Wittig reaction of a series of diazodiketones: Synthesis and structure of fluorine-containing vinyldiazoketones

Article abstract of DOI:10.1055/s-2005-872180

Reaction of (alkyloxycarbonyl)- and (benzoyl)- methylenetriphenylphosphoranes with fluorine-containing diazodiketones leads to olefination of the perfluoroacyl carbonyl group and formation of fluorinated vinyldiazoketones. The analogous reaction with non-

Full text of DOI:10.1055/s-2005-872180

PAPER
2871
Wittig Reaction of a Series of Diazodiketones: Synthesis and Structure of
Fluorine-Containing Vinyldiazoketones
S
ynthesis and Stru
a
c
ture of Flu
l
orine-
e
ontaining
r
V
inyldia
i
zoketo
j
a
St. Petersburg State University, Department of Organic Chemistry, University pr. 26, 198504 St. Petersburg, Russia
E-mail: vnikola@VN6646.spb.edu
b
Universität Leipzig, Institut für Organische Chemie, Johannisallee 29, 04103 Leipzig, Germany
E-mail: hennig@organik.chemie.uni-leipzig.de
Received 31 December 2004; revised 1 June 2005
used in the reaction with diazocarbonyl compounds 1 in
order to estimate the scope and limitations of the process.
Abstract: Reaction of (alkyloxycarbonyl)- and (benzoyl)-methyl-
enetriphenylphosphoranes with fluorine-containing diazodiketones
leads to olefination of the perfluoroacyl carbonyl group and forma-
tion of fluorinated vinyldiazoketones. The analogous reaction with
non-fluorinated diazodiketones does not proceed under the same
conditions. The resulting fluorine-containing vinyldiazoketones
have an E-configuration regardless of the nature and size of the sub-
stituents.
Key words: aliphatic diazo compounds, Wittig reaction, fluorine-
containing vinyldiazoketones, 1,3-diketones, diazo transfer reaction
The Wittig reaction is one of the most powerful means to
introduce carbon–carbon double bonds into organic mol-
ecules. It is applicable to a large number of aliphatic, aro-
matic, carbo- and heterocyclic compounds possessing
different functional groups which do not interfere with
this effective and widely used process.1,2
Figure 1
All starting diazodiketones 1 were obtained in a one-step
procedure from the corresponding 1,3-diketones 3 using a
diazo transfer reaction (Scheme 1).8
However, analysis of the literature showed that of all the
carbonyl compounds previously used in the Wittig reac-
tion, aliphatic diazocarbonyl compounds have been rarely
investigated.3–5 Therefore, the application of the Wittig re-
action to diazocarbonyl substrates could increase the
scope of this process as well as enhance the synthetic po-
tential of aliphatic diazo compounds since the target prod-
ucts – vinyldiazocarbonyl compounds – are very
attractive for organic synthesis.3,5–7
The main objective of our project was to investigate the
reaction of fluoroalkyl-containing and non-fluorinated 2-
diazo-1,3-diketones 1 (F- and H-diazodiketones) with
Wittig reagents to elucidate both the chemo- and stereose-
lectivity of this process and thereby to elaborate an effec-
tive approach to the structure of vinyldiazoketones. For
this purpose a range of F- and a few H-diazodiketones
(1a–j) were chosen with both alkyl and aryl substituents;
also the steric effect (Me, Bu, t-Bu, Ar) exhibited by the
substituent adjacent to the diazo group was investigated
(Figure 1).
Scheme 1 a) ArSO2N3/base, CH2Cl2, 20 °C; b) H2O/base; side reac-
tion in the case of RF
Since fluorinated diazodiketones 1a–h are easily hydro-
lyzed even in the presence of traces of alkali and water,9
their synthesis was carried out using a modified diazo
transfer reaction,10 which prevents the reaction mixture
coming into contact with moisture at all stages of the pro-
cess. Furthermore, several bases (trimethylamine, DBU,
and potassium fluoride on aluminum oxide)11 were tested
as catalysts in the reaction with diketone 3a to optimize
the yields of F-diazodiketones 1. The best results (49–
54% yield), with the not easily accessible F-diazodiketone
1a, were accomplished using DBU in a solution of dichlo-
romethane (Table 1).
Investigations were carried out with easily accessible
(alkoxycarbonyl)methylenetriphenylphosphoranes 2a,b.
Several (acyl)methylenephosphoranes 2c–e were also
The reaction of diazodiketones 1a–j with phosphoranes
2a–e was studied under usual Wittig reaction conditions
(18–20 °C, Et2O solution; Scheme 2).1,2
SYNTHESIS 2005, No. 17, pp 2871–2874
Advanced online publication: 17.08.2005
DOI: 10.1055/s-2005-872180; Art ID: T16204SS
x
x.
x
x
.
2
0
0
5
© Georg Thieme Verlag Stuttgart · New York

2872
V. M. Zakharova et al.
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The F-diazo compounds 4a–h,k,l were purified by chro-
matography on silica gel and characterized by a variety of
spectroscopic methods (Table 3).
Compound RH/RF
R1
Yield (%) (Base)
1a
CF3
Me
54 (DBU); 27 (Me3N);
49 (KF/Al2O3)
Attempts to carry out the Wittig reaction of F-diazodike-
tone 1c with (formyl)- and (acetyl)methylenephospho-
ranes 2d,e failed. In both cases no products similar to
vinyldiazoketones 4 were identified in the reaction mix-
ture, by TLC, even after a few days. Even varying the re-
action conditions (inverse order of reagent addition,
substitution of Et2O by THF or benzene, lowering the re-
action temperature, etc.) did not change the result.
1b
1c
1d
1e
1f
CF3
CF3
CF3
CF3
CF3
CF3
C3F7
Me
Et
58 (DBU)
66 (DBU)
48 (DBU)
82 (DBU)
66 (DBU)
64 (DBU)
55 (DBU)
65 (Et3N)
58 (Et3N)
Bu
t-Bu
Pentyl
p-Tolyl
b-C10H7
Ph
The reaction of non-fluorinated diazodiketones 1i,j with
Wittig reagent 2a was also attempted. However, it was
found that these H-diazodiketones as well as H-a-diazo-
b-ketoesters12 did not react with (alkoxycarbonyl)methyl-
enephosphorane 2a under the usual conditions.
1g
1h
1i
Me
The resulting fluorinated vinyldiazoketones 4a–h,k,l are
bright yellow oils, which are stable for many months
when refrigerated at –5 to –10 °C. The structure of the
1j
Me
t-Bu
previously unknown fluorine-containing vinyldiazoke-
1
tones 4 was established by means of IR, H, 13C, and 19
F
NMR spectroscopy (Table 3), and their composition was
confirmed by elemental analysis.
The IR spectra of F-vinyldiazoketones 4a–h,k, revealed
strong diazo group absorption bands at 2080–2095 cm–1;
this is a 50–60 cm–1 shift to lower frequency in compari-
son to the starting F-diazodiketones 1.10 Valence vibra-
tions of non-fluoroalkyl-substituted (H-acyl) carbonyl
groups are located almost at the same position (1640–
1670 cm–1) as the initial diazo compounds 1 (1640–1680
cm–1),10 demonstrating that only the perfluorinated acyl
group of F-diazodiketone 1 takes part in the Wittig reac-
tion.
Diagnostic signals for the diazo group in 13C NMR spectra
for F-vinyldiazoketones 4a–h,k were observed at 61–66
ppm. They are shifted to a higher field (15–20 ppm) com-
pared to F-diazodiketones 1.10 A new set of signals corre-
sponding to the two C-alkene atoms (C=CHCOR2 group)
with the typical coupling pattern (2JC-F = 33 and 3JC-F = 5
Hz) appeared at 127–130 ppm and 125–131 ppm, whereas
the signal of the perfluoroacetyl carbonyl group of F-di-
azodiketones 1 at 170–171 ppm disappeared. Non-fluoro-
alkyl-substituted carbonyl groups are located at 183–195
ppm.10
Scheme 2
It was found that F-diazodiketones 1a–h react easily with
(alkoxycarbonyl)methylenephosphoranes 2a,b giving rise
to fluorine-containing vinyldiazoketones 4a–h with mod-
erate to good yields in three to four hours (Table 2).
The reaction of (benzoyl)methylenephosphorane 2c with
F-diazodiketones 1a,c in toluene (6 d for 1a; 14 d for 1c)
also results in vinyldiazoketones 4k,l, but only in low
yields (Table 2).
Table 2 Yields of Fluorinated Vinyldiazoketones 4a–h,k,l
Compound RF
R1
R2
Yield (%)a
4a
4b
4c
4d
4e
4f
CF3
Me
OMe
OEt
OMe
OMe
OMe
OMe
OEt
OMe
Ph
79
65
84
76
69
63
72
42
32
18
CF3
CF3
CF3
CF3
CF3
CF3
C3F7
CF3
CF3
Et
Bu
Thus, both the 13C NMR and IR spectra unambiguously
suggest that the reaction of F-diazodiketones 1a–h with
t-Bu
Pentyl
p-Tolyl
b-C10H7
Ph
methylenetriphenylphosphoranes
2a–c
proceeds
chemoselectively at the perfluoroacyl carbonyl group
while the H-acyl group remains intact during the reaction.
4g
4h
4k
4l
Only one set of signals was found in the 1H and 13C NMR
spectra of 4a–h in CDCl3 solution at room temperature,
therefore it is possible to conclude that only one regio- and
stereoisomer of each vinyldiazoketone is formed in this
case.
Me
Bu
Ph
a Satisfactory microanalyses were obtained: C 0.35, H 0.17, N
0.38, with exception for 4a,b,l (in C) and 4f–h (in N).
Vinyldiazoketones 4k,l, possessing a bulky benzoyl sub-
stituent at the double bond, gave two sets of signals in the
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PAPER
Synthesis and Structure of Fluorine-Containing Vinyldiazoketones
2873
1
ratio ca. 3:1 and 2:1 in the H and 13C NMR spectra In accordance with the literature data, Wittig reaction of
(Table 3). Most likely, what is observed in this case is an unsymmetrically substituted a-fluoroalkyl carbonyl com-
equilibrium between the s-Z and s-E stereoisomers at the pounds normally results in the formation of olefins with E
CO–CN2 bond;13 the broadening of some signals configuration at the new double bond.15,16 Therefore, one
(Table 3) supports this speculation to some extent. Also, can expect that vinyldiazoketones 4 should also have an E
we cannot exclude the existence of an equilibrium in the configuration.
solution with vinyldiazo-3H-pyrazole.14
This assumption was verified by an additional study of vi-
nyldiazoketones 4a–h,k using HOESY experiments on 1H
Table 3 NMR Spectroscopic Data for Vinyldiazoketones 4a–h,k,l
Com-
pound
IR (cm–1)
1H NMR, d (ppm), J (Hz)
12C NMR, d (ppm), J (Hz)
19F NMR, d
(ppm), J (Hz)
CN2
CO
COR1
1720
4a
4b
2080
1650
2.16 (s, 3 H), 3.72 (s, 3 H), 6.52 25.72, 52.63, 65.47, 122.73 (q, 1JC-F
(s, 1 H)
=
–67.30
275.8), 126.81 (q, 3JC-F = 4.6), 128.01 (q,
2JC-F = 34.5), 163.64, 188.16
2095
2080
1675
1660
1730
1730
1.55 (t, J = 7.7, 3 H), 1.31 (t,
8.27, 14.07, 31.46, 61.79, 65.11, 122.24 –67.02
J = 6.9, 3 H), 2.51 (q, J = 7.7, 2 (q, 1JC-F = 275.9), 127.31 (q, 3JC-F = 4.2),
H), 4.25 (q, J = 7.0, 2 H), 6.59
127.86 (q, 2JC-F = 33.3), 163.22, 191.51
(s, 1 H)
4c
0.93 (t, J = 7.7, 3 H), 1.37 (m, 2 14.05, 22.53, 26.76, 38.12, 52.84, 65.15, –67.11
1
H), 1.65 (m, 2 H), 2.48 (t, J =
7.0, 2 H), 3.69 (s, 3 H), 6.58 (s, 1 JC-F = 4.6), 128.00 (q, 2JC-F = 32.9),
H) 163.98, 191.23
122.58 (q, JC-F = 275.9), 126.94 (q,
3
4d
4e
2080
2095
1650
1670
1720
1735
1.28 (s, 9 H), 3.77 (s, 3 H), 6.60 26.45, 44.65, 52.41, 61.91, 122.28 (q,
(s, 1 H)
–77.44
1JC-F = 275.9), 126.78 (q, 3JC-F = 4.6),
130.21 (q, 2JC-F = 33.3), 163.59, 195.91
0.91 (t, J = 7.7, 3 H), 1.30 (m, 2 14.19, 22.71, 24.41, 36.62, 38.39, 52.87, –66.85
H), 1.31 (m, 2 H), 1.66 (m, 2 H), 64.88, 122.53 (q, 1JC-F = 275.9), 126.96
2.47 (t, J = 7.3, 2 H), 3.79 (s, 3 (q, 3JC-F = 4.6), 128.87 (q, 2JC-F = 33.0),
H), 6.58 (s, 1 H)
164.00, 191.30
4f
2080
2090
1670
1640
1730
1725
2.35 (s, 3 H), 3.63 (s, 3 H), 6.44 2.61, 52.36, 65.75, 122.28 (q, 1JC-F
=
–66.23
(s, 1H), 7.19 (d, J = 7.6, 2 H),
7.49 (d, J = 7.6, 2 H)
275.9), 125.12 (q, 3JC-F = 4.6), 127.84,
129.29, 129.70 (q, 2JC-F = 33.1), 133.75,
143.10, 163.57, 186.52
4g
1.11 (t, J = 7.0, 3 H), 4.05 (q,
13.88, 61.67, 66.13, 122.37 (q, 1JC-F
=
–74.28
J = 6.9, 2 H), 6.49 (s, 1 H), 7.51– 275.9), 124.05, 125.88 (q, 3JC-F = 4.6),
7.59 (m, 7 H)
126.99, 127.86, 128.27, 128.56, 128.63,
129.12, 129.15 (q, 2JC-F = 32.2), 132.28,
133.75, 135. 00, 163.15, 186.66
4h
2085
2095
1645
1675
1725
1675
3.75 (s, 3 H), 6.56 (s, 3 H), 7.45 52.62, 66.21, 108.66 (tq, 1JC-F = 266.1,
(t, J = 7.7, 2 H), 7.54 (t, J = 7.6, 2JC-F = 38.3), 114.37 (tt, 1JC-F = 258.9,
–80.57 (t,
J = 8.5, 3 F),
–112.11 (s, 2
F), –126.50 (s,
2 F)
1 H), 7.62 (d, J = 7.7, 2 H)
2JC-F = 31.3), 117.66 (qt, 1JC-F = 288.8,
2JC-F = 34.2), 127.57, 128.18 (t, 2JC-F
=
=
25.3), 128.78, 129.23, 129.51 (t, 3JC-F
7.9), 132.33, 135.38, 136.62, 163.41,
186.35
4k
4l
2.16 (s, 3 H), 7.41 ( br s, 1 H),
25.77, 65.91, 122.54 (q, 1JC-F = 275.8),
128.72 (q, 2JC-F = 33.3), 128.76, 129.00,
–66.54 (br)
7.49 (t, J = 7.2, 2 H), 7.60 (t,
J = 7.2, 1 H), 7.91 (d, J = 7.2, 2 129.23, 131.29 (q, 3JC-F = 4.2), 136.47,
H)
188.01, 189.36
0.85 (t, J = 7.6, 3 H), 1.22 (m, 2
H), 1.52 (m, 2 H), 2.41 (t, J =
6.9, 2 H), 7.38 (s, 1 H), 7.50 (t,
J = 7.7, 2 H), 7.60 (t, J = 7.7, 1
H), 7.91 (d, J = 7.7, 2 H)
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2874
V. M. Zakharova et al.
PAPER
and 19F nuclei. A clear interaction between fluorine atoms
of the RF-group and the hydrogen atom on the double
bond was established. Furthermore, a weak interaction of
the same F-atoms with hydrogens in the non-fluorinated
R1 group of F-vinyldiazoketones 4f,h was found. There-
fore, one can conclude that vinyldiazoketones 4 have the
expected E-configuration (Figure 2).
DBU (or another base) (4.5 mmol) was added dropwise to a mag-
netically stirred solution of 3-nitro-4-methyl-benzenesulfonyl azide
(20 mmol) and 1,3-diketone 3 (18 mmol) in CH2Cl2 (20 mL) under
cooling (0–5 °C) over 5–10 min. The reaction mixture was stirred
for 2–3 h, filtered through a short plug of silica gel (3 g), and washed
with CH2Cl2–hexane (2:1, 5 × 5 mL). Solvents from the combined
organic phases were removed in vacuo (or at atmospheric pressure
in the case of 1a), and the residue was purified by distillation under
vacuum (for 1i,j) or by column chromatography on silica gel (for
1a–h) to give diazodiketones 1.
Vinyldiazoketones 4a–h,k,l; General Procedure
F-Diazodiketone 1 (4 mmol) was added dropwise to a stirred sus-
pension of methylene triphenylphosphoranes 2a,b,d,e (4.8 mmol)
in Et2O (5 mL; toluene for 2c). After the complete disappearance of
1 from the reaction mixture (3–4 h, in the case of phosphoranes
2c,d,e starting diazo compounds 1a,c were still present even after
6–14 d), the solid matter was removed by filtration, the resultant fil-
trate was concentrated in vacuo, and the residue purified by column
chromatography to furnish F-vinyldiazoketones 4a–h,k,l as bright
yellow-orange oils. Vinyldiazoketones 4b,c,e were additionally pu-
rified by repeated column chromatography to give analytically pure
samples.
Figure 2
The considerable variation in the reactivity of fluorinated
1a–h and non-fluorinated 1i,j diazodiketones during the
Wittig reaction, as well as the discrepancy in the chemical
behavior of H- and F-acyl carbonyl, can be explained by
the enhanced electrophilic character of the carbonyl C-
atom in the perfluoroacyl substituent. This observation
has already been made for ordinary fluoroalkyl containing
ketones;15 it was determined for the first time in this series
of diazocarbonyl compounds with two electron-accepting
groups at the a,a¢-position to the C=O moiety. Moderate
yields obtained with (benzoyl)methylenephosphorane 2c,
and negative results with (formyl)- and (acetyl)methyl-
enephosphoranes 2d,e may be attributed to the weak reac-
tivity of these Wittig reagents bearing acyl groups.17 The
process is probably complicated by the easily occurring
consecutive reaction of the newly formed conjugated sys-
tem in vinyldiazoketone 4, which reacts with one more
molecule of phosporanes 2d,e to give polyolefinic struc-
tures.
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the perfluoroacyl carbonyl group furnishing the corre-
sponding fluorinated vinyldiazoketones with E configura-
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2-Diazo-1,3-diketones 1a–j; General Procedure
The diazo transfer reaction to prepare F-diazodiketones 1a–h was
performed in carefully dried equipment, with moisture excluded at
all stages of the process.10 Reaction with non-fluorinated 1,3-dike-
tones was carried out in the usual manner.8
Synthesis 2005, No. 17, 2871–2874 © Thieme Stuttgart · New York