Modular synthesis of the ClickFerrophos ligand family and their use in rhodium- and ruthenium-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tetasy.2009.09.004

A series of diphosphine ClickFerrophos ligands (CF), based on a triazoleferrocene backbone, was synthesized in a four-step sequence via click chemistry methodology. In addition to the four previously synthesized ligands CF1, CF4, CF7 and CF10, six novel C

Full text of DOI:10.1016/j.tetasy.2009.09.004

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Tetrahedron: Asymmetry 20 (2009) 2185–2191
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Modular synthesis of the ClickFerrophos ligand family and their
use in rhodium- and ruthenium-catalyzed asymmetric hydrogenation
*
Hiroshi Oki, Ichiro Oura, Tatsuhito Nakamura, Kenichi Ogata, Shin-ichi Fukuzawa
Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of diphosphine ClickFerrophos ligands (CF), based on a triazoleferrocene backbone, was synthe-
sized in a four-step sequence via click chemistry methodology. In addition to the four previously synthe-
sized ligands CF1, CF4, CF7 and CF10, six novel CF ligands CF2–3 and CF5–8 were prepared.
Hydrogenation reactions of alkenes and ketones were significantly improved upon by using CF ligands
as rhodium- or ruthenium-complexes in which the % ee values can be optimized by choosing the appro-
priate CF ligand depending on the substrate.
Received 4 August 2009
Accepted 3 September 2009
Available online 30 September 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
ten representative ClickFerrophos ligands CF1–10 with various ste-
ric and electronic environments of the 4-aryl group (R3) and the
Ferrocenylphosphines constitute a well-established class of li-
gands for transition metals which often catalyze asymmetric reac-
tions with high enantioselectivity.1 In previous papers, we reported
on a class of ferrocenyl-triazole-based 1,5-diphosphine ligands
(ClickFerrophos ligands, CF1–10, Chart 1),2 which were readily pre-
pared by click chemistry methodology.3 Subsequently, these li-
gands were found to be highly effective for rhodium- and
ruthenium-catalyzed asymmetric hydrogenations of alkenes and
ketones giving high enantioselectivities of up to 99.7% and 99%
ee, respectively.2a In addition to hydrogenations, ClickFerrophos li-
gands were successfully applied towards the copper-catalyzed
asymmetric 1,3-dipolar addition of azomethine ylide with elec-
tron-deficient alkenes2b and towards the reductive aldol reaction
of ethyl acrylate with ketones.2c Studies have shown that the phos-
phino substituents of the ClickFerrophos ligands affect the enanti-
oselectivity of the reactions. Diphenylphosphine derivative CF1
was the most effective for the hydrogenation and 1,3-dipolar addi-
tion reactions with azomethine ylides, whereas the dicyclohexyl-
phosphine derivative CF7 was the most effective for reductive
aldol reactions. The modularity within the family of ClickFerrophos
ligands, therefore, can allow for the specific fine tuning of the cat-
alytic properties depending on the reactions. In addition to modi-
fications of the phosphino substituents, the 4-aryl group on the
triazole ring can be varied by using various terminal aryl acety-
lenes in the click reactions. The key intermediate for this ligand
family is the enantiomerically pure ligand framework; the triazole
backbone 4 can be obtained via click chemistry from ortho-bromof-
errocenylethyl azide 3, which is prepared from Ugi’s amine 14
(Scheme 1). Herein we report the synthesis and reactivities of
phosphino substituents (R1 and R2). The effectiveness of the ligands
CF1-10 was evaluated in the hydrogenation of alkenes and ketones
with respect to enantioselectivities.
2. Results and discussion
2.1. Synthesis of ClickFerrophos ligands
As shown in Scheme 1, Ugi’s amine 1 was subjected to ortho-
lithiation, then trapped with bromine (using 1,2-dibromo-1,1,2,
Me
PR1
Fe
2
N
N
N
PR2
2
R3
ClickFerrophos
CF1: R1 = R2 = R3 = Ph
CF2: R1 = R2 = Ph, R3 = o-MeC6H4
CF3: R1 = R2 = Ph, R3 = o-FC6H4
CF4: R1 = R2 = Ph, R3 = H
CF5: R1 = R2 = 3,5-xyl, R3 = Ph
CF6: R1 = R2 = 3,5-xyl, R3 = o-FC6H4
CF7: R1 = R2 = Cy, R3 = Ph
CF8: R1 = R3 = Ph, R2 = 3,5-xyl
CF9: R1 = R3 = Ph, R2 = 3,5-(CF3)2C6H3
CF10: R1 = R3 = Ph, R2 = Cy
* Corresponding author. Tel.: +81 (0) 338171916; fax: +81 (0) 338171895.
E-mail address: orgsynth@kc.chuo-u.ac.jp (S. Fukuzawa).
Chart 1. ClickFerrophos (CF) family.
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.09.004

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H. Oki et al. / Tetrahedron: Asymmetry 20 (2009) 2185–2191
Me
Me
Me
Fe
R3
1) 2 n-BuLi
2) 2 R12PCl
Me
Br
1) MeI
PR1
Fe
Fe
X
Fe Br
2
N
N
N
2) NaN3
N
Me2N
N3
click chemistry
N
N
PR1
2
3
1: X = H
2: X = Br
R3
R3
4a: R3 = Ph
CF1-CF7
4b: R3 = o-MeC6H4
3
4c
4d
: R = o-FC6H4
3
: R = Me3Si
R3 = H
1) n-BuLi/Ether
2) R12PCl
Me
PR1
Fe
1) n-BuLi/THF
2) R22PCl
Me
2
PR1
Fe
2
N
N
N
N
PR2
N
N
2
R3
R3
5: R3 = Ph
CF8-CF10
Scheme 1. Synthesis of ClickFerrophos CF1–CF10.
Table 1
Enantioselective hydrogenation of enamidesa
2-tetrafluoroethane) to afford 2. Retentive displacement of the
amino group by an azide group afforded ortho-bromoferrocenyl
azide 3,4a which was subjected to click chemistry5 to give the tria-
zole backbones 4 in good yields. In a previous paper, we used the
ortho-iodo analogue of ferrocenyl azide 3; the click reaction of the
azide to the triazole was improved from 75% to 85–90% by using
the ortho-bromo ferrocenes.6 The 4-(2-substituted phenyl) triazole
derivatives with electron-donating (R3 = o-MeC6H4) and electron-
withdrawing (R3 = o-FC6H4) groups were prepared using the corre-
sponding 2-substituted phenylacetylenes. Di-lithiation of 4 at the
5-triazole and 2-ferrocenyl positions, followed by trapping with
R2PCl afforded CF1–3 and CF5–7. In contrast, CF4 was prepared
using trimethylsilylacetylene instead of the phenylacetylenes, and
involved an extra step to remove the silyl group prior to di-phosph-
ination.2c,d As shown in Scheme 1, CF8–10 were obtained via suc-
cessive phosphinations of firstly the ortho-cyclopentadienyl ring
to afford mono-phosphine 5, followed by the 5-triazole ring. It
should be noted that the phosphino groups (R1, R2) of CF8–10 are
dissimilar to each other.
H2 (1 atm)
Rh/CF (1 mol%)
NHAc
R2
NHAc
R2
R1
R1
toluene/MeOH (1/1)
rt, 2 h
8a-9
6a-7
: R1 = Ph, R2 = CO2Me
6a
7: R1 = H, R2 = Ph
Entry
Ligand
Enamide
6a
7
Conv. (%)
ee (%)b
Conv. (%)
ee (%)b
1
2
3
4
5
6
7
8
9
CF1
CF2
CF3
CF4
CF5
CF6
CF7
CF8
CF9
CF10
99
99
99
99
99
99
Trace
99
50
99
86
98
93
95
98
—
90
83
67
99
99
99
99
99
99
60
99
35
99
84
54
88
86
90
85
27
81
35
11
10
99
2.2. Hydrogenation of enamides
a
Enamide (1 mmol), [Rh(nbd)2]BF4 (0.010 mol), ligand (0.011 mol), toluene/
MeOH (2/2 mL); rt, H2 (1 atm).
Ligands (S,Rp)-CF1–10 were evaluated as rhodium complexes in
b
Determined by HPLC (Chiralcel AD-H).
the hydrogenation of enamides such as methyl
a-acetamidocinna-
mate 6a (R1 = Ph, R2 = CO2Me) and -acetamidostyrene (7: R1 = H,
a
R2 = Ph).7 After generating the rhodium catalysts in situ using
[Rh(nbd)2]BF4 (1 mol % loading), the hydrogenations were carried
out in toluene/MeOH (1:1) at rt for 2 h under hydrogen (atmo-
spheric pressure). The resulting enantioselectivities (% ee) of the
reactions are listed in Table 1. The hydrogenation reactions of 6a
and 7 proceeded to give 8a and 9, respectively, in good to quanti-
tative yields except for CF7 and CF9. In the case of 6a, the original
CF1 (entry 1) was the most effective and afforded the highest
enantioselectivity (99% ee R).2a For 7, the sterically hindered phos-
phine CF5 (entry 5) was the most effective with an enantioselectiv-
ity of 90% ee. The use of CF2 (entry 2), with an electron-donating
group (o-MeC6H4), gave lower values of ee for both 6a (86% ee)
and 7 (54% ee), whereas the use of CF3 (entry 3), with an elec-
tron-withdrawing group (o-FC6H4), gave values of ee that were
comparable as those of CF1 for both 6a (98% ee) and 7 (88% ee).
In the absence of a 4-aryl group (CF4, entry 4), the ee was lower
for 6a but comparable to that of CF1 for 7. Sterically hindered
CF5 with two di(3,5-xylyl)phosphine units and CF8 with one
di(3,5-xylyl)phosphine unit, were efficient in the hydrogenation
reactions with high ee values, while CF9, with one di(3,5-
(CF3)2C6H3)phosphine unit, generated a less active catalyst.
Consequently, for hydrogenations of substituted methyl (Z)-a-
acetamidocinnamates 6a–6i, CF1 was chosen as the ligand due to
its effectiveness and facile preparation. The reactions were carried
out under the same conditions as described above, and the results
are summarized in Table 2. In all cases, the reactions proceeded
quantitatively with excellent enantioselectivities—every product
possessed the R-configuration [using (S,Rp)-CF1] regardless of the
electronic nature or position of the substituents on the aromatic

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H. Oki et al. / Tetrahedron: Asymmetry 20 (2009) 2185–2191
2187
Table 2
was less effective for the hydrogenation of enamides (Table 1, en-
try 2). CF2 was also effective for dibenzoylmethane 12 giving (S,S)-
1,3-diphenyl-1,3-propanediol 13 in >99% ee, while it was not so
effective for ethyl benzoylacetate 14 (96% ee) although CF1 (98%
ee) still afforded high% ee (Scheme 2). Sterically hindered phos-
phines CF5, CF6 and CF8 were also effective in yielding high
enantioselectivities (88–90% ee). CF5 was revealed to be the most
effective ligand considering that it gave the highest de value
although the ee value was slightly lower than that of CF2 (entry
5). Thus, by using the family of our new CF ligands, the enantiose-
lectivities were improved upon compared to that of CF1 (84% ee).
The CF4 complex, without a substituent at the 4-position, was
the least effective in the hydrogenation of 10 with an enantioselec-
tivity of merely 48% ee—in contrast, it was effective in the hydro-
genation of enamides.
Asymmetric hydrogenation of substituted methyl
a
-acetamidocinnamatea
COOMe
H2
COOMe
Rh/CF1
NHAc
NHAc
toluene/MeOH
rt, 2 h
R
R
6a-6i
8a-8i
Entry
Substrate (R)
Conv (%)
ee (%) (Config)b
1
2
3
4
5
6
7
8
9
6a (H)
99
99
99
99
99
99
99
99
99
98 (R)
98 (R)
97 (R)
97 (R)
98 (R)
98 (R)
98 (R)
98 (R)
99 (R)
6b (p-Me)
6c (o-Me)
6d (p-MeO)
6e (p-Cl)
6f (p-F)
6g (m-F)
6h (o-F)
6i (p-NO2)
OH OH
Ph
O
O
H2, Ru/CF2
a
Enamide (1 mmol), [Rh(nbd)2]BF4 (0.010 mol), ligand (0.011 mol), toluene/
Ph
Ph
Ph
>99% conv.
MeOH (2/2 mL); rt, H2 (1 atm).
b
Determined by HPLC (Chiralcel AD-H).
13
>99% ee (S,S)
12
ring. For example, both p-MeO and p-NO2 substituents gave excel-
lent enantioselectivities (entries 4 and 9, respectively). Our results
indicate that the rhodium–CF1 complex can function as a general
OH
O
O
O
H2, Ru/CF2
Ph
OEt
Ph
OEt
>99% conv.
catalyst for the asymmetric hydrogenation of substituted (Z)-a-
15
14
acetamidocinnamates giving enantiomerically pure amino acids.
Additionally, the excellent catalytic activities of rhodium–CF1
complexes towards asymmetric hydrogenations of other substi-
96% ee (S)
Scheme 2. Hydrogenation of dibenzoylmethane and ethyl benzoylacetate.
tuted alkenes, such as itaconic acid/ester and a-acetamido acrylic
acid/ester,2a further support the utilization of the rhodium-CF cat-
alysts in the hydrogenation of alkenes.
3. Conclusion
Our studies have demonstrated that the fine tuning of CF li-
gands, as rhodium- or ruthenium-complexes, can optimize (maxi-
mize) the enantioselectivities of asymmetric hydrogenations.
Compared to the original CF1, the use of sterically hindered phos-
phine CF5 significantly improves the efficiencies and enantiomeric
2.3. Hydrogenation of ketones
Ligands CF1–8 were evaluated as ruthenium complexes in
the asymmetric hydrogenation of 2-carboethoxycyclopentanone
10.8 The hydrogenation was carried out using 0.5 mol % of [Ru-
(cod)(metallyl)2]/HBr and (S,Rp)-CF ligand in EtOH under hydrogen
(10 atm) at 50 °C for 24 h. As listed in Table 3, the reactions pro-
ceeded quantitatively to afford product (R,R)-11 diastereoselec-
tively (92–97% de). The ruthenium–CF2 complex (entry 2), with a
4-o-MePh substituent, was the most effective catalyst with a high
enantioselectivity of 92% ee, whereas the rhodium–CF2 complex
excesses for the hydrogenations of
a-acetamidostyrene 7 and 2-
carboethoxycyclopentanone 10. The choice of the most suitable li-
gand was essential for substrates to obtain the highest enantiose-
lectivity.9 The sterically demanding ligand CF5 seemed to be the
ligand of choice amongst the ClickFerrophos family.
4. Experimental
4.1. General
Table 3
Enantioselective hydrogenation of 2-carboethoxycyclopentanone by
a Ru/CF
The 1H and 13C NMR spectra were recorded using a Varian Mer-
cury 300 NMR (300 MHz) spectrometer as solutions in CDCl3. The
chemical shifts are reported in d units downfield from the internal
reference, Me4Si. The optical rotations were determined by a JASCO
P-2200 instrument. The HPLC analyses were carried out on a JASCO
PU-1580 apparatus equipped with a multi-wavelength detector
(MD 2010) using chiral columns (Chiralcel AD-H, OJ-H). Prepara-
tive TLC was conducted using a 20 ꢀ 20 cm glass sheet coated with
a 2 mm thick layer of Merck Kieselgel 60 PF254. All products of
asymmetric reactions were reported compounds and characterized
by spectroscopic methods by reference to the literature.
complexa
OH
O
O
H2 (10 atm)
O
Ru/CF (0.5 mol%)
OEt
OEt
EtOH
rt, 2 h
10
11
Entry
Ligand
de (%)b
ee (%) (Config)b
1
2
3
4
5
6
8
CF1
CF2
CF3
CF4
CF5
CF6
CF8
95
94
93
92
97
93
97
84 (R,R)
92 (R,R)
85 (R,R)
48 (R,R)
90 (R,R)
89 (R,R)
88 (R,R)
4.2. Preparation of (S,Rp)-(Rp)-1-bromo-2-[(S)-1-azidoethyl]-
ferrocene 3
a
Ketone (2 mmol), [Ru(cod)(metallyl)2]/HBr(0.010 mol), ligand (0.011 mol),
A 100mL round-bottomed flask equipped with a condenser was
charged with (S,Rp)-(1Rp)-bromo-2-(1S-dimethylaminoethyl)ferrocene
EtOH (4 mL); 50 °C, H2 (10 atm).
b
Determined by GC (CP-Chirasil-Dex CB).

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H. Oki et al. / Tetrahedron: Asymmetry 20 (2009) 2185–2191
2 (1.01 g, 3.00 mmol),5 methyl iodide (0.7 mL, 12.0 mmol) and dry ace-
tone (25 mL). An aqueous solution (25 mL) of sodium azide (0.98 g,
15.0 mmol) was then added to the flask and the resulting mixture
was heated at reflux with magnetic stirring for 1 h. The mixture was
allowed to cool to room temperature and stirred overnight. The reac-
tion was quenched with water and the resulting solution was ex-
tracted with CH2Cl2 (20 ꢀ 3 mL). The combined extracts were
washed (brine), dried (MgSO4) and the solvent was removed on a ro-
tary evaporator to leave a reddish brown residue. The residue was sub-
jected to column chromatography on silica gel (hexane/ethyl
acetate = 4/1 as eluent) to give pure 3. Dark red oil; yield, 0.90 g,
methane to give pure CF2. Yellow solid; yield, 170 mg, 0.23 mmol,
77%; mp = 226 °C. ½a D25
ꢁ
¼ þ220 (c 0.32, CHCl3). 1H NMR (300 MHz,
CDCl3) d 1.24 (s, 3H), 1.93 (d, 3H, J = 6.8 Hz), 4.00 (s, 5H+1H), 4.52
(s, 1H), 4.95 (s, 1H), 6.28 (d, 1H, J = 7.6 Hz), 6.5–7.6 (m, 24H). 13C
NMR (75 MHz, CDCl3) d 19.6, 22.7, 54.0 (dd, J = 9.1 Hz, 15.8 Hz),
69.8, 70.6, 71.0 (d, J = 5.1 Hz), 71.7 (d, J = 4.6 Hz), 75.5 (d,
J = 11.8 Hz), 93.2 (d, J = 28.2 Hz), 124.1, 127.1, 127.2 (d,
J = 7.9 Hz), 127.4, 127.5 (d, J = 5.2 Hz), 127.8 (d, J = 5.2 Hz), 128.0
(d, J = 8.2 Hz), 128.3, 128.4, 128.7, 129.1 (d, J = 20.9 Hz), 129.4,
130.6, 130.9, 131.1 (d, J = 16.0 Hz), 131.5 (d, J = 4.2 Hz), 132.6 (d,
J = 19.2 Hz), 133.3, 133.8 (d, J = 4.6 Hz), 135.7 (d, J = 21.9 Hz),
137.9, 138.1 (d, J = 7.5 Hz), 140.1 (d, J = 8.1 Hz), 151.7 (d,
J = 3.5 Hz). 31P NMR (121.5 MHz, CDCl3) d ꢃ36.2 (d, J = 29.6 Hz),
ꢃ24.7 (d, J = 33.3 Hz). HRMS (ESI): calcd for C45H39FeN3P2 (M+H+)
740.2042, found 740.2078.
2.67 mmol, 90%; ½a D25
ꢁ
¼ þ74 (c 0.34, CHCl3). 1H NMR (300 MHz,
CDCl3) d = 1.67 (d, 3H, J = 6.9 Hz), 4.17 (s, 1H), 4.19 (s, 6H), 4.53 (s,
1H), 4.61 (q, 1H, J = 6.9 Hz). 13C NMR (CDCl3) d = 19.0, 55.3, 64.2,
66.5, 70.9, 71.3, 79.0, 86.0. HRMS: calcd for C12H12BrFeN3 (M+H+)
332.9560, found 332.9584.
4.5. ClickFerrophos CF12a
4.3. General procedure for the preparation of (S,Rp)-(Rp)-1-
bromo-2-{(S)-1-[4-aryl-1H1,2,3-triazol-1-yl]ethyl}ferrocene 4
Yield, 81%. Yellow solid; mp = 190–191 °C. ½a D25
¼ þ183 (c 0.31,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3) d 1.76 (d, 3H, J = 6.9 Hz), 3.86 (s,
1H), 4.06 (s, 5H), 4.48 (t, 1H, J = 2.6 Hz), 4.92 (s, 1H), 6.53 (q, 1H,
J = 6.9 Hz), 6.6–7.1 (m, 14H), 7.3–7.6 (m, 11H). 13C NMR (75 MHz,
A 100mL round-bottomed flask containing a magnetic stirring
bar was charged with 3 (156 mg, 0.47 mmol), 2-methylphenylacet-
ylene (66
lL, 0.52 mmol), t-butanol (1 mL) and water (1 mL). So-
CDCl3) d 22.2, 54.0 (dd, J = 9.3, 17.7), 69.7, 70.3, 71.0 (d,
dium ascorbate (24 mg, 0.10 mmol) was added to the flask
followed by CuSO4ꢂ5H2O (13 mg, 0.05 mmol) and the resulting
mixture was magnetically stirred for 24 h. The mixture was then
extracted with CH2Cl2 (10 ꢀ 3 mL). The combined extracts were
washed (brine), dried (MgSO4) and the solvent was removed on a
rotary evaporator to leave a yellow residue. The residue was sub-
jected to column chromatography on silica gel (hexane/ethyl ace-
tate = 2/1 as eluent) to give pure 4b (R3 = o-MeC6H4). Yellow
J = 3.8 Hz), 71.7 (d, J = 5.1 Hz), 75.2 (d, J = 10.4 Hz), 92.8 (d,
J = 26.8 Hz), 126.8, 127.0 (d, J = 12.8 Hz), 127.6 (d, J = 11.8 Hz),
127.7, 127.9 (d, J = 7.7 Hz), 128.0, 128.7 (d, J = 7.2 Hz), 129.0,
129.2 (d, J = 7.2 Hz), 131.1 (d, J = 16.9), 131.8 (d, J = 18.5 Hz),
133.2 (d, 23.1 Hz), 135.5 (d, J = 21.2 Hz), 137.4 (d, J = 9.4 Hz),
139.8 (d, J = 7.6 Hz), 151.8. 31P NMR (121.5 MHz, CDCl3) d ꢃ35.1
(d, J = 34.4 Hz), ꢃ23.8 (d, J = 34.4 Hz). HRMS (ESI): cacld for
C44H37FeN3P2 (M+H+) 726.1875, found 726.1865.
solid; yield, 185 mg, 0.41 mmol, 87%; mp = 118 °C. ½a D25
¼ þ118
ꢁ
(c 0.34, CHCl3). 1H NMR (300 MHz, CDCl3) d = 2.00 (d, 3H,
J = 7.0 Hz), 2.37 (s, 3H), 4.21 (s, 5H+1H), 4.39 (s, 1H), 4.50 (s, 1H),
5.86 (q, 1H, J = 7.0 Hz), 7.25–7.34 (m, 3H), 7.39 (s, 1H), 7.6–7.7
(m, 1H). 13C NMR (CDCl3) d 20.6, 21.3, 55.0, 65.0, 66.9, 71.1, 71.5,
79.1, 84.7, 120.3, 125.8, 127.8, 128.7, 130.0, 130.6, 135.4, 146.1.
HRMS (ESI): calcd for C21H20BrFeN3 (M+H) 450.0265, found
450.0269.
4.6. ClickFerrophos CF3
Yield, 74%. Yellow solid; mp = 236 °C. ½a D25
¼ þ175 (c 0.33,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3) d 1.75 (d, 3H, J = 7.0), 3.85 (s,
1H), 4.05 (s, 5H), 4.48 (s, 1H), 4.94 (s, 1H), 6.12 (t, 1H, J = 7.5 Hz),
6.5–7.11 (m, 14H), 7.38–7.60 (m, 10H). 13C NMR (75 MHz, CDCl3)
d
22.1, 54.1 (dd, J = 9.9 Hz, 15.7 Hz), 69.8, 70.5, 71.2 (d,
Compound 4c: Yellow solid; yield, 85%; mp = 78 °C.
J = 2.5 Hz), 71.8 (d, J = 5.2 Hz), 75.3 (d, J = 11.3 Hz), 93.0 (d,
J = 25.7 Hz), 114.6 (d, J = 21.9 Hz), 119.6 (d, J = 15.5 Hz), 122.7 (d,
J = 3.5 Hz), 127.1, 127.5 (d, J = 7.1 Hz), 127.9 (d, J = 5.5 Hz), 128.1
(d, J = 8.0 Hz), 128.4, 128.5 (d, J = 7.4 Hz), 129.2, 129.3, 129.4,
131.0, 131.2 (d, J = 11.5 Hz), 132.1 (d, J = 5.5 Hz), 132.3, 132.6 (d,
J = 20.3 Hz), 133.6 (d, J = 2.9 Hz), 133.8 (d, J = 2.3 Hz), 135.7 (d,
J = 21.3 Hz), 137.6 (d, 8.6 Hz), 140.6 (d, J = 9.1 Hz), 146.0 (d,
J = 4.0 Hz), 159.8 (d, J = 247.6 Hz). 31P NMR (121.5 MHz, CDCl3) d
ꢃ34.9 (d, J = 40.7 Hz), ꢃ24.0 (d, J = 40.7 Hz). 19F NMR (282 MHz,
CDCl3) d ꢃ110.9 (s). HRMS (ESI): calcd for C44H36FeFN3P2 (M+H+)
743.1719, found 743.1712.
½
a 2D5
ꢁ
¼ þ116 (c 0.34, CHCl3). 1H NMR (300 MHz, CDCl3) d = 2.06
(d, 3H, J = 7.0 Hz), 4.25 (s, 5H+1H), 4.44 (s, 1H), 4.53 (s, 1H), 5.91
(q, 1H, J = 7.0 Hz), 7.03–7.26 (m, 3H), 7.68 (s, 1H), 8,24–8.29 (m,
1H). 13C NMR (CDCl3) d 20.8, 55.3, 65.0, 66.9, 71.2, 71.5, 79.1,
84.6, 115.4 (d, J = 21.6 Hz), 118.7 (d, J = 12.2 Hz), 121.0 (d,
J = 12.8 Hz), 124.4 (d, J = 3.1 Hz), 127.6 (d, J = 3.6 Hz), 128.9 (d,
J = 8.4 Hz), 140.3 (d, J = 1.7 Hz), 159.0 (d, J = 247.6 Hz). 19F NMR
(282 MHz, CDCl3) d ꢃ115.1 (s). HRMS (ESI): calcd for C20H17BrFeN3
(M+H) 454.0014, found 454.0069.
4.4. General procedure for preparation of ClickFerrophos CF1–CF7
4.7. ClickFerrophos CF42c
A 20 mL Schlenk tube containing a magnetic stirring bar was
charged with triazole ferrocene 4b (135 mg, 0.30 mmol) and dry
THF (3 mL) under a slight pressure of nitrogen. The flask was
Yield, 73%. Yellow solid; mp = 167–168 °C. ½a D25
¼ þ95 (c 0.34,
ꢁ
CHCl3). 1H NMR (300 MHz, CDCl3) d 1.61 (d, 3H, J = 6.8 Hz), 3.81
(s, 1H), 4.10 (s, 5H), 4.45 (t, 1H, J = 2.6 Hz), 4.90 (s, 1H), 6.30 (m,
1H), 6.6–7.6 (m, 21H). 13C NMR (CDCl3) d 21.6, 53.9 (dd, J = 9.2,
11.7), 69.8, 70.2, 70.8 (d, J = 3.7 Hz), 71.8 (d, J = 4.9 Hz), 75.3 (d,
J = 10.2 Hz), 92.4 (d, J = 26.0 Hz), 127.0, 127.7 (d, J = 5.5 Hz), 127.9
(d, J = 8.1 Hz), 128.1 (d, J = 6.8 Hz), 128.3 (d, J = 7.2 Hz), 128.7,
128.8, 129.5 (d, J = 42.5 Hz), 130.9 (d, J = 16.9 Hz), 132.4 (d,
J = 18.6), 133.1 (d, J = 7.2), 133.4 (d, J = 2.5 Hz), 133.5 (d, J = 7.9),
134.0 (d, 21.5 Hz), 135.4 (d, J = 21.1 Hz), 137.1 (d, J = 8.5 Hz),
138.6, 139.1 (d, J = 9.6 Hz). 31P NMR (121.5 MHz, CDCl3) d ꢃ40.4
(d, J = 37.0 Hz), ꢃ24.5 (d, J = 37.0 Hz). HRMS (ESI): calcd for
C38H33FeN3P2 (M+H+) 650.1577, found 650.1573.
cooled at ꢃ78 °C, and
0.8 mmol, 1.6 M) was then added using a syringe through the sep-
tum with magnetic stirring. After 10 min, Ph2PCl (140 L,
a hexane solution of n-BuLi (0.5 mL,
l
0.8 mmol) was injected into the mixture at ꢃ78 °C. When the addi-
tion was completed, the mixture was allowed to warm to room
temperature and then stirred for an additional 2 h. The reaction
was quenched with saturated NH4Cl, and the solution was then ex-
tracted with diethyl ether (30 mL ꢀ 3). The combined extracts
were washed (brine), dried (Na2SO4), filtered and the solvent was
removed on a rotary evaporator to leave a yellow solid. The crude
product was purified by recrystallization from hexane/dichloro-