Two-stage synthesis of 3-(perfluoroalkyl)-substituted vinyldiazocarbonyl compounds and their nonfluorinated counterparts: A comparative study

Article abstract of DOI:10.1055/s-0032-1318309

Two approaches for the synthesis of fluorinated (F) and nonfluorinated (H) 4-(alkoxycarbonyl)-substituted cis- and trans-vinyldiazocarbonyl compounds with substituents of variable stereoelectronic nature (H, Me, Ph, CF₃, OTBS) at the C-3 atom of the vinyl double bond from the relevant 1,3-dicarbonyl compounds were compared: a pathway using the Wittig reaction followed by a diazo transfer reaction was most efficient for the synthesis of the H-vinyldiazocarbonyl compounds (total yields of up to 60%), while the yields of their F-analogues under similar conditions did not exceed 16-37%. An approach via diazo transfer followed by the Wittig reaction, in contrast, is more effective for the preparation of F-vinyldiazocarbonyl compounds (total yields 37-69%). The configuration of the resulting F- and H-vinyldiazocarbonyl compounds is evidently controlled by the steric bulk of the substituent at the C-3 atom of the vinyl double bond and, in addition, depends on the specific synthetic pathway. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0032-1318309

PAPER
▌1215
paper
Two-Stage Synthesis of 3-(Perfluoroalkyl)-Substituted Vinyldiazocarbonyl
Compounds and Their Nonfluorinated Counterparts: A Comparative Study
Two-Stage Synthesis of Vinyldiazocarbonyls
Murat B. Supurgibekov,a G. K. Surya Prakash,*b Valerij A. Nikolaev*a
a
Saint Petersburg State University, Department of Organic Chemistry, University pr. 26, 198504, Saint Petersburg, Russian Federation
Fax +7(812)4286733; E-mail: vnikola@VN6646.spb.edu
b
University of Southern California, 837 Bloom Walk, Los Angeles, CA 90089-1661, USA
Fax +1(213)7408607; E-mail: gprakash@usc.edu
Received: 17.12.2012; Accepted after revision: 04.02.2013
CO2Alk
O
CO2Alk
R1
OAlk
Abstract: Two approaches for the synthesis of fluorinated (F) and
nonfluorinated (H) 4-(alkoxycarbonyl)-substituted cis- and trans-
vinyldiazocarbonyl compounds with substituents of variable stereo-
electronic nature (H, Me, Ph, CF3, OTBS) at the C-3 atom of the vi-
nyl double bond from the relevant 1,3-dicarbonyl compounds were
compared: a pathway using the Wittig reaction followed by a diazo
transfer reaction was most efficient for the synthesis of the H-vinyl-
diazocarbonyl compounds (total yields of up to 60%), while the
yields of their F-analogues under similar conditions did not exceed
16–37%. An approach via diazo transfer followed by the Wittig re-
action, in contrast, is more effective for the preparation of F-vinyl-
diazocarbonyl compounds (total yields 37–69%). The configuration
of the resulting F- and H-vinyldiazocarbonyl compounds is evident-
ly controlled by the steric bulk of the substituent at the C-3 atom of
the vinyl double bond and, in addition, depends on the specific syn-
thetic pathway.
R1
R1
N
R2
N
R2OC
N
R2OC
N
H
N2
R1 = CF3, C3F7 (cis)
R1 = H, Me (trans)
Scheme 1 Assumed stereocontrol in the cyclization of vinyldiazo-
carbonyl compounds
To experimentally check this assumption, we needed to
prepare a series of 4-(alkoxycarbonyl)-substituted 2-vi-
nyldiazocarbonyl compounds with cis and trans configu-
ration of the vinyl double bond, the synthesis of which is
the focus of this research.
Basically, in the chemistry of aliphatic diazo compounds,
two fundamentally different approaches are used for the
incorporation of the diazo function in a target molecule8
which, as applied to the synthesis of 2-vinyldiazocarbonyl
compounds 1 from 1,3-dicarbonyl compounds 2, can be
stated in the following manner (Scheme 2):
Key words: (perfluoroalkyl)-containing vinyldiazocarbonyl com-
pounds, diazo transfer, Wittig reaction, 1,3-diketones
In recent years, reactions of -vinyl--diazocarbonyl
compounds with the elimination or retention of ‘dinitro-
gen’ of the diazo group have gained significant attention
and importance for the generation of diversified reactive
intermediates, such as metallocarbenes,1 carbenes,2
ylides3 and cyclopropenes.4 They are also widely used for
the synthesis of a great variety of heterocyclic com-
pounds.5
(i) approach ‘A,B’ involves the initial creation of a 2-
vinylcarbonyl compound9 (A) followed by incorporation
of the diazo function (B) using, for example, a diazo trans-
fer reaction;
(ii) approach ‘B,A’ involves first the preparation of a di-
azocarbonyl precursor (B), followed by creation of a vinyl
moiety adjacent to the diazo group (A) with a certain syn-
thetic protocol.
During a study of thermal reactions of a series of vinyldi-
azocarbonyl compounds (VDCC) with retention of the
CN2 moiety, it was recently established that 3-RF-substi-
tuted vinyldiazocarbonyl compounds (R1 = CF3, C3F7)
readily take part in tandem Staudinger–diaza-Wittig reac-
tions to produce pyridazines, but do not undergo 1,5-elec-
trocyclization, whereas their nonfluorinated analogues
(R1 = H, Me) easily cyclize to pyrazoles, but remain intact
under Staudinger–diaza-Wittig reaction conditions
(Scheme 1).6 It was assumed that the different reactivity
of vinyldiazocarbonyl compounds in these processes is
due to a different stereochemical arrangement of the
CO2Alk and CN2 groups (cis or trans)7 on the vinyl dou-
ble bond.6c
CO2Alk
approach ‘A,B’
O
B
R1
R2
CO2Alk
O
A
O
O
R1
R2
R1
R2
B
O
O
A
N2
2
R1
R2
R1 = Alk, RF
approach ‘B,A’
1
N2
Scheme 2 Two approaches for the synthesis of 2-vinyldiazocarbonyl
compounds 1 from 1,3-dicarbonyl substrates 2
Each of the reaction protocols ‘A’ and ‘B’ has already
been used by others for the preparation of a number of vi-
nyldiazocarbonyl compounds;1,6,10a,b,11 however, a com-
parative evaluation of the above approaches with respect
to their validity for the synthesis of 3-(fluoroalkyl)-con-
SYNTHESIS 2013, 45, 1215–1226
Advanced online publication: 04.04.2013
DOI: 10.1055/s-0032-1318309; Art ID: SS-2012-T0974-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1216
M. B. Supurgibekov et al.
PAPER
taining and nonfluorinated vinyldiazocarbonyl com- Stage ‘A’: Synthesis of the vinylcarbonyl compounds us-
pounds has not been previously realized. ing the Wittig reaction
The main goal of our research was to assess the efficacy Although there are well-known examples for the synthesis
of the approaches ‘A,B’ and ‘B,A’ starting from 1,3-di- of 3-substituted vinylcarbonyl compounds,12 there is to
carbonyl compounds 2 for the preparation of (fluoroal- the best of our knowledge no common method suitable for
kyl)-containing (F) and nonfluorinated (H) 4- the preparation of these compounds. One of the practical
(alkoxycarbonyl)-substituted cis- and trans-vinyldiazo- approaches for their synthesis that one can envision is the
carbonyl compounds 1 bearing various substituents R1 at Wittig reaction of rather easily available 1,3-dicarbonyl
the C-3 atom of the vinyl fragment of the molecule.
compounds. However, only one example of this reaction
was available in the literature; namely, treatment of acet-
A series of H- and F-vinyldiazocarbonyl compounds 1a–
i containing a substituent R1 with various electronic and
steric requirements (R1 = H, Me, RF, Ph, OTBS) and dis-
ylacetone
with
(ethoxycarbonylmethylene)triphe-
nylphosphorane.13
similar character of the carbonyl group on the diazo car- We have established that the efficacy and selectivity of
bon atom (CO2Alk, COAlk) were used for this study, as the Wittig reaction with 1,3-dicarbonyl compounds 2c–
well as the cyclic diazo compounds 1j,k with fixed cis g,j,k depends considerably on the nature of the carbonyl
configuration of the compound (Figure 1).
group and the Wittig reagent used, and the reaction condi-
tions employed.
1
a
b
c
d
e
f
g
h
i
R1
H
R2
Alk
Me
Me
Et
Me
Et
Me
Me
Et
a) Wittig reaction with nonfluorinated 1,3-dicarbonyl
compounds 2c–e: Reaction of the acetoacetate 2c with
phosphoranes 3a,b (3a: R = Ph, Alk = Me; 3b: R = Ph,
Alk = Et) (in benzene solution, at 80 °C for 48 h), fol-
lowed by chromatographic purification, gave vinyl esters
4c,c in yields of 52–63% (Table 1, entry 1). At the same
time, the similar reaction of acetylacetone (2d) with tri-
phenylphosphorane 3a in benzene, dichloromethane,
chloroform or dioxane gave very low yields of the target-
ed vinyl ketone 4d (5–18%); the most satisfactory yield of
4d (38%) was obtained by performing the reaction in ace-
tonitrile (Table 1, entry 2).
OMe
OMe
OEt
Me
OEt
OMe
Me
CO2Alk
O
CO2Et
CO2Et
Me
Me
Me
Ph
CF3
CF3
C3F7
n(H2C)
R1
R2
N2
N2
1j n = 1
1k n = 2
OEt
1a–i
OTBS OMe
Me
Figure 1 Structures of the vinyldiazocarbonyl compounds 1a–k tar-
geted in this study
Furthermore, the structural variations employed in our re-
search would help to determine the feasibility of both ap-
proaches for the synthesis of F- and H-vinyldiazocarbonyl
compounds with different configurations of the vinyl dou-
ble bond and to estimate the scope and limitations of the
reactions studied.
Wittig reaction of keto esters 2c with phosphoranes 3a,b
proceeded chemoselectively on the acetyl carbonyl group
(COCH3), as demonstrated by the disappearance of the
signal for the carbonyl C-atom of the H-acyl group at
around 190–200 ppm in the 13C NMR spectra of the iso-
Approach ‘A,B’
1
13
lated compounds 4c,c. Also, based on H and C NMR
spectroscopic data, the reactions of acetoacetate 2c and
Table 1 Synthesis of the -Vinylcarbonyl Compounds 4c–g,j,k Using the Wittig Reaction
R1
CO2Alk
O
CO2Alk
O
+ R3P=CHCO2Alk
O
O
3a–c
+
+
R2
R1
R2
R2
R1
– R3P=O
R1
R2
O
O
2c–g,j,k
5d,g
4c–g,j,k
Yield (%) of 4 and 5
Entry
2
R1
R2
R = Ph
R = n-Bu
Alk
4
5d,g
1
2
3
4
5
6
7
c
d
e
f
Me
OEt
Me
52–63
5–38
–
Et (Me)
Me
c (c)
Me
d
13–35
Ph
OEt
OMe
Me
85
Et
e
CF3
83–86
75–85
57–60
50
Me (Et)
Me
f (f)
g
j
CF3
g
j
5–23
(CH2)3
(CH2)4
OEt
OEt
Et
k
Et
k
Synthesis 2013, 45, 1215–1226
© Georg Thieme Verlag Stuttgart · New York

PAPER
Two-Stage Synthesis of Vinyldiazocarbonyls
1217
acetylacetone (2d) with Wittig reagent 3a produced a b) Wittig reaction with fluorine-containing 1,3-dicarbonyl
mixture of isomers of vinyl ester 4c (Alk = Me) and vinyl compounds 2f,g: The reaction of F-2f,g with phosphorane
ketone 4d in a ratio of 3:3:2:2 and 2:1:7:2, respectively 3a (in benzene at 80 °C, within 30 min) produced vinyl-
(two stereoisomers of each regioisomer, Table 1), while carbonyl compounds F-4f,f,g in yields of 75–86% (Table
with phosphorane 3b (Alk = Et) the reaction with 2c gave 1, entries 4 and 5). According to 1H and 13C NMR spectra,
two stereoisomers of 3-methylglutaconate 4c in the ratio vinyl ester F-4f (Alk = Et) and vinyl ketone F-4g were
5:3. Since at the next stage ‘B’ (diazo transfer reaction), found to be mixtures of two isomers in a ratio of 1:1 and
under the action of 1,8-diazabicyclo[5.4.0]undec-7-ene 2:1, respectively. On using phosphorane 3a instead of the
(DBU), one would expect generation of the same interme- ethyl analogue 3b, only one isomer of vinyl acetate F-4f
diate anion A from all four (or two) isomers of vinylcar- was obtained.
bonyl compounds 4c,d,g (see Table 2), separation of the
mixtures of regio- and stereoisomers of vinyl compounds
4c,d,g was not undertaken. On prolonged heating of the
reaction mixture with vinyl ketones 4d,g, self-condensa-
Wittig reaction of phosphorane 3a with dicarbonyl com-
pounds F-4f,g took place chemoselectively on the perflu-
oroacetyl carbonyl group, as evidenced by the
disappearance of the distinctive quartet for the F-acyl
tion occurred and considerable amounts of the α-pyra-
group carbonyl C-atom at around 160–175 ppm and the
nones 5d,g12a,b,14 were formed, significantly diminishing
growth of signals for the C-3–CF3 fragment at around
the yields of the target compounds 4d,g.
138–139 ppm in the 13C NMR spectra.
Ethyl benzoylacetate (2e) did not react with phosphorane
Stage ‘B’: Synthesis of the 2-vinyldiazocarbonyl com-
3b (Alk = Et) under similar reaction conditions. In this
pounds 1a–g,j
connection, for olefination of the keto ester 2e, the tri-n-
Vinyldiazocarbonyl compounds 1a–g,j were prepared
from the corresponding vinyl ketones and esters 4b–g,j
obtained at stage ‘A’, as well as from commercially avail-
able dimethyl glutaconate (4a, mixture of trans/cis-
isomers ~8:2), using a diazo transfer reaction3a,7 with 4-
butylphosphorane 3c was used, which has been shown to
be a more active olefination agent than triphenylphospho-
ranes in some cases.15 The reaction of keto ester 2e with
tri-n-butyl(ethoxycarbonylmethylene)phosphorane (3c)
in toluene under reflux for 23 hours gave 3-phenyl-substi-
tuted glutaconate 4e in high yield (85%), as a single ste-
acetamidobenzenesulfonyl
azide
(p-ABSA)
and
1
DBU6b,c,10a (Table 2).
reoisomer based on H and 13C NMR spectroscopic
analysis (Table 1, entry 3).
a) Synthesis of H-vinyldiazocarbonyl compounds 1a–
e,j,k: The yields of the nonfluorinated diazo compounds
H-1a–e,j at this stage generally exceeded 50%, based on
the 1H and 13C NMR spectra, and all vinyl compounds H-
4a–e,j gave rise to only one isomer of the target diazo
compounds H-1a–e,j. In the reaction mixtures of H-vinyl
Reaction of carbocyclic keto esters 2j,k with phosphorane
3b gives rise to thermodynamically more stable regioiso-
mers with an endocyclic double bond in the vinyl esters
4j,k (Table 1, entries 6 and 7).
Table 2 Results of the Diazo Transfer Reaction with -Vinylcarbonyl Compounds 4a–g,j,k
O
CO2Alk
R1
R2
CO2Alk
O
CO2Alk
O
+
ArSO2N3
O
–
DBU
R1
R2
– ArSO2NH2
N
R1
R2
AlkO2C
R1
R2
N
N2
1a–g,j
H
A
4a–g,j,k
6a–d
Entry
R1
R2
Alk
1
Yield (%)
6
Yield (%)
1
2
3
4
5
6
7
8
9
H
OMe
OMe
OEt
Me
Me
Me
Et
a
b
c
d
e
f
63–85
56
a
b
c
3–10
27
Me
Me
73
15
Me
Me
Et
45–60
72
d
35–52
Ph
OEt
OMe
Me
CF3
CF3
(CH2)3
(CH2)4
Me
Me
Et
18a
g
j
23–43
60
OEt
OEt
Et
k
–
a Based on 1H NMR spectroscopic data.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1215–1226

1218
M. B. Supurgibekov et al.
PAPER
diazo compounds 4a–d, pyrazoles 6a–d were usually also
Table 3 Synthesis of Diazodicarbonyl Compounds 7b,c,e–i
identified (3–52%, based on 1H NMR spectra).
O
O
O
p-ABSA
DBU or Et3N
The diazo transfer reaction with carbocyclic vinyl ester H-
4j also gave rise to the anticipated vinyldiazo ester 1j in
good yield (60%); however, a similar reaction with its ho-
mologue 4k did not produce the desired diazo ester 1k in-
dependent of the base employed in the diazo transfer
process (DBU or Et3N, 72 h). From the reaction mixture
after workup, only starting carbocyclic vinyl ester 4k was
recovered. Application of triisopropylbenzenesulfonyl
azide (TIPBSA), which is usually employed in diazo
transfer reactions with sterically demanding sub-
strates,3a,16 also failed.
O
O
TFAA, Py
OMe
R1
R2
R1
R2
N2
N2
2b,c,e–i
7b,c,e–i
Entry
2
R1
R2
7
Yield (%)
1
2
3
4
5
6
b (c)
e (e)
f (f)
g
Me
OMe (OEt)
OMe (OEt)
OMe (OEt)
Me
b (c) 75–85
Ph
e (e) 89–90
f (f) 66, 85a
CF3
CF3
C3F7
g
h
i
43–55
61
b) Synthesis of (fluoroalkyl)-containing vinyl diazo com-
pounds 1f,g: Compounds F-1f,g were obtained similarly
to their nonfluorinated analogues H-1a–d; however, in
contrast to the vinyl diazo acetates H-1a–c, where the
yields were up to 85%, the efficacy of the diazo transfer
reaction with vinylcarbonyl compounds F-4f,g was much
lower. Under optimized reaction conditions, the yields of
vinyl diazo ketone F-1g and vinyl diazo ester F-1f were
43% and 18%, respectively (Table 2, entries 7 and 6). Vi-
nyl diazo ketone F-1g, in contrast to vinyl diazo acetate F-
1f, was found to be a mixture of stereoisomers (1:1).
h
OEt
i
CH2CO2Me
OMe
72
a By acylation of methyl diazoacetate with TFAA.
pyrazoles H-6c,e was formed. Reaction under more se-
vere conditions was not undertaken, since at elevated tem-
perature the diazodicarbonyl compounds are thermally
rather unstable.18
b) Olefination of F-diazodicarbonyl compounds:
Low yields of the fluorinated diazo compounds F-1f,g
most likely are a consequence of a slow diazo transfer re-
action with vinylcarbonyl compounds F-4f,g compared to
their H-analogues, with reaction of the azide with DBU
proceeding much faster than the diazo transfer reaction.
Moreover, the yield of vinyl ketone F-1g, apparently, was
decreased due to the parallel formation of pyranone 5g
from the initial vinyl ester F-4g (Table 1, entry 5).
Wittig reaction of (fluoroalkyl)-containing diazodicar-
bonyl compounds 7f–h, on the other hand, proceeded eas-
ily under very mild conditions, at room temperature, and
in high yields (64–93%) (Table 4). Reaction was che-
moselective and occurred only at the F-acyl carbonyl
group, while H-acetyl or alkoxycarbonyl groups remained
intact in the reactions with phosphoranes 3a,b.
c) Alternative ways to create a vinyl group in the structure
of the diazocarbonyl compound:
Approach ‘B,A’
Stage ‘B’: Synthesis of diazodicarbonyl compounds 7b,c,e–
(i) Cross-coupling of ethyl diazoacetate: Diethyl cis-di-
azoglutaconate (1a) was obtained via cross-coupling of
ethyl 3-iodoacrylate with ethyl diazoacetate using
Pd(PPh3)4.19 The diazoacetate is not stable enough in the
presence of the palladium catalyst used, producing diethyl
fumarate due to decomposition; however, employing a 2–
3-fold excess of the diazo compound provided a way for
the preparation of the vinyl diazo ester 1a in yields up to
58–64%.
i
Nonfluorinated diazodicarbonyl compounds H-7b,c,e,e,i
employed in this study were obtained using the general di-
azo transfer procedure with triethylamine as a base10a (Ta-
ble 3, entries 1, 2 and 6). Fluorinated analogues F-7f–h
were prepared with DBU using our previously developed
procedure for the synthesis of F-diazodicarbonyl
compounds10c,d (Table 3, entries 3–5).
The methyl ester of 2-diazo-4,4,4-trifluoro-3-oxobutanoic
acid (7f, R2 = OMe) was also prepared via acylation of
methyl diazoacetate with trifluoroacetic anhydride,17
which provided better yields of F-diazo keto ester 7f than
the diazo transfer reaction (Table 3, entry 3).
(ii) Dehydration of diazo alcohols as an alternative pathway
for the preparation of vinyldiazocarbonyl compounds20
was tested with the 3-methyl- and 3-phenyl-substituted di-
azo alcohols 9c,e (R = Me, Ph) prepared by condensation
of the diazodicarbonyl compounds 7c,e (ethyl esters) with
methyl lithioacetate, followed by dehydration of the re-
sulting diazo alcohols (Table 5).20b–d
Stage ‘A’
a) Interaction of H-diazodicarbonyl compounds with Wit-
A positive result for the dehydration of the pure diazo al-
cohols 9 was achieved only with the 3-methyl-substituted
diazo compound 7c (33% of 1c′ using POCl3 as the dehy-
drating agent). A one-pot reaction of diazo alcohols 9c′,e′
(by addition of Tf2O, or TFAA, or TsCl directly to the re-
action mixture with the lithium salt of the diazo alcohols
tig reagents:
Attempts to perform the Wittig reaction with H-diazodi-
carbonyl compounds failed. Thus, after prolonged (7–10
d) reflux of the diazo compounds H-7c,e with phospho-
rane 3b in diethyl ether, none of the expected H-vinyldi-
azocarbonyl compounds 1c,e or the corresponding
Synthesis 2013, 45, 1215–1226
© Georg Thieme Verlag Stuttgart · New York

PAPER
Two-Stage Synthesis of Vinyldiazocarbonyls
1219
Table 4 Olefination of Diazodicarbonyl Compounds 7c,e–h via the Wittig Reaction
CO2Alk
F3C
Ph3P=CH-CO2Alk
Et2O, r.t.
OMe
O
O
O
+
R1
R2
N
R1
R2
MeO2C
N
– Ph3P=O
N2
7c,e–h
N2
1f–h
8f,g
Entry
7c,e–h
R1
R2
Yield (%) of 1f–h
Yield (%) of 8f,g
1
2
3
4
5
c
e
f
Me
Ph
OEt
OEt
–
–
–
–
CF3
CF3
C3F7
OMe
Me
87–93
64–68
83
5–11
14–18
–
g
h
OEt
Table 5 Attempts to Synthesize the Vinyl Diazo Esters 1c′,e′ via Diazo Alcohols 9c′,e′
CO2Me
CO2Et
CO2Me
CO2Et
O
POCl3
or Tf2O
CO2Me
HO
R
CO2Et
AcOH
R
+
Li
N2
N2
N2
7
9c′,e′
1c′
Entry
7
R
Yield (%) of 9
Dehydration agent
Yield (%) of 1
1
2
c
e
Me
Ph
79–99
78–83
POCl3
Tf2O
33
–
9c′,e′ at the condensation step) was also only successful ing the approach ‘B,A’, attempts were undertaken to cre-
for the synthesis of vinyl diazo ester 1c′ (yield: 37%).
ate the olefinic fragment in the carbonyl substrate with the
help of the HWE22 and Peterson23 methods. In these ex-
periments, diazo keto esters 7b,e were employed as model
carbonyl compounds.
(iii) Silylation of the enol form of the diazocarbonyl
compound 7i: The reaction of dimethyl 2-diazo-3-oxo-
pentanedioate (7i) with tert-butyldimethylsilyl trifluoro-
methanesulfonate (TBSOTf) in the presence of HWE reaction with diazo keto esters 7b,e and butyllithi-
triethylamine21 gave rise through enol-7i to a mixture of um or lithium diisopropylamide as a base24 proved to be
the trans/cis-isomers (~20:1) of vinyl diazo compound 1i not advantageous. Application of the Still–Gennari
in more than 80% total yield (Scheme 3).
modification25 of the HWE reaction also failed, though
fluoroalkyl groups in the structure of the Still–Gennari re-
agent, as compared to alkyl substituents, usually favors
the formation of alkenes in this process.26 The employ-
ment of the Masamune adaptation27 of the HWE reaction,
used by Guillaume and co-workers for the synthesis of F-
vinyl diazo acetates,11a in the olefination reactions of the
nonfluorinated diazodicarbonyl compounds H-7b,e with
N-ethyldiisopropylamine or DBU as the base was also
found to be ineffective. Similarly, attempts to carry out
olefination of the diazo keto esters H-7b,e via the Peterson
procedure28 were also not successful.
The silyl group of the vinyl diazo ester 1i is very sensitive
to even traces of water. Thus, only the sole use of com-
pletely anhydrous silica gel and eluents for chromatogra-
phy permitted isolation and full characterization of both
isomers by spectroscopic methods.
d) Attempts to olefinate the H-diazo keto esters 7b,e via
the Horner–Wadsworth–Emmons (HWE) and Peterson
reactions:
Since the Wittig reaction was found to be ineffective for
the synthesis of the H-vinyldiazocarbonyl compounds us-
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Et3N
TBSOTf
CO2Me
TBSO
O
HO
– CF3SO2OH
N2
1i; 81%
N2
enol-7i
N2
7i
trans/cis ~ 20:1
Scheme 3 Silylation of the diazodicarbonyl compound 7i
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1215–1226

1220
M. B. Supurgibekov et al.
PAPER
With repect to the stereochemistry of the H- and F-vinyl- with confidence of the stereochemistry of the major si-
diazocarbonyl compounds 1a–i, the configuration of the lylation product of the diazo keto ester 7i to the trans-1i
obtained compounds 1a–d,f–h has been established previ- configuration. At the same time, the minor isomer was as-
ously by NMR spectroscopy, and X-ray crystal structure cribed the cis-1i configuration, since studies revealed an
analysis of diazo compounds and derived phosphazines NOE between the 4-H atom of the vinyl double bond and
(1a,6c,20a 1b–d,6c 1f,g6c,11c). The stereochemistry of the 2- the protons of the tert-butylsilyl group (Figure 2).
vinyldiazocarbonyl compounds 1e,i, prepared in our cur-
rent work, was also elucidated by NMR spectroscopy.
In summary, a comparison of the efficacy of the two ap-
proaches ‘A,B’ and ‘B,A’ for the synthesis of 4-(alkoxy-
Thus, vinyl diazo ester H-1e, possessing a bulky phenyl carbonyl)-substituted H- and F-vinyldiazocarbonyl
substituent on the vinyl double bond, has cis configuration compounds has enabled us to come to the following con-
which is clearly evident from the NOE between the ortho clusions (Table 6):
protons of the phenyl group and the 4-H atom of the dou-
ble bond (Figure 2).
Approach ‘A,B’ is most adequate for the preparation of
the nonfluorinated vinyl diazo compounds H-1a–e,j, pro-
viding a pathway for their synthesis with total yields of up
MeO2C
TBSO
H
H
CO2Et
CO2Et
to 61% in two stages, while the yields of the F-vinyldiaz-
ocarbonyl compounds under similar conditions do not ex-
ceed 16–37%.
NOE
NOE
CO2Me
Ph
N2
N2
Approach ‘B,A’, in contrast, is much more efficient for
the synthesis of the F-vinyldiazocarbonyl compounds,
where the total yields in two stages of this process are in
the range of 37–69%. At the same time, the approach
‘B,A’ with H-vinyldiazocarbonyl compounds was not
successful, since at moderate temperatures the starting H-
diazodicarbonyl compounds did not react with phospho-
ranes (stage ‘B’), while increasing the temperature of the
reaction mixture resulted in the notable decomposition of
these diazo compounds. The successful olefination of
these diazocarbonyl compounds using the Wittig reaction
apparently requires the availability of a rather strong elec-
tron-withdrawing substituent adjacent to the reacting car-
bonyl group, such as a perfluoroalkyl11a,c,d or α-carbonyl11b
trans-1i
cis-1e
H
CO2Me
NOE
CO2Me
TBSO
N2
cis-1i
Figure 2 The structures of cis- and trans-vinyl diazo esters 1e and 1i
as revealed by NOE studies
The NOE studies of major isomer 1i indicated interaction
of the protons of the methoxycarbonyl and tert-butylsilyl
groups on the vinyl double bond, enabling assignment
Table 6 Overall Results of the Synthesis of the trans- and cis-2-Vinyldiazocarbonyl Compounds 1a–j Using Approaches ‘A,B’ and ‘B,A’
AlkO2C
CO2Alk
CO2Et
O
O
CO2Et
R1
R2
R1
R2
N2
N2
1j
N2
trans-1a–d,g,i
cis-1a,e–j
trans-1
R1, R2, Alk
Approach; yield (%)
cis-1
R1, R2, Alk
Approach; yield (%)
a
H, OMe, Me
Me, OAlk, Alk
Me, OEt, Me
Me, Me, Me
85a
a
e
f
H, OEt, Et
B,A;b 49–64
A,B; 61
b,c
c′
d
A,B; 29–46
B,A;c 33–37
A,B; 23
Ph, OEt, Et
CF3, OMe, Me
CF3, Me, Me
C3F7, OEt, Et
OTBS, OMe, Me
cycloalkyl, OEt, Et
B,A; 57–69
B,A; 28–37
B,A; 51
g
h
i
g
CF3, Me, Me
OTBS, OMe, Me
A,B; 16–37d
B,A;e 46
i
B,A;e 2
j
A,B; 34–36
a Yield of diazo transfer (stage ‘B’) with commercial dimethyl glutaconate.
b Olefination (stage ‘A’) via cross-coupling with diazocarbonyl compound.
c Olefination (stage ‘A’) via dehydration of diazo alcohol.
d Mixture of cis- and trans-stereoisomers (1:1).
e Olefination (stage ‘A’) using silylation of diazodicarbonyl compound.
Synthesis 2013, 45, 1215–1226
© Georg Thieme Verlag Stuttgart · New York

PAPER
Two-Stage Synthesis of Vinyldiazocarbonyls
1221
was carried out on neutral silica gel (Chemapol, L 40/100 or Merck
70–230 mesh) with petroleum ether (PE; 40–70 °C) and Et2O as el-
uents in gradient regime.
group. In this connection, the realization of the pathway
‘B,A’ with the nonfluorinated diazodicarbonyl com-
pounds, which do not have such an additional activation
of the carbonyl group, failed. Analogously, the attempts to
olefinate H-diazodicarbonyl compounds with the help of
HWE, Peterson and Still–Gennari procedures also proved
unsuccessful.
H- and F-Vinylcarbonyl Compounds 4b–d,f,g,j,k Using the
Wittig Reaction (Approach ‘A,B’, Stage ‘A’, Table 1)
Protocol a: A mixture of phosphorane 3a (12.2 mmol, 1 equiv) and
1,3-dicarbonyl compound 2d (183.0 mmol, 15 equiv) in CH2Cl2 (40
mL) was kept under reflux for 2–6 d, until the completion of the re-
action (by TLC and 1H NMR spectroscopy). The reaction mixture
was extracted with 5% aq NaOH to remove the excess dicarbonyl
compound, and the organic layer was washed with water and dried
with MgSO4. The solvent was removed under reduced pressure, the
resulting orange solid was triturated with PE–Et2O (1:1) and re-
moved by filtration, the filtrate was concentrated, and the residue
was distilled under reduced pressure.
The main limitation of the approach ‘A,B’ for the prepa-
ration of H-vinyldiazocarbonyl compounds is 1,5-electro-
cyclization to the respective pyrazoles 6, but carrying out
the reaction under reduced temperature (0–5 °C) permits
considerable minimization of this side reaction.
The major side reaction of the fluoroalkyl-containing di-
azocarbonyl compounds F-1 with the Wittig reagent was
found to be the formation of pyridazines 8. The occur-
rence of this process is most likely derived from the partial
addition of phosphorane 3a on the terminal N-atom of the
diazo function of compounds F-1, followed by dissocia-
tion of this adduct onto triphenylphosphine and the corre-
sponding azine.29 The subsequent reactions of the
phosphine with the F-vinyldiazocarbonyl compounds cis-
1f,g and intramolecular diaza-Wittig cyclization of phos-
pazine formed via a tandem process gives rise to the pyr-
idazines 8 in the reaction mixture.6c,11
Protocol b: The reaction and workup procedure were performed as
in protocol a, with benzene as the reaction solvent at 80 °C for 48 h.
The residue was separated by column chromatography on silica gel
(PE–EtOAc).
Protocol c: The reaction and workup procedure were run similarly
to protocol a, using MeCN, CHCl3 or dioxane as the reaction sol-
vent at 70 °C for 20 h.
Protocol d: A mixture of a phosphorane 3a,b (42–77 mmol, 1.2
equiv) and a 1,3-dicarbonyl compound 2 (35–64 mmol, 1 equiv) in
benzene (30–60 mL) was kept under reflux until disappearance of
1
the phosphorane 3a,b (by TLC and H NMR spectroscopy). The
solvent was removed under reduced pressure, the resulting orange
solid was triturated with PE–Et2O (1:1) and removed by filtration,
the filtrate was concentrated, and the residue was distilled under re-
duced pressure.
The configuration of the resulting F- and H-vinyldiazo-
carbonyl compounds is evidently governed by the steric
bulk and/or the nature of the substituent at the C-3 atom of
the 4-(alkoxycarbonyl)-substituted vinyldiazocarbonyl
compounds 1. Thus, diazo transfer on the vinylcarbonyl
compounds 4 or olefination of the diazodicarbonyl com-
pounds 7 with a relatively less bulky substituent (H, Me)
at the C-3 atom of the molecule normally produced the
trans-isomer of the vinyl diazo compounds 1, while more
bulky substituents (Ph, CF3) at the C-3 position of the
vinylcarbonyl compound led to the formation of the cis-
isomer of the vinyldiazocarbonyl compounds 1.
Ethyl Methyl 3-Methylpent-2-enedioate (4c′, Alk = Me)30
Obtained from (methoxycarbonylmethylene)triphenylphosphorane
(3a, 42 mmol) and ethyl acetoacetate (2c, 35 mmol) using protocol
b, followed by purification with column chromatography on silica
gel (20 g, hexane–EtOAc).
Yield: 4.1 g (63%); colorless oil; mixture of isomers (3:3:2:2).
Rf = 0.81 (PE–EtOAc, 3:1).
1H NMR (300 MHz, CDCl3): δ = 5.81, 5.80, 5.74, 5.73 (s, 4
CH=CR1, 3:3:2:2), 4.13 (q, J = 7.0 Hz, 2 CH2), 4.11 (q, J = 7.0 Hz,
2 CH2), 3.70, 3.69 (s, 2 CH2), 3.64 (br s, 2 CH2), 3.66 (s, 4 OCH3),
2.19, 1.93 (s, 4 CH3), 1.23 (t, J = 7.0 Hz, 2 CH3), 1.22 (t, J = 7.0 Hz,
2 CH3).
13C NMR (75 MHz, CDCl3): δ = 170.8, 170.4, 170.2, 169.8, 166.6,
166.5, 166.1, 166.0, 151.5, 151.3, 150.8, 150.7, 119.7, 119.4, 119.2,
118.8, 61.0, 60.8, 59.9, 59.8, 52.1, 51.9, 51.1, 51.1, 46.0, 45.7, 38.6,
38.3, 25.7, 25.6, 18.9, 18.8, 14.3, 14.2.
At the same time, the relative configuration of the formed
vinyldiazo compounds evidently depends in some cases
on the specific synthetic pathway. Thus, Wittig olefina-
tion of the diazo keto ester F-7g using phosphorane 3a
(stage ‘A’ of the approach ‘B,A’) stereoselectively fur-
nished only one isomer, the cis-isomer of vinyl diazo ke-
tone F-1g, while the diazo transfer reaction with the
vinylcarbonyl compound F-4g (stage ‘B’ of the approach
‘A,B’) gave rise to the same vinyldiazo compound F-1g,
but as a mixture of the cis- and trans-stereoisomers (in a
1:1 ratio).
Diethyl 3-Methylpent-2-enedioate (4c, Alk = Et)31
Prepared from (ethoxycarbonylmethylene)triphenylphosphorane
(3b, 42 mmol) and ethyl acetoacetate (2c, 35 mmol) via protocol b
(reaction time: 20 h), followed by purification with column chroma-
tography on silica gel (20 g, hexane–EtOAc).
Yield: 3.64 g (52%); colorless oil; mixture of isomers (5:3).
Rf = 0.81 (PE–EtOAc, 3:1).
1H, 13C and 19F NMR spectra were recorded in CDCl3 solution using
TMS or CHCl3 as internal standards at 300 or 400 MHz (1H), 75 or
100 MHz (13C), and 375 MHz (19F) with Varian Gemini-300, Bruker
DPX-300, or Bruker DRX-400 NMR spectrometers. Microanalysis
was performed on a Heraeus CHN Rapid Analyzer. IR spectra were
recorded on an ATI Mattson Genesis Series FTIR spectrophotome-
ter. MS data were measured on a micrOTOF 10223 mass spectrom-
eter. All reactions were carried out in carefully purified and dried
solvents and were monitored by thin-layer chromatography (TLC)
on plates of Silufol UV/VIS 254 nm (Kavalier) using UV light and
iodine as visualizing agents. Preparative column chromatography
1H NMR (300 MHz, CDCl3): δ = 5.85, 5.77 (s, 2 CH=CR1, 5:3),
4.16 (q, J = 7.0 Hz, CH2), 4.13 (q, J = 7.0 Hz, CH2), 3.74, 3.13 (s, 2
CH2, 5:3), 2.23, 1.97 (s, 2 CH3, 3:5), 1.28 (t, J = 7.0 Hz, CH3), 1.26
(t, J = 7.0 Hz, CH3).
13C NMR (75 MHz, CDCl3): δ = 170.7, 170.3, 166.5, 166.4, 151.3,
151.1, 119.9, 119.6, 61.2, 60.2, 46.4, 35.9, 26.0, 19.2, 14.6, 14.5.
Methyl 3-Methyl-5-oxohex-2-enoate (4d)12c
Derived from (methoxycarbonylmethylene)triphenylphosphorane
(3a, 12.2 mmol) and acetylacetone (2d, 183 mmol), using protocol
© Georg Thieme Verlag Stuttgart · New York
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1222
M. B. Supurgibekov et al.
PAPER
c with MeCN for 20 h. After separation of the reaction mixture by
column chromatography on silica gel (25 g, hexane–EtOAc), vinyl
ketone 4d and pyranone 5d were isolated.
1H NMR (300 MHz, CDCl3): δ = 6.83, 6.56 (s, 2 CH=CR1, 1:2),
3.85, 3.65 (s, 2 CH2), 3.76, 3.72 (s, 2 OCH3), 2.35, 2.27 (s, 2 CH3,
1:2).
Yield of vinyl ketone 4d: 0.1–0.72 g (5–38%); colorless oil; bp 52–
53 °C/0.1–0.2 mmHg; mixture of isomers (2:1:7:2).
13C NMR (75 MHz, CDCl3): δ = 201.0, 198.0, 168.9, 165.3, 139.2
(q, 2JC-F = 31.9 Hz), 135.1 (q, 2JC-F = 30.9 Hz), 130.1 (q, 3JC-F = 5.0
Hz), 124.7 (q, 3JC-F = 5.0 Hz), 123.2 (q, 1JC-F = 274.3 Hz), 121.0 (q,
1JC-F = 274.3 Hz), 52.7, 52.4, 32.2, 31.9, 41.4, 32.0.
Rf = 0.27 (PE–EtOAc, 3:1).
1H NMR (300 MHz, CDCl3): δ = 6.24, 6.14, 5.85, 5.73 (s, 4
CH=CR1, 2:1:7:2), 3.80, 3.66 (br s, 4 CH2), 3.65 (br s, 4 OCH3),
2.21, 2.17, 1.92, 1.91 (s, 4 CH3).
13C NMR (75 MHz, CDCl3): δ = 204.7, 204.6, 198.4, 198.2, 170.8,
170.6, 166.7, 166.5, 152.6, 152.0, 149.0, 148.9, 126.9, 126.3, 119.5,
118.2, 55.2, 52.1, 51.9, 51.0, 48.2, 45.8, 31.8, 31.6, 30.0, 29.7, 26.9,
25.9.
MS (EI, 70 eV): m/z = 210.2 [M]+.
6-Methyl-4-(trifluoromethyl)-2H-pyran-2-one (5g)
Yield: 0.29–1.31 g (5–23%); white solid; mp 41–42 °C; sublimed at
25–30 °C/1 mmHg.
Rf = 0.44 (PE–EtOAc, 2:1).
1H NMR (300 MHz, CDCl3): δ = 6.38 (s, 1 H), 6.05 (s, 1 H), 2.26
(s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 164.8, 160.7, 144.6 (q, 2JC-F = 34.4
Hz), 121.0 (q, 1JC-F = 274.3 Hz), 110.6 (q, 3JC-F = 4.5 Hz), 98.5 (q,
3JC-F = 2.0 Hz), 20.0.
4,6-Dimethyl-2H-pyran-2-one (5d)14
Yield: 0.2–0.53 g (13–35%); white solid; mp 48–50 °C.
1H NMR (300 MHz, CDCl3): δ = 5.90 (s, 1 H), 5.82 (s, 1 H), 2.18
(s, 3 H), 2.08 (s, 3 H).
Anal. Calcd for C7H5F3O2: C, 47.2; H, 2.8. Found: C, 46.92, 47.35;
H, 2.81, 2.82.
Dimethyl 3-(Trifluoromethyl)pent-2-enedioate (4f, Alk = Me)
Obtained from (methoxycarbonylmethylene)triphenylphosphorane
(3a, 71 mmol) and methyl 4,4,4-trifluoro-3-oxobutanoate (2f, 59
mmol)32 using protocol d (reaction time: 30 min), and purification
by distillation.
Ethyl 2-(Ethoxycarbonyl)cyclopent-1-ene-1-acetate (4j)12e
Obtained from (ethoxycarbonylmethylene)triphenylphosphorane
(3b, 72–77 mmol) and ethyl 2-oxocyclopentanecarboxylate (2j, 60–
64 mmol) using protocol d (reaction time: 48 h), followed by puri-
fication by distillation.
Yield: 11.47 g (86%); colorless oil; bp 79–82 °C/10 mmHg.
Rf = 0.67 (PE–EtOAc, 3:1).
Yield: 7.73–8.69 g (57–60%); colorless oil; bp 65–75 °C/0.5–1
mmHg.
1H NMR (300 MHz, CDCl3): δ = 6.55 (s, 1 H), 3.78 (s, 3 H), 3.76
(s, 2 H), 3.73 (s, 3 H).
Rf = 0.51 (EtOAc).
13C NMR (75 MHz, CDCl3): δ = 168.9, 165.1, 138.5 (q, 2JC-F = 30.9
Hz), 125.2 (q, 3JC-F = 6.0 Hz), 123.0 (q, 1JC-F = 274.3 Hz), 52.8, 52.5,
32.1.
1H NMR (400 MHz, CDCl3): δ = 4.17 (q, J = 7.0 Hz, 2 H), 4.13 (q,
J = 6.6 Hz, 2 H), 3.66 (br s, 2 H), 2.67–2.63 (m, 2 H), 2.58–2.55 (m,
2 H), 1.90–1.82 (m, 2 H), 1.27 (t, J = 6.6 Hz, 3 H), 1.25 (t, J = 7.0
Hz, 3 H).
MS (EI, 70 eV): m/z = 226.2 [M]+.
13C NMR (75 MHz, CDCl3): δ = 170.3, 165.5, 149.9, 130.7, 60.6,
59.8, 38.5, 35.4, 33.3, 21.3, 14.6, 14.5.
Ethyl Methyl 3-(Trifluoromethyl)pent-2-enedioate (4f′,
Alk = Et)
Prepared from (ethoxycarbonylmethylene)triphenylphosphorane
(3b, 39 mmol) and methyl 4,4,4-trifluoro-3-oxobutanoate (2f, 32
mmol) using protocol b (reaction time: 30 min), followed by distil-
lation.
Ethyl 2-(Ethoxycarbonyl)cyclohex-1-ene-1-acetate (4k)
Synthesized from (ethoxycarbonylmethylene)triphenylphospho-
rane (3b, 60 mmol) and ethyl 2-oxocyclohexanecarboxylate (2k, 72
mmol) using protocol d (reaction time: 48 h), followed by purifica-
tion by distillation.
Yield: 6.61 g (83%); colorless oil; bp 101–102 °C/20 mmHg; mix-
ture of isomers (1:1).
Yield: 7.21 g (50%); colorless oil; bp 80–85 °C/0.5 mmHg.
Rf = 0.67 (PE–EtOAc, 3:1).
1H NMR (300 MHz, CDCl3): δ = 6.55 (br s, 2 CH=CR1), 4.23 (q,
J = 7.2 Hz, CH2), 4.21 (q, J = 7.2 Hz, CH2), 3.79 (s, 2 OCH3), 3.76,
3.74 (s, 2 CH2, 1:1), 1.31 (t, J = 7.2 Hz, CH3), 1.27 (t, J = 7.2 Hz,
CH3).
13C NMR (75 MHz, CDCl3): δ = 168.9, 168.3, 165.1, 164.6, 138.8
(q, 2JC-F = 31.9 Hz), 138.4 (q, 2JC-F = 31.9 Hz), 125.7 (q, 3JC-F = 6.0
Hz), 125.1 (q, 3JC-F = 6.0 Hz), 123.1 (q, 1JC-F = 275.3 Hz), 123.0 (q,
1JC-F = 275.3 Hz), 61.8, 61.7, 52.8, 52.5, 32.4, 32.1, 14.4.
Rf = 0.51 (EtOAc).
1H NMR (400 MHz, CDCl3): δ = 4.15 (q, J = 7.0 Hz, 2 H), 4.13 (q,
J = 7.0 Hz, 2 H), 3.42 (br s, 2 H), 2.34–2.31 (m, 2 H), 2.21–2.18 (m,
2 H), 1.65–1.61 (m, 4 H), 1.26 (t, J = 7.0 Hz, 3 H), 1.25 (t, J = 7.0
Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.2, 168.1, 142.1, 127.7, 60.5,
60.1, 40.6, 32.8, 26.3, 22.1, 22.0, 14.6, 14.5.
MS (EI, 70 eV): m/z = 194.1 [M – 46.2]+.
MS (EI, 70 eV): m/z = 240.2 [M]+.
H-Vinylcarbonyl Compound 4e (Diethyl 3-Phenylpent-2-ene-
dioate)
Methyl 5-Oxo-3-(trifluoromethyl)hex-2-enoate (4g)
Derived from (methoxycarbonylmethylene)triphenylphosphorane
(3a, 47 mmol) and 1,1,1-trifluoropentane-2,4-dione (2g, 39 mmol)
using protocol d (reaction time: 10–30 min). After separation of the
reaction mixture by column chromatography on silica gel (25 g,
hexane–EtOAc), vinyl ketone 4g and pyranone 5g were obtained.
A mixture of tri-n-butyl(ethoxycarbonylmethylene)phosphorane
(3c,33 0.12 mol) and ethyl benzoylacetate (2e, 0.1 mol) in toluene
(20 mL) was kept under reflux for 23 h, until the completion of the
1
reaction (by TLC and H NMR spectroscopy). The mixture was
concentrated under reduced pressure and separated by flash chro-
matography on silica gel (200 g; hexane–Et2O, 1:4). The resulting
vinyl acetate 4e was distilled.
Yield of vinyl ketone 4g: 6.15–6.97 g (75–85%); colorless oil; bp
25–30 °C/1 mmHg; mixture of isomers (1:2).
Yield: 22.3 g (85%); colorless oil; bp 130–140 °C/0.1 mmHg.
Rf = 0.41 (PE–EtOAc, 3:1).
Rf = 0.42 (hexane–Et2O, 2:1).
IR (neat): 1734, 1708, 1629, 1446 cm–1.
Synthesis 2013, 45, 1215–1226
© Georg Thieme Verlag Stuttgart · New York

PAPER
Two-Stage Synthesis of Vinyldiazocarbonyls
1223
1H NMR (400 MHz, CDCl3): δ = 7.46–7.43 (m, 2 H), 7.37–7.35 (m,
3 H), 6.27 (s, 1 H), 4.20 (q, J = 7.3 Hz, 2 H), 4.16 (s, 2 H), 4.12 (q,
J = 7.3 Hz, 2 H), 1.30 (t, J = 7.3 Hz, 3 H), 1.18 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.4, 164.0, 143.4, 138.2, 129.7,
128.4, 127.8, 116.0, 63.9, 61.0, 60.1, 14.1, 13.9.
+
HRMS (ESI): m/z [M –28 + H]+ calcd for C15H17O4 : 261.1127;
13C NMR (100 MHz, CDCl3): δ = 170.0, 166.0, 150.8, 140.5, 129.0,
found: 261.1127.
128.5, 126.3, 119.8, 60.6, 60.0, 36.8, 14.0, 13.9.
Methyl cis- and trans-4-Diazo-5-oxo-3-(trifluoromethyl)hex-2-
enoate (1g)6c,11c
Yield: 3.57 g (43%); yellow oil; bp 45–50 °C/1–2 mmHg; mixture
of stereoisomers (1:1).
+
HRMS (ESI): m/z [M + H]+ calcd for C15H19O4 : 263.1283; found:
263.1287.
Vinyldiazocarbonyl Compounds 1a–g,j via a Diazo Transfer
Reaction (Approach ‘A,B’, Stage ‘B’, Table 2); General Proce-
dure
Rf = 0.34 (PE–Et2O, 2:1).
cis-Isomer 1g
To a stirred soln of a vinylcarbonyl compound 4a–g,j,k (12–21
mmol, 1 equiv) and p-ABSA (13.2–23.1 mmol, 1.1 equiv) in
CH2Cl2 (10–30 mL) at 0 °C, DBU (12–21 mmol, 1 equiv) was add-
ed dropwise. The reaction mixture was stirred at r.t. for 2–3 h, then
filtered through a short plug of silica gel (5–10 g) eluting with
CH2Cl2 or Et2O–PE (1:1, 25–50 mL). The solvents from the com-
bined organic eluates were removed under reduced pressure and the
residue was distilled (in the case of 1g) or purified by chromatogra-
phy on silica gel (1a–f,j) to give vinyldiazocarbonyl compounds 1.
1H NMR (300 MHz, CDCl3): δ = 6.60 (s, 1 H), 3.81 (s, 3 H), 2.25
(s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 188.1, 163.6, 128.0 (q, 2JC-F = 34.5
Hz), 126.8 (q, 3JC-F = 4.6 Hz), 122.7 (q, 1JC-F = 275.8 Hz), 65.4, 52.6,
25.7.
trans-Isomer 1g
1H NMR (300 MHz, CDCl3): δ = 7.01 (s, 1 H), 3.82 (s, 3 H), 2.34
(s, 3 H).
Dimethyl trans-4-Diazopent-2-enedioate (1a)6b,34
Yield: 1.88 g (85%); yellow solid; mp 72–73 °C.
13C NMR (75 MHz, CDCl3): δ = 188.9, 164.8, 127.6 (q, 2JC-F = 34.5
Hz), 127.4 (q, 3JC-F = 4.6 Hz), 121.6 (q, 1JC-F = 275.8 Hz), 66.2, 60.7,
26.7.
1H NMR (400 MHz, CDCl3): δ = 7.33 (d, 3JH-H = 16.2 Hz, 1 H), 5.73
(d, 3JH-H = 16.2 Hz, 1 H), 3.85 (s, 3 H), 3.75 (s, 3 H).
Ethyl α-Diazo-2-(ethoxycarbonyl)cyclopent-1-ene-1-acetate
UV/Vis (EtOH): λmax (log ε) = 259 (3.91), 297 nm (3.92).
UV/Vis (MeCN): λmax (log ε) = 259 (4.04), 294 nm (4.10).
UV/Vis (hexane): λmax (log ε) = 255 (3.9), 293 nm (4.0).
(1j)
Yield: 3.18 g (60%); yellow solid; mp 52–53 °C.
Rf = 0.64 (hexane–EtOAc, 1:1).
IR (neat): 2108, 1696, 1593 cm–1.
Dimethyl trans-4-Diazo-3-methylpent-2-enedioate (1b)6b
1H NMR (300 MHz, CDCl3): δ = 4.25 (q, J = 7.0 Hz, 2 H), 4.20 (q,
J = 7.0 Hz, 2 H), 2.96–2.91 (m, 2 H), 2.73–2.68 (m, 2 H), 1.95–1.87
(m, 2 H), 1.30 (t, J = 7.0 Hz, 3 H), 1.29 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 164.6, 164.4, 141.3, 124.8, 63.5,
61.0, 60.1, 37.3, 33.5, 22.1, 14.4, 14.3.
Yield: 1.33 g (56%); yellow oil.
Rf = 0.35 (PE–EtOAc, 5:1).
1H NMR (400 MHz, CDCl3): δ = 6.51 (q, 4JH-H = 1.2 Hz, 1 H), 3.81
(s, 3 H), 3.69 (s, 3 H), 2.36 (d, 4JH-H = 1.2 Hz, 3 H).
+
HRMS (ESI): m/z [M – 28]+ calcd for C12H16O4 : 224.1048; found:
224.1038.
Diethyl trans-4-Diazo-3-methylpent-2-enedioate (1c)
Yield: 1.98 g (73%); yellow solid; mp 15–18 °C.
Rf = 0.35 (PE–EtOAc, 5:1).
Diazodicarbonyl Compounds 7b,e–i (Approach ‘B,A’, Stage
‘B’, Table 3)
1H NMR (300 MHz, CDCl3): δ = 6.51 (s, 1 H), 4.28 (q, J = 7.3 Hz,
2 H), 4.15 (q, J = 7.3 Hz, 2 H), 2.36 (s, 3 H), 1.31 (t, J = 7.3 Hz, 3
H), 1.27 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 167.0, 163.8, 140.6, 112.1, 69.3,
61.6, 60.0, 14.7.
The diazo transfer reaction with nonfluorinated 1,3-diketones and
esters H-2b,e,i was carried out in the usual manner;8 the same reac-
tion with F-dicarbonyl compounds 2f–h was performed in oven-
dried equipment, excluding entry of moisture in the system at all
stages of the process.8c,d,11d
MS (EI, 70 eV): m/z = 198.2 [M – 28]+.
Methyl 2-Diazoacetoacetate (7b)35a
Prepared from methyl acetoacetate (5.2 g, 45 mmol), p-ABSA (9.6
g, 40 mmol) and Et3N (8.1 g, 11 mL, 80 mmol) in CH2Cl2 (90 mL)
for 2 h.
Methyl trans-4-Diazo-3-methyl-5-oxohex-2-enoate (1d)
Yield: 2.3 g (60%); yellow solid; mp 55–57 °C.
Rf = 0.64 (PE–EtOAc, 3:1).
IR (KBr): 2087, 1716, 1662 cm–1.
Yield: 4.8 g (85%).
1H NMR (300 MHz, CDCl3): δ = 6.66 (s, 1 H), 3.69 (s, 3 H), 2.32
1H NMR (300 MHz, CDCl3): δ = 3.83 (s, 3 H), 2.47 (s, 3 H).
(s, 6 H).
Ethyl 2-Diazoacetoacetate (7c)11d
Prepared from ethyl acetoacetate (4.16 g, 32 mmol), m-
O2NC6H4SO2N3 (7.75 g, 32 mmol) and Et3N (6.4 g, 8.8 mL, 64
mmol) in CH2Cl2 (70 mL) for 2 h.
13C NMR (75 MHz, CDCl3): δ = 188.9, 167.0, 139.8, 113.9, 66.1,
51.1, 27.7, 15.9.
MS (EI, 70 eV): m/z = 182.1 [M]+.
Yield: 4.29 g (86%); bp 40–42 °C/0.6 mmHg.
UV/Vis (MeCN): λmax (log ε) = 216 (4.05), 282 nm (3.97).
Ethyl 2-Diazobenzoylacetate (7e, R2 = OEt)35b
Prepared from ethyl benzoylacetate (2.7 g, 14 mmol), m-
O2NC6H4SO2N3 (3.4 g, 14 mmol) and Et3N (2.8 g, 3.9 mL, 28
mmol) in CH2Cl2 (40 mL) for 4 h.
Diethyl cis-4-Diazo-3-phenylpent-2-enedioate (1e)
Yield: 2.49 g (72%); yellow oil.
Rf = 0.40 (hexane–Et2O, 2:1).
IR (neat): 2112, 1704, 1592, 1493 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.47–7.45 (m, 2 H), 7.40–7.37 (m,
3 H), 6.02 (s, 1 H), 4.23 (q, J = 7.2 Hz, 2 H), 4.10 (q, J = 7.2 Hz, 2
H), 1.30 (t, J = 7.2 Hz, 3 H), 1.09 (t, J = 7.2 Hz, 3 H).
Yield: 2.7 g (90%); bp 95–99 °C/1 mmHg.
© Georg Thieme Verlag Stuttgart · New York
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M. B. Supurgibekov et al.
PAPER
Methyl 2-Diazobenzoylacetate (7e′, R2 = OMe)35a
Prepared from methyl benzoylacetate (3.7 g, 20 mmol), p-ABSA
(5.0 g, 20 mmol) and Et3N (4.0 g, 5.6 mL, 40 mmol) in CH2Cl2 (35
mL) for 5 h.
respectively, there was no indication of the formation of the H-vinyl
diazo acetates 1c,e or the associated pyrazoles 6c,e (by TLC and 1H
NMR spectroscopy of the reaction mixtures). In the case of the Wit-
tig reactions with F-diazodicarbonyl compounds 7f–h, after com-
plete disappearance of 7f–h in the reaction mixture (1–2 h), the solid
matter was removed by filtration, and the resultant filtrate was con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography (hexane–Et2O) or by distillation to furnish the
vinyldiazocarbonyl compounds 1f–h and pyridazines 8f,g.
Yield: 3.6 g (89%).
1H NMR (400 MHz, CDCl3): δ = 7.64–7.61 (m, 2 H), 7.55–7.51 (m,
1 H), 7.44–7.41 (m, 2 H), 3.79 (s, 3 H).
Ethyl 2-Diazo-4,4,4-trifluoro-3-oxobutanoate (7f′, R2 = OEt)11d
Prepared from ethyl 4,4,4-trifluoro-3-oxobutanoate (3.9 g, 21
mmol), m-O2NC6H4SO2N3 (4.9 g, 21 mmol) and DBU (3.2 g, 21
mmol) in CH2Cl2 (50 mL) for 0.5 h.
Dimethyl cis-4-Diazo-3-(trifluoromethyl)pent-2-enedioate (1f)
Prepared from methyl 2-diazo-4,4,4-trifluoro-3-oxobutanoate (7f;
4.0 g, 20 mmol) and (methoxycarbonylmethylene)triphe-
nylphosphorane (3a; 8.36 g, 25 mmol).
Yield: 4.2 g (66%); bp 35–37 °C/0.6 mmHg.
Yield: 4.65 g (93%); yellow oil; bp 65–70 °C/1 mmHg.
Rf = 0.38 (hexane–Et2O, 2:1).
IR (neat): 2109, 1720 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.44 (s, 1 H), 3.80 (s, 3 H), 3.78
(s, 3 H).
3-Diazo-1,1,1-trifluoropentane-2,4-dione (7g)10d
Prepared from 1,1,1-trifluoropentane-2,4-dione (10.8 g, 70 mmol),
p-ABSA (18.6 g, 77 mmol) and DBU (5.3 g, 5.3 mL, 35 mmol) in
CH2Cl2 (80 mL) for 1 h.
Yield: 6.93 g (55%); bp 55 °C/18 mmHg.
2
Ethyl 2-Diazo-4,4,5,5,6,6,6-heptafluoro-3-oxohexanoate (7h)11d
Prepared from ethyl 4,4,5,5,6,6,6-heptafluoro-3-oxohexanoate
(3.76 g, 13 mmol), m-O2NC6H4SO2N3 (3.03 g, 13 mmol) and DBU
(2.0 g, 13 mmol) in CH2Cl2 (40 mL) for 0.5 h.
13C NMR (100 MHz, CDCl3): δ = 163.7, 163.4, 128.3 (q, JC-F
=
33.2 Hz), 123.8, 121.9 (q, 1JC-F = 276.1 Hz), 58.2, 52.5, 52.2.
19F NMR (376 MHz, CDCl3): δ = –66.13.
+
HRMS (ESI): m/z [M – 28 + H]+ calcd for C8H8O4F3 : 225.0374;
Yield: 2.47 g (61%); bp 44–48 °C/0.6 mmHg.
found: 225.0374.
Dimethyl 2-Diazo-3-oxopentanedioate (7i)35c
Prepared from dimethyl 3-oxopentanedioate (4.4 g, 25 mmol), p-
ABSA (5 g, 20 mmol) and Et3N (4 g, 5.6 mL, 40 mmol) in CH2Cl2
(50 mL) for 1.5 h.
Methyl 6-Methoxy-4-(trifluoromethyl)pyridazine-3-carboxyl-
ate (8f)11d
Yield: 519 mg (11%).
1H NMR (400 MHz, CDCl3): δ = 7.29 (s, 1 H), 4.25 (s, 3 H), 4.03
(s, 3 H).
Yield: 2.85 g (72%).
1H NMR (400 MHz, CDCl3): δ = 3.87 (s, 2 H), 3.84 (s, 3 H), 3.73
(s, 3 H).
Methyl cis-4-Diazo-5-oxo-3-(trifluoromethyl)hex-2-enoate
(1g)11c
Prepared from 3-diazo-1,1,1-trifluoropentane-2,4-dione (7g; 3.4 g,
22 mmol) and (methoxycarbonylmethylene)triphenylphosphorane
(3a; 9.0 g, 27 mmol).
Methyl 2-Diazo-4,4,4-trifluoro-3-oxobutanoate (7f, R2 = OMe)
via Acylation of Methyl Diazoacetate with Trifluoroacetic An-
hydride
TFAA (20 mL, 0.146 mol) in CH2Cl2 (20 mL) was added dropwise
at 0 °C during 30 min to a soln of methyl diazoacetate (~0.14 mol)
in CH2Cl2 (140 mL) (obtained according to the literature34 and used
without any further purification) with added pyridine (11.2 mL,
0.146 mol). The reaction mixture was stirred at r.t. for 12 h, then
concentrated at atmospheric pressure to a volume of ~120 mL and
treated with pentane–Et2O (1:1, 100 mL). The precipitate was re-
moved by filtration, and the filtrate was washed with sat. NaCl soln
(20 mL) and dried with MgSO4 overnight. The solvents were re-
moved under reduced pressure; distillation of the residue gave the
methyl ester 7f.
Yield: 3.68 g (93%).
1H NMR (400 MHz, CDCl3): δ = 6.52 (s, 1 H), 3.72 (s, 3 H), 2.16
(s, 3 H).
3-Acetyl-6-methoxy-4-(trifluoromethyl)pyridazine (8g)6a
Yield: 872 mg (18%).
1H NMR (400 MHz, CDCl3): δ = 7.29 (s, 1 H), 4.24 (s, 3 H), 2.76
(s, 3 H).
Ethyl cis-2-Diazo-3-[(ethoxycarbonyl)methylene]-4,4,5,5,6,6,6-
heptafluorohexanoate (1h)11d
Prepared from ethyl 2-diazo-4,4,5,5,6,6,6-heptafluoro-3-oxohex-
anoate (7h; 0.40 g, 1.3 mmol) and (ethoxycarbonylmethylene)tri-
phenylphosphorane (3b; 0.68 g, 1.95 mmol).
Yield: 23.3 g (85%); yellow liquid; bp 55–60 °C/10 mmHg.
Rf = 0.38 (hexane–Et2O, 2:1).
IR (neat): 2146, 1750, 1675 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.90 (s, 3 H).
Yield: 415 mg (83%); bp 38–40 °C/0.5 mmHg.
13C NMR (100 MHz, CDCl3): δ = 171.1 (q, 2JC-F = 40.1 Hz), 159.0,
Alternative Preparations of Vinyldiazocarbonyl Compounds
1a,c′,i
115.6 (q, 1JC-F = 288.8 Hz), 62.5, 53.1.
19F NMR (376 MHz, CDCl3): δ = –74.56.
HRMS (ESI): m/z [M + H]+ calcd for C5H4N2O3F3 : 197.0174;
Diethyl cis-4-Diazopent-2-enedioate (Diethyl cis-Diazogluta-
conate, 1a)
+
Compound 1a was prepared by cross-coupling of ethyl 3-iodoacry-
late with ethyl diazoacetate;19 prepared from ethyl (2Z)-3-iodoacry-
late (452 mg, 2 mmol), ethyl diazoacetate (570 mg, 5 mmol), Et3N
(304 mg, 3 mmol), TBAB (644 mg, 2 mmol) and Pd(PPh3)4 (104
mg, 0.1 mmol) in acetone (10 mL) for 2 h at 35 °C.
found: 197.0171.
Interaction of H- and F-Diazodicarbonyl Compounds 7c,e–h
with Phosphoranes 3a,b (Approach ‘B,A’, Stage ‘A’, Table 4);
General Procedure
To a stirred suspension of a triphenylphosphorane 3a,b (16.6–20
mmol, 1.0 equiv) in Et2O (50–60 mL), a soln of a diazodicarbonyl
compound 7c,e–h (16.6–20 mmol, 1.0 equiv) was added in one por-
tion (H-7c,e) or dropwise (F-7f–h). After the diazodicarbonyl com-
pounds H-7c,e with phosphorane 3b were refluxed for 7 and 10 d,
Yield: 270 mg (64%).
1H NMR (400 MHz, CDCl3): δ = 6.52 (d, 3JH-H = 12.1 Hz, 1 H), 5.63
(d, 3JH-H = 12.1 Hz, 1 H), 4.29 (q, J = 7.4 Hz, 2 H), 4.15 (q, J = 7.0
Hz, 2 H), 1.31 (t, J = 7.0 Hz, 3 H), 1.27 (t, J = 7.4 Hz, 3 H).
Synthesis 2013, 45, 1215–1226
© Georg Thieme Verlag Stuttgart · New York

PAPER
Two-Stage Synthesis of Vinyldiazocarbonyls
1225
Ethyl trans-4-Diazo-3-methyl-4-(methoxycarbonyl)but-2-eno-
ate (1c′) via Dehydration of Diazo Alcohol 9c′ (Table 5)
13C NMR (75 MHz, CDCl3): δ = 167.4, 163.8, 141.0, 111.5, 69.4,
61.6, 51.3, 15.9, 14.7.
Anal. Calcd for C9H12N2O4: C, 50.94; H, 5.70; N, 13.20. Found: C,
51.12, 51.14; H, 5.68, 5.67; N, 13.19, 13.30.
1-Ethyl 2-Diazo-3-hydroxy-3-methyl-4-(methoxycarbonyl)bu-
tanoate (9c′, Alk = Me)
To a flame-dried 10–20-mL flask with methyl acetate (0.5 g, 7
mmol, 2.0 equiv) in anhyd THF (15 mL), a soln of 2 M LDA in hex-
ane (3.5 mL, 2 equiv) was added under argon atmosphere, and the
mixture was stirred at –78 °C for 1 h. A soln of diazo keto ester 7c
(0.55 g, 3.5 mmol, 1.0 equiv) in THF (5 mL) was added to the reac-
tion mixture during 5 min so that the temperature did not rise
above –70 °C, and the mixture was stirred for an additional 1.5 h
until the reaction was completed (monitored by TLC). Then, a soln
of glacial AcOH (7 mmol, 2 equiv) in abs THF (5 mL) was added
dropwise, the reaction mixture was heated to r.t. and stirred for an
additional 20 min, and was then filtered through neutral alumina (10
g) and washed with Et2O (30–40 mL). The obtained solution was
dried with MgSO4 and the solvents were completely removed under
reduced pressure to give the diazo alcohol 9c′ (of 99% purity by 1H
NMR spectroscopy), which was purified by column chromatogra-
phy on silica gel.
Compound 1i via Silylation of the Diazodicarbonyl Compound
7i (Scheme 3)
To a soln of dimethyl 2-diazo-3-oxopentanedioate (7i; 1.62 g, 8.1
mmol) and Et3N (9.8 g, 9.8 mmol) in anhyd CH2Cl2 (25 mL), which
was placed in a flame-dried 50-mL flask, TBSOTf (2.1 g, 9.8 mmol)
was added dropwise under argon atmosphere at 0–5 °C. The reac-
tion mixture was stirred at 0–5 °C for 1 h, then filtered through sil-
ica gel (2 g) and eluted with hexane–Et2O (5:1, 100 mL). The
resultant filtrate was concentrated under reduced pressure to give 1i
as a mixture of cis- and trans-stereoisomers [total yield: 2.1 g
(81%)], which was separated by column chromatography on silica
gel (hexane–Et2O, 1:100 to 1:10).
Dimethyl cis-3-(tert-Butyldimethylsilyloxy)-4-diazopent-2-ene-
dioate (cis-1i)
Yield: 76 mg (3%); bright yellow-orange oil.
Yield: 0.81 g (99%); yellow oil.
Rf = 0.55 (hexane–EtOAc, 1:1).
1H NMR (400 MHz, CDCl3): δ = 5.26 (s, 1 H), 3.75 (s, 3 H), 3.65
(s, 3 H), 0.92 (s, 9 H), 0.24 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 165.9, 163.4, 155.5, 99.8, 65.2,
52.1, 50.7, 25.4, 18.2, –4.8.
HRMS (ESI): m/z [M + H]+ calcd for C13H23N2O5Si: 315.1376;
found: 315.1371.
Rf = 0.33 (PE–MTBE, 1:1).
1H NMR (400 MHz, CDCl3): δ = 4.64 (br s, 1 H), 4.20 (q, 3JH-H
=
7.2 Hz, 2 H), 3.70 (s, 3 H), 3.05 (d, 2JH-H = 16.4 Hz, 1 H), 2.83 (d,
2JH-H = 16.4 Hz, 1 H), 1.53 (s, 3 H), 1.26 (t, 3JH-H = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 171.8, 166.2, 68.0, 63.4, 60.7,
51.4, 43.9, 26.3, 13.8.
HRMS (ESI): m/z [M – 28 + H]+ calcd for C9H15O5 : 203.0919;
found: 203.0921.
+
Dimethyl trans-3-(tert-Butyldimethylsilyloxy)-4-diazopent-2-
enedioate (trans-1i)
Yield: 1.63 g (64%); bright yellow-orange oil.
Ethyl 2-Diazo-3-hydroxy-4-(methoxycarbonyl)-3-phenylbu-
tanoate (9e′, Alk = Me)
Prepared from methyl acetate (0.60 g, 8.0 mmol, 2.0 equiv), 2 M
LDA in hexane (4 mL, 2 equiv) and diazo keto ester 7e (0.87 g, 4.0
mmol, 1.0 equiv).
Rf = 0.55 (hexane–EtOAc, 1:1).
IR (neat): 2115, 1716, 1604 cm–1.
1H NMR (400 MHz, CDCl3): δ = 6.07 (s, 1 H), 3.81 (s, 3 H), 3.64
(s, 3 H), 0.97 (s, 9 H), 0.21 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 165.3, 162.9, 149.9, 97.8, 68.6,
52.1, 50.5, 25.5, 18.3, –4.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H23N2O5Si: 315.1376;
Yield: 0.97 g (83%); yellow oil.
Rf = 0.35 (PE–MTBE, 1:1).
1H NMR (300 MHz, CDCl3): δ = 7.56–7.53 (m, 2 H), 7.40–7.31 (m,
3 H), 5.33 (br s, 1 H), 4.20 (q, 3JH-H = 7.1 Hz, 2 H), 3.71 (s, 3 H),
3.58 (d, 2JH-H = 16.7 Hz, 1 H), 3.07 (d, 2JH-H = 16.7 Hz, 1 H), 1.26
(t, 3JH-H = 7.1 Hz, 3 H).
found: 315.1371.
13C NMR (75 MHz, CDCl3): δ = 173.2, 166.1, 143.9, 128.9, 128.5,
125.5, 73.0, 65.9, 61.1, 52.5, 43.7, 14.7.
Acknowledgment
Partial support of this work with a short-term fellowship to M.B.S.
from the Loker Hydrocarbon Research Institute is gratefully ack-
nowledged.
Anal. Calcd for C14H16N2O5: C, 57.53; H, 5.52; N, 9.58. Found: C,
57.95, 57.56; H, 5.73, 5.72; N, 9.54, 9.23.
Ethyl trans-4-Diazo-3-methyl-4-(methoxycarbonyl)but-2-eno-
ate (1c′)
Supporting Information for this article is available online at
To a soln of diazo alcohol 9c′ (0.3 g, 1.3 mmol, 1.0 equiv) and Et3N
(0.39 g, 3.9 mmol, 3 equiv) in anhyd CH2Cl2 (5 mL), a soln of
POCl3 (0.40 g, 2.6 mmol, 2 equiv) in anhyd CH2Cl2 (5 mL) was add-
ed at 0 °C during 5 min. The mixture was stirred at r.t. until the de-
hydration was finished (reaction time: 20 h, monitored by TLC and
1H NMR spectroscopy); during the process, the mixture became
dark and a precipitate was formed. The reaction mixture was filtered
through silica gel (5 g) and washed with Et2O (10 mL), the solvents
were removed under reduced pressure and the residue was recrys-
tallized (Et2O–PE) to provide 1c′ as a yellow solid; yield: 85 mg
(33%); mp 55–56 °C.
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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References
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1215–1226

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M. B. Supurgibekov et al.
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(7) From hereon, we use the ‘cis’ and ‘trans’ designation of
spatial arrangement of functional groups (CO2Alk, CN2)
around the vinyl double bond, ignoring the priority of the
CF3 substituent, since application of the IUPAC Z,E
nomenclature in this case implies the same Z or E symbols
for (fluoroalkyl)-containing and fluorine-free vinyl
substrates with opposite configuration.
(21) (a) Davies, H. M. L.; Hu, B. Heterocycles 1993, 35, 385.
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(9) For uniformity in the names of the targeted compounds (2-
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rules.
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(32) The starting methyl trifluorobutanoate 2f was prepared by a
standard procedure.32a It can contain a quantity of the ethyl
trifluorobutanoate formed due to base-catalyzed
transesterification during Claisen condensation.32b In this
case, the ethyl derivative impurity can also be present in the
associated vinyl acetate 4f and further reaction products.
(a) Burdon, J.; McLoughlim, V. C. R. Tetrahedron 1964, 20,
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Synthesis 2013, 45, 1215–1226
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