecarboxylate, was designed
a-fluorohydrazones by showing results of reactions
with various nucleophiles under mild basic conditions. In this reac-
a
⇑
Corresponding author. Tel./fax: +81 76 234 4439.
E-mail address: tsuyoshi@p.kanazawa-u.ac.jp (T. Taniguchi).
a
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.110

R. Yunoki et al. / Tetrahedron Letters 54 (2013) 4102–4105
4103
Table 1
Scope of nucleophiles
NHEWG
F
NHEWG
Nu
Nucleophile
Base
N
N
R1
R1
NHCO2Me
NHCO2Me
Nu
N
N
R2 R3
R2 R3
Nucleophile (1.5 equiv)
α-fluorohydrazonesa
3−17b
F
K2CO3 (3 equiv)
Ph
Ph
1 (1.0 equiv)
2a−jg
THF, rt
NNHBoc
OMe
3: 30 min, 74%c
NNHBoc
N
Ph
Ph
Ph
Ph
Entry
Nucleophile
Nu
Time
Yield (%)
O
4: 5.5 h, 97%c
1a
2a
3c
4d
MeOHb
MeO
CF3CH2O
AcO
2a
15 min
3 h
68
91
49
81
CF3CH2OHb
AcONa
2b
2c
2d
NNHTs
NNHAc
4 h
2 h
Me2NHÁHCle
Me2N
CH(CO2Me)2
CH(CO2Me)2
Ph
5: 12 h, 57%
6: 24 h, 32%
5
2e
7 h
95
O
NH
O
N
6f
7
TMSN3
PhSH
N3
PhS
2f
2g
5 min
3 h
89
95
NNHCO2Me
OMe
NNHCO2Me
OMe
NNHCO2Me
CH(CO2Me)2
8: 24 h, 80%c
Ph
O
Ph
7: 10 min, 71%c
9: 30 min, 87%
p-Tol
S
8
9
p-TolSO2Na
2h
2i
2.5 h
24 h
69
82
O
NNHCO2Me
NNHCO2Me
SPh
(CO2Me)2CH
(CO2Me)2CH2
Ph
N
BnO
O
O
O
10: 6 h, 95%
11: 6 h, 97%
CO2Et
CO2Et
10d
2j
4 h
64
NNHCO2Me
NNHCO2Me
CH(CO2Me)2
12: 6.5 h, 67%
Me
CH(CO2Me)2
gIsomer ratios (approximately estimated by 1H NMR): 2a (65:35), 2b (78:22), 2c
(>95:5), 2d (>95:5), 2e (76:24), 2f (80:20), 2g (58:42), 2h (55:45), 2i (75:25), 2j
(>95:5).
13: 48 h, 65%
Me
NNHCO2Me
OMe
NNHCO2Me
N3
a
1.5 equiv of K2CO3 was used.
Used as a solvent instead of THF.
DMF was used as a solvent instead of THF.
65 °C.
b
Ph
Ph
c
Me
Me
d
14: 1 h, 65%
15: 30 min, 75%
e
3 equiv.
NNHCO2Me
OMe
NNHCO2Me
f
DBU was used instead of K2CO3.
NMe2
Me
Ph
Ph
Me
Me
Me
as a model substrate to test nucleophiles. Results of reactions of 1
with a variety of nucleophiles are summarized in Table 1. Treat-
ment of 1 with potassium carbonate (1.5 equiv) in methanol
16: 1 h, 75%c
17: 2 h, 79%c
Figure 1. Scope of substrates. Same conditions are used for each nucleophile.
aStarting materials were used as mixtures of two isomers (ca. 80:20À95:5) unless
otherwise noted. bIsomer ratios (approximately estimated by 1H NMR): 3 (>95:5), 4
(>95:5), 5 (91:9), 6 (>95:5), 7 (>95:5), 8 (>95:5), 9 (82:18), 10 (94:6), 11 (70:30), 12
(83:17), 13 (75:25), 14 (>95:5), 15 (91:9), 16 (>95:5), 17 (95:5). cSingle isomers of
starting materials were used.
(0.2 M) at room temperature caused methanolysis to afford
a-
methoxyhydrazone 2a in 68% yield (entry 1).11 The reaction with
2,2,2-trifluoroethanol gave the corresponding substituted product
2b in excellent yield under similar conditions (entry 2). Acetoxyla-
tion of 1 with sodium acetate proceeded in N,N-dimethylformam-
ide (DMF) to give compound 2c in moderate yield (entry 3).
Reactions of 1 with amines such as dimethylamine and morpholine
were fast and afforded the corresponding amine compounds 2d
and 2c in 81% and 95% yields (entries 4 and 5).12 When sodium
azide was used for azidation of 1, azide compound 2f was obtained,
but the yield was moderate (46%, not shown in Table 1). We soon
found that a combination of trimethylsilylazide (TMSN3) and 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) gave 2f in improved yield
(89%) (entry 6). Sulfur nucleophiles such as benzenethiol and so-
dium p-toluenesufinate readily reacted with 1 to provide the corre-
sponding sulfide 2g and sulfone 2h in good yields (entries 7 and 8).
When dimethylmalonate and ethyl 2-oxocyclohexanecarboxylate
were employed as nucleophiles, CÀC bond formation on the CÀF
bond of 1 occurred to give compounds 2i and 2j (entries 9 and 10).
NNHCO2Me
F
NNHCO2Me
OMe
MeOK (5 equiv)
Ph
Ph
Ph
Ph
MeOH, rt
30 min
F
OMe
19: 92%
18
NNHCO2Me
NNHCO2Me
OMe
MeOK (5 equiv)
F
F
MeOH, reflux
72 h
OMe
F
OMe
21: 80%
20
Scheme 2. Reactions of di- and trifluorohydrazone derivatives.
a
,a
-Difluorohydrazone 18 (single isomer) reacted with methox-
ide anions to give dimethylacetal 19 (single isomer) (Scheme 2).9
Examples of reactions between various
a-fluorohydrazones and
nucleophiles are shown in Figure 1. -Fluorohydrazones bearing
a
In this reaction, replacement of potassium carbonate by potassium
tert-butoxycarbonyl or p-toluenesulfonyl groups gave the corre-
methoxide (5 equiv) gave a better result. Interestingly,
luorohydrazone 20 (single isomer) also underwent a substitution
reaction of all fluorine atoms to give -trimethoxyhydrazone
a,a,a-trif-
sponding substituted products 3À5 in good yields, whereas prod-
uct
6 was obtained in only 32% yield from an acetylated
a,a,a
hydrazone material. This might be due to the difference in the elec-
tronic properties of carbamates and amides. Substitution reactions
of hydrazones possessing other side chains, such as phenyl, benzyl,
benzyloxybutyl, heptenyl, and isopropyl, smoothly produced vari-
ous substituted derivatives 7À13 in good yields. Secondary and
tertiary fluoro derivatives also caused substitution reactions with
oxygen and nitrogen nucleophiles and afforded products 14À17.
21 (single isomer) in high yield, though a high temperature (reflux
in methanol) and long reaction time (72 h) were required
(Scheme 2).9,13
Exposure of
complicated the result, and no substituted product was isolated
from the reaction mixture. In addition, -trifluoroketone 23
did not react with potassium methoxide at all (Scheme 3). Com-
a-fluoroketone 22 to the methanolysis conditions
a,a,a

4104
R. Yunoki et al. / Tetrahedron Letters 54 (2013) 4102–4105
145–154; (c) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183; (d) Clot,
O
K2CO3
E.; Eisenstein, O.; Jasim, N.; Macgregor, S. A.; McGrady, J. E.; Perutz, R. N. Acc.
Chem. Res. 2011, 44, 333–348; (e) Kuehnel, M. F.; Lentz, D.; Braun, T. Angew.
Chem., Int. Ed. 2013, 52, 3328–3348.
complex mixture
F
Ph
Ph
MeOH, rt
6 h
22
O
5. Selected recent examples: (a) Choi, J.; Wang, D. Y.; Kundu, S.; Choliy, Y.; Emge,
T. J.; Krogh-Jespersen, K.; Goldman, A. S. Science 2011, 332, 1545–1548; (b)
Yanai, H.; Okada, H.; Sato, A.; Okada, M.; Taguchi, T. Tetrahedron Lett. 2011, 52,
2997–3000; (c) Bergeron, M.; Johnson, T.; Paquin, J.-F. Angew. Chem., Int. Ed.
2011, 50, 11112–11116; (d) Tobisu, M.; Xu, T.; Shimasaki, T.; Chatani, N. J. Am.
Chem. Soc. 2011, 133, 19505–19511; (e) Yu, D.; Shen, Q.; Lu, L. J. Org. Chem.
2012, 77, 1798–1804; (f) Blessley, G.; Holden, P.; Walker, M.; Brown, J. M.;
Gouverneur, V. Org. Lett. 2012, 14, 2754–2757; (g) Iida, T.; Hashimoto, R.;
Aikawa, K.; Ito, S.; Mikami, K. Angew. Chem., Int. Ed. 2012, 51, 9535–9538; (h)
Haufe, G.; Suzuki, S.; Yasui, H.; Terada, C.; Kitayama, T.; Shiro, M.; Shibata, N.
Angew. Chem., Int. Ed. 2012, 51, 12275–12279; (i) Ohashi, M.; Saijo, H.; Shibata,
M.; Ogoshi, S. Eur. J. Org. Chem. 2013, 443–447; (j) Fan, H.; Fout, A. R.; Bailey, B.
C.; Pink, M.; Baik, M.-H.; Mindiola, D. J. Dalton Trans. 2013, 42, 4163–4174; (k)
Stahl, T.; Klare, H. F. T.; Oestreich, M. J. Am. Chem. Soc. 2013, 135, 248–1251.
MeOK
F
F
no reaction
MeOH
23
F
reflux
72 h
Scheme 3. Exposure of fluoroketones to the methanolysis conditions.
NNHCO2Me
NNHCO2Me
K2CO3 (1.5 equiv)
X
OMe
Ph
MeOH, rt
5−40 min
Ph
24
7
X = Cl, Br
24% (X = Cl)
6. Recent examples of nucleophilic substitution reactions with a-haloketones: (a)
30% (X = Br)
Wong, F. F.; Chang, P.-W.; Lin, H.-C.; You, B.-J.; Huang, J.-J.; Lin, S.-K. J.
Organomet. Chem. 2009, 694, 3452–3455; (b) Singh, S.; Singh, P.; Rai, V. K.;
Kapoor, R.; Yadav, L. D. S. Tetrahedron Lett. 2011, 52, 125–128; (c) Donohoe, T.
J.; Kabeshov, M. A.; Rathi, A. H.; Smith, I. E. D. Org. Biomol. Chem. 2012, 10,
1093–1101; (d) Novák, P.; Lishchynskyi, A.; Grushin, V. V. J. Am. Chem. Soc.
2012, 134, 16167–16170.
CH2(CO2Me)2 (1.5 equiv)
K2CO3 (3 equiv)
NNHCO2Me
CH(CO2Me)2
24
X = Cl, Br
Ph
THF, rt
>24 h
8
21% (X = Cl)
12% (X = Br)
7. Recent examples of reactions using
a-fluoroketones: (a) Fuglseth, E.; Sundby,
E.; Hoff, B. H. J. Fluorine Chem. 2009, 130, 600–603; (b) Thvedt, T. H. K.; Fuglseth,
E.; Sundby, E.; Hoff, B. H. Tetrahedron 2010, 66, 6733–6743; (c) Ryabukhin, S. V.;
Naumchik, V. S.; Plaskon, A. S.; Grygorenko, O. O.; Tolmachev, A. A. J. Org. Chem.
2011, 76, 5774–5781; (d) Guo, C.; Wang, R.-W.; Guo, Y.; Qing, F.-L. J. Fluorine
Chem. 2012, 133, 86–96.
Scheme 4. Reactions of a-chloro- and bromohydrazones.
bined with the production of 16 and 17, these results support the
mechanism shown in Scheme 1.
8. (a) Sacks, C. E.; Fuchs, P. L. J. Am. Chem. Soc. 1975, 97, 7372–7374; (b) Hatcher, J.
M.; Coltart, D. M. J. Am. Chem. Soc. 2010, 132, 4546–4547; (c) Chen, J.-R.; Dong,
W.-R.; Candy, M.; Pan, F.-F.; Jörres, M.; Bolm, C. J. Am. Chem. Soc. 2012, 134,
Interestingly, reactivity of
a-chloro- and bromohydrazones was
6924–6927; Similar elimination reactions of a-haloimines have been reported:
clearly different from that of
a-fluorohydrazones (Scheme 4).
(d) Stevens, C. V.; De Kimpe, N. G.; Katritzky, A. R. Tetrahedron Lett. 1994, 35,
3763–3766; (e) Jacobs, J.; Van, T. N.; Stevens, C. V.; Markusse, P.; Cooman, P. D.;
Maat, L.; De Kimpe, N. Tetrahedron Lett. 2009, 50, 3698–3701.
When chloro- and bromohydrazones 24 (mixture of two isomers:
ca. 55:45 and 85:15) were subjected to the methanolysis condi-
tions, product 7 was obtained in only low yield along with multiple
unidentified products. Likewise, reactions with dimethylmalonate
gave product 8 in low yield. Although we did not test other reac-
tion conditions such as a low temperature, it seems to be difficult
9. (a) Knunyants, I. L.; Bargamova, M. D.; Pletnev, S. I. Russ. Chem. Bull. 1980, 29,
1336–1341; (b) Pletnev, S. I.; Bargamova, M. D.; Knunyants, I. L. Russ. Chem.
Bull. 1981, 30, 852–855; (c) Bargamova, M. D.; Pletnev, S. I.; Knunyants, I. L.
Russ. Chem. Bull. 1982, 32, 1289; (d) Kiselyov, A. S. Tetrahedron Lett. 1995, 36,
1383–1386; (e) Pilgram, K. H.; Skiles, R. D. J. Heterocycl. Chem. 1998, 25, 139–
143; (f) Usachev, B. I.; Obydennov, D. L.; Kodess, M. I.; Sosnovskikh, V. Y.
Tetrahedron Lett. 2009, 50, 4446–4448; (g) Ermolenko, M. S.; Guillou, S.; Janin,
Y. L. Tetrahedron 2013, 69, 257–263.
to control substitution reactions of
ones by the simple procedure used in the reactions of
razones because of their high reactivity.14 These contrasting results
proved that -fluorohydrazones were excellent precursors in sub-
a-chloro- and bromohydraz-
a-fluorohyd-
10. For preparation of a-fluoroketones: Kitazume, T.; Asai, M.; Lin, J. T.; Yamazaki,
T. J. Fluorine Chem. 1987, 35, 477–488.
11. General procedure for methanolysis of
a
-fluorohydrazones: to a solution of a-
a
fluorohydrazone (0.2 mmol) in MeOH (1 mL, 0.2 M) was added K2CO3 (41.5 mg,
0.3 mmol), and the mixture was stirred at room temperature. The reaction
mixture was diluted with water and extracted with EtOAc. The organic layer
was washed with brine and dried with Na2SO4. After removal of the solvent
under reduced pressure, the residue was purified by silica gel chromatography
stitution reactions.
In conclusion, we revealed that
a-fluorohydrazone derivatives
were good precursors in nucleophilic substitution reactions, which
could be conducted under mild basic conditions to give various
substituted products. No expensive and toxic reagent is required,
and the experimental procedure is very simple. Since hydrazones
(n-hexane/EtOAc) to give the corresponding
Spectroscopic data of the representative product are shown as below.
Methyl 2-(1-methoxy-4-phenylbutan-2-ylidene)hydrazinecarboxylate
a-methoxyhydrazones.
(2a):
colorless oil. Mixture of two isomers (65:35). 1H NMR (600 MHz, CDCl3):
d = 7.35–7.20 (5H and 5H, m, for major and minor), 4.09 (2H, s, for minor), 4.00
(2H, s, for major), 3.81 and 3.77 (3H and 3H, both br, for major and minor), 3.38
(3H, s, for minor), 3.33 (3H, s, for major), 2.89–2.84 (2H and 2H, m, for major
and minor), 2.59–2,54 (2H and 2H, m, for major and minor) ppm; 13C NMR
(100 MHz, CDCl3): d = 128.9, 128.5, 128.4, 128.1, 126.8, 126.2, 77.2, 74.9, 58.9,
can be used as masked ketones or amine precursors,
razones are promising as useful building blocks. Furthermore, the
original stability of -fluorohydrazones would be advantageous
a-fluorohyd-
a
when they are used as building blocks. This work has illustrated
a good example of the positive use of CÀF bonds in synthetic
chemistry. Further studies such as studies on CÀC bond formation
reactions with organometallic reagents are currently underway.
58.3, 38.0, 33.2, 31.1 ppm; IR (CDCl3): 2360, 1743, 1508, 1456, 1236 cmÀ1
;
HRMS (DART): calcd for C13H19N2O3 [M+H+]: 251.1396; found: 251.1397.
12. General procedure for reactions of
a-fluorohydrazones with nucleophiles: to a
solution of -fluorohydrazone (0.2 mmol) in THF (1 mL, 0.2 M) were added
a
nucleophile (0.3 mmol) and K2CO2 (82.9 mg, 0.6 mmol), and the mixture was
stirred at room temperature. The reaction mixture was diluted with water and
extracted with EtOAc. The organic layer was washed with brine and dried with
Na2SO4. After removal of the solvent under reduced pressure, the residue was
purified by silica gel chromatography (n-hexane/EtOAc) to give the
Acknowledgments
This work was supported by Grants-in-Aid from the Ministry of
Education, Culture, Sports, Science and Technology of Japan
(MEXT).
corresponding
a
-substituted
hydrazones.
Spectroscopic
data
of
representative products are shown as below.
Methyl 2-(1-morpholino-3-phenylpropan-2-ylidene)hydrazinecarboxylate (10):
Colorless oil. Mixture of two isomers (94:6). 1H NMR (600MHz, CDCl3):
d = 7.64 (1H, s, for major, a minor peak is ambiguous), 7.34–7.25 (3H and 3H,
m, for major and minor), 7.18 (2H and 2H, d, J = 7.6Hz, for major and minor),
3.78–3.57 (11H and 11H, m, for major and minor), 3.16 (2H, s, for major), 3.12
(2H, s, for minor), 2.45 (2H, br s, for major), 2.19 (2H, br, for minor) ppm; 13C
NMR (150MHz, CDCl3): d = 134.2, 129.2, 129.1, 128.6, 128.3, 127.1, 66.9, 66.6,
References and notes
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94, 373–431; (b) Burdeniuc, J.; Jedlicka, B.; Crabtree, R. H. Chem. Ber. 1997, 130,
63.9, 53.5, 52.4, 33.1 ppm; IR (CDCl3): 2358, 1736, 1508, 1455, 1238 cmÀ1
;
HRMS (DART): calcd for C15H22N3O3 [M+H+]: 292.1661; found: 292.1668.
Dimethyl 2-(2-(2-(methoxycarbonyl)hydrazono)hept-6-en-1-yl)malonate (12):
colorless oil. Mixture of two isomers (83:17). 1H NMR (600 MHz, CDCl3):
d = 8.80 (1H, br, for minor), 7.83 (1H, br, for major), 5.81–5.75 (1H and 1H, m,

R. Yunoki et al. / Tetrahedron Letters 54 (2013) 4102–4105
4105
for major and minor), 5.08–5.04 (2H, m, for major), 5.01 (1H, dq, J = 17.0.
1.7 Hz, for minor), 4.98–4.95 (1H, m, for minor), 3.97 (1H, br, for major), 3.70
and 3.76 (total 9H and 9H, both s, for major and minor), 3.62 (1H, t, J = 7.0 Hz,
for minor), 2.89 (2H, d, J = 7.6 Hz, for major), 2.78 (2H, d, J = 7.8 Hz, for minor),
2.27 (2H, t-like, J = 7.9 Hz, for minor), 2.18 (2H, t-like, J = 7.9 Hz, for major),
2.12–2.07 (2H, m, for major and minor), 1.69–1.61 (2H, m, for major and
minor) ppm ; 13C NMR (150 MHz, CDCl3): d = 169.7, 137.9, 137.1, 116.2, 115.1,
53.3, 52.6, 48.1, 48.0, 35.7, 34.9, 33.23, 33.17, 28.5, 25.9, 24.0 ppm; IR (CDCl3):
1749, 1731, 1504, 1460, 1230 cmÀ1; HRMS (DART): calcd for C14H23N2O6
[M+H+]: 315.1556; found: 315.1539.
13. Examples of nitrogen atom-assisted elimination of fluorine atoms on
trifluoromethyl groups: (a) Wydra, R. L.; Patterson, S. E.; Strekowski, L. J.
Heterocycl. Chem. 1990, 27, 803–805; (b) O’Mahony, G.; Pitts, A. K. Org. Lett.
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14. Although we did not identify all byproducts, a dimerization-like compound
produced by a self-reaction was tentatively identified as a main byproduct.
This would be because
a-chloro- and bromohydrazones can be usual
electrophiles like -chloro- and bromoketones.
a