Diethyl fluoronitromethylphosphonate: Synthesis and application in nucleophilic fluoroalkyl additions

Article abstract of DOI:10.1002/chem.201303817

Diethyl fluoronitromethylphosphonate (3), a previously unknown compound, was synthesized by electrophilic fluorination of diethyl nitromethylphosphonate with Selectfluor. Base-induced decomposition of 3 was studied by NMR spectroscopy, which identified diethyl fluorophosphate and fluoronitromethane as the main decomposition products. C H acidities [pKa values in dimethyl sulfoxide (DMSO)] of 3, 1-fluoro-1-phenylsulfonylmethanephosphonate (1; McCarthy's reagent), tetraethyl fluoromethylenebisphosphonate (2), and some nonfluorinated phosphonates were computed, and a good correlation between calculated and experimental pKa values was found. The calculated C-H acidities increased in the sequence 2<1<3. Diethyl fluoronitromethylphosphonate (3) was applied in the Horner-Wadsworth-Emmons reaction with aldehydes and trifluoromethyl ketones to provide new 1-fluoro-1-nitroalkenes with good to high stereoselectivities. Alkylation of 3 was successful only with iodomethane, however, conjugate additions of 3 to Michael acceptors such as a,b-unsaturated carbonyl compounds, sulfones, and nitro compounds allowed access to variously modified diethyl 1-fluoro-1-nitrophosphonates.

Full text of DOI:10.1002/chem.201303817

DOI: 10.1002/chem.201303817
Full Paper
&
Fluorination
Diethyl Fluoronitromethylphosphonate:
Synthesis and Application in Nucleophilic Fluoroalkyl Additions
[a]
ˇ
Stanislav Opekar, Radek Pohl, Pavel Beran, Lubomꢀr Rulꢀsek, and Petr Beier*
Abstract: Diethyl fluoronitromethylphosphonate (3), a previ-
ously unknown compound, was synthesized by electrophilic
fluorination of diethyl nitromethylphosphonate with Select-
fluor. Base-induced decomposition of 3 was studied by NMR
spectroscopy, which identified diethyl fluorophosphate and
values was found. The calculated CÀH acidities increased in
the sequence 2<1<3. Diethyl fluoronitromethylphospho-
nate (3) was applied in the Horner–Wadsworth–Emmons re-
action with aldehydes and trifluoromethyl ketones to pro-
vide new 1-fluoro-1-nitroalkenes with good to high stereose-
fluoronitromethane as the main decomposition products. CÀ lectivities. Alkylation of 3 was successful only with iodome-
H acidities [pKa values in dimethyl sulfoxide (DMSO)] of 3, 1-
fluoro-1-phenylsulfonylmethanephosphonate (1; McCarthy’s
reagent), tetraethyl fluoromethylenebisphosphonate (2), and
some nonfluorinated phosphonates were computed, and
a good correlation between calculated and experimental pKa
thane, however, conjugate additions of 3 to Michael accept-
ors such as a,b-unsaturated carbonyl compounds, sulfones,
and nitro compounds allowed access to variously modified
diethyl 1-fluoro-1-nitrophosphonates.
Introduction
Organic phosphates are ubiquitous in nature and display vari-
ous important functions in living organisms such as protein ac-
tivation, metabolism, information storage and transfer, cell sig-
naling, and others.[1] It has long been understood that phos-
phonates containing nonhydrolyzable CÀP bonds, are efficient
phosphate mimics.[2] Furthermore, the concept of closer phos-
phate mimicking by a-fluorinated phosphonates, introduced
by Blackburn and co-workers,[3] opened the area of applying
various a-fluorophosphonates in biomedical studies.[4] Indeed,
a-fluorinated phosphonates are often employed as enzyme in-
hibitors and metabolic probes.[4,5]
Figure 1. Examples of synthetically useful monofluoromethyl phosphonates.
Wadsworth–Emmons reaction with aldehydes or ketones) or 1-
fluoro-1-nitrophosphonates (by alkylation reactions or conju-
gate additions). The nonfluorinated derivative of 3, diethyl ni-
tromethylphosphonate (4), was used, for example, in the syn-
thesis of diethyl [nitro(diazo)methyl]phosphonate, which was
further converted into cyclopropane a-nitro-a-phosphonates[11]
in a nitro-Mannich reaction with imines generated in situ to
give N-protected 2-amino-1-nitroalkanephosphonates,[12] or in
1,3-dipolar cycloaddition with alkenes and 1-alkynes to give 3-
diethoxyphosphoryl-4,5-dihydroisoxazoles and 3-diethoxyphos-
phorylisoxazoles, respectively.[13] 1-Fluoro-1-nitroalkenes are
not known, but their nonfluorinated aromatic derivatives (b-ni-
trostyrenes) have been reported to exhibit a variety of biologi-
cal activities such as the ability to down-regulate the immune
response in humans.[14] Moreover, b-nitrostyrenes are described
as selective human telomerase inhibitors,[15] are cytotoxic for
human cancer cell lines,[14] and represent a novel class of anti-
bacterial agents.[16] The attachment of other substituents such
as fluorine to the b-position of the b-nitrostyrene skeleton
would be expected to lead to significant changes in chemical
properties and bioactivities. In contrast to 1-fluoro-1-nitroal-
A number of monofluorinated phosphonates, including fluo-
romethylphosphonate,[6] (cyanofluoromethyl)phosphonate,[7] 2-
(diethoxyphosphoryl)-2-fluoroacetate,[8] 1-fluoro-1-phenylsulfo-
nylmethanephosphonate (McCarthy’s reagent; 1),[9] and tet-
raethyl fluoromethylenebisphosphonate (2)[3d,10] were prepared
and used as building blocks in the synthesis of a variety of flu-
orine-containing phosphonates, other fluorinated compounds,
and medicinal targets (Figure 1).[4]
However, diethyl fluoronitromethylphosphonate (3) is un-
known and could represent a valuable building block for the
synthesis of novel 1-fluoro-1-nitroalkenes (by the Horner–
ˇ
[a] S. Opekar, Dr. R. Pohl, P. Beran, Dr. L. Rulꢀsek, Dr. P. Beier
Institute of Organic Chemistry and Biochemistry, v.v.i.
Academy of Sciences of the Czech Republic
Flemingovo nꢁm. 2, 166 10 Prague 6 (Czech Republic)
Fax: (+420)233-331-733
E-mail: beier@email.cz
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201303817.
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1
kenes, 1-fluoro-1-nitroalkanes are known and have been pre-
pared by electrophilic fluorination of nitroalkanes.[17]
with a 500 MHz NMR spectrometer in CDCl3. However, in H
coupled 19F and 13C NMR spectra, coupling to both the phos-
phorus atom and to the CHF proton was clearly visible. In
comparison, McCarthy’s reagent (1)[18] and fluorobisphospho-
In this paper, we describe the synthesis of compound 3, its
stability and decomposition pathways in the presence of
bases, calculate the pKa of a-hydrogen dissociation, and show
synthetic application of 3 in HWE reactions, alkylations, and
conjugate additions. Our findings open new possibilities for
the synthesis of selectively fluorinated compounds.
nate 2[10b] have much larger values of JP,H (6.6 and 13.6 Hz, re-
2
spectively). It is known[19] that geminal proton–phosphorus
coupling constants of conformationally restricted phosphanes
and phosphane oxides depend on the H-C-P-electron pair, and
H-C-P=O dihedral angles and values close to 0 Hz were found
at approximately 808 and 1808 angles. Our systems have, how-
ever, low barriers for rotation around the PÀC bond.
Results and Discussion
The formation of fluorophosphate 5 during the synthesis of
3 was at first surprising but became clear when the stability of
3 and its decomposition products were investigated. Phospho-
nate 3 has limited stability at ambient temperate and in the
presence of bases; however, in pure form it can be
Diethyl fluoronitromethylphosphonate (3) was synthesized by
electrophilic fluorination of diethyl nitromethylphosphonate (4)
(Table 1).[17a] Phosphonate 4, in the presence of sodium hydride
or alkali metal hexamethyldisilazide and Selectfluor as an elec-
stored under argon at 48C or below for several
months without any significant decomposition. Addi-
Table 1. Optimization of diethyl nitromethylphosphonate fluorination.[a]
tion of diisopropylamine to a solution of 3 in THF
gave rise to salt 6 and partial hydrolysis to monoester
7
caused by the presence of residual water
(Scheme 1).
Salt 6 slowly decomposes to diethyl fluorophos-
phate (5) and fluoronitromethane (8), possibly involv-
ing carbene 9. However, the presence of 9 was not
confirmed despite attempts to trap it as the corre-
sponding cyclopropane derivative using styrene in
the presence or absence of [Rh2(OAc)4] (in THF or
DMF, À50 to 258C, 1–20 h).
Base
(equiv)
Solvent
(vol. ratio)
Selectfluor
(equiv)
T
[8C]
Yield of 3 Yield of 5
[%][b]
[%][b]
1
2
3
4
5
6
7
8
9
NaH (1.0)
NaH (1.1)
nBuLi (1.1)
THF/DMF (3:1)
THF/DMF (3:1)
THF/DMF (3:1)
1.0
1.5
1.1
1.1
1.1
0–25 32 (12)
27
43
0
0–25
16
0
À60 to 25
0–25
NaHMDS (1.1) THF/DMF (3:1)
15
2
56
33
0
LiHMDS (1.1)
KOH (1.5)
KOH (1.0)
KOH (0.5)
KOH (0.1)
THF/DMF (3:1)
0–25
MeCN/H2O (1:1) 1.0
MeCN/H2O (2:1) 1.5
MeCN/H2O (2:1) 1.5
MeCN/H2O (2:1) 1.5
25 42 (20)
The decomposition of 3 with diisopropylamine
(1 equiv) was followed by 19F NMR spectroscopic
analysis (Figure 3) and the final products after one
week of reaction time were diethyl fluorophosphate
(5) and fluoronitromethane (8), each formed at about
40–50% NMR yield. The formation of 5 could be ex-
plained by decomposition of salt 6 to the fluoride
ion, which reacts with 3 to give 5 and 8. This is con-
0
0
0
67 (48)
38 (25)
13
0
0
0
[a] Reactions were carried out using 4 (1 mmol, 1 equiv). [b] Conversions were esti-
mated by GC/MS analysis; isolated yield given in brackets.
trophilic fluorinating agent in mixtures of tetrahydrofuran
(THF) and N,N-dimethylformamide (DMF), provided the desired
product in low yields with the formation of significant
amounts of toxic diethyl fluorophosphate (5). On the other
hand, the use of an equimolar amount of potassium hydroxide
in aqueous acetonitrile gave the product in good yield, free of
any fluorophosphate (Table 1, entry 7). Employing N-fluoroben-
zenesulfonimide (NFSI) as fluorinating agent did not lead to
improvements in the yield of 3. By using the conditions shown
in Table 1, entry 7 and replacing Selectfluor with NFSI gave
only 7% yield of 3 (based on NMR spectroscopic analysis). An-
hydrous conditions (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
in THF) for NFSI fluorination of 4 provided only 16% 3 (based
on NMR spectroscopic analysis).
sistent with control experiments that showed that 3 and a solu-
tion of tetrabutylammonium fluoride (TBAF) in THF at 258C
give 5 and 8. The same products of decomposition of 3 were
also observed with other bases such as Cs2CO3 or NaOEt in
DMF;
1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU),
1,4-
1H NMR spectra revealed diastereotopic (nonequivalent)
ethoxy groups on the phosphorus atom due to the presence
of a chiral center on the a-carbon. An unusually low geminal
coupling constant between the phosphorus atom and the CHF
proton (2JP,H) of 3 was observed (Figure 2). The coupling con-
stant was 0.3 Hz in [D8]THF and no coupling could be observed
Scheme 1. Proposed mechanism of decomposition of 3 with diisopropyl-
amine.
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Figure 3. 19F NMR spectra indicating the time-course of the reaction of 3
with diisopropylamine in THF at 258C.
not able to determine the pKa of 3 experimentally by electro-
migration methods due to its instability under basic condi-
tions. Therefore, pKa values were estimated by quantum
chemistry calculations by using the RI-PBE+D3/def2-TZVP//RI-
PBE+D3/def2-SVP ‘model chemistry’ together with the
COSMO-RS solvation method (dimethyl sulfoxide).[20] The com-
puted data were carefully benchmarked against available liter-
ature data[21] for phosphonates 10–13 (Table 2) and it can be
seen that the difference between calculated and experimental
Table 2. Experimental and computed pKa values of selected diethyl phos-
phonates in DMSO.
Entry
Compound
R
X
pKa, calcd (exp.)
1
2
3
1
2
3
PhSO2
P(O)(OEt)2
NO2
F
F
F
17.6
21.4
8.1
4
5
6
7
8
9
10
4
NO2
CN
CO2Et
Ph
TMS
H
H
H
H
H
H
H
9.2
10
11
12
13
14
15
15.2 (16.4)[21b]
18.7 (18.6)[21b]
26.4 (27.6)[21a]
30.4 (28.8)[21a]
19.6
P(O)(OEt)2
PhSO2
15.7
Figure 2. NMR spectra of 3 in CDCl3: a) 1H (500 MHz), b) 19F (470 MHz), c) 13
C
values was, in most cases, between 1 and 2 pKa units [more
precisely, MAD(exp/theory)ꢀ1], which we consider to be ex-
cellent agreement for ‘ab initio’ predictions of acidity (pKa) con-
stants. These results gives us good confidence in the calculat-
ed values for the target systems (1–4, 14, and 15). As expect-
ed, fluorinated phosphonate 3 is more acidic than nonfluori-
nated 4 (DpKa =1.1 in favor of the former) and acidity in-
creased quite significantly in the sequence 2<1<3 and 14<
15<4. However, it is more difficult to explain the observed
higher acidity of nonfluorinated 15 vs. fluorinated 1 (and also
(126 MHz), d) 31P (202 MHz).
diazabicyclo[2.2.2]octane (DABCO), or NaH in THF; and DBU in
DMF. With iPr2NEt in THF, no reaction took place.
For synthetic utilization of 3, it was important to determine
its pKa value (corresponding dissociation of the proton at the
a position) and compare it with pKa values of related fluorinat-
ed and nonfluorinated phosphonates. Unfortunately, we were
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not give the desired gem-1-fluoro-1-aminoalkene but,
instead, led to the formation of (4-methoxyphenyl)a-
cetonitrile (Scheme 3).
Table 3. HWE reaction of 3 with benzaldehyde; optimization of reaction conditions.[a]
Alkylation of 3 with alkyl halide proved to be diffi-
cult (Table 5). High yields of alkylated products 18
were observed only with en excess of iodomethane
and DBU as the base in THF (Table 5, entry 3). Other
investigated bases (NaH, NaOEt, DABCO, Cs2CO3,
Hꢂnig’s base in THF or DMF) were completely ineffec-
tive, whereas with diisopropylamine in THF only
traces of 18a were formed (Table 5, entry 4). Unfortu-
nately, by using DBU as base, alkylating reagents
other than iodomethane were either poorly reactive
(1-iodobutane, allyl bromide) or unreactive (benzyl
bromide or tosylate), and increasing the reaction
temperature did not improve the yield because of
concomitant decomposition of 3.
Entry
Base
(equiv)
Solvent
T
[8C]
t
[h]
Yield of 16a
Z/E[c]
[%][b]
1
2
3
4
Cs2CO3 (1.0)
NaH (1.1)
tBuOK (1.1)[d]
KOH (1.8)
iPr2NH (1.0)
NaH (1.5)
iPr2NH (1.5)
DBU (1.5)
MeCN
THF
25
1
2
2
0.5
2
2
2
2
0
67
0
–
À78 to 0
À78 to 0
0
À78 to 0
À78 to 0
À78 to 0
À78 to 0
90:10
–
THF
MeCN[e]
THF
6
–
5
66
73
80
6
71:29
89:11
72:28
–
6[f]
7[f]
8[f]
THF
THF
THF
[a] Reactions were carried out using 3 (0.23 mmol, 1 equiv) and PhCHO (1 equiv)
unless otherwise noted. [b] Isolated yield. [c] Determined by 1H NMR spectroscopic
analysis of the isolated product. [d] With added 18-crown-6 (1.1). [e] Containing 1.5
vol.% water. [f] Excess 3 (1.5 equiv) was used.
On the other hand, derivatization of 3 by conju-
gate addition to Michael acceptors has borne fruit.
Several basic conditions for the desired transforma-
tion were tested and, once again, diisopropylamine
14 vs. 2) and we consider it a rather surprising finding. Appa-
rently, the cumulative effect of three electron-withdrawing (de-
activating) groups does not obey simple additive rules and
quantum chemical calculations need to be used to obtain (at
least semi)quantitatively correct results.
in THF was identified as the best. The reaction of 3 with
methyl vinyl ketone (19a) proceeded smoothly and the corre-
sponding Michael adduct 20a was obtained in almost quanti-
With compound 3 in hand, attention turned towards investi-
gation of the Horner–Wadsworth–Emmons reaction with ben-
zaldehyde as a model carbonyl compound to give (2-fluoro-2-
nitrovinyl)benzene (16a). Several basic conditions were tested
and the most competent bases were found to be sodium hy-
dride (Table 3, entry 6) or diisopropylamine in THF
(Table 3, entry 7). Other investigated bases led to the
decomposition of 3 and the formation of 5 as the
Scheme 2. Reduction of b-fluoro-b-nitrostyrene (16a).
Table 4. HWE reaction of 3 with aldehydes and ketones.[a]
main product. Sodium hydride provided slightly
higher Z stereoselectivities than diisopropylamine.
The optimized reaction conditions (Table 3, en-
tries 6 and 7) were used in a scope and limitation
study of the HWE reaction with various aldehydes
and ketones (Table 4). Aliphatic aldehydes, including
racemic citronellal, and aromatic aldehydes bearing
both electron-acceptor and electron-donor groups
provided 1-fluoro-1-nitroalkenes 16 in high yields
and good Z stereoselectivities. In the case of 4-nitro-
benzaldehyde, (Z)-16 f formed almost exclusively. 3-
(3,5-Dichlorophenoxy)benzaldehyde provided the flu-
orinated analogue of DPNS, a potent inhibitor of
human telomerase.[15] Ketones were found to be
largely unreactive, except for the highly electrophilic
trifluoroacetophenone, which underwent the reaction
in good yield and high stereoselectivity but only in
the presence of sodium hydride.
Entry
R1
R2
Z/E[b]
16
Yield[c]
[%]
Z/E[d]
1
2
Ph
nC6H13
H
H
–
a
b
80
77
72:28
75:25
91:9
3
H
80:20
c
63
72:28
4
5
6
7
8
4-ClC6H4
4-MeOC6H4
4-NO2C6H4
3-(3,5-dichlorophenoxy)phenyl
Ph
Ph
Ph
Ph
Ph
H
H
H
H
Me
Ph
Me
CF3
CF3
78:22
67:33
>98:2
84:16
d
e
f
g
h
i
h
j
j
81
71
73
69
0
0
0
0
53
65:35
73:27
>98:2
77:23
–
–
–
–
–
–
9
–
–
–
10[e]
11
12[e]
2:98
Reduction of b-fluoro-b-nitrostyrene (16a) with
sodium borohydride in methanol proceeded smooth-
ly to give 17a[17a] in good yield (Scheme 2). However,
attempts to reduce the nitro group of 16e with hy-
drogen in the presence of Raney nickel catalyst did
[a] Reactions were carried out using the carbonyl compound (0.23 mmol, 1 equiv), 3
(1.5 equiv), and iPr2NH (1.5 equiv) in THF (1.5 mL) unless noted otherwise. [b] Deter-
mined by 19F NMR spectroscopic analysis of the crude reaction mixture. [c] Isolated
yield. [d] Determined by 1H NMR spectroscopic analysis of the isolated product.
[e] Using NaH (1.5 equiv) as the base.
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Scheme 4. Dephosphorylation of 20a with TBAF.
Scheme 3. Reduction of 16e with hydrogen in the presence of catalytic
Raney-nickel.
er, excess base and 3 were necessary to achieve a good yield.
Phenyl vinyl sulfone, butyl acrylate, b-nitrostyrene (19e), and
alkylidene-malononitrile 19 f provided the addition products
20e and 20 f in good yields and low diastereoselectivities. In
contrast, addition to 2-cyclohexenone (19g) did not give any
addition product and the addition to diethyl vinylphosphonate
(19h) provided product 20h in the crude mixture; however,
isolation by column chromatography gave only dephosphory-
lated 21h. Similarly, dephosphorylated products 21c,
21e, and 21 f were observed in the crude reaction
mixtures after conjugate addition of 3 to appropriate
Michael acceptors. These compounds resulted from
the reaction of 20 with fluoride anion derived from
decomposition of excess 3. Indeed, a control experi-
ment revealed that 20a undergoes dephosphoryla-
tion with TBAF in THF (Scheme 4). A similar dephos-
tative yield (Table 6, entry 1). Even substochiometric amounts
(0.3 equiv) of diisopropylamine or morpholine were sufficient
for complete conversion into 20a, but unfortunately these cat-
alytic conditions could not be applied to other Michael accept-
ors. Phenyl vinyl ketone (19b) also reacted well with 3; howev-
Table 5. Alkylation of 3 with alkyl halides.[a]
Entry
Base
RX
Solvent
T
t
18 Yield
phorylation process was observed for ethyl 2-(dia-
lkoxyphosphoryl)acetates and dialkyl (cyanomethyl)-
phosphonates.[22]
(equiv)
(equiv)
[8C]
[h]
[%][b]
1
2
3
4
5
6
DBU (1)
DBU (1)
DBU (1.2)
iPr2NH (1.1) MeI (1.5)
DBU (1.2)
DBU (1.2)
MeI (1.5)
MeI (1.5)
MeI (4)
THF
DMF
THF
THF
THF
0–25
À30 to 25
0–10
À78 to 0
0–25
1
2
1
1
2
2
a
a
a
a
b
c
26 (22)
0
85 (72)
5
A comparison of reactivities of carbanions derived
from a-fluorophosphonates 1–3 reveals that the
carbanion of 3 has relatively low nucleophilicity and
steric bulk. This limits the scope of HWE reactions
and alkylations compared with those of 1[9] and 2.[10]
On the other hand, conjugate additions to both a-
and b-substituted Michael acceptors are possible.
nBuI (4)
Allyl bromide (4) THF
15
14
0–10
[a] Reaction conditions: 3 (0.33 mmol, 1 equiv), base, RX, THF or DMF (2 mL). [b] Based
on 19F NMR spectroscopic analysis using PhCF3 as internal standard; isolated yield in
brackets.
Conclusion
Table 6. Conjugate additions of 3 to Michael acceptors.[a]
A new fluorinated C1 reagent, diethyl fluoronitrome-
thylphosphonate (3), was prepared and utilized in
the stereoselective synthesis of new 1-fluoro-1-nitro-
alkenes by the Horner–Wadsworth–Emmons reaction
with carbonyl compounds. Methylation with iodome-
thane and conjugate addition to Michael acceptors
provided 1-fluoro-1-nitrophosphonates. Base-cata-
lyzed decomposition of 3 was studied and fluoroni-
tromethane and diethyl fluorophophate were identi-
fied as the main decomposition products. Based on
quantum chemical calculations, the acidities of the a-
hydrogen atoms increase in the series 2<1<3. Thus,
3 is the strongest CÀH acid of the three phospho-
nates, but the carbanion is the least nucleophilic. The
title reagent proved to be highly useful in the syn-
thesis of fluorinated organic molecules and promises
to find many potential applications in life-science-re-
lated applications. Further exploration of the fluoroal-
kylation chemistry of 3 is underway in our laboratory.
Entry
3
19
R1
R2
R3 iPr2NH
20, Yield
21, Yield
(equiv) (equiv)
(equiv)
[%][b]
[%][c]
1
1.0
1.0
2.0
1.0
2.0
2.0
2.0
2.0
2.0
a (1.5)
a (1.5)
b (1.0)
c (1.0)
d (1.0)
e (1.0)
f (1.0)
g (1.0)
h (1.0)
C(O)Me H
C(O)Me H
C(O)Ph
SO2Ph
CO2nBu H
NO2
CO2Et CO2Et nBu 2.0
H
H
H
H
H
1.0
0.3
2.0
1.0
2.0
a, 97
a, 88
b, 82
c, 48
d, 66
e, 67[e]
f, 46[f]
g, 0[c]
h, 0[c]
2[d]
3
H
H
4
5
6
7
8
9
c, 8
H
Ph 2.0
e, 11
f, 27
H
-(CH2)3C(O)- 2.0
2.0
PO3Et2
H
H
h, 47[b]
[a] Reaction conditions: 3 (0.23–20.46 mmol, 1–2 equiv), iPr2NH (1–2 equiv), and 19
(1–1.5 equiv) in THF (1–2 mL). [b] Isolated yield. [c] Based on 19F NMR spectroscopic
analysis using PhCF3 as internal standard. [d] MeCN was used as a solvent instead of
THF. [e] dr=51:49. [f] dr=53:47.
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Acknowledgements
This work was supported by the Academy of Sciences of the
Czech Republic (RVO: 61388963) and the Grant Agency of the
Czech Republic (203/08/P310).
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Keywords: C1 building blocks
addition · phosphanes · synthetic methods
· fluorine · nucleophilic
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Received: September 30, 2013
Published online on December 16, 2013
Chem. Eur. J. 2014, 20, 1453 – 1458
www.chemeurj.org
1458
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