Chiral, Sterically Demanding N-Heterocyclic Carbenes Fused into a Heterobiaryl Skeleton: Design, Synthesis, and Structural Analysis

Article abstract of DOI:10.1021/acs.organomet.5b00046

A series of Cu(I), Ag(I), and Au(I) complexes incorporating a new family of imidazopyridin-3-ylidene ligands substituted by a diphenylpyrrolidino group at N(1) and aryl groups at C(5) has been synthesized and their structures determined by X-ray diffracti

Full text of DOI:10.1021/acs.organomet.5b00046

Article
pubs.acs.org/Organometallics
Chiral, Sterically Demanding N‑Heterocyclic Carbenes Fused into a
Heterobiaryl Skeleton: Design, Synthesis, and Structural Analysis
‡
†
†
†
,†
‡
́
Manuela Espina, Ivan Rivilla, Ana Conde, M. Mar Díaz-Requejo, Pedro J. Perez,* Eleuterio Alvarez,
́
Rosario Fernandez,§ and Jose M. Lassaletta*,‡
́
́
†Laboratorio de Catal
CIQSO-Centro de Investigacion
‡Instituto Investigaciones Químicas (CSIC-USe), Avda. Amer
§Departamento de Química Organ
ica, C/Prof. García Gonzal
́
isis Homogen
́
ea, Departamento de Química y Ciencia de los Materiales, Unidad Asociada al CSIC,
́
en Química Sostenible, Universidad de Huelva, Campus de El Carmen, 21007 Huelva, Spain
́
ico Vespucio, 49, 41092 Sevilla, Spain
́
ez, 1, 41012 Sevilla, Spain
́
S
* Supporting Information
ABSTRACT: A series of Cu(I), Ag(I), and Au(I) complexes
incorporating a new family of imidazopyridin-3-ylidene ligands
substituted by a diphenylpyrrolidino group at N(1) and aryl
groups at C(5) has been synthesized and their structures
determined by X-ray diffraction analysis. This structural study
has revealed an extremely high steric protection of the metal
center by the bulky heterobicyclic carbenes, while the inversion
at the exocyclic N(sp3) atom provides a remarkable flexibility.
Scheme 1. Heterobicyclic Carbenes in a Biaryl Skeleton
INTRODUCTION
■
The design of new ligands with tailored steric and electronic
properties is one of the essential tools for the development of
new catalytic reactions and/or the resolution of activity or
(stereo)selectivity issues. In particular, very strong ligand effects
have been observed in Au(I)1 and Ag(I)2 catalyzed reactions,
where electron-rich phosphorus-based ligands in a biaryl
framework (Figure 1) constitute one of the most successful
system in a heterobicyclic skeleton. In particular, NHCs derived
from the imidazo[1,5-a]pyridin-3-ylidene II7 and the 1,2,4-
triazolo[4,3-a]- pyridin-3-ylidene III8 moieties have been
developed and their transition metal complexes have been
applied in catalysis.9 We have now focused on merging the
successful design elements of Buchwald’s biaryl phosphine X-
PHOS ligands with the excellent catalytic properties of NHCs
and, at the same time, incorporate a chiral element for potential
applications in asymmetric catalysis. On this basis, we envisaged
that the combination of the strategies leading to I and II/III,
i.e., the introduction of C2-symmetric cyclic N,N-dialkylamino
groups into a heterobicyclic framework, would result in a
system IV, which, incorporating aryl groups at position 5,
should closely mimic the privileged X-PHOS architecture. It is
worth highlighting that the inclusion of the diamino carbene in
the heterobicyclic system avoids N−C(carbene) rotations,
Figure 1. Biaryl phosphine ligands.
families of ligands. The dialkyl biphenylphosphine family (X-
PHOS) developed by Buchwald and co-workers,3 on one side,
and the chiral C2-symmetric bidentate phosphines such as
BINAP3 and functionalized analogues (including BIPHEP,
SEGPHOS, GARPHOS, DIFLUOROPHOS, etc.),4 as well as
heterobidentate X-MOP5 ligands benefit from a biaryl frame-
work that provides a considerable steric protection by the
aromatic shield. We have been interested in the design and
applications of new families of N-heterocyclic carbene (NHC)
ligands, an area where we have initially reported on the
introduction of N-dialkylamino groups as a strategy to
incorporate chirality into NHCs of type I6 (Scheme 1). Our
work has also shown that the electronic properties of these
ligands can be tuned by inclusion of the diamino carbene
Received: January 20, 2015
Published: March 20, 2015
© 2015 American Chemical Society
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Article
a
thereby fixing the direction of the σ-orbital parallel to the biaryl
axis. In this contribution, we disclose the results collected on
the basis of this rational design from which a series of coinage
metal complexes have been prepared and characterized. The
effect of the ligand onto the pocket around the metal center has
been investigated providing general features about the steric
protection that bulky heterobicyclic carbene ligands infer on
those complexes.
Table 1. Synthesis of Imidazopyridinium Salts 7a−h
b
b
4
Ar
6 (%)
method
7 (%)
4a
4b
4c
4d
4e
4f
Ph
6a (59)
6b (90)
6c (76)
6d (78)
6e (59)
6f (77)
6g (64)
6h (84)
A
A
A
A
A
A
A
7a (74)
7b (83)
7c (86)
7d (80)
7e (73)
7f (89)
7g (80)
7h (86)
4-F-C6H4
4-OMe-C6H4
4-tBu-C6H4
3,5-(CF3)2-C6H3
2,6-(OMe)2-C6H3
Mes
4g
4h
RESULTS AND DISCUSSION
■
2,4,6-(iPr)3-C6H2
B
Synthesis of Ligand Precursors. The synthesis of ligands
IV and their metal complexes is envisaged by deprotonation or
direct metalation of the corresponding imidazo[1,5-a]-
pyridinium salts 7. The synthesis of the latter was planned
through a two-step sequence route: (a) base-promoted
alkylation of N-[(2S,5S)-2,5-diphenylpyrrolidin-1-yl]formamide
510 with 6-aryl-2-bromomethylpyridines 4 and (b) cyclization
of the resulting N-formylhydrazines 6 (Scheme 2). The
a
b
Reactions performed at 1−6 mmol scale. Isolated yields after
column chromatography.
subsequent transmetalations to access the corresponding gold
complexes 9a−h. Finally, copper−NHC complexes 10a,b,f−h
were obtained after deprotonation of the azolium salts 7 with
KOtBu and coordination of the resulting free carbenes to CuCl.
In order to have a reference compound to evaluate the steric
and structural effects by the chiral diphenylpyrrolidino group
compared with a very bulky group, we decided to synthesize
also the N-adamantyl analogues, substituted at C5 by the bulky
2,4,6-triisopropylphenyl group (Scheme 4). A similar approach
starting from 4h and N-(1)-adamantyl formamide 11 provided
intermediate 12 in 70% yield. As for 6h, the cyclization of this
bulky formamide worked best using Tf2O/Et3N as the
condensation agent. The resulting azolium 13 was then
transformed into the silver and gold complexes 14 and 15
using the same procedures as for the dialkylamino-substituted
derivatives.
Scheme 2. Synthesis of the Ligand Precursors
Structural Analysis. In addition to the azolium 7b, silver
and gold complexes 8a,b,e,h and 6a,h could be crystallized as
single crystals and their structures were analyzed by X-ray
diffraction. As it was previously observed in 1,3-Bis(N,N-
dialkylamino)-imidazolin-2-ylidenes5 and N-dialkylamino-N′-
a
alkylimidazol-2-ylidenes,5b the X-ray structures of compounds 8
and 9 revealed in general no conjugation between the
dialkylamino group and the diaminocarbene electronic system,
as deduced by the degree of pyramidalization observed at the
exocyclic nitrogen and the low coplanarity between the
pyrrolidine ring and the heterocycle (expressed by the
C2(5)−N3−N2−C1 dihedral angles). The steric bulk of the
NHC ligands in these structures were estimated using the
percent buried volume (%VBur) descriptor introduced by
Clavier and Nolan,13 using the SambVca software developed
by Cavallo and co-workers.14,15 In all cases, the steric bulkiness
proved to be exceptionally high, with %VBur values ranging from
41.5 to a record 59.9% (Figure 2). Not surprisingly, with the
exception of 8e, the high steric demand of the ligands favor a
linear coordination mode.16
The structure of the azolium salt 7b exhibits some interesting
singularities. The %VBur values of 58.0 and 58.2 observed for
the two independent molecules in the molecular cell of azolium
7b are, in average, the highest within the series, as the smaller H
atom at C(1) allows nonpermitted conformations in other
cases. In particular, the heterobiaryl moiety can reach
conformations closer to coplanarity [dihedral angles of ca.
44° for both 7b(1) and 7b(2) were observed], and one of the
molecules [7b(1)] also showed a significant conjugation
between the pyrrolidine ring and the heterocycle, as inferred
from the coplanarity of both rings and the low pyramidalization
of the exocyclic N(sp3) atom. The structures of metal
complexes 8 and 9 also showed a remarkable degree of
required bromomethylpyridines 4 were readily prepared from
the parent alcohols 3, obtained by Suzuki−Miyaura coupling of
6-bromopyridine methanol 1 and aryl boronic acids (Ar = 4-
tBu-C6H4, 3,5-(CF3)2-C6H3, and Mes) or by reduction of
aldehydes 2 [Ar = 4-F-C6H4, 4-OMe-C6H4, and 2,4,6-(iPr)3-
C6H2]. Following this simple sequence, a series of 5-aryl-N-
[(2S,5S)-2,5-diphenylpyrrolidino]-imidazo[1,5-a]pyridinium
chlorides 7a−h were obtained via formylhydrazines 6a−h in
satisfactory yields (Table 1). The cyclization was performed by
treatment with POCl3 except for the most hindered substrate
(Ar = 2,4,6-(iPr)3-C6H2) 7h, which was best obtained using
Tf2O/Et3N as the condensation agent.11 In both cases the
azolium products were transformed into the chlorides 7a−h
after anion exchange (Dowex 22-Cl). The azolium 7b was
crystallized, and its structure was analyzed by X-ray diffraction
studies (Figure 2).
Synthesis of Metal Complexes. With the ligand
precursors in hand, we started the metalation studies using
the method developed by Lin and co-workers12 for the
synthesis of silver carbenes. Thus, treatment of azolium salts
7a−h with Ag2O smoothly afforded the expected complexes
8a−h in good to excellent yields (Scheme 3 and Table 2).
These complexes were used as carbene transfer agents in
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Figure 2. X-ray structures of 7b, 8a, 8b, 9b, 8e, 8h, 9h, 14, and 15. Chloride counteranions (for 7b) and H atoms (except those involved in CH−
metal interactions) are omitted for clarity.
flexibility:17 although the coplanarity of the heterobiaryl unit is
obviously more hindered (dihedral angles >64° were observed
in all cases), there is still some flexibility associated with N−N
bond rotations [see, for instance, structures of 9h(1) versus
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Scheme 3. Metalation Reactions
Figure 3. Conformational flexibility in the diphenylpyrrolidino group.
8a(2) and 8b(2) are, to the best of our knowledge, the highest
reported for any monodentate NHC ligand so far.18 The
folding in this conformation also results in a weak but
significant C(2)H−Ag interaction (distances, Ag(2)−H(46)
of 2.57 Å and Ag(1)−H(17) of 2.56 Å). Even the
triisopropylphenyl derivatives 8h and 9h, with the pyrrolidine
N-pyramidalized in the less hindered pseudo syn-conformation,
present lower %VBur values (between 51.5 and 53.6%),
demonstrating that the effect of the N(3) Walden inversion
is more determining than the substitution pattern at the aryl
group at C(5). Finally, the N-adamantyl silver and gold
analogues 11 and 12 are also crystalline compounds, suitable
for X-ray diffraction analysis. The comparison of these
structures with the diphenylpyrrolidine analogues 5h and 6h
revealed that the diphenylpyrrolidine is a very bulky group,
providing quantifiable levels of steric bulk similar or higher than
the adamantyl group, even in the less demanding conformation
(these structures are in all cases characterized by the less
hindered Walden conformation in the pyrrolidine ring).
Table 2. Synthesis of Complexes 8, 9, and 10
Ar
8 (%)
9 (%)
10 (%)
Ph
8a (98)
8b (97)
8c (98)
8d (99)
8e (78)
8f (97)
8g (98)
8h (80)
9a (67)
9b (97)
9c (74)
9d (74)
9e (90)
9f (81)
9g (68)
9h (95)
10a (59)
10b (55)
4-F-C6H4
4-OMe-C6H4
4-tBu-C6H4
3,5-(CF3)2-C6H3
2,6-(OMe)2-C6H3
Mes
10f (50)
10g (60)
10h (55)
2,3,6-(iPr)3-C6H2
Scheme 4. Synthesis of N-Adamantyl Derivatives
CONCLUSIONS
■
In summary, the introduction of the (2S,5S)-2,5-diphenylpyr-
rolidino group into the N(2) position of 5-aryl substituted
imidazo[1,5-a]pyridin-3-ylidenes provides an NHC ligand
family that mimics the privileged architecture of Buchwald’s
biaryl phosphines. Moreover, the synthesis and structural
analysis of several coinage metal complexes containing these
ligands reveal exceptionally high levels of steric bulk, reaching
record %VBur values within the NHC family of ligands.
Moreover, this structural study reveals also a considerable
level of flexibility associated with the conformational changes in
the pyrrolidine ring.
EXPERIMENTAL SECTION
■
General Considerations. Air- and moisture-sensitive manipu-
lations were carried out under an argon atmosphere using standard
Schlenk techniques. All solvents were dried using a Solvent
Purification System (Innovative Technologies). 1H NMR spectra
were recorded at 300, 400, or 500 MHz; 13C NMR spectra were
recorded at 75, 100, or 125 MHz with the solvent peak used as the
internal reference. Column chromatography was performed on silica
gel (Merck Kieselgel 60). Analytical TLC was performed on aluminum
backed plates (1.5 × 5 cm) precoated (0.25 mm) with silica gel
(Merck, Silica Gel 60 F254). Compounds were visualized by exposure
to UV light or by dipping the plates in a solution of 5%
(NH4)2Mo7O24·4H2O in 95% EtOH (w/v) followed by heating.
The following starting materials were purchased from commercial
sources and used without further purification: 6-(bromopyridin-2-
yl)methanol (1), phenylboronic acid, 4-(tert-butyl)phenyl)boronic
acid, [3,5-bis(trifluoromethyl)phenyl]boronic acid, (2,6-
dimethoxyphenyl)boronic acid, mesitylboronic acid, 6-(4-fluorophen-
yl)-2-pyridinecarboxaldehyde (2b), and 6-(4-methoxyphenyl)-2-pyr-
idinecarboxaldehyde (2c). N-(Adamantyl)-formamide19 and 1-amino-
9h(2)] and/or Walden inversions at N(3) resulting in
structures with the N lone pair oriented in syn- or anti-
periplanar arrangements with respect to the C(carbene)−metal
bond. Thus, in several cases the two independent molecules in
the molecular cell [8a(1) vs 8a(2) and 8b(1) vs 8b(2)] or the
two ligands in the same molecule (8e) show a dramatic increase
of the bulkiness as a consequence of that inversion, as
represented in Figure 3. Thus, the %VBur steric descriptor
rises from 42.8 to 59.5% in 5a, from 44.2 to 59.9% in 8b, and
from 47.3 to 54.7% in 8e. Remarkably, the values recorded for
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(2S,5S)-2,5-diphenylpyrrolidine10 were prepared according to liter-
ature procedures.
and quenched by addition of saturated NaHCO3 solution (40 mL).
The aqueous layer was extracted with Et2O (3 × 10 mL), and the
combined organic layer was washed with brine and dried over
anhydrous Na2SO4. The solvent was removed under reduced pressure,
and the residue was purified by flash chromatography on silica gel
(15:1 cyclohexane/Et2O) to afford 350 mg (77%) of 2h as a light
yellow crystalline solid. 1H NMR (500 MHz, CDCl3) δ 10.08 (s, 1H),
Cross-Coupling of 6-(Bromopyridin-2-yl)methanol 1 with
Aryl Boronic Acids. General Procedure for the Synthesis of
3a,d−g. Compound 1 (5−10 mmol) was added to a solution of
Pd(PPh3)4 (3 mol %) in DME (20 mL), and the mixture was stirred
for 30 min. The aryl boronic acid (1.4 equiv) and a solution of 2 M
Na2CO3 (2 equiv) were added, and the mixture was stirred at 90 °C
overnight. Upon cooling, the organic layer was collected and the water
layer was extracted with CH2Cl2 (3 × 10 mL). The combined organic
layer was dried over Na2SO4, concentrated, and the residue was
purified by flash chromatography on silica gel. Starting materials,
yields, solvents used for chromatography, and characterization data for
compounds 3a,d−g are as follows.
3
7.95−7.88 (m, 2H), 7.50 (d, JHH = 7.5 Hz, 1H), 7.09 (s, 2H), 2.93
3
3
(hept, JHH = 6.5 Hz, 1H), 2.42 (hept, JHH = 7.0 Hz, 2H), 1.27 (d,
3JHH = 7.0 Hz, 6H), 1.11 (d, JHH = 7.0 Hz, 6H), 1.08 (d, JHH = 6.5
3
3
Hz, 6H). 13C NMR (125 MHz, CDCl3) δ 194.0, 160.9, 152.4, 149.3,
146.1, 136.6, 129.3, 120.9, 119.3, 114.1, 34.4, 30.4, 24.1, 24.0, 23.9.
HRMS (CI) m/z calcd for C21H27NO 309.2093, found 309.2097. Mp:
210−211 °C.
[(6-Phenyl)pyridin-2-yl]methanol (3a).20 From 1 (1.00 g, 5.10
mmol) and phenylboronic acid (0.87 g, 7.14 mmol), the general
procedure was applied, and the product was purified by flash
chromatography (1:3 AcOEt/cyclohexane) to yield 0.77 g (82%) of
know 3a as a white solid.
General Procedure for the Aldehyde Reduction. Synthesis
of Compounds 3b,c,h. NaBH4 (2 equiv) was added to a cooled (0
°C) solution of 2b,c,h (ca. 5 mmol) in MeOH (50 mL) and the
mixture was stirred at room temperature for 10 h. Saturated NH4Cl
(30 mL) and K2CO3 (1 equiv) were added and the mixture was stirred
for 15 min. The solids were removed by filtration and washed with
CH2Cl2 (3 × 15 mL). The combined organic layer was washed with
brine (15 mL) and dried with Na2SO4. The solvent was removed
under reduced pressure and the resulting residue was purified by flash
chromatography on silica gel. Starting materials, yields, solvents used
for chromatography and characterization data for compounds 3b,c,h
are as follows:
[6-(4-tert-Butylphenyl)pyridin-2-yl]methanol (3d).21 From 1 (1.00
g, 5.10 mmol) and (4-(tert-butyl)phenyl)boronic acid (1.27 g, 7.14
mmol), the general procedure was applied, and the product was
purified by flash chromatography (1:4 AcOEt/n-hexane) to yield 1.19
g (97%) of 3d as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.99 (d,
3JHH = 8.7 Hz, 2H), 7.76 (t, 3JHH = 7.8 Hz, 1H), 7.65 (d, 3JHH = 7.8 Hz,
1H), 7.53 (d, 3JHH = 8.7 Hz, 2H), 7.15 (d, 3JHH = 7.8 Hz, 1H), 4.83 (s,
2H), 4.23 (s, 1H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
158.4, 156.0, 152.3, 137.3, 135.9, 126.5, 125.6, 118.6, 118.3, 63.8, 34.6,
31.2. HRMS (CI) m/z calcd for C16H20NO (M + H) 242.1545, found
242.1539. Mp: 54−56 °C.
[6-(4-Fluorophenyl)pyridin-2-yl]methanol (3b).24 From 2b (1.08
g, 5.37 mmol), the general procedure was applied, and the product was
purified by flash chromatography (1:3 AcOEt/n-hexane) to yield 1.07
g (97%) of known 3b as a white solid. 1H NMR (400 MHz, CDCl3) δ
3
3
[6-(3,5-Bis(trifluoromethyl)phenyl)pyridin-2-yl]methanol (3e).
From 1 (0.90 g, 4.57 mmol) and [3,5-bis(trifluoromethyl)phenyl]-
boronic acid (1.65 g, 6.4 mmol), the general procedure was applied,
and the product was purified by flash chromatography (1:5 AcOEt/n-
8.00−7.92 (m, 2H), 7.71 (t, JHH = 7.8 Hz, 1H), 7.56 (d, JHH = 7.8
Hz, 1H), 7.16−7.08 (m, 3H), 4.78 (s, 2H), 4.18−3.85 (sa, 1H). 13C
1
NMR (100 MHz, CDCl3) δ 163.7 (d, JCF3 = 248.8 Hz), 158.8, 155.2,
137.7, 135.0 (d, 4JCF = 3.8 Hz), 128.8 (d, JCF = 8.5 Hz), 118.8, 115.7
1
2
hexane) to yield 1.37 g (93%) of 3e as a white solid. H NMR (400
(d, JCF = 21.7 Hz), 64.1.
3
[6-(4-Methoxyphenyl)pyridin-2-yl]methanol (3c).25 From 6-(4-
methoxyphenyl)picolinaldehyde (1.09 g, 5.12 mmol), the general
procedure was applied, and the product was purified by flash
chromatography (1:2 AcOEt/n-hexane) to yield 1.00 g (90%) of 3c
as a white solid. H NMR (400 MHz, CDCl3) δ 7.95 (d, JHH = 8.5
Hz, 2H), 7.67 (t, 3JHH = 7.6 Hz, 1H), 7.54 (d, 3JHH = 7.6 Hz, 1H), 7.06
(d, 3JHH = 7.6 Hz, 1H), 6.97 (d, 3JHH = 8.5 Hz, 2H), 4.76 (s, 2H), 4.13
(sa, 1H), 3.84 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 160.6, 158.2,
155.6, 137.2, 131.3, 128.0, 118.1, 117.8, 114.0, 63.8, 55.2. HRMS (CI)
m/z calcd for C13H13NO2 215.0946, found 215.0946.
MHz, CDCl3) δ 8.44 (s, 2H), 7.91 (s, 1H), 7.83 (t, JHH = 7.8 Hz,
1H), 7.70 (d, 3JHH = 7.8 Hz, 1H), 7.31 (d, 3JHH = 7.8 Hz, 1H), 4.84 (s,
2H), 3.67 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 159.6, 152.9,
2
1
140.7, 137.8, 132.0 (q, JCF = 33.1 Hz), 126.8, 123.2 (q, JCF = 271.0
Hz), 122.5, 120.3, 119.2, 64.1. HRMS (CI) m/z calcd for
(C14H10F6NO (M + H) 322.0667, found 322.0675. Mp: 93−95 °C.
[6-(2,6-Dimethoxyphenyl)pyridin-2-yl]methanol (3f). From 1
(2.00 g, 10.64 mmol) and (2,6-dimethoxyphenyl)boronic acid (2.70
g, 14.89 mmol), the general procedure was applied, and the product
was purified by flash chromatography (3:1 AcOEt/cyclohexane) to
yield 2.30 g (88%) of 3f as a white solid. 1H NMR (400 MHz, CDCl3)
δ 7.74−7.59 (m, 1H), 7.56−7.43 (m, 1H), 7.30 (t, 3JHH = 8.4 Hz, 1H),
1
3
(6-(2,4,6-Triisopropylphenyl)pyridin-2-yl)methanol (3h). From 2h
(1.70 g, 5.50 mmol), the general procedure was applied, and the
product was purified by flash chromatography (1:9 AcOEt/toluene) to
yield 1.15 g (67%) of 3h as a white solid. 1H NMR (400 MHz,
3
3
7.18 (dd, JHH = 10.9, 7.7 Hz, 1H), 6.63 (d, JHH = 8.4 Hz, 2H), 4.76
(s, 2H), 3.87 (s, 1H), 3.69 (s, 6H). 13C NMR (100 MHz, CDCl3) δ
158.4, 157.9, 153.2, 136.3, 131.9, 129.7, 128.5, 124.7, 118.7, 118.4,
104.2, 64.2, 55.9. HRMS (CI) m/z calcd for C14H16NO3 (M + H)
246.1130, found 246.1122. Mp: 121−123 °C.
3
3
CDCl3) δ 7.74 (t, JHH = 7.7 Hz, 1H), 7.20 (dd, JHH = 7.7, 3.0 Hz,
3
2H), 7.09 (s, 2H), 4.81 (s, 2H), 4.02 (s, 1H), 2.95 (hept, JHH = 6.9
Hz, 1H), 2.46 (hept, 3JHH = 6.9 Hz, 2H), 1.30 (d, 3JHH = 6.9 Hz, 6H),
(6-Mesitylpyridin-2-yl)methanol (3g).22 From 1 (1.00 g, 5.10
mmol) and mesitylboronic acid (1.17 g, 7.14 mmol), the general
procedure was applied, and the product was purified by flash
chromatography (1:3 AcOEt/cyclohexane) to yield 1.15 g (99%) of
3f as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (t, 3JHH = 7.7
1.11 (dd, JHH = 7.7, 6.9 Hz, 12H). 13C NMR (100 MHz, CDCl3) δ
3
159.2, 158.5, 149.2, 146.6, 136.6, 136.1, 123.9, 121.1, 118.5, 64.2, 34.7,
30.7, 24.4, 24.4, 24.4. HRMS (CI) m/z calcd for C21H30NO (M + H)
312.2327, found 312.2328. Mp: 164−166 °C.
Synthesis of 2-Bromomethylpyridines 4a−h. General Pro-
cedure. To a cooled (0 °C) solution of 3a−h (typically 5 mmol) in
dry CH2Cl2 (10 mL/mmol) were added CBr4 (1.2 equiv) and PPh3
(1.2 equiv), and the mixture was stirred for 3 h. The solvent was
removed in vacuo and the residue was purified by flash
chromatography on silica gel. Starting materials, yields, solvents used
for chromatography, and characterization data for compounds 4a−h
are as follows.
3
3
Hz, 1H), 7.16 (d, JHH = 7.7 Hz, 1H), 7.12 (d, JHH = 7.7 Hz, 1H),
6.96 (s, 2H), 4.79 (s, 2H), 4.04 (s, 1H), 2.34 (s, 3H), 2.03 (s, 6H). 13C
NMR (100 MHz, CDCl3) δ 158.6, 158.6, 137.6, 137.3, 136.8, 135.7,
128.3, 123.2, 118.1, 63.9, 20.9, 20.1. HRMS (CI) m/z calcd for
C15H17NO 227.1310, found 227.1302. Mp: 126−128 °C.
6-(2,4,6-Triisopropylphenyl)picolinaldehyde 2h. This compound
was prepared by a modification of the known procedure:23 tBuLi (1.7
M in pentane, 1.5 mL, 2.5 mmol) was added to a cooled (−78 °C)
solution of 2-bromo-6-(2,4,6-triisopropylphenyl)pyridine (533 mg,
1.48 mmol) in anhydrous THF (10 mL). The reaction mixture was
allowed to warm to room temperature and stirred for 2 h. DMF (0.34
mL, 4.44 mmol) was added, and the mixture was stirred for 12
additional hours, then cooled to −40 °C, diluted with Et2O (40 mL),
2-(Bromomethyl)-6-phenylpyridine (4a).26 From 3a (0.77 g, 4.17
mmol), the general procedure was applied, and the crude mixture was
purified by flash chromatography (1:4 AcOEt/cyclohexane) to yield
1
0.94 g (91%) of known 4a as a white solid. H NMR (400 MHz,
3
CDCl3) δ 8.06−7.98 (m, 2H), 7.76 (t, JHH = 7.8 Hz, 1H), 7.64 (d,
3JHH = 7.8 Hz, 1H), 7.52−7.37 (m, 4H), 4.64 (s, 2H). 13C NMR (100
1332
DOI: 10.1021/acs.organomet.5b00046
Organometallics 2015, 34, 1328−1338

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Article
MHz, CDCl3) δ 157.1, 156.6, 138.8, 137.6, 129.1, 128.7, 126.9, 121.6,
119.6.
30.8, 24.6, 24.5, 24.4. HRMS (CI) m/z calcd for C21H28NBr (M + H)
374.1883, found 374.1458. Mp: 179−181 °C.
Synthesis of N-[(2S,5S)-2,5-Diphenylpyrrolidin-1-yl]formamide
(5). Acetic formic anhydride (1.18 g, 13.36 mmol) was added
dropwise over 10 min to a solution of 1-amino-(2S,5S)-2,5-
diphenylpyrrolidine (2.12 g, 8.9 mmol) in THF (30 mL), and the
mixture was stirred for 1 h at room temperature. The solvent was
removed under reduced pressure, and the residue was purified by flash
chromatography on silica gel (1:2 EtOAc/n-hexane to afford 2.11 g
2-(Bromomethyl)-6-(4-fluorophenyl)pyridine (4b). From 3b (1.00
g, 4.92 mmol), the general procedure was applied, and the crude
mixture was purified by flash chromatography (1:3 AcOEt/cyclo-
1
hexane) to yield 1.20 g (91%) of 4b as a white solid. H NMR (400
3
MHz,CDCl3) δ 8.15−7.90 (m, 2H), 7.74 (t, JHH = 7.8 Hz, 1H), 7.59
(dd, 3JHH = 7.8, 0.6 Hz, 1H), 7.38 (dd, 3JHH = 7.7, 0.7 Hz, 1H), 7.22−
7.07 (m, 2H), 4.61 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 163.72 (d,
1
4
1JCF = 248.9 Hz), 156.8, 156.2, 137.9, 135.1 (d, JCF = 3.3 Hz), 128.9
(89%) of 5 as a crystalline solid. H NMR (400 MHz, CDCl3) δ 7.91
(d, 3JHH = 10.8 Hz, 1H), 7.44−7.27 (m, 10H), 5.73 (d, 3JHH = 10.8 Hz,
1H), 4.32−4.19 (m, 2H), 2.64−2.48 (m, 2H), 2.21−2.07 (m, 2H). 13C
NMR (100 MHz, CDCl3) δ 165.6, 139.3, 128.7, 128.3, 128.0, 68.1,
30.1. HRMS (CI) m/z calcd for C17H19N2O (M + H) 267.1497, found
3
2
(d, JCF = 8.4 Hz), 121.8, 119.4, 115.7 (d, JCF = 21.5 Hz), 34.2.
2-(Bromomethyl)-6-[(4-methoxy)phenyl]pyridine (4c). From 3c
(1.15 g, 5.32 mmol), the general procedure was applied, and the crude
mixture was purified by flash chromatography (1:3 AcOEt/cyclo-
267.1499. [α]20 −242.3 (c, 0.8, CHCl3). Mp: 126−129 °C. The
1
D
hexane) to yield 1.28 g (87%) of 4c as a white solid. H NMR (400
MHz, CDCl3) δ 8.01−7.95 (m, 2H), 7.71 (t, 3JHH = 7.8 Hz, 1H), 7.57
enantiomeric excess (ee >99%) was determined by HPLC (Chiralpak
AD, n-Hex-iPrOH 95:5, 1 mL/min, 30 °C, tr(minor) = 12.5 min, tr(major)
= 19.4 min, tr(meso) = 22.9 min).
3
3
(d, JHH = 7.8 Hz, 1H), 7.33 (d, JHH = 7.8 Hz, 1H), 7.03−6.95 (m,
2H), 4.62 (s, 2H), 3.86 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
160.5, 156.7, 156.4, 137.6, 131.4, 128.2, 120.9, 118.8, 114.0, 55.2, 34.2.
HRMS (CI) m/z calcd for C13H13NOBr (M + H) 279.0082, found
279.0074. Mp: 87−90 °C.
General Procedure for the Synthesis of Formamides 6a−h.
Formyl hydrazine 5 (1.78−5.86 mmol) was added portionwise to a
suspension of NaH (2.2 equiv) in dry THF (10 mL/mmol), and the
mixture was stirred for 5 min. Bromomethylpyridine 4a−h (1 equiv)
was then added in portions, and the mixture was stirred at room
temperature overnight and quenched with water, and the insoluble
materials were removed by filtration. The aqueous layer was extracted
with CH2Cl2 (3 × 15 mL), and the combined organic layer was
washed with brine and dried over anhydrous Na2SO4. Evaporation of
the solvent under reduced pressure furnished the crude product,
typically as solid, which was purified by flash chromatography. Starting
materials, yields, solvents used for chromatography, and character-
ization data for compounds 6a−h are as follows.
2-(Bromomethyl)-6-[4-(tert-butyl)phenyl]pyridine (4d). From 3d
(1.23 g, 5.10 mmol), the general procedure was applied, and the crude
mixture was purified by flash chromatography (1:10 AcOEt/cyclo-
1
hexane) to yield 1.49 g (96%) of 4d as a white solid. H NMR (300
3
3
MHz, CDCl3) δ 7.93 (d, JHH = 8.3 Hz, 2H), 7.72 (t, JHH = 7.8 Hz,
1H), 7.60 (d, 3JHH = 7.8 Hz, 1H), 7.49 (d, 3JHH = 8.3 Hz, 2H), 7.36 (d,
3JHH = 7.8 Hz, 1H), 4.63 (s, 2H), 1.35 (s, 9H). 13C NMR (100 MHz,
CDCl3) δ 157.5, 156.8, 152.7, 138.1, 136.3, 127.1, 126.1, 121.8, 119.9,
35.0, 34.5, 31.6. HRMS (CI) m/z calcd for C16H19NBr (M + H)
304.0701, found 304.0687. Mp: 78−83 °C.
2-(3,5-Bis-trifluoromethyl)phenyl-6-(bromomethyl)pyridine
(4e).27 From 3e (1.37 g, 4.27 mmol), the general procedure was
applied, and the crude mixture was purified by flash chromatography
(1:5 AcOEt/n-hexane) to yield 1.55 g (95%) of 4e as a white solid. 1H
Data for 6a. From 4a (0.94 g, 3.80 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:5 AcOEt/cyclohexane) to yield 967 mg (59%)
1
of 6a as a yellow foam. H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H),
7.96 (d, 3JHH = 7.7 Hz, 2H), 7.52−7.36 (m, 5H), 7.31−7.08 (m, 10H),
6.55 (d, 3JHH = 7.7 Hz, 1H), 4.63−4.50 (m, 3H), 3.68 (d, 2JHH = 15.8
Hz, 1H), 2.61−2.42 (m, 2H), 2.12−2.08 (m, 2H). 13C NMR (100
MHz, CDCl3) δ 165.9, 162.1, 156.3, 155.5, 140.5, 136.8, 128.7, 128.5,
128.4, 127.8, 127.6, 126.7, 121.0, 118.4, 66.3, 50.7, 30.9. HRMS (CI)
NMR (400 MHz, CDCl3) δ 8.49 (s, 2H), 7.93 (s, 1H), 7.86 (t, 3JHH
=
7.8 Hz, 1H), 7.73 (d, 3JHH = 7.8 Hz, 1H), 7.53 (d, 3JHH = 7.8 Hz, 1H),
4.65 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 157.4, 153.6, 140.5,
2
1
138.3, 131.9 (q, JCF = 33.3 Hz), 126.9, 123.3, 123.1 (q, JCF = 270.7
Hz), 122.5, 119.6, 33.4. HRMS (CI) m/z calcd for C14H8NBrF6
382.9744, found 382.9737. Mp: 87−90 °C.
m/z calcd for C29H28N3O (M + H) 434.2232, found 434.2243. [α]20
D
−102.2 (c, 0.5, CHCl3).
2-(Bromomethyl)-6-[(2,6-dimethoxy)phenyl]pyridine (4f). From
3f (2.6 g, 10.64 mmol), the general procedure was applied, and the
crude mixture was purified by flash chromatography (1:3 AcOEt/
Data for 6b. From 4b (1.10 g, 4.13 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 1.68 g (90%) of 6b
1
cyclohexane) to yield 1.66 g (51%) of 4f as a white solid. H NMR
1
as a white foam. H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.95−
(300 MHz, CDCl3) δ 7.73 (t, 3JHH = 7.7 Hz, 1H), 7.42 (dd, 3JHH = 7.7,
0.8 Hz, 1H), 7.31 (t, 3JHH = 8.4 Hz, 1H), 7.21 (dd, 3JHH = 7.7, 0.8 Hz,
1H), 6.64 (d, 3JHH = 8.4 Hz, 2H), 4.64 (s, 2H), 3.73 (s, 6H). 13C NMR
(75 MHz, CDCl3) δ 158.1, 156.2, 154.5, 136.7, 129.9, 125.5, 121.6,
118.8, 104.5, 56.1, 34.5. HRMS (CI) m/z calcd for (C14H15NO2Br (M
+ H) 308.0286, found 308.0276. Mp: 108−111 °C.
7.87 (m, 2H), 7.39 (d, 3JHH = 7.8 Hz, 1H), 7.32−7.08 (m, 13H), 6.54
3
2
(d, JHH = 7.8 Hz, 1H), 4.64−4.58 (m, 2H), 4.49 (d, JHH = 15.8 Hz,
1H), 3.63 (d, 2JHH = 15.8 Hz, 1H), 2.59−2.49 (m, 2H), 2.12−2.02 (m,
2H). 13C NMR (100 MHz, CDCl3) δ 165.9, 163.4 (d, JCF = 246.7
1
Hz), 162.2, 156.4, 154.5, 140.5, 136.8, 128.5, 128.4, 127.9, 127.7,
2
120.8, 118.1, 115.4 (d, JCF = 21.5 Hz), 65.8, 50.5, 30.7. HRMS (CI)
2-(Bromomethyl)-6-mesitylpyridine (4g). From 3g (1.16 g, 5.10
mmol), the general procedure was applied, and the crude mixture was
purified by flash chromatography (1:4 AcOEt/n-hexane) to yield 1.20
g (81%) of 4g as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.76 (t,
m/z calcd for C29H27N3OF (M + H) 452.2138, found 452.2139.
[α]20 −145.2 (c 0.5, CHCl3).
D
Data for 6c. From 4c (1.00 g, 3.60 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 1.28 g (76%) of 6c
as a white foam. 1H NMR (500 MHz, CDCl3) δ 8.22 (s, 1H), 7.91 (d,
3JHH = 8.6 Hz, 2H), 7.37 (d, 3JHH = 7.8 Hz, 1H), 7.30−7.09 (m, 11H),
3JHH = 7.7 Hz, 1H), 7.41 (dd, 3JHH = 7.7, 0.8 Hz, 1H), 7.15 (dd, 3JHH
=
7.7, 0.8 Hz, 1H), 6.94 (s, 2H), 4.61 (s, 2H), 2.32 (s, 3H), 2.04 (s, 6H).
13C NMR (125 MHz, CDCl3) δ 160.4, 157.1, 138.1, 137.8, 137.5,
136.1, 128.9, 124.4, 121.6, 34.5, 21.5, 20.6. HRMS (CI) m/z calcd for
C15H17NBr (M + H) 290.0544, found 290.0529. Mp: 56−59 °C.
2-(Bromomethyl)-6-[(2,4,6-triisopropyl)phenyl]pyridine (4h).
From 3h (1.15 g, 3.69 mmol), the general procedure was applied,
and the crude mixture was purified by flash chromatography (1:3
3
3
6.99 (d, JHH = 8.6 Hz, 2H), 6.50 (d, JHH = 7.8 Hz, 1H), 4.62−4.58
2
2
(m, 2H), 4.51 (d, JHH = 14.9 Hz, 1H), 3.86 (s, 3H), 3.62 (d, JHH
=
14.9 Hz, 1H), 2.57−2.45 (m, 2H), 2.16−1.99 (m, 2H). 13C NMR (125
MHz, CDCl3) δ 166.1, 162.4, 160.4, 156.5, 155.5, 140.8, 136.8, 128.6,
128.1, 127.9, 125.1, 120.5, 117.7, 114.1, 65.6, 55.4, 51.1, 31.1. HRMS
(CI) m/z calcd for C30H30N3O2 (M + H) 464.2338, found 464.2330.
1
AcOEt/cyclohexane) to yield 1.06 g (77%) of 4h as a white solid. H
NMR (300 MHz, CDCl3) δ 7.66 (t, 3JHH = 7.8 Hz, 1H), 7.33 (dd, 3JHH
[α]20 −146.8° (c 1.0, CHCl3).
D
3
= 7.8, 0.6 Hz, 1H), 7.15 (t, JHH = 9.0 Hz, 1H), 6.99 (s, 2H), 4.52 (s,
Data for 6d. From 4d (0.76 g, 2.50 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:4 AcOEt/cyclohexane) to yield 957 mg (78%)
2H), 2.85 (hept, 3JHH = 6.9 Hz, 1H), 2.47−2.31 (m, 2H), 1.20 (d, 3JHH
= 6.9 Hz, 6H), 1.12−0.94 (m, 12H). 13C NMR (75 MHz, CDCl3) δ
160.6, 156.8, 149.4, 146.6, 137.2, 124.7, 121.5, 121.3, 120.8, 34.9, 34.6,
1
of 6d as a yellow foam. H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H),
1333
DOI: 10.1021/acs.organomet.5b00046
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Organometallics
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7.92 (d, 3JHH = 8.3 Hz, 2H), 7.52 (d, 3JHH = 8.3 Hz, 2H), 7.43 (d, 3JHH
159.0, 148.8, 146.1, 136.4, 136.2, 123.1, 120.8, 119.4, 57.1, 45.5, 42.4,
35.9, 34.5, 30.3, 29.5, 24.2, 24.1, 23.8. HRMS (CI) m/z calcd for
C32H44N2O 472.3454, found 472.3446. Mp: 137−140 °C.
3
= 7.8 Hz, 1H), 7.32−7.12 (m, 11H), 6.55 (d, JHH = 7.8 Hz, 1H),
4.64−4.58 (m, 2H), 4.55 (d, 2JHH = 15.0 Hz, 1H), 3.65 (d, 2JHH = 15.0
Hz, 1H), 2.64−2.44 (m, 2H), 2.23−2.01 (m, 2H), 1.39 (s, 9H). 13C
NMR (100 MHz, CDCl3) δ 165.9, 156.3, 155.6, 140.5, 136.6, 128.4,
127.9, 127.7, 126.4, 125.5, 120.8, 120.1, 118.1, 66.1, 50.8, 34.5, 31.2,
30.9. HRMS (CI) m/z calcd for C33H36N3O (M + H) 490.2858, found
Synthesis of Azolium Chlorides 7a−g Using POCl3: General
Procedure. POCl3 (1.1 equiv) was added to a solution of formamide
6a−h (1.50−5.86 mmol) in toluene (10 mL/mmol), and the mixture
was stirred at 80 °C overnight. The reaction mixture was quenched
with a solution of satd. NaHCO3, and the resulting suspension was
filtered. The filtrate was extracted with CH2Cl2 (3 × 15 mL), and the
combined organic layer was washed with brine and dried over
anhydrous Na2SO4, and the solvent was removed in vacuo. The
residue was dissolved in MeOH and treated with Dowex 22-Cl for 3 h.
The solvent was removed in vacuo, and the residue was purified by
flash chromatography. Starting materials, yields, solvents used for
chromatography, and characterization data for compounds 7a−h are as
follows.
490.2852. [α]20 −126.7 (c 0.3, CHCl3).
D
Data for 6e. From 4e (0.89 g, 2.31 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:4 AcOEt/cyclohexane) to yield 775 mg (59%)
1
of 6e as a yellow foam. H NMR (400 MHz, CDCl3) δ 8.43 (s, 2H),
8.33 (s, 1H), 7.92 (s, 1H), 7.52 (d, 3JHH = 7.8 Hz, 1H), 7.35−7.08 (m,
11H), 6.62 (d, 3JHH = 7.8 Hz, 1H), 4.63−4.55 (m, 2H), 4.51 (d, 2JHH
=
2
15.9 Hz, 1H), 3.62 (d, JHH = 15.9 Hz, 1H), 2.65−2.48 (m, 2H),
2.22−1.95 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 166.2, 157.2,
2
Data for 7a. From 6a (0.94 g, 3.80 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (15:1 CH2Cl2:MeOH) to yield 1.92 g (74%) of 7a
as a brown solid. 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 8.52 (s,
151.9, 140.8, 140.5, 137.2, 131.9 (q, JCF = 33.2 Hz), 128.5, 127.8,
126.7, 123.3 (q, 1JCF = 271.1 Hz), 122.5, 122.2, 118.3, 66.1, 49.9, 30.8.
HRMS (CI) m/z calcd for C31H26N3OF6 (M + H) 570.1980, found
570.1969. [α]20 −126.4 (c 1.0, CHCl3).
D
1H), 7.70 (d, 3JHH = 9.3 Hz, 1H), 7.60−7.50 (m, 3H), 7.46 (d, 3JHH
=
Data for 6f. From 4f (1.49 g, 4.83 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:2 AcOEt/cyclohexane) to yield 2.05 g (77%) of
3
7.6 Hz, 4H), 7.30−7.16 (m, 8H), 7.07 (dd, JHH = 9.3, 6.9 Hz, 1H),
6.75 (d, 3JHH = 6.9 Hz, 1H), 5.38−5.34 (m, 2H), 2.83−2.57 (m, 2H),
2.42−2.31 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 137.6, 134.7,
131.2, 130.3, 129.9, 129.1, 128.8, 128.6, 128.1, 128.0, 124.7, 121.8,
117.9, 117.8, 115.5, 68.5, 31.4. HRMS (FAB) m/z calcd for C29H26N3
1
6f as a yellow foam. H NMR (300 MHz, CDCl3) δ 8.01 (s, 1H),
7.39−7.25 (m, 2H), 7.26−7.09 (m, 10H), 7.05 (dd, 3JHH = 9.3, 2.3 Hz,
1H), 6.73−6.59 (m, 3H), 4.68−4.60 (m, 3H), 3.89 (d, 2JHH = 15.3 Hz,
1H), 3.70 (s, 6H), 2.55−2.35 (m, 2H), 2.23−2.05 (m, 2H). 13C NMR
(75 MHz, CDCl3) δ 165.1, 158.1, 156.7, 153.1, 135.9, 129.6, 128.9,
128.5, 128.2, 127.8, 127.6, 124.4, 121.3, 119.3, 104.3, 68.2, 55.8, 52.3,
31.1. HRMS (CI) m/z calcd for C31H31N3O3 (M + H) 494.2444,
(M − Cl) 416.2127, found 416.2112. [α]20 −130.0 (c 0.1, CHCl3).
D
Data for 7b. From 6b (1.68 g, 3.72 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (15:1 CH2Cl2:MeOH) to yield 1.45 g (83%) of 7b
as a brown foam. 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 8.47 (s,
found 494.2432. [α]20 −136.6 (c 0.5, CHCl3).
D
3
1H), 7.61 (d, 3JHH = 9.3 Hz, 1H), 7.49 (d, JHH = 7.6 Hz, 4H), 7.42−
Data for 6g. From 4g (1.70 g, 5.86 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:4 AcOEt/cyclohexane) to yield 1.79 g (64%) of
7.36 (m, 2H), 7.33−7.18 (m, 8H), 7.12−7.06 (m, 1H), 6.77 (d, 3JHH
=
6.9 Hz, 1H), 5.44−5.38 (m, 2H), 2.79−2.65 (m, 2H), 2.45−2.38 (m,
1
2H). 13C NMR (100 MHz, CDCl3) δ 163.8 (d, JCF = 251.4 Hz),
1
6g as a yellow foam. H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H),
3
7.32−7.11 (m, 11H), 6.95−6.90 (m, 3H), 6.45 (d, 3JHH = 7.7 Hz, 1H),
4.62−4.55 (m, 2H), 4.44 (d, 2JHH = 16.3 Hz, 1H), 3.85 (d, 2JHH = 16.3
Hz, 1H), 2.55−2.48 (m, 2H), 2.31 (s, 3H), 2.16−2.05 (m, 2H), 2.01
(s, 6H). 13C NMR (100 MHz, CDCl3) δ 165.7, 158.3, 156.2, 137.5,
137.2, 136.0, 135.5, 128.5, 128.3, 128.0, 127.8, 122.4, 119.6, 65.4, 51.3,
30.9, 20.8, 20.1. HRMS (CI) m/z calcd for C32H34N3O (M + H)
137.7, 134.0, 130.6 (d, JCF = 8.5 Hz), 129.0, 128.8, 128.5, 128.1,
2
127.6, 126.3, 124.8, 122.9, 118.0, 117.6, 117.1 (d, JCF = 21.9 Hz),
114.5, 68.2, 31.2. HRMS (FAB) m/z calcd for C29H25N3F (M − Cl)
434.2033, found 434.2025. [α]20 −94.5 (c 0.1, CHCl3).
D
Data for 7c. From 6c (1.18 g, 2.54 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (15:1 CH2Cl2:MeOH) to yield 1.05 g (86%) of 7c
as a brown solid. 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.55 (s,
476.2702, found 476.2709. [α]20 −103.3 (c 1.0, CHCl3).
D
Data for 6h. From 4h (655 mg, 1.75 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:10 AcOEt:cyclohexane) to yield 819 mg (84%)
3
1H), 7.60 (d, 3JHH = 9.3 Hz, 1H), 7.44 (d, JHH = 6.9 Hz, 4H), 7.29−
7.15 (m, 8H), 7.07−6.98 (m, 3H), 6.70 (d, 3JHH = 6.9 Hz, 1H), 5.37−
4.30 (m, 2H), 3.87 (s, 3H), 2.76−2.63 (m, 2H), 2.42−2.25 (m, 2H).
13C NMR (100 MHz, CDCl3) δ 161.5, 137.6, 134.7, 129.6, 129.2,
128.8, 128.6, 128.1, 124.8, 122.3, 122.0, 117.4, 117.2, 115.2, 114.9,
68.3, 55.5, 31.2. HRMS (FAB) m/z calcd for C30H28N3O (M − Cl)
1
of 6h as a yellow foam. H NMR (500 MHz, CDCl3) δ 8.24 (s, 1H),
7.28−7.18 (m, 11H), 7.12−7.06 (m, 2H), 6.98 (d, 3JHH = 7.5 Hz, 1H),
6.45 (d, 3JHH = 7.5 Hz, 1H), 4.64−4.56 (m, 2H), 4.47 (d, 2JHH = 16.5
Hz, 1H), 3.89 (d, 2JHH = 16.5 Hz, 1H), 2.98−2.92 (m, 1H), 2.62−2.56
(m, 1H), 2.47−2.41 (m, 3H), 2.21−2.13 (m, 2H), 1.29 (d, 3JHH = 6.9
446.2232, found 446.2239. [α]20 −61.4 (c 0.1, CHCl3).
D
3
3
Data for 7d. From 6d (0.96 g, 1.93 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (20:1 CH2Cl2:MeOH) to yield 0.80 g (81%) of 7d
as a brown foam. 1H NMR (400 MHz, CDCl3) δ 9.06 (s, 1H), 8.34 (s,
1H), 7.70 (d, 3JHH = 9.2 Hz, 1H), 7.54 (d, 3JHH = 8.3 Hz, 2H), 7.47 (d,
3JHH = 6.8 Hz, 4H), 7.33−7.15 (m, 8H), 7.07 (dd, 3JHH = 9.2, 6.8 Hz,
1H), 6.74 (d, 3JHH = 6.8 Hz, 1H), 5.38−5.32 (m, 2H), 2.81−2.64 (m,
2H), 2.49−2.28 (m, 2H), 1.38 (s, 9H). 13C NMR (100 MHz, CDCl3)
δ 154.7, 137.6, 134.6, 129.3, 128.8, 128.6, 128.1, 127.7, 127.4, 126.7,
124.7, 121.5, 117.8, 117.7, 115.6, 68.6, 35.0, 31.3, 31.0. HRMS (FAB)
Hz, 6H), 1.18 (d, JHH = 6.9 Hz, 3H), 1.12 (d, JHH = 6.9 Hz, 3H),
1.10 (d, JHH = 4.3 Hz, 3H), 1.07 (d, JHH = 4.3 Hz, 3H). 13C NMR
(125 MHz, CDCl3) δ 166.3, 158.9, 156.5, 149.1, 146.6, 146.5, 136.7,
135.9, 129.2, 128.6, 128.3, 123.3, 121.3, 121.2, 120.1, 66.8, 51.7, 31.6,
34.9, 30.8, 30.5, 24.8, 24.7, 24.5, 24.4, 24.2. HRMS (CI) m/z calcd for
3
3
C38H46N3O (M + H) 560.3641, found 560.3621. [α]20 −97.2 (c 0.9,
D
CHCl3).
Synthesis of N-(Adamantyl)-N-{[6-(2,4,6-triisopropyl)-
phenyl]pyridin-2-methyl}formamide (12). Formamide 12 was
prepared following the general procedure for the synthesis of
compounds 6a−h, but using N-(adamantyl)-formamide 11 (0.8
mmol) and 4h (1 equiv) as starting materials and allowing the
reaction to complete at 50 °C for 48 h. The crude mixture was purified
by flash chromatography (1:4 AcOEt/n-hexane) to yield 0.27 g (70%)
of 12 as a crystalline white solid. 1H NMR (400 MHz, CDCl3) δ 8.74
m/z calcd for C33H34N3 (M − Cl) 472.2753, found 472.2774. [α]20
−63.7 (c 0.1, CHCl3).
D
Data for 7e. From 6e (0.78 mg, 1.37 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (20:1 CH2Cl2:MeOH) to yield 0.59 g (73%) of 7e
as a brown foam. 1H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 8.97 (s,
(s, 1H), 7.68 (t, 3JHH = 8.0 Hz, 1H), 7.24 (d, 3JHH = 7.6 Hz, 1H), 7.15
3
3
(d, 3JHH = 7.2 Hz, 1H), 7.08 (s, 2H), 4.85 (s, 2H), 2.94 (hept, JHH
=
1H), 8.10 (s, 1H), 7.82−7.75 (m, 3H), 7.51 (d, JHH = 7.2 Hz, 4H),
3
3
3
6.8 Hz, 1H), 2.49 (hept, JHH = 6.8 Hz, 2H), 2.13−2.09 (m, 3H),
1.94−1.90 (m, 6H), 1.72−1.58 (m, 6H), 1.28 (d, 3JHH = 7.2 Hz, 6H),
1.15−1.07 (m, 12H). 13C NMR (100 MHz, CDCl3) δ 162.0, 159.0,
7.32−7.18 (m, 6H), 7.14 (t, JHH = 6.9 Hz, 1H), 6.85 (d, JHH = 6.9
Hz, 1H), 5.46−5.42 (m, 2H), 2.79−2.64 (m, 2H), 2.51−2.39 (m, 2H).
13C NMR (100 MHz, CDCl3) δ 137.5, 133.2 (q, JCF = 34.2 Hz),
2
1334
DOI: 10.1021/acs.organomet.5b00046
Organometallics 2015, 34, 1328−1338

Organometallics
Article
132.5, 131.5, 128.9, 128.7, 128.7, 128.6, 128.1, 124.9, 124.5, 123.3,
122.5 (q, JCF = 271.5 Hz), 119.7, 119.2, 115.3, 68.5, 31.8. HRMS
evaporated in vacuo. Starting materials, yields, and characterization
data for compounds 8a−h and 14 are as follows.28
1
Data for 8a. From 7a (45 mg, 0.1 mmol), the general procedure
(FAB) m/z calcd for C31H24N3F6 (M − Cl) 552.1874, found
1
552.1887. [α]20 −57.1 (c 0.2, CHCl3).
was applied to yield 55 mg (98%) of 8a as a yellow solid. H NMR
D
(500 MHz, CDCl3) δ 7.63−7.40 (m, 3H), 7.33−7.13 (m, 12H), 6.96
(d, 3JHH = 9.2 Hz, 1H), 6.79 (s, 1H), 6.73 (dd, 3JHH = 9.2, 6.8 Hz, 1H),
6.33 (d, 3JHH = 6.8 Hz, 1H), 5.40−4.59 (m, 2H), 2.72−2.60 (m, 2H),
Data for 7f. From 6f (0.72 g, 1.50 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (15:1 CH2Cl2:MeOH) to yield 1.76 g (89%) of 7f
as a brown foam. 1H NMR (300 MHz, CDCl3) δ 8.62 (s, 1H), 8.34 (s,
1H), 7.61 (d, 3JHH = 9.3 Hz, 1H), 7.51 (t, 3JHH = 8.7 Hz, 1H), 7.42 (d,
2.35−2.17 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 171.4 (d, 1JCAg
=
1
275, 238 Hz), 171.4 (d, JCAg = 238 Hz), 139.4, 138.9, 133.2, 130.4,
3
3JHH = 7.2 Hz, 4H), 7.30−7.11 (m, 6H), 7.05 (dd, JHH = 9.3, 7.2 Hz,
129.6, 128.9, 128.8, 128.2, 128.1, 127.5, 122.5, 116.4, 114.9, 110.3,
110.3, 67.6, 30.7. [α]20 −130.9 (c, 0.1, CHCl3). Crystallization was
D
1H), 6.78−6.63 (m, 3H), 5.34−5.27 (m, 2H), 3.64 (s, 3H), 3.60 (s,
3H), 2.82−2.60 (m, 2H), 2.46−2.25 (m, 2H). 13C NMR (125 MHz,
CDCl3) δ 157.8, 157.7, 137.4, 133.2, 128.7, 128.6, 128.4, 128.3, 127.8,
124.5, 122.5, 120.2, 117.3, 113.9, 106.8, 104.4, 104.2, 68.5, 56.3, 56.1,
31.3. HRMS (FAB) m/z calcd for C31H30N3O2 (M − Cl) 476.2338,
performed at −28 °C by slow diffusion of pentane in a CH2Cl2
solution of the complex.
Data for 8b. From 7b (47 mg, 0.1 mmol), the general procedure
1
was applied to yield 56 mg (97%) of 8b as a white solid. H NMR
3
found 476.2331. [α]20 −75.9 (c, 0.1, CHCl3).
(400 MHz, CDCl3) δ 7.35−7.14 (m, 14H), 7.01 (d, JHH = 9.3 Hz,
D
3
3
1H), 6.82 (s, 1H), 6.75 (dd, JHH = 9.3, 6.4 Hz, 1H), 6.34 (d, JHH
=
Data for 7g. From 6g (0.72 g, 1.50 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (9:1 CH2Cl2:MeOH) to yield 0.59 g (80%) of 7g
as a brown foam. 1H NMR (400 MHz, CDCl3) δ 9.48 (s, 1H), 7.93 (d,
6.4 Hz, 1H), 5.38−4.50 (m, 2H), 2.74−2.62 (m, 2H), 2.33−2.21 (m,
2H). 13C NMR (100 MHz, CDCl3) δ 170.3 (d, 1JCAg = 275 Hz), 170.3
(d, 1JCAg = 237 Hz), 164.1 (d, 1JCF = 212.2 Hz), 138.8, 138.4, 131.0 (d,
3JCF = 6.7 Hz), 130.1, 128.9, 128.8, 128.2, 128.1, 127.6, 125.1, 122.4,
3
3JHH = 9.4 Hz, 1H), 7.44 (s, 1H), 7.38 (d, JHH = 7.5 Hz, 4H), 7.23−
2
116.9 (d, JCF = 18.9 Hz), 115.3, 110.5, 110.6, 67.5, 30.7. [α]20
7.13 (m, 6H), 7.10 (dd, 3JHH = 9.4, 6.8 Hz, 1H), 6.96 (s, 2H), 6.64 (d,
3JHH = 6.8 Hz, 1H), 5.27−5.21 (m, 2H), 2.73−2.62 (m, 2H), 2.43−
2.29 (m, 5H), 1.60 (s, 3H), 1.51 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 141.3, 137.1, 136.72, 136.69, 132.8, 129.2, 129.1, 128.9,
128.7, 128.5, 127.9, 125.9, 124.8, 120.2, 118.7, 118.2, 116.5, 68.1, 31.1,
21.2, 18.9, 18.5. HRMS (FAB) m/z calcd for C32H32N3 (M − Cl)
D
−115.2 (c, 0.2, CHCl3). Crystallization was performed at −28 °C by
slow diffusion of pentane in a CH2Cl2 solution of the complex.
Data for 8c. From 7c (48 mg, 0.1 mmol), the general procedure
1
was applied to yield 58 mg (98%) of 8c as a yellow solid. H NMR
(400 MHz, CDCl3) δ 7.29−7.19 (m, 10H), 7.18−7.12 (m, 2H), 7.05
(d, 3JHH = 8.6 Hz, 2H), 6.95 (d, 3JHH = 9.3 Hz, 1H), 6.77 (d, 3JHH = 1.8
458.2596, found 458.2593. [α]20 −86.9 (c, 0.1, CHCl3).
3
3
D
Hz, 1H), 6.73 (dd, JHH = 9.3, 6.6 Hz, 1H), 6.34 (dd, JHH = 6.6, 1.0
Hz, 1H), 5.61−4.61 (m, 2H), 3.95 (s, 3H), 2.83−2.53 (m, 2H), 2.33−
Synthesis of Azolium Chlorides 7h,13 Using Tf2O: General
Procedure. Dry Et3N (1.1 equiv) was added dropwise to a cooled
(−40 °C) solution of formamides 6h or 12 (0.55−1.36 mmol) in dry
CH2Cl2 (6 mL/mmol), and the mixture was stirred for 5 min. Tf2O
(1.1 equiv) was slowly added, and the mixture was allowed to warm to
room temperature and stirred for 4 h. The residue was purified by flash
chromatography (30:1 CH2Cl2/MeOH). The product was dissolved in
MeOH and treated with Dowex 22-Cl for 3 h. Starting materials,
yields, and characterization data for compounds 7h and 13 are as
follows.
2.17 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 171.4 (d, JCAg = 276
Hz), 171.4 (d, JCAg = 239 Hz), 161.4, 139.5, 138.9, 130.2, 128.8,
1
1
128.2, 128.1, 127.5, 125.3, 122.5, 116.2, 115.4, 114.7, 110.1, 110.0,
67.5, 56.0, 30.9. [α]20 −98.0 (c 0.1, CHCl3).
D
Data for 8d. From 7c (51 mg, 0.1 mmol), the general procedure
1
was applied to yield 61 mg (99%) of 8d as a white solid. H NMR
3
(500 MHz, CDCl3) δ 7.56 (d, JHH = 8.1 Hz, 2H), 7.37−7.18 (m,
12H), 6.92 (d, 3JHH = 9.2 Hz, 1H), 6.76−6.69 (m, 2H), 6.37−6.32 (m,
1H), 5.72−4.18 (m, 2H), 2.74−2.61 (m, 2H), 2.32−2.20 (m, 2H),
1.45 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 171.6 (d, JCAg = 275
Data for 7h. From 6h (0.76 g, 1.36 mmol), the general procedure
1
1
was applied to yield 0.68 g (86%) of 7h as a brown foam. H NMR
1
Hz), 171.6 (d, JCAg = 238 Hz), 153.8, 139.7, 138.9, 130.2, 130.1,
3
(400 MHz, CDCl3) δ 9.67 (s, 1H), 7.87 (d, JHH = 8.0 Hz, 1H), 7.63
130.1, 128.8, 128.5, 128.2, 127.5, 126.6, 122.5, 116.3, 114.6, 109.6,
3
109.6, 67.4, 35.0, 31.5, 31.2. [α]20 −156.3 (c 0.1, CHCl3).
(s, 1H), 7.47−7.40 (m, 3H), 7.24−7.09 (m, 9H), 6.69 (d, JHH = 8.1
D
Hz, 1H), 5.36−5.30 (m, 2H), 3.02−2.94 (m, 1H), 2.68−2.63 (m, 2H),
2.41−2.36 (m, 2H), 1.99−1.93 (m, 1H), 1.76−1.70 (m, 1H), 1.31 (d,
Data for 8e. From 7e (59 mg, 0.1 mmol), the general procedure
1
was applied to yield 54 mg (78%) of 8e as a yellow solid. H NMR
3
3
3JHH = 6.8 Hz, 6H), 1.02 (d, JHH = 6.7 Hz, 3H), 0.93 (d, JHH = 6.7
(500 MHz, CDCl3) δ 8.06 (s, 1H), 7.72 (sa, 1H), 7.56 (sa, 1H),
7.32−7.18 (m, 9H), 7.16−7.08 (m, 2H), 7.10 (d, 3JHH = 9.1 Hz, 1H),
6.93 (s, 1H), 6.80 (dd, 3JHH = 9.1, 6.8 Hz, 1H), 6.41 (d, 3JHH = 6.8 Hz,
1H), 5.15−4.95 (m, 2H), 2.77−2.55 (m, 2H), 2.31−2.24 (m, 2H). 13C
NMR (125 MHz, CDCl3) δ 170.5 (d, 1JCAg = 274 Hz), 170.5 (d, 1JCAg
= 238 Hz), 138.6, 136.1, 135.1, 133.8 (q, 2JCF = 33.2 Hz), 129.5, 128.9,
Hz, 3H), 0.86 (d, 3JHH = 6.7 Hz, 3H), 0.66 (d, 3JHH = 6.8 Hz, 3H). 13
C
NMR (125 MHz, CDCl3) δ 152.8, 147.9, 147.7, 137.3, 132.4, 129.4,
128.9, 128.7, 128.1, 124.4, 124.1, 122.4, 122.3, 120.6, 119.6, 118.7,
117.6, 69.1, 34.5, 32.1, 31.0, 30.9, 24.9, 24.8, 24.0, 23.9, 23.8, 23.8.
HRMS (FAB) m/z calcd for C38H44N3 (M − Cl) 542.3535, found
542.3541. [α]20 −106.0 (c 0.1, CHCl3).
1
128.4, 128.2, 124.5, 122.8 (q, JCF = 271.6 Hz), 122.2, 118.1, 116.5,
D
111.7, 111.6, 67.7, 30.9. [α]20D −130.1 (c 0.1, CHCl3). Crystallization
was performed at −28 °C by slow diffusion of pentane in a CH2Cl2
solution of the complex.
Data for 13. From 12 (0.26 g, 0.55 mmol), the general procedure
1
was applied to yield 0.24 g (90%) of 13 as a brown solid. H NMR
3
(400 MHz, CDCl3) δ 9.73 (s, 1H), 8.37 (d, JHH = 9.2 Hz, 1H), 7.81
(s, 1H), 7.28 (dd, 3JHH = 6.8, 4.8 Hz, 1H), 7.16 (s, 2H), 6.86 (d, 3JHH
=
Data for 8f. From 7f (51 mg, 0.1 mmol), the general procedure was
3
1
6.4 Hz, 1H), 2.96 (hept, JHH = 6.8 Hz, 1H), 2.28−2.18 (m, 3H),
applied to yield 60 mg (97%) of 8f as a yellow solid. H NMR (500
3
2.17−2.10 (m, 8H), 1.75−1.72 (m, 6H), 1.28 (d, 3JHH = 6.8 Hz, 6H),
MHz, CDCl3) δ 7.57 (t, JHH = 8.4 Hz, 1H), 7.37−7.12 (m, 10H),
6.93 (d, 3JHH = 9.2 Hz, 1H), 6.79−6.66 (m, 3H), 6.63 (s, 1H), 6.37 (d,
3JHH = 6.6 Hz, 1H), 5.46−4.52 (m, 2H), 3.72 (s, 3H), 3.59 (s, 3H),
2.70−2.65 (m, 2H), 2.30−2.27 (m, 2H). 13C NMR (125 MHz,
CDCl3) δ 170.8 (d, 1JCAg = 278 Hz), 170.8 (d, 1JCAg = 241 Hz), 158.0,
158.0, 138.9, 133.2, 132.5, 130.1, 130.1, 128.6, 128.5, 128.1, 127.5,
126.8, 126.4, 125.1, 122.5, 116.3, 116.2, 110.8, 108.9, 108.8, 105.1,
105.0, 68.5, 65.7, 56.1, 56.1, 31.9, 29.4. [α]20D −141.8 (c, 0.1, CHCl3).
Data for 8g. From 7g (49 mg, 0.1 mmol), the general procedure
3
3
1.07 (d, JHH = 6.8 Hz, 6H), 0.98 (d, JHH = 6.8 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ 152.8, 147.9, 133.0, 131.6, 124.5, 124.2, 122.6,
119.9, 119.9, 117.4, 116.0, 62.3, 43.1, 35.1, 34.4, 31.1, 29.4, 24.8, 24.3,
23.8. HRMS (FAB) m/z calcd for C32H43N2 (M − Cl) 455.3426,
found 455.3416. Mp: 148−150 °C. Crystallization was performed at
room temperature by slow diffusion of n-hexane in a CH2Cl2 solution
of the complex.
General Procedure for Synthesis of Silver Complexes 8a−h
and 14. To a solution of 7a−h or 13 (typically 0.1 mmol) in dry
CH2Cl2 (20 mL/mmol) was added solid Ag2O (1.2 equiv), and the
mixture was stirred in the darkness at room temperature for 3 h. The
solution was filtered through a Celite plug, and the filtrate was
1
was applied to yield 59 mg (98%) of 8g as a yellow solid. H NMR
3
(500 MHz, CDCl3) δ 7.37−7.14 (m, 10H), 7.04 (d, JHH = 11.2 Hz,
3
3
2H), 6.99 (d, JHH = 9.3 Hz, 1H), 6.82 (s, 1H), 6.77 (dd, JHH = 9.3,
3
6.7 Hz, 1H), 6.30 (d, JHH = 6.7 Hz, 1H), 5.34−5.26 (m, 1H), 4.84−
1335
DOI: 10.1021/acs.organomet.5b00046
Organometallics 2015, 34, 1328−1338

Organometallics
Article
4.77 (m, 1H), 2.70−2.64 (m, 2H), 2.45 (s, 3H), 2.34−2.22 (m, 2H),
1.82 (s, 3H), 1.73 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 170.5 (d,
1JCAg = 273 Hz), 170.5 (d, 1JCAg = 239 Hz), 141.2, 138.8, 138.1, 138.1,
136.2, 136.2, 129.6, 129.6, 129.4, 129.4, 129.3, 128.7, 128.7, 128.1,
127.6, 122.6, 116.2, 114.8, 110.2, 110.2, 67.9, 66.7, 31.4, 29.6, 21.6,
Data for 9c. From 8c (133 mg, 0.22 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 110 mg (74%) of
1
9c as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.54−7.46 (m,
2H), 7.36−7.29 (m, 1H), 7.27−7.21 (m, 9H), 7.17−7.08 (m, 2H),
6.89 (d, 3JHH = 9.3 Hz, 1H), 6.72 (dd, 3JHH = 9.3, 6.6 Hz, 1H), 6.64 (s,
1H), 6.37 (d, 3JHH = 6.6 Hz, 1H), 5.55−5.50 (m, 1H), 4.79−4.73 (m,
1H), 3.97 (s, 3H), 2.78−2.74 (m, 1H), 2.66−2.62 (m, 1H), 2.41−2.38
(m, 1H), 2.24−2.18 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 163.8,
161.6, 139.0, 138.9, 131.1, 129.6, 128.7, 128.6, 128.4, 128.0, 127.6,
126.3, 122.5, 116.3, 115.8, 114.9, 108.3, 69.0, 65.3, 56.1, 33.4, 28.4.
HRMS (FAB) m/z calcd for C30H27N3OAu (M − Cl) 642.1820,
19.47, 19.20. [α]20 −150.3 (c, 0.1, CHCl3).
D
Data for 8h. From 7g (100 mg, 0.17 mmol) and Ag2O (85.7 mg
0.37 mmol), the general procedure was applied to yield 95 mg (80%)
of 8h as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.38−7.31 (m,
2H), 7.21−7.15 (m, 10H), 6.93 (d, 3JHH = 9.3 Hz, 1H), 6.74 (dd, 3JHH
3
= 9.3, 6.7 Hz, 1H), 6.69 (s, 1H), 6.34 (d, JHH = 6.7 Hz, 1H), 5.32−
5.27 (m, 1H), 4.75−4.70 (m, 1H), 3.04−2.98 (m, 1H), 2.64−2.78 (m,
2H), 2.30−2.26 (m, 1H), 2.18−2.13 (m, 2H), 2.05−1.98 (m, 1H),
1.38 (d, 3JHH = 6.9 Hz, 6H), 1.19 (d, 3JHH = 6.6 Hz, 3H), 1.05 (d, 3JHH
found 642.1833. [α]20 −73.4 (c, 0.1, CH2Cl2). Mp: 113−115 °C.
D
Data for 9d. From 8d (126 mg, 0.20 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:2 AcOEt/n-hexane) to yield 103 mg (74%) of
3
3
= 6.5 Hz, 3H), 1.00 (d, JHH = 6.6 Hz, 3H), 0.98 (d, JHH = 6.7 Hz,
3H). 13C NMR (125 MHz, CDCl3) δ 171.4 (d, 1JCAg = 273 Hz), 171.4
(d, JCAg = 236 Hz), 151.9, 146.5, 146.4, 138.7, 137.5, 129.58, 129.52,
1
1
9d as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.65−7.56 (m,
128.4, 128.0, 127.4, 127.2, 126.6, 126.2, 122.2, 122.1, 122.0, 116.1,
115.5, 109.1, 109.0, 68.5, 65.8, 34.4, 32.7, 31.1, 30.9, 28.9, 24.9, 24.8,
24.2, 24.1, 24.0. Crystallization was performed at −28 °C by slow
diffusion of pentane in a CH2Cl2 solution of the complex.
2H), 7.55−7.49 (m, 2H), 7.42−7.33 (m, 1H), 7.28−7.16 (m, 9H),
6.88 (d, 3JHH = 9.2 Hz, 1H), 6.73 (dd, 3JHH = 9.2, 6.6 Hz, 1H), 6.63 (s,
1H), 6.37 (d, 3JHH = 6.6 Hz, 1H), 5.55−5.49 (m, 1H), 4.78−4.73 (m,
1H), 2.84−2.71 (m, 1H), 2.66−2.56 (m, 1H), 2.43−2.30 (m, 1H),
2.25−2.14 (m, 1H), 1.49 (s, 9H). 13C NMR (100 MHz, CDCl3) δ
163.7, 153.7, 139.0, 138.7, 130.8, 129.4, 129.2, 128.5, 128.4, 128.2,
127.8, 127.4, 125.9, 122.3, 116.1, 115.5, 107.8, 68.8, 64.9, 34.9, 33.3,
31.4, 28.1. HRMS (FAB) m/z calcd for C33H33N3ClAu (M − Cl)
668.2340, found 668.2346. [α]20D −109.0 (c, 0.1, CH2Cl2). Mp: 108−
110 °C.
Data for 14. From 13 (152 mg, 0.31 mmol), the general procedure
was applied to yield 167 mg (78%) of 14 as a white crystalline solid.
3
1H NMR (400 MHz, CDCl3) δ 7.64 (s, 1H), 7.44 (d, JHH = 9.2 Hz,
3
3
1H), 7.23 (s, 2H), 6.96 (dd, JHH = 9.1, 6.6 Hz, 1H), 6.53 (d, JHH
=
3
6.0 Hz, 1H), 3.04 (hept, JHH = 7.2 Hz, 1H), 2.42−2.40 (m, 6H),
2.39−2.29 (m, 2H), 2.28−2.25 (m, 3H), 1.84−1.68 (m, 6H), 1.41 (d,
3
3
3JHH = 6.9 Hz, 6H), 1.23 (d, JHH = 6.9 Hz, 6H), 1.12 (d, JHH = 6.8
Data for 9e. From 8e (121 mg, 0.17 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 120 mg (90%) of
Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 152.1, 146.7, 138.2, 130.2,
130.1, 127.7, 122.7, 122.0, 116.9, 116.0, 109.0, 108.9, 59.6, 44.7, 35.8,
34.6, 31.3, 29.9, 25.1, 24.4, 24.2. Crystallization was performed at room
temperature by slow diffusion of n-hexane in a CH2Cl2 solution of the
complex.
1
9e as a light−yellow solid. H NMR (400 MHz, CDCl3) δ 8.12 (s,
1H), 7.81 (s, 1H), 7.70 (s, 1H), 7.50−7.43 (m, 2H), 7.32−7.19 (m,
3
3
8H), 7.05 (d, JHH = 9.1 Hz, 1H), 6.83 (s, 1H), 6.81 (dd, JHH = 9.1,
3
General Procedure for Synthesis of Gold Complexes 8a−h
and 15. To a solution of silver(I) complex 8a−h or 14 (0.05−0.24
mmol) in dry CH2Cl2 (20 mL/mmol) was added AuCl(SMe2) (1
equiv), and the mixture was stirred in the darkness, at room
temperature for 3 h. The mixture was filtered through a Celite plug,
the solvent was evaporated in vacuo, and the residue was purified by
flash chromatography. Starting material, yields, solvents used for
chromatography, and characterization data for compounds 9a−h and
15 are as follows.
6.4 Hz, 1H), 6.45 (d, JHH = 6.4 Hz, 1H), 5.62−5.57 (m, 1H), 4.82−
4.77 (m, 1H), 2.74−2.62 (m, 2H), 2.35−2.29 (m, 2H). 13C NMR
2
(100 MHz, CDCl3) δ 163.9, 138.9, 138.5, 135.8, 135.7, 132.2 (q, JCF
= 34.2 Hz), 130.2, 130.2, 129.4, 128.7, 128.3, 127.9, 124.1, 123.2 (q,
1
1JCF = 273.1 Hz), 123.1 (q, JCF = 273.6 Hz), 122.2, 118.1, 117.1,
109.9, 68.9, 66.3, 33.0, 29.6. HRMS (FAB) m/z calcd for
(C31H23N3F6Au−Cl) 748.1462, found 748.1486. [α]20 −106.9 (c,
D
0.1, CH2Cl2). Mp: 104−106 °C.
Data for 9f. From 8f (133 mg, 0.21 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 177 mg (81%) of 9f
Data for 9a. From 8a (138 mg, 0.24 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 104 mg (67%) of
1
3
as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.59 (t, JHH = 8.4
1
9a as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.68−7.63 (m,
Hz, 1H), 7.54−7.48 (m, 2H), 7.30−7.11 (m, 8H), 6.85 (d, 3JHH = 9.3
Hz, 1H), 6.75−6.67 (m, 3H), 6.51 (s, 1H), 6.38 (d, JHH = 6.6 Hz,
1H), 7.62−7.36 (m, 5H), 7.33−7.19 (m, 9H), 6.92 (d, 3JHH = 9.3 Hz,
3
3
3
1H), 6.74 (dd, JHH = 9.3, 6.6 Hz, 1H), 6.67 (s, 1H), 6.38 (d, JHH
=
1H), 5.49−5.45 (m, 1H), 4.72−4.65 (m, 1H), 3.82 (s, 3H), 3.63 (s,
3H), 2.81−2.68 (m, 1H), 2.66−2.54 (m, 1H), 2.39−2.29 (m, 1H),
2.24−2.10 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 162.9, 158.5,
158.4, 132.6, 132.0, 129.5, 128.6, 128.4, 128.3, 128.2, 127.6, 122.6,
117.0, 116.2, 112.0, 107.4, 105.0, 104.7, 68.8, 64.8, 56.1, 56.0, 33.4,
27.7. HRMS (FAB) m/z calcd for C34H37N3O4SAu [M − Cl +
6.6 Hz, 1H), 5.59−5.52 (m, 1H), 4.78−4.73 (m, 1H), 2.87−2.73 (m,
1H), 2.65−2.59 (m, 1H), 2.38−2.32 (m, 1H), 2.24−2.18 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 163.8, 139.0, 138.8, 134.0, 130.1, 129.7,
129.5, 129.0, 128.7, 128.5, 128.4, 128.0, 127.6, 122.4, 116.5, 115.8,
108.4, 68.8, 65.3, 33.2, 28.5. HRMS (FAB) m/z calcd for
C29H25N3CAu (M − Cl) 612.1714, found 612.1715. [α]20 −135.8
D
thioglycerol (matrix)] 780.2170, found 780.2150. [α]20 −211.4 (c,
D
(c, 0.05, CH2Cl2). Mp: 193−195 °C.
0.02, CH2Cl2). Mp: 130−132 °C.
Data for 9b. From 8b (34 mg, 0.06 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 38 mg (97%) of 9a
as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.52−7.41 (m, 2H),
7.39−7.29 (m, 2H), 7.25−7.11 (m, 10H), 6.89 (d, 3JHH = 9.2 Hz, 1H),
6.70 (dd, 3JHH = 9.2, 6.7 Hz, 1H), 6.65 (s, 1H), 6.31 (d, 3JHH = 6.7 Hz,
1H), 5.50−5.46 (m, 1H), 4.76−4.72 (m, 1H), 2.75−2.70 (m, 1H),
2.62−2.55 (m, 1H), 2.32−2.27 (m, 1H), 2.23−2.17 (m, 1H). 13C
Data for 9g. From 8g (134 mg, 0.22 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:3 AcOEt/n-hexane) to yield 100 mg (68%) of
1
9g as a yellow solid. H NMR (400 MHz, CDCl3) δ 7.55−7.46 (m,
3
2H), 7.29−7.13 (m, 8H), 7.10 (s, 1H), 7.07 (s, 1H), 6.92 (d, JHH
=
3
9.2 Hz, 1H), 6.76 (dd, JHH = 9.2, 6.6 Hz, 1H), 6.69 (s, 1H), 6.32 (d,
3JHH = 6.2 Hz, 1H), 5.58−5.50 (m, 1H), 4.82−4.76 (m, 1H), 2.81−
2.68 (m, 1H), 2.65−2.54 (m, 1H), 2.49 (s, 3H), 2.43−2.33 (m, 1H),
2.28−2.15 (m, 1H), 1.98 (s, 3H), 1.84 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 163.0, 140.7, 137.7, 137.0, 136.8, 130.3, 129.1, 128.9, 128.8,
128.6, 128.5, 128.4, 127.9, 127.5, 122.6, 116.2, 115.7, 108.4, 68.5, 65.5,
33.3, 28.7, 21.5, 19.7. HRMS (FAB) m/z calcd for C32H31N3Au (M −
1
NMR (100 MHz, CDCl3) δ 164.2 (d, JCF = 248.8 Hz), 163.9, 138.8,
138.0, 131.8, 130.0, 129.5, 128.7, 128.6, 128.5, 128.1, 127.9, 127.7,
127.4, 122.3, 116.8, 116.4, 116.2, 108.7, 68.9, 65.5, 32.2, 28.6. HRMS
(FAB) m/z calcd for C32H32FN3O2SAu [M − Cl + thioglycerol
(matrix)] 738.1865, found 738.1860. [α]20 −171.8 (c, 0.1, CHCl3).
D
Cl) 654.2184, found 654.2216. [α]20 −211.4 (c, 0.02, CH2Cl2). Mp:
Mp: 121−123 °C. Crystallization was performed at −28 °C by slow
diffusion of pentane in a CH2Cl2 solution of the complex.
D
134−136 °C.
1336
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Organometallics 2015, 34, 1328−1338

Organometallics
Article
Data for 9h. From 8g (31 mg, 0.05 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:2 AcOEt/n-hexane) to yield 34 mg (95%) of 9h
3.72 (d, 3JHH = 1.1 Hz, 3H), 3.58 (d, 3JHH = 1.0 Hz, 3H), 2.66 (d, 3JHH
= 11.3 Hz, 2H), 2.25 (s, 2H). δ 13C NMR (100 MHz, CDCl3) δ 153.3,
148.5, 148.3, 137.8, 132.8, 130.0, 129.5, 129.3, 129.2, 128.6, 125.0,
124.7, 122.9, 122.8, 121.1, 120.2, 119.4, 118.0, 69.6, 64.1, 35.1, 32.6,
31.4, 25.4, 24.6. HRMS (FAB) m/z calcd for C32H33N3O2Cu (M −
Cl) 589.1157, found 589.1139.
1
3
as a white solid. H NMR (400 MHz, CDCl3) δ 7.49 (d, JHH = 7.2
3
Hz, 2H), 7.20−7.10 (m, 10H), 6.87 (d, JHH = 9.2 Hz, 1H), 6.70 (t,
3
3JHH = 7.5 Hz, 1H), 6.63 (s, 1H), 6.31 (d, JHH = 6.5 Hz, 1H), 5.52−
Data for 10g. From 7g (50 mg, 0.10 mmol), the general procedure
5.47 (m, 1H), 4.78−4.73 (m, 1H), 3.02−2.99 (m, 1H), 2.71−2.65 (m,
1H), 2.56−2.50 (m, 1H), 2.38−2.34 (m, 1H), 2.25−2.20 (m, 1H),
2.15−2.06 (m, 1H), 2.02−1.99 (m, 1H), 1.41−1.33 (m, 9H), 1.14 (d,
1
was applied to yield 36 mg (60%) of 10g as a brown solid. H NMR
(400 MHz, CDCl3) δ 7.48 (d, 3JHH = 7.1 Hz, 3H), 7.26 (d, 3JHH = 1.1
3
3
3
3JHH = 6.7 Hz, 3H), 1.08 (d, JHH = 6.7 Hz, 3H), 0.96 (d, JHH = 6.7
Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.3, 152.0, 147.0, 146.9,
139.0, 138.9, 137.5, 129.1, 128.6, 128.5, 128.4, 128.3, 127.8, 127.4,
122.2, 122.0, 121.9, 116.4, 116.2, 108.1, 68.3, 65.4, 34.8, 33.6, 31.6,
31.4, 28.5, 25.3, 25.1, 24.5, 24.5, 23.9, 23.9. HRMS (FAB) m/z calcd
Hz, 1H), 7.19 (s, 8H), 7.06 (d, JHH = 12.7 Hz, 2H), 6.95−6.87 (m,
3
3
1H), 6.66 (d, JHH = 1.2 Hz, 1H), 6.30 (dd, JHH = 6.6, 1.3 Hz, 1H),
5.52 (s, 1H), 4.76 (s, 1H), 2.46 (s, 4H), 1.95 (s, 3H), 1.81 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 163.2, 140.9, 139.1, 138.9, 137.9, 137.2,
137.1, 130.5, 129.3, 129.1, 129.0, 128.8, 128.7, 128.6, 128.5, 128.1,
127.6, 122.8, 116.4, 115.9, 108.5, 108.4, 68.7, 65.6, 33.5, 28.8, 21.7,
20.0. HRMS (FAB) m/z calcd for C33H35N3Cu (M − Cl) 571.1816,
found 571.1808.
for C38H43N3Au (M − Cl) 738.3123, found 738.3026. [α]20 −139.9
(c, 0.1, CHCl3). Mp: 286−288 °C. Crystallization was performed at
−28 °C by slow diffusion of pentane in a CH2Cl2 solution of the
complex.
D
Data for 10h. From 7h (50 mg, 0.09 mmol), the general procedure
1
was applied to yield 35 mg (55%) of 10h as a brown solid. H NMR
Data for 15. From 14 (167 mg, 0.24 mmol), the general procedure
was applied, and the crude mixture was purified by flash
chromatography (1:7 AcOEt/toluene) to yield 180 mg (97%) of 15
(400 MHz, CDCl3) δ 7.50−7.44 (m, 5H), 7.25−7.21 (m, 8H), 6.98
3
3
(d, JHH = 9.1, 3H), 6.77 (m, 2H), 6.34 (d, JHH = 6.0 Hz, 1H), 5.43
(bs, 1H), 4.84 (bs, 1H), 2.98 (m, 1H), 2.16 (m, 1H), 2.04 (m, 1H),
1.36 (d, 3JHH = 6.6 Hz, 6H), 1.20 (d, 3JHH = 6.4 Hz, 3H), 1.07 (d, 3JHH
1
1
as a white crystalline solid. H NMR (400 MHz, CDCl3) δ H NMR
3
(400 MHz, CDCl3) δ 7.60 (s, 1H), 7.42 (d, JHH = 9.1 Hz, 1H), 7.17
= 6.5 Hz, 6H), 1.00 (d, JHH = 6.5 Hz, 3H). 13C NMR (80 MHz,
3
(s, 2H), 6.95 (t, 3JHH = 7.6 Hz, 1H), 6.52 (d, 3JHH = 6.4 Hz, 1H), 3.02
3
CDCl3) δ 152.1, 146.9, 146.9, 137.8, 129.4, 128.6, 128.2, 122.5, 122.4,
122.4, 116.1, 115.7, 115.5, 109.2, 94.5, 68.7, 53.1, 34.9, 33.1, 31.4, 31.4,
30.3, 29.7, 25.0, 24.2, 23.9. HRMS (FAB) m/z calcd for C39H47N3Cu
(M − Cl) 655.2755, found 655.2746.
(hept, JHH = 7.0 Hz, 1H), 2.69−2.65 (m, 6H), 2.36−2.29 (m, 2H),
2.28−2.23 (m, 3H), 1.84−1.71 (m, 6H), 1.40 (d, 3JHH = 6.9 Hz, 6H),
1.29 (d, JHH = 6.4 Hz, 6H), 1.10 (d, JHH = 6.6 Hz, 6H). 13C NMR
(100 MHz, CDCl3) δ 161.8, 151.8, 146.8, 138.0, 129.7, 129.3, 122.1,
121.0, 117.0, 116.9, 108.6, 60.8, 43.9, 35.8, 34.7, 31.6, 30.0, 25.3, 24.4,
23.7. HRMS (FAB) m/z calcd for C32H42N2Au (M − Cl) 651.3014,
found 651.2996. Mp: 228−231 °C. Crystallization was performed at
room temperature by slow diffusion of n-hexane in a CH2Cl2 solution
of the complex.
3
3
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization data for new
compounds and crystallographic data for 5, 7b, 8a, 8b, 8e, 8h,
9b, 9h, 14, and 15. This material is available free of charge via
the Internet at http://pubs.acs.org.
General Procedure for Synthesis of Copper Complexes
10a,b,f−h. To a solution of 7a,b,f−h (typically 0.1 mmol) in dry
THF (10 mL) was added KOtBu (1.2 equiv), and the mixture was
stirred for 1 h at room temperature. The suspension was filtered
through Celite, and the solvent was removed in vacuo. A solution of
CuCl (1.2 equiv) in dry THF was added (10 mL), and the mixture was
stirred for 4 h at room temperature, filtered, and concentrated in vacuo
to afford the product 10. Starting material, yields, and characterization
data for compounds 10a,b,f−h are as follows.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: perez@dqcm.uhu.es.
*E-mail: jmlassa@iiq.csic.es.
Notes
Data for 10a. From 7a (100 mg, 0.22 mmol), the general
procedure was applied to yield 67 mg (59%) of 10a as a brown solid.
1H NMR (500 MHz, CDCl3) δ 7.63−7.37 (m, 3H), 7.31−7.19 (m,
The authors declare no competing financial interest.
12H), 6.89 (d, 3JHH = 9.3 Hz, 1H), 6.72 (ddd, 3JHH = 9.3, 6.6, 1.0, Hz,
ACKNOWLEDGMENTS
This work was funded by MINECO (grants CTQ2013-48164-
C2-1-P, CTQ2013-48164-C2-2-P, and CTQ2011-28942-C02-
■
3
1H), 6.64 (s, 1H), 6.35 (dt, JHH = 6.8, 1.0 Hz, 1H), 5.50 (m, 1H),
4.73 (m, 1H), 2.34 (m, 2H), 2.20 (m, 2H). 13C NMR (125 MHz,
CDCl3) δ 164.69, 139.90, 139.67, 134.90, 131.95, 131.12, 130.99,
130.67, 130.37, 130.14, 130.05, 129.87, 129.61, 129.56, 129.45, 129.37,
128.88, 128.76, 128.53, 128.33, 123.33, 118.08, 117.42, 117.27, 116.73,
109.21, 71.58, 69.74, 66.19, 54.41, 34.16, 33.27, 30.65, 29.35. HRMS
(FAB) m/z calcd for C30H29N3Cu (M − Cl) 529.1346, found
529.1340.
́
01), European FEDER funds, and the Junta de Andalucia
(Grants 2012/FQM 1078 and P10 FQM 06292).
REFERENCES
■
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1
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3
3JCF = 8.5 Hz), 130.8, 130.0 (d, JCF = 4.7 Hz), 129.6, 129.0, 128.9,
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1
́
(6) (a) Alcarazo, M.; Roseblade, S. J.; Alonso, E.; Fernandez, R.;
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́
Alvarez, E.; Lahoz, F. J.; Lassaletta, J. M. J. Am. Chem. Soc. 2004, 126,
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́
13242−13243. (b) Ros, A.; Monge, D.; Alcarazo, M.; Alvarez, E.;
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3
3
3H), 6.63 (d, JHH = 1.9 Hz, 1H), 6.37 (dt, JHH = 6.6, 1.1 Hz, 1H),
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DOI: 10.1021/acs.organomet.5b00046
Organometallics 2015, 34, 1328−1338

Organometallics
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9.
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DOI: 10.1021/acs.organomet.5b00046
Organometallics 2015, 34, 1328−1338