Diastereoselective Synthesis of Dialkylated Bis(phosphino)ferrocenes: Their Use in Promoting Silver-Mediated Nucleophilic Fluorination of Chloroquinolines

Article abstract of DOI:10.1002/ejic.201600502

The diastereoselective synthesis of dialkylated ferrocenyl bis(phosphane)s bearing aryl, alkyl, and hetero- or polycyclic substituents on the phosphino groups is reported, together with their characterization in the solid state by X-ray structure analysis

Full text of DOI:10.1002/ejic.201600502

DOI: 10.1002/ejic.201600502
Full Paper
Diastereoselective Synthesis
Diastereoselective Synthesis of Dialkylated
Bis(phosphino)ferrocenes: Their Use in Promoting Silver-
Mediated Nucleophilic Fluorination of Chloroquinolines
[
a]
[a]
[a]
[b]
Julien Roger,* Sylviane Royer, Hélène Cattey, Aleksandr Savateev,
[b]
[b]
[a,c]
Radomyr V. Smaliy, Aleksandr N. Kostyuk, and Jean-Cyrille Hierso*
Dedicated to our friend I. R. Butler for his inspiring and innovative work on ferrocene functionalization
Abstract: The diastereoselective synthesis of dialkylated ferro- namely, furyl-, isopropyl-, cyclohexyl-, phenyl-, mesityl-phos-
cenyl bis(phosphane)s bearing aryl, alkyl, and hetero- or poly- phino, and benzophosphindole, is achieved and gives new alk-
cyclic substituents on the phosphino groups is reported, to- ylated ferrocenyl diphosphanes in moderate to high yields. In-
gether with their characterization in the solid state by X-ray vestigations are conducted to apply these robust alkylated di-
structure analysis and in solution by multinuclear NMR spectro- phosphanes as auxiliaries in the very challenging palladium-
scopy. Introduction of various alkyl groups on the ferrocene catalyzed nucleophilic fluorination of chloroquinolines at the C–
backbone, namely, tert-butyl, isopropyl, and trimethylsilyl, has Cl bond. Unexpectedly, a significant favorable effect from the
a significant influence on the stereoselectivity of the ensuing ferrocenyl phosphanes is evidenced by using the commercial
lithiation/phosphination reactions. Only the introduction of the AgF reagent for this fluorination that renders any palladium
tert-butyl groups ensures both a high yield and perfect dia- addition useless. This innovative nucleophilic fluorination thus
stereoselectivity, which leads to the exclusive formation of the avoids harsh conditions (strictly anhydrous) and highly special-
rac planar chiral tert-butylated diphosphanes. The introduction ized reagents.
of electron-rich and -poor phosphorus-based functional groups,
Introduction
polyphosphanes, efficient conformational control of the ferro-
cene backbone was introduced by using the steric effects of
bulky tert-butyl groups placed on each of the cyclopentadienyl
Functionalized ferrocene derivatives have a wide range of appli-
cations related to homogeneous catalysis, electrochemistry, ma-
terial sciences, and biomedical researches. The unique combi-
nation of the axial rigidity and rotational flexibility of the ferro-
cene platform attracted the interest of synthetic chemists early
on for the design of phosphane-based compounds mainly used
as ligands for transition metals.
substituted ferrocenyl phosphanes incorporating multiple phos-
phino groups arranged in a well-controlled geometry (see com-
(
Cp) rings. The synthesis of the ferrocenyl diphosphane conge-
ners (see compound 3 in Scheme 1) by assembling substituted
phosphino)cyclopentadienyl salts systematically led to mix-
[
1]
(
[7]
tures of diastereoisomers. This synthetic complication im-
peded the development and investigation of substituted ferro-
cenyl diphosphanes as ligands for transition-metal catalysis.
Substituted ferrocenyl diphosphanes thus remain underdevel-
oped, whereas related, but structurally simpler, dppf analogues
[
2–4]
Our group developed highly
[
5–7]
pound 1 and 2 in Scheme 1).
success as ligands in palladium-catalyzed organic synthesis re-
These species were used with
[
dppf = 1,1′-bis(diphenylphosphino)ferrocene] and its ana-
[1a,1b,12,13]
logues have found many applications.
actions directed towards selective C–C and C–heteroatom (i.e.,
Because of the interest of ferrocenyl phosphanes in palla-
dium-catalyzed C–heteroatom (i.e., C–N, C–O, and C–S) bond
formation, we envisioned that simple and robust chelator can-
C–N, C–O, and C–S) bond formation.[
8–11]
For such a class of
–
[
a] Institut de Chimie Moléculaire de l'Université de Bourgogne,
ICMUB UMR-CNRS 6302), Université de Bourgogne Franche-Comté (UBFC),
avenue Alain Savary, 21078 Dijon, France
didates may help in C–F bond formation from “F ” nucleophile
(
9
sources. Palladium–ligand systems that were able to achieve
very challenging trans-halogenation from triflate, bromide, and
iodide derivatives to fluorinated analogues were only recently
E-mail: julien.roger@u-bourgogne.fr
hiersojc@u-bourgogne.fr
http://www.icmub.fr
[
14]
reported.
However, only highly sophisticated monophos-
[
[
b] Institute of Organic Chemistry, National Academy of Sciences,
phane ligands were used to date, and the employment of chlor-
ide substrates was not reported. Additionally, metal-catalyzed
selective nucleophilic fluorination of heteroarenes, which is
5
Murmanska Str., 02660 Kyiv, Ukraine
c] Institut Universitaire de France (IUF),
03 Boulevard Saint Michel, 75005 Paris Cedex, France
1
[
15]
complementary to electrophilic fluorination,
is very topical,
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejic.201600502.
as such fluorinated compounds are present in pharmaceuticals,
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Scheme 1. Substituted ferrocenyl di- and triphosphanes synthesized by cyclopentadienyl salt assembly.
agrochemicals, molecular materials, and medical imaging radio- trol is exerted during the synthesis.[7,20] Workup and purification
[
16]
tracers.
chemistry
Consequently, relevant approaches from copper procedures are thus unavoidable, which limits the global effi-
[
17]
[18,19]
or by using direct SNAr,
albeit under strictly ciency of the process. To circumvent this issue, we anticipated
anhydrous conditions, have been reported. Thus, examination that ferrocenyl dilithium salts 4 (Scheme 2) may be key compo-
of performances from air-stable robust system under less sensi- nents of the synthesis of polysubstituted ferrocenylphosphanes.
tive conditions remains pertinent.
Indeed, we recently observed that functionalization of 4a led
We focused the present work on the synthesis of novel di- to planar chiral rac derivatives with high diastereoselectivity.[21]
substituted ferrocenyl diphosphanes alkylated at the metallo- We were eager to determine whether this could be extended
cene backbone by different groups, including tert-butyl and re- to related compounds 4b and 4c. We first targeted the dia-
lated alkyl groups. We investigated synthetic routes to obtain stereoselective synthesis of novel tert-butylated symmetric di-
diastereomerically pure ferrocenyl diphosphanes. For substi- phosphanes 5 bearing aryl, alkyl, and hetero- or polycyclic sub-
tuted diphosphanes, the influence of backbone steric control stituents (Cy = cyclohexyl, Bpi = benzophosphindole, Mes =
Me
on the stereoselectivity of the successive lithiation/phosphin- 2,4,6-trimethylphenyl, Fu = 2-methyl-5-furyl).
ation reactions was clearly evidenced. To assess this steric con-
Diphosphanes 6 bear substituents that were believed to help
trol, the X-ray structures in the solid state of each diphosphane
with conformational control of the ferrocene platform, espe-
class were determined. The selenation of tertiary phosphanes
cially the isopropyl and trimethylsilyl groups, which are struc-
turally related to tert-butyl but are, respectively, less and more
1
to give J
coupling constant values is reported as a means
P, S e
to estimate the electron-donating properties of the synthesized
substituted diphosphanes. Consequently, a new class of alkyl-
ated planar chiral diphosphanes with a constrained conforma-
tion was readily accessible by diastereoselective synthesis.
These species were tested in the very challenging palladium-
catalyzed C–Cl nucleophilic fluorination of chloroquinolines.
Unexpectedly, a significant favorable effect from the ferrocenyl
phosphane without additional palladium was evidenced by us-
ing the commercial AgF reagent for fluorination. This work evi-
dences thus that in combination with AgF, phosphanes in sub-
stoichiometric amounts can be used as powerful systems for
the fluorination of chloroarenes.
congested.
1
,1′-Di(tert-butyl)ferrocene was easily synthesized in high
yield starting from 6,6-dimethylfulvene in two steps (Scheme 3).
Selective dilithiation was then achieved by using tert-butyllith-
ium in the presence of tetramethylethylenediamine (TMEDA) in
THF at 0 °C to form 4a in fairly good yield (67 %). Diastereomeri-
cally pure ferrocenyl diphosphanes 5a–f were obtained from
treatment of 4a with the corresponding electrophiles in THF at
–
80 °C. Good to excellent yields of 5a–c were obtained (73, 80,
and 88 %, respectively). The yields were lower with the use
of chlorobenzophosphindole, bis(2,4,6-trimethylphenyl)phos-
phorus chloride, and bromobis(methylfuryl)phosphane as elec-
trophiles (5d–f; yields of 42, 53, and 30 %, respectively), mostly
because of their lower stability under the reaction conditions.
Results and Discussion
Compound 5f also underwent partial decomposition during
Synthesis and Characterization of Polysubstituted
Ferrocenyl Diphosphanes
purification, even if activated silica gel and dry solvents were
3
1
used. The P NMR spectroscopy data of 5a–f are reported in
The modular synthesis of ferrocenyl diphosphanes from the as- Table 1. We estimated the electron-donating character of novel
1
sembly of cyclopentadienyl salts forms mixtures of planar chiral phosphanes 5a–f by measuring the JP, Se coupling constants of
rac and achiral meso diastereomers, as no stereochemical con- their diselenide derivatives [Se(5a–f) in Table 1].
Scheme 2. Synthesis of alkylated ferrocenyl diphosphanes (major diastereoisomer is planar chiral rac).
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Scheme 3. Diastereoselective synthesis of ferrocenyl diphosphanes 5a–e.
Table 1. 31P NMR (CDCl
cenyl diphosphanes 5a–f and Se(5a–f).
, 182 MHz) spectroscopy data of tert-butylated ferro-
cene selenide, Se(dppf), were reported to be 730 and 737 Hz,
3
[
a]
[22a,22c]
1
respectively.
The J
values determined for 5d and 5e
P, Se
δ(31P) [ppm]
δ(31P=Se) [ppm]
1JP, S e [Hz]
(736 and 735 Hz, respectively) indicate a basic character of the
Complex
PR
P(iPr)
PCy
PMes
PPh
2
phosphino groups, very similar to dppf. Unsurprisingly, com-
5
5
5
5
5
5
a
b
c
d
e
f
2
1.3
–8.6
–37.1
–20.1
–22.9
–65.3
58.9
50.7
16.5
31.5
23.0
–6.5
710
705
700
736
735
759
1
pounds 5a, 5b, and 5c with J values of 710, 705, and 700 Hz
P, Se
2
1
2
are highly electron-donating, whereas the JP, Se value of 5f
2
found at 759 Hz is indicative of the electron-poor character of
this diphosphane. The highest “donation character” of the
mesityl groups compared to the cyclohexyl and isopropyl alkyl
groups is, however, noticeable.
Solid-state characterization from the growth of single crys-
tals was also achieved. The X-ray structure determined for origi-
nal heterocyclic ferrocene 5e discloses two independent
P(Bpi)
P(FuMe)
2
[
a] Benchmark 1
respectively.
3
JP, S e values for Se=PPh and Se(dppf) are 730 and 737 Hz,
An increase in these coupling constants indicates an increase enantiomers in the asymmetric units (Figure 1). Both molecules
in the s character of the phosphorus lone-pair orbital, that is, have almost identical geometrical parameters. For the sake of
an electron-withdrawing effect of the phosphane on the selen- clarity in the following discussion, the labeling is given only
[
22]
1
ium. As a benchmark, the J value for triphenylphosphane for one molecule, and the corresponding parameters for the
P, Se
selenide, Se=PPh , and for 1,1′-bis(diphenylphosphino)ferro- enantiomer are given in brackets. The molecules belong to the
3
Figure 1. Molecular structures of diphosphane 5e. Only one enantiomer is represented and hydrogen atoms are omitted for clarity. Selected bond lengths
[Å], distances [Å], angles [°], and corresponding parameters for the second enantiomer are given in brackets: Fe1–Ct1 1.6564(11) [1.6616(11)], Fe1–Ct2
1
5
.6586(11) [1.6629(11)], C1–P1 1.812(2) [1.815(2)], C6–P2 1.819(2) [1.816(2)], P1···P2 3.3932(9) [3.3377(9)], Ct1–Fe1–Ct2 179.28(6) [179.55(6)], P1–Ct1–Ct2–P2
.74(3) [–9.54(3)].
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C2 point group. Superposition of the two molecules, after inver-
In the X-ray structure determined for phosphino ferrocene
sion, leads to a root mean square deviation (RMSD) equal to 5c, the Cp rings adopt a staggered conformation, different from
.20 Å and a maximal distance difference equal to 0.49 Å for 5e but still with a cisoid conformation of the phosphino groups.
0
atoms belonging to the tert-butyl groups. The Cp rings are in an Consequently, the spatial separation between the two phos-
almost perfect eclipsed conformation, and the two phosphino phorus atoms is longer than that for 5e [P1···P2 4.3792(7) Å],
group are arranged one above the other with short distances together with a larger torsion angle [P1–Ct1–Ct2–P2 47.10(3)°]
P1···P2 3.3932(9) Å [3.3377(9) Å] and tight torsion angles P1– (Figure 2).
Ct1–Ct2–P2 5.74(3)° [–9.54(3)°]. The conformation of the ferro-
Compounds 6a and 6b, analogues of 5d and 5e, respec-
cene backbone of this diphosphane is consistent with those of tively, were then synthesized from 4b (Scheme 4). The synthesis
[
5]
related tetraphosphanes and, as such, might be attributed to of the 1,1′-diisopropylferrocene precursor was achieved in a
efficient steric conformational control of the tert-butyl groups. high yield of 89 % from a mixture of (isopropyl)cyclopentadiene
In compound 5e, the benzophosphindole groups adopt an exo isomers. Under conditions that were identical to those used to
position relative to the ferrocene.
synthesize 4a, diastereoselective dilithiation was achieved,
Figure 2. Molecular structures of diphosphane 5c. Only one half of a dichloromethane solvent molecule and hydrogen atoms are omitted for clarity. Selected
bond lengths [Å], distances [Å], and angles [°]: Fe–Ct1 1.6589(8), Fe–Ct2 1.6597(8), C1–P1 1.815(2), C6–P2 1.816(2), P1···P2 4.3792(7), Ct1–Fe–Ct2 175.81(5),
P1–Ct1–Ct2–P2 47.10(3).
Scheme 4. Synthetic roads to alkylated ferrocenyl diphosphanes 6a–d: there is a decrease in diastereoselectivity relative to that observed for tert-butylated
compounds 5a–f.
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1
which gave pure 4b in 68 % yield. Then, the introduction of 741 Hz, which were close to the Se(dppf) J value. The values
P, Se
1
benzophosphindole groups from the reaction of 4b with of J for Se(6b) and Se(6d) were found to be 736 and 712 Hz,
P, Se
chlorobenzophosphindole was difficult and gave 6b in only a respectively, which confirmed the overwhelming effects of the
moderate yield of 27 % (compared to 42 % for 5d). We recov- functional groups of the phosphanes on their basicity.
ered about 50 % of diisopropylferrocene and 20 % of a mono-
phosphination product after purification.
Table 2. 31P NMR (CDCl
cenyl diphosphanes 5a–f and Se(5a–f).
, 182 MHz) spectroscopy data of tert-butylated ferro-
However, more importantly, compound 6b was isolated as a
5:15 mixture of rac and meso isomers. This indicated a signifi-
3
8
cant loss of diastereoselectivity in the reaction relative to that
observed for the conversion of 4a into 5d. This suggested that
the lower steric hindrance of the iPr groups relative to that of
the tBu groups was detrimental to diastereoselectivity control.
Compound 6a was isolated in a higher, but still moderate, 51 %
yield, even if a one-pot reaction was performed starting from
diisopropylferrocene. Diastereoselectivity in favor of the rac iso-
mers, albeit not total, was found better than for the synthesis
of 6b with a ratio of 90:10.
Complex
R(Cp)
δ(31P) [ppm]
δ(31P=Se) [ppm]
1JP, S e [Hz]
dppf
5d
H
tBu
iPr
Me
Ph
–19.8
–20.1
–17.2
–21.1
–24.0
28.2
31.5
31.7
30.7
31.4
737
736
735
738
741
6
6
a
c
3
Si
[a]
trityl-dppf
3
C
[
a] From ref.[7a,b]
The X-ray diffraction structures were resolved for 6a and 6c
The synthesis of 4c was better achieved from ferrocene di-
rectly by following a reported procedure (Scheme 4).
[
23]
from single crystals. Figure 3 illustrates the molecular structure
of 6a. The phosphino groups adopt a transoid conformation
with a wide torsion angle of P1–Ct1–Ct2–P2 127.29(3)°. The
P···P spatial distance of 6.1935(9) Å is, therefore, much longer
than that in 5c or 5e {4.3792(7) or 3.3932(9) Å [3.3377(9) Å],
respectively} and is clearly a consequence of a lower degree of
steric control from the smaller iPr groups than from the tert-
butyl groups, as shown by their mutual arrangement.
The
one-pot synthesis of 6c was indeed reported to provide a yield
of 45 % without isolation of the dilithium ferrocene intermedi-
ate salt and would have led to the chiral planar isomer only.
Compound 4c was found to be fairly air sensitive and much
less stable than analogues 4a and 4b. Thus, pure 6c and 6d
were obtained in moderate yields of 35 and 33 %, respectively,
from one-pot protocols without isolation of 4c. In our hands,
unsatisfactory diastereoselectivity was again observed, and in
The molecular structure of 6c is illustrated in Figure 4. The
each case, an isomeric mixture was obtained with ratios of asymmetric unit contains two independent enantiomers be-
0:10 and 93:7 for the rac and meso diastereoisomers, respec- longing to the C2 point group. Both molecules have almost
9
tively. Only tert-butylated compounds were thus involved in identical geometrical parameters. Superposition of the two
fully diastereoselective processes. The 31P NMR spectroscopy molecules, after inversion, leads to a RMSD equal to 0.58 Å and
data gathered for the cyclopentadienyl-substituted bis(diphen- a maximal distance difference equal to 1.42 Å for atoms belong-
ylphosphino)ferrocenes and their selenide derivatives are col- ing to the phenyl groups. The Cp rings are in a staggered con-
lected in Table 2. The effects of the R substituents, tert-butyl, formation with a cisoid conformation of the phosphino groups
isopropyl, trimethylsilyl, and trityl, on the electron-donating fea- {P1···P2 4.2333(5) Å [4.1405(6) Å], torsion angle P1–Ct1–Ct2–P2
tures of the diphenylphosphino groups are minor, as confirmed 37.19(2)° [–34.02(3)°]}, which is reminiscent of those obtained
3
1
1
by the P chemical shifts and J values ranging from 735 to for 5e.
P, Se
Figure 3. Molecular structures of compound 6a. Hydrogen atoms are omitted for clarity. Selected bond lengths [Å], distances [Å], and angles [°]: Fe–Ct1
1
.6531(13), Fe–Ct2 1.6532(11), C1–P1 1.811(3), C21–P2 1.823(2), P1···P2 6.1935(9), Ct1–Fe–Ct2 178.71(6), P1–Ct1–Ct2–P2 127.29(3).
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Figure 4. Molecular structures of compounds 6c. Only one enantiomer is represented and hydrogen atoms are omitted for clarity. Selected bond lengths [Å],
distances [Å], angles [°], and corresponding parameters for the second enantiomer are given in brackets: Fe1–Ct1 1.6558(8) [1.6594(8)], Fe1–Ct2 1.6576(8)
[
[
1.6599(8)], C1–P1 1.8141(16) [1.8138(16)], C6–P2 1.8168(16) [1.8150(16)], C3–Si1 1.8674(16) [1.8727(17)], C9–Si2 1.8678(16) [1.8703(17)], P1···P2 4.2333(5)
4.1405(6)], Ct1–Fe1–Ct2 177.35(4) [176.46(4)], P1–Ct1–Ct2–P2 37.19(2) [–34.02(3)], Si1–Ct1–Ct2–Si2 117.03(2) [–116.21(2)].
Effects of Ferrocenyl Diphosphanes in the Nucleophilic
Fluorination of 2-Chloroquinolines
Table 3. Palladium fluorination of 2-chloroquinoline (7).[a]
The nucleophilic fluorination of 2-chloroquinoline was first ex-
amined under conditions similar to those reported by Buchwald
[
14a,14c]
for related transhalogenation.
In the presence of
3
[
PdCl(η -C H )] (2.5 mol-%) and AgF (3.0 equiv.) in dry toluene
3
5 2
with the new ferrocenyl diphosphanes (10 mol-%) under an at-
mosphere of argon, we were glad to achieve promising conver-
sions in the presence of the alkylated diphosphanes (Table 3,
entries 3–8). This was not achieved in the absence of the phos-
phane (Table 3, entry 1) or by using the dppf ligand (Table 3,
entry 2).
Even if tert-butylated bis(diphenylphosphino)ferrocene 5d
was by far found to be the most efficient (Table 3, entry 6),
under these conditions the reaction was extremely sensitive to
Entry
Diphosphane
Yield[b] of 8 [%]
Yield[b] of 9 [%]
1
2
3
4
5
6
7
8
9
–
3
0
2
1
0
0
3
dppf
5a
5b
5c
5d
5e
6a
6b
6c
18
55
62
3
97
25
90
2
[
c]
c]
0
4
0
[
22[
0
d]
1
1
0
1
19
39
moisture and possible trace amounts of O and side reactions
2
6d
with palladium were highly favored (e.g., dehalogenation, ho-
mocoupling). The action of palladium was also responsible for
partial fluorination of the diphosphanes, as attested by the NMR
[a] Besides the formation of fluorinated 8, dehalogenation to 9 may occur.
[b] Yields determined by GC and NMR spectroscopy. [c] Homocoupling of 7.
[d] The formation of unidentified side products was observed.
3
1
19
spectroscopy data: δ( P) = 45.12 ppm and δ( F) = –73.29 ppm
1
[24]
with J = 1020 Hz.
Further investigations focused on opti-
P, F
mizing the reactions by using diphosphane 5d also indicated
By using 3.0 equivalents of AgF in the absence of diphos-
severe troubles with reproducibility, possibly linked to the qual- phane 5d, the transhalogenation of 2-chloroquinoline (7) to 2-
II
ity of Pd . However, during the course of conducting blank ex- fluoroquinoline (8) was achieved in only a very low yield
periments by removing each component from the catalytic sys- (Table 4, entry 1). The absence of palladium, however, left 7
tem, we were surprised to observe that removal of palladium unchanged. In the presence of various substoichiometric
overcame the limitations above described. Therefore, further amounts of 5d, ranging from 10 to 100 mol-% (Table 4, en-
optimization was achieved with the palladium-free system by tries 2–5), the selective conversion of 7 into 8 reach up to 95 %
–
[25]
using 5d and various sources of nucleophilic “F ” or additives, by using 50 mol-% of 5d (Table 4, entry 4).
without drastic drying of the toluene solvent, as reported in addition of a larger amount of 5d was deleterious to the con-
Curiously, the
Table 4.
version (Table 4, entry 5). Monitoring of the reaction mixture
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Table 4. Palladium-free fluorination of 2-chloroquinoline (7).[a]
Entry
5d
mol-%]
Source of F–
[equiv.]
Additive
[mol-%]
Yield[b] of 8
[%]
[
1
2
3
4
5
6
7
8
9
–
AgF (3.0)
AgF (3.0)
AgF (3.0)
AgF (3.0)
AgF (3.0)
AgF (1.0)
AgF (2.0)
–
–
–
–
–
–
–
–
2
30
53
10
25
50
100
50
50
50
50
50
50
50
[
c]
Scheme 5. Fluorination of quinoline and isoquinoline derivatives.
92
58
32
50
<1
16
29
<1
0
Conclusions
AgF
2
(3.0)
CsF (3.0)
CsF (3.0)
CsF (3.0)
KF (3.0)
AgNO
AgNO
AgNO
AgNO
3
3
3
3
(20)
The diastereoselective synthesis of novel disubstituted ferro-
cenyl diphosphanes bearing aryl, alkyl, and hetero- and poly-
cyclic substituents on the phosphorus atom was achieved.
Steric control of the ferrocene backbone was the result of the
introduction of tert-butyl, isopropyl, and trimethylsilyl groups
on the backbone before lithiation in the presence of TMEDA.
Subsequent phosphination and lithiation sequences favored
the rac stereochemistry in the final substituted diphosphane
ferrocenes. Symmetric diphosphanes were synthesized in good
to excellent yields, especially if the ferrocene bearing tert-butyl
substituents was used. Only tert-butyl groups ensured perfect
diastereoselectivity in the formation of the diphosphanes. Char-
acterization of typical products by X-ray structure analysis and
multinuclear NMR spectroscopy was reported. The air-stable,
moisture-insensitive diphosphanes demonstrated their utility in
the nucleophilic fluorination of 2-chloroquinoline derivatives by
using AgF under conditions for which dry toluene was not re-
quired and the addition of palladium was deleterious to select-
ivity.
1
1
1
0
1
2
(100)
(300)
(300)
[
7
a] Dehalogenation to 9 was no longer observed, incomplete conversion left
unchanged. [b] Yields determined by GC and NMR spectroscopy. [c] Aver-
age of three consistent runs ranging from 87 to 95 %.
by 31P NMR spectroscopy under operating conditions indicated
the absence of signals in the range of –250 to 150 ppm that
could be correlated with coordination of phosphane to silver in
some paramagnetic edifice. Changes in the amount of AgF
added indicated that a quantity lower than 3.0 equivalents was
less efficient for fluorination (Table 4, entries 6 and 7). Concern-
ing the nucleophilic source, AgF , a rather marginally used rea-
gent, was recently identified by Fier and Hartwig as a highly
efficient fluorination reagent for direct nucleophilic S Ar of pyr-
idine derivatives.
2
N
[
18]
Under our conditions, AgF was inefficient
2
as a transhalogenation agent (Table 4, entry 8).
We checked if other sources of silver could be catalytically
–
used in combination with sources of nucleophilic “F ”. The com-
monly used CsF reagent was tested in combination with 20 to
1
00 mol-% AgNO , but only modest conversion of 7 was Experimental Section
3
achieved (Table 4, entries 9 and 10). An excess amount of Ag-
General Conditions: All reagents were purchased from commercial
suppliers and were used without purification. All reactions were
performed under an atmosphere of dry argon in oven-dried glass-
ware by using Schlenk and vacuum-line techniques. Solvents were
NO was even more deleterious to the transhalogenation reac-
tion. Finally, the cheaper KF reagent was also useless (Table 4,
entry 11).
3
The most favorable conditions that we found for this clean dried and deoxygenated before distillation from sodium benzophe-
transhalogenation (Table 4, entry 4) were applied to other quin- none ketyl. The identities and purities of the products were estab-
lished at the “Chemical Analysis Platform and Molecular Synthesis
University of Burgundy” by using high-resolution mass spectrome-
oline substrates with some success (Scheme 5). Functional
groups such as methyl, cyano, and nitro were tolerated on the
quinoline (substrates 9a–c, respectively), and the reaction was
also selectively applied to α-chlorinated quinoline isomer 9d;
fluorinated analogues 10a–d were delivered in good yields
above 75 %.
1
try, elemental analysis, and multinuclear NMR spectroscopy. H NMR
(
300 MHz) and 13C NMR (75 or 125 MHz) spectra were recorded
with a Bruker AVANCE III instrument in CDCl solutions. Chemical
3
1
13
shifts are reported in ppm relative to CHCl ( H: 7.26 ppm and C:
3
77.16 ppm) and coupling constants J are given in Hz. High-resolu-
This work shows that phosphanes in substoichiometric
tion mass spectra were obtained with a Thermo LTQ-Orbitrap XL
amounts in combination with AgF can provide a powerful sys- with ESI source. Flash chromatography was performed on silica gel
tem for the fluorination of chloroarenes. Further work is ongo- (230–400 mesh). Elemental analysis experiments were performed
ing to understand the precise role of the diphosphane, which with a Thermo Electron Flash EA 1112 Series.
is expected to interact either with the silver salt or the C2 chlor-
ide, or possibly both. It may be anticipated that further optimi-
zation of the phosphane auxiliary may help to extend the scope for this paper. These data can be obtained free of charge from The
CCDC 1477185 (for 5c), 1405169 (for 5e), 1405627 (for 6a), and
1405168 (for 6c) contain the supplementary crystallographic data
of this system.
Cambridge Crystallographic Data Centre.
Eur. J. Inorg. Chem. 0000, 0–0
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7
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1,1′-Bis(Diisopropylphosphino)-3,3′-di(tert-butyl)ferrocene (5a): 1,1′-Bis(benzophosphindole)-3,3′-di(tert-butyl)ferrocene (5e):
To a solution of dilithium 1,1′-di(tert-butyl)ferrocene TMEDA salt
2.08 g, 4.88 mmol) in THF (50 mL) at –80 °C was added dropwise
To a solution of dilithium 1,1′-di(tert-butyl)ferrocene TMEDA salt
(
(1.38 g, 3.23 mmol) in THF (20 mL) at –80 °C was added dropwise
[
26]
a solution of ClPiPr (1.56 mL, 9.76 mmol) in THF (25 mL). After the
a solution of [ClP(Bpi)]
(1.41 g, 6.47 mmol) in THF (20 mL). After
2
addition, the mixture was warmed to room temperature and stirred
overnight. Then, the solvent was removed in vacuo. The crude prod-
uct was purified by column chromatography on silica gel (EtOAc/
heptane, 3:97). Compound 5a was isolated in a pure form as a red
the addition, the mixture was warmed to room temperature and
stirred overnight. Then, the solvent was removed in vacuo. The
crude product was purified by column chromatography on silica
gel (toluene/heptane, 2:3). Compound 5e was isolated in a pure
1
crystalline solid (1.89 g, 73 % yield). The analyses are similar to re- form as an orange crystalline solid (0.9 g, 42 % yield). H NMR
ported data from non-diastereoselective synthesis.[
7a]
(300 MHz, CDCl ): δ = 1.20 [s, 18 H, H(tBu)], 3.68 (m, 2 H, HCp), 4.07
3
(
m, 2 H, HCp), 4.04 (m, 2 H, HCp), 4.54 (m, 2 H, HCp), 7.29 (dt, J =
7.44 and 1.21 Hz, 2 H, HBpi), 7.40 (m, 4 H, HBpi), 7.52 (dt, J = 7.44
5b): To a solution of dilithium 1,1′-di(tert-butyl)ferrocene TMEDA and 1.21 Hz, 2 H, HBpi), 7.79 (m, 2 H, HBpi), 7.88 (d, J = 7.63 Hz, 2
1
(
,1′-Bis(dicyclohexylphosphino)-3,3′-di(tert-butyl)ferrocene
salt (2.45 g, 5.75 mmol) in THF (50 mL) at –80 °C was added drop- H, HBpi), 7.96 (d, J = 7.63 Hz, 2 H, HBpi), 7.40 (m, 2 H, HBpi) ppm.
1
3
1
wise a solution of ClPCy (2.53 mL, 11.5 mmol) in THF (25 mL). After
C{ H} NMR (75 MHz, CDCl ): δ = 30.8 [s, C(tBu)], 31.9 [s, Me(tBu)],
2
3
the addition, the mixture was warmed to room temperature and
stirred overnight. Then, the solvent was removed in vacuo. The
crude product was purified by column chromatography on silica
gel (EtOAc/heptane, 5:95). Compound 5b was isolated in a pure
67.5 (s, CCp), 68.6 (s, CCp), 70.8 (q, JC,P = 11.9 Hz, CCp), 77.2 (m,
CCp), 105.4 (t, JC,P = 2.5 Hz, CCp), 121.1 (s, CBpi), 121.5 (s, CBpi),
126.9 (t, JC,P = 3.6 Hz, CBpi), 127.4 (t, JC,P = 3.6 Hz, CBpi), 128.1 (s,
CBpi), 128.7 (s, CBpi), 129.8 (t, JC,P = 12.4 Hz, CBpi), 131.4 (t, JC,P
=
1
form as a red crystalline solid (3.18 g, 80 % yield). H NMR (300 MHz,
12.4 Hz, CBpi), 141.1 (m, CBpi), 142.4 (m, CBpi), 144.3 (m, CBpi),
3
145.0 (t, JC,P = 2.2 Hz, CBpi) ppm. 31P{ H} NMR (121.5 MHz, CDCl ):
1
3
CDCl ): δ = 0.85–1.85 (m, 44 H, HCy), 1.24 [s, 18 H, H(tBu)], 3.89 (m,
1
3
1
+
2
H, HCp), 3.95 (m, 2 H, HCp), 4.07 (m, 2 H, HCp) ppm. C{ H} NMR
δ = –22.97 ppm. HRMS (ESI+, CH Cl /MeOH): calcd. for C H FeP
[M] 662.195465; found 662.19626. C42H40FeP (662.57): calcd. C
2
2
42 40
2
+
(
75 MHz, CDCl ): δ = 22.9 (d, J = 15.4 Hz, CCy), 26.4 (d, JC,P
=
3
C,P
2
7
.7 Hz, CCy), 26.6 (d, JC,P = 5.1 Hz, CCy), 27.2–27.7 (m, CCy), 28.7 (d,
76.14, H 6.09; found C 75.61, H 6.18.
JC,P = 3.9 Hz, CCy), 29.6 (d, JC,P = 6.4 Hz, CCy), 30.7 [s, C(tBu)], 31.5
1
,1′-Bis[di(5-methyl-2-furyl)phosphino]-3,3′-di(tert-butyl)-
(d, JC,P = 19.6 Hz, CCy), 31.9 [s, Me(tBu)], 31.9 [s, Me(tBu)], 32.7–33.1
ferrocene (5f): To a solution of dilithium 1,1′-di(tert-butyl)ferrocene
(
7
m, CCy), 34.2 (d, JC,P = 14.9 Hz, CCy), 67.2 (s, CCp), 68.5 (m, CCp),
TMEDA salt (4.15 g, 9.74 mmol) in THF (50 mL) at –80 °C was added
2.8 (s, CCp), 73.1 (s, CCp), 103.8 (d, JC,P = 5.6 Hz, CCp) ppm. 31P{ H}
1
Me
dropwise a solution of BrP(Fu )2 (5.32 g, 19.48 mmol) in THF (20
NMR (121.5 MHz, CDCl ): δ = –8.57 ppm. HRMS (ESI+, CH Cl /
3
2
2
mL). After the addition, the mixture was warmed to room tempera-
ture and stirred overnight. Then, the solvent was removed in vacuo.
The crude product was purified by column chromatography on sil-
ica gel (EtOAc/heptane, 3:97). Compound 5f was isolated in a pure
+
+
MeOH): calcd. for C H FeP [M + H] 691.42239; found 691.42109.
42
69
2
C H FeP (691.80): calcd. C 73.03, H 9.92; found C 72.51, H 9.37.
42
69
2
1
,1′-Bis[di(2,4,6-methylphosphino)]-3,3′-di(tert-butyl)ferrocene
form as an orange crystalline solid after recrystallization from MeOH
(5c): To a solution of dilithium 1,1′-di(tert-butyl)ferrocene TMEDA
1
(
1.13 g, 30 % yield). H NMR (300 MHz, CDCl ): δ = 1.10 [s, 18 H,
3
salt (0.7 g, 1.64 mmol) in THF (30 mL) at –40 °C was added dropwise
H(tBu)], 2.26 (s, 6 H, MeFu), 2.36 (s, 6 H, MeFu), 3.97 (m, 2 H, HCp),
a solution of ClPMes (1.00 g, 3.28 mmol) in THF (40 mL). After the
2
4
2
.07 (m, 2 H, HCp), 4.29 (m, 2 H, HCp), 5.88 (m, 2 H, HFu), 6.02 (m,
addition, the mixture was warmed to room temperature and stirred
overnight. Then, the solvent was removed in vacuo. The crude prod-
uct was purified by column chromatography on silica gel (EtOAc/
heptane, 3:97). Compound 5c was isolated in a pure form as an
H, HFu), 6.28 (m, 2 H, HFu), 6.81 (m, 2 H, HFu) ppm. 13C{ H} NMR
1
(
75 MHz, CDCl ): δ = 14.1 (s, MeFu), 14.2 (s, MeFu), 30.6 [s, C(tBu)],
3
3
1.7 [s, Me(tBu)], 69.4 (s, CCp), 72.2 (s, CCp), 72.7 (m, CCp), 72.9 (t,
JC,P = 18.2 Hz, CCp), 105.3 (t, JC,P = 4.0 Hz, CFu), 106.8 (m, CFu),
07.0 (t, JC,P = 4.0 Hz, CFu), 107.2 (d, JC,P = 5.7 Hz, CCp), 119.3 (t,
JC,P = 15.3 Hz, CFu), 122.2 (d, JC,P = 2.5 Hz, CFu), 122.7 (t, JC,P
.3 Hz, CFu), 150.2 (d, JC,P = 6.9 Hz, CFu), 150.3 (d, JC,P = 6.9 Hz,
CFu), 152.2 (m, CFu), 156.2 (t, J = 1.5 Hz, CFu), 156.8 (m, CFu)
orange crystalline solid after recrystallization from MeOH (1.13 g,
1
1
3
2
4
0 % yield). H NMR (300 MHz, CDCl ): δ = 0.81 [s, 18 H, H(tBu)],
3
=
.19 (br. s, 18 H, MeMes), 2.22 (br. s, 18 H, MeMes), 3.99 (m, 2 H, HCp),
.067 (m, 2 H, HCp), 4.26 (m, 2 H, HCp), 6.66 (br. s, 4 H, HMes), 6.83
br. s, 4 H, HMes) ppm. C{ H} NMR (75 MHz, CDCl ): δ = 20.7 [s,
8
1
3
1
C,P
(
3
31
1
ppm. P{ H} NMR (121.5 MHz, CDCl ): δ = –65.25 ppm. HRMS (ESI+,
CH Cl /MeOH): calcd. for C38H44FeO4P2 [M] 682.55780; found
3
Me(Mes)], 20.9 [s, Me(Mes)], 30.5 [s, C(tBu)], 30.6 [s, Me(tBu)], 66.7 (s,
CCp), 72.2 (s, CCp), 75.1 (s, CCp), 75.6 (s, CCp), 77.7 (t, JC,P = 14.8 Hz,
+
+
2
2
6
6
82.20697. C H FeO P (682.56): calcd. C 66.87, H 6.50; found C
6.09, H 6.67.
38 44 4 2
CCp), 104.6 (t, JC,P = 3.5 Hz, CCp), 109.9 (br. s, CMes), 131.3 (d, JC,P
=
1
3.8 Hz, CMes), 134.2 (d, J = 32.5 Hz, CMes), 135.8 (s, CMes), 138.5
C,P
1
(
s, CMes) ppm. 31P{ H} NMR (121.5 MHz, CDCl ): δ = –37.08 ppm.
1,1′-Bis(diphenylphosphino)-3,3′-diisopropylferrocene (6a): To a
solution of dilithium 1,1′-diisopropylferrocene TMEDA salt (0.23 g,
0.34 mmol) in diethyl ether (20 mL) at –80 °C was added dropwise
3
HRMS (ESI+, CH Cl /MeOH): calcd. for C54H68FeP2+ [M + H]
+
2
2
8
35.42239; found 835.42021. C H FeP (834.93): calcd. C 77.68, H
54 68 2
8
.21; found C 77.51, H 8.34.
a solution of ClPiPr (0.11 mL, 0.68 mmol) in diethyl ether (10 mL).
2
After the addition, the mixture was warmed to room temperature
and stirred overnight. Then, the solvent was removed in vacuo. The
crude product was purified by column chromatography on silica
gel (toluene/heptane, 2:3). Compound 6a was isolated in a pure
1
,1′-Bis(diphenylphosphino)-3,3′-di(tert-butyl)ferrocene (5d): To
a solution of dilithium 1,1′-di(tert-butyl)ferrocene TMEDA salt (2 g,
.96 mmol) in THF (20 mL) at –80 °C was added dropwise a solution
of ClPPh (1.74 mL, 9.39 mmol) in THF (20 mL). After the addition,
4
form after recrystallization from acetonitrile as a yellow crystalline
2
1
the mixture was warmed to room temperature and stirred over- solid (0.110 g, 51 % yield). H NMR (300 MHz, CDCl ): δ = 1.02 [d,
3
night. Then, the solvent was removed in vacuo. The crude product
was purified by column chromatography on silica gel (EtOAc/hept-
J = 6.5 Hz, 6 H, Me(iPr)], 1.09 [d, J = 6.5 Hz, 6 H, Me(iPr)], 2.34 (m,
J = 6.5 Hz, 2 H, CHMe ), 3.51 (s, 2 H, HCp), 3.96 (s, 2 H, HCp), 4.20
2
ane, 3:97). Compound 5d was isolated in a pure form as an orange (s, 2 H, HCp), 7.26 (m, 16 H, HPh), 7.33–7.28 (m, 4 H, HPh) ppm.
1
3
1
crystalline solid (2.74 g, 88 % yield). The analyses were similar to
C{ H} NMR (75 MHz, CDCl ): δ = 23.0 [s, Me(iPr)], 24.7 [s, Me(iPr)],
3
reported data from non-diastereoselective synthesis.[20]
27.5 [s, C(iPr)], 70.5 (t, JCP = 2.2 Hz, CCp), 71.6 (s, JCP = 2.5 Hz, CCp),
Eur. J. Inorg. Chem. 0000, 0–0
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8
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
3
1
7
1
4.8 (t, JCP = 24.7 Hz, CCp), 75.4 (dd, JCP = 4.9 and 2.1 Hz, CCp),
00.9 (t, JCP = 2.6 Hz, CCp), 128.1 (s, CPh), 128.1 (s, CPh), 128.2 (s,
C{ H} NMR (75 MHz, CDCl ): δ = 0.6 (s, SiCH ), 18.8 (m, J
=
3
3
C,P
3.4 Hz, CiPr), 20.1 (d, JC,P = 12.9 Hz, CiPr), 20.8 (d, JC,P = 16.5 Hz,
CPh), 128.2 (s, CPh), 128.8 (s, CPh), 133.1 (d, JCP = 21.2 Hz, CPh), CiPr), 22.3 (d, JC,P = 20.6 Hz, CiPr), 23.3 (m, CiPr), 24.5 (m, CiPr), 72.8
34.5 (d, JCP = 21.2 Hz, CPh), 138.8 (d, J = 9.9 Hz, CPh), 140.5 (d, (s, CCp), 75.0 (s, CCp), 77.1 (s, CCp), 78.7 (d, J = 20.3 Hz, CCp), 80.2
1
CP
C,P
3
1
1
31
1
JCP = 9.9 Hz, CPh) ppm. P{ H} NMR (121.5 MHz, CDCl ): δ =
(d, JC,P = 21.3 Hz, CCp) ppm. P{ H} NMR (121.5 MHz, CDCl ): δ =
–1.43 ppm. HRMS (ESI+, CH Cl /MeOH): calcd. for C H FeP Si [M
3
3
+
+
–17.22 ppm. HRMS (ESI+, CH Cl /MeOH): calcd. for C H FeP [M
2
2
40 41
2
2
2
28 52
2 2
+
+
+
H] 639.20129; found 639.20129. C H FeP (639.56): calcd. C + H] 563.25104; found 563.24977. C H FeP Si (562.69): calcd. C
4
0
41
2
28 52
2
2
7
5.24, H 6.31; found C 74.63, H 7.43.
59.77, H 9.31; found C 58.75, H 8.58.
1
,1′-Bis(benzophosphindole)-3,3′-diisopropylferrocene (6b): To
Silver-Mediated Fluorination Reactions:
A
Schlenk tube
a solution of dilithium 1,1′-diisopropylferrocene TMEDA salt (1.22 g, equipped with a stirring bar was charged with the pyridine deriva-
3
.07 mmol) in THF (30 mL) at –80 °C was added dropwise a solution
tive (1 mmol), ligand (0.5 mmol) and AgF (3 mmol) under an inert
[26]
of [ClP(Bpi)]
(1.33 g, 6.47 mmol) in THF (30 mL). After the addi- atmosphere before toluene (3 mL) was added. The mixture was
tion, the mixture was warmed to room temperature and stirred
overnight. Then, the solvent was removed in vacuo. The crude prod-
uct was purified by column chromatography on silica gel (toluene/
heptane, 2:3). Compound 6b was isolated as a mixture of rac and
meso forms (ratio 85:15) as an orange crystalline solid (0.51 g, 27 %
yield). Even after several recrystallizations under different condi-
stirred at 120 °C for 17 h in an oil bath. At room temperature, the
mixture was then diluted with ethyl acetate, filtered on silica gel,
and concentrated in vacuo for analysis by GC and NMR spectro-
scopy. The crude product was purified by column chromatography
on silica gel (EtOAc/heptane).
-Fluoroquinoline (8): Analyses were similar to reported data.[19a]
2
1
tions, some impurities were still present. Data for 6b-rac: H NMR
1
H NMR (300 MHz, CDCl ): δ = 7.09 (dd, J = 8.7 and 2.8 Hz, 1 H),
3
(
300 MHz, CDCl ): δ = 1.09 [d, J = 6.5 Hz, 6 H, Me(iPr)], 1.13 [d, J =
3
7
.54 (m, 1 H), 7.74 (m, 1 H), 7.83 (m, 1 H), 7.94 (d, J = 8.4 Hz, 1
6
.5 Hz, 6 H, Me(iPr)], 2.62 (m, J = 6.5 Hz, 2 H, CHMe ), 3.52 (s, 2 H,
19
2
H), 8.25 (t, J = 8.4 Hz, 1 H) ppm. F NMR (282 MHz, CDCl ): δ =
3
HCp), 3.98 (s, 2 H, HCp), 4.11 (s, 2 H, HCp), 7.30–7.52 (m, 8 H, HBpi),
–61.7 ppm.
1
3
1
7
2
2
7
.74–7.96 (m, 8 H, HBpi) ppm. C{ H} NMR (75.0 MHz, CDCl ): δ =
3
4
-Methyl-2-fluoroquinoline (10a): Analyses were similar to re-
3.0 [s, Me(iPr)], 24.5 [s, Me(iPr)], 27.6 (s, CHMe ), 68.3 (m, JCP
.3 Hz, CCp), 69.5 (m, JCP = 2.1 Hz, CCp), 72.5 (d, JCP = 22.7 Hz, CCp),
7.2 (s, CBpi), 100.2 (t, JCP = 2.4 Hz, CCp), 121.1 (s, CBpi), 121.4 (s,
=
2
[
27] 1
ported data.
H NMR (300 MHz, CDCl ): δ = 2.71 (d, J = 8.4 Hz, 3
3
H), 6.91 (m, 1 H), 7.53 (td, J = 8.2 and 1.0 Hz, 1 H), 7.71 (td, J = 8.2
and 1.0 Hz, 1 H), 7.94 (m, 2 H) ppm. 19F NMR (282 MHz, CDCl ): δ =
CBpi), 127.0 (m, CBpi), 127.2 (m, CBpi), 128.6 (d, JCP = 20.8 Hz, CBpi),
30.2 (d, JCP = 23.0 Hz, CBpi), 131.0 (d, JCP = 21.9 Hz, CBpi), 141.4
m, CBpi), 142.8 (m, CBpi), 143.4 (d, J = 4.3 Hz, CBpi), 144.0 (m,
3
–63.0 ppm.
1
(
CP
2-Fluoro-3-cyanopyridine (10b): Analyses were similar to reported
31
1
CBpi) ppm. P{ H} NMR (121.5 MHz, CDCl ): δ = –20.19 (rac) and
[28] 1
3
data.
H NMR (300 MHz, CDCl ): δ = 7.62 (td, J = 8.0 and 2.0 Hz,
3
–
20.71 (meso) ppm. HRMS (ESI+, CH Cl /MeOH): calcd. for
19
2
2
1 H), 8.08 (td, J = 8.0 and 2.0 Hz, 1 H), 8.47 (m, 1 H) ppm. F NMR
+
+
C H FeP [M] 634.16416; found 634.16580. C H FeP (634.52):
40
36
2
40 36
2
(282 MHz, CDCl ): δ = –63.0 ppm.
3
calcd. C 75.72, H 5.72; found C 76.21, H 6.44.
2
data.
-Fluoro-3-nitropyridine (10c): Analyses were similar to reported
[
29] 1
1
(
,1′-Bis(diphenylphosphino)-3,3′-bis(trimethylsilane)ferrocene
H NMR (300 MHz, CDCl ): δ = 7.47 (dd, J = 8.0 and 4.75 Hz,
3
6c):[
23b]
To a solution of dilithium 1,1′-bis(trimethylsilane)ferrocene 1 H), 8.22 (dd, J = 8.0 and 1.75 Hz, 1 H), 8.22 (dd, J = 4.75 and
1.75 Hz, 1 H) ppm. 19F NMR (282 MHz, CDCl ): δ = –67.6 ppm.
TMEDA salt (1.88 g, 4.1 mmol) in THF (50 mL) at –80 °C was added
3
dropwise a solution of ClPPh (1.51 mL, 8.2 mmol) in THF (30 mL).
2
1
data.
-Fluoro-isoquinoline (10d): Analyses were similar to reported
After the addition, the mixture was warmed to room temperature
and stirred overnight. Then, the solvent was removed in vacuo. The
crude product was purified by column chromatography on silica
[
30] 1
H NMR (300 MHz, CDCl ): δ = 7.50 (m, 1 H), 7.63 (td, J =
3
8
8
.2 and 1.2 Hz, 1 H), 7.75 (td, J = 6.9 and 1.3 Hz, 1 H), 7.84 (m, 1 H),
.03 (dd, J = 5.8 and 1.2 Hz, 1 H), 8.15 (m, 1 H) ppm. F NMR
1
9
gel (toluene/heptane, 2:3 + 1 % Et N). Compound 6c was isolated
3
(282 MHz, CDCl ): δ = –71.2 ppm.
1
3
in a pure form as an orange crystalline solid (1.00 g, 35 % yield). H
NMR (300 MHz, CDCl ): δ = 0.0 (s, 18 H, Me Si), 3.90 (m, 2 H, HCp),
3
3
4
7
–
.07 (m, 2 H, HCp), 4.19 (m, 2 H, HCp), 7.19–7.32 (m, 16 H, HPh), Acknowledgments
3
1
1
.60 (m, 4 H, HPh) ppm. P{ H} NMR (121.5 MHz, CDCl ): δ =
3
This work was funded by the Université de Bourgogne, the Cen-
tre National de la Recherche Scientifique (CNRS), and the Con-
seil Régional de Bourgogne (PARI II CDEA and 3MIM program).
Cooperation between the institutes IOC-NASU and ICMUB
21.12 ppm.
1
,1′-Bis(diisopropylphosphino)-3,3′-bis(trimethylsilane)-
ferrocene (6d): To a solution of dilithium 1,1′-bis(trimethylsi-
lane)ferrocene TMEDA salt (2.61 g, 5.7 mmol) in THF (50 mL) at
(UMR-CNRS 6302) was funded by the CNRS and the Ukrainian
–80 °C was added dropwise a solution of ClPiPr2 (1.9 mL,
Academy of Sciences (NASU) through the PHC DNIPRO 2016
program number 34645VM). Thanks are due to Y. Vlasenko for
1
1.97 mmol) in THF (20 mL). After the addition, the mixture was
warmed to room temperature and stirred overnight. Then, the sol-
vent was removed in vacuo. The crude product was purified by solving the X-ray structure of diphosphane 6a.
column chromatography on silica gel (heptane 100 %). Compound
6
d was isolated in a pure form after recrystallization from MeOH as
Keywords: Sandwich complexes · Diastereoselectivity ·
Phosphanes · Fluorination · Halex reaction
1
a red crystalline solid (1.13 g, 33 % yield). H NMR (300 MHz, CDCl ):
δ = 0.26 (s, 18 H, Me Si), 0.74 [d, J = 7.0 Hz, 3 H, Me(iPr)], 0.77 [d,
3
3
J = 7.0 Hz, 3 H, Me(iPr)], 1.02 [d, J = 7.0 Hz, 3 H, Me(iPr)], 1.07 [d, J =
7
7
7
4
.0 Hz, 3 H, Me(iPr)], 1.15 [d, J = 7.0 Hz, 3 H, Me(iPr)], 1.19 [d, J =
.0 Hz, 3 H, Me(iPr)], 1.32 [d, J = 7.0 Hz, 3 H, Me(iPr)], 1.39 [d, J =
.0 Hz, 3 H, Me(iPr)], 1.83 (m, 2 H, CHMe ), 2.06 (m, 2 H, CHMe ),
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Published Online: ■
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Full Paper
Diastereoselective Synthesis
J. Roger,* S. Royer, H. Cattey,
A. Savateev, R. V. Smaliy,
A. N. Kostyuk, J.-C. Hierso* ........... 1–11
Diastereoselective Synthesis of Di-
alkylated Bis(phosphino)ferrocenes:
Their Use in Promoting Silver-Medi-
ated Nucleophilic Fluorination of
Chloroquinolines
The diastereoselective synthesis of di- spectroscopy. In combination with
alkylated ferrocenyl bis(phosphane)s AgF, these ferrocenyl diphosphanes al-
bearing aryl, alkyl, and hetero/poly- low the selective fluorination of 2-
cyclic groups on the phosphorus atom chloroquinoline derivatives, whereas
is reported together with their charac- palladium is highly deleterious.
terization by X-ray analysis and NMR
DOI: 10.1002/ejic.201600502
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim