Efficient intramolecular C-H insertion catalyzed by iridium porphyrin complexes

Article abstract of DOI:10.1055/s-0032-1317296

Octaethylporphyrin and tetraphenylporphyrin Ir(I) and Ir(III) complexes are useful catalysts for intramolecular C-H insertion processes of stabilized diazo compounds. While the Ir(I) complex TPP[Ir(CO)is the most efficient and selective catalyst, the othe

Full text of DOI:10.1055/s-0032-1317296

LETTER
▌2469
letter
Efficient Intramolecular C–H Insertion Catalyzed by Iridium Porphyrin
Complexes
Efficient Intramolecular C–H Insertion
Cristóbal López-Sánchez, Míriam Álvarez-Corral, Manuel Muñoz-Dorado, Ignacio Rodríguez-García*
Department of Organic Chemistry, University of Almería, 04120 Almería, Spain
Fax +34(950)015481; E-mail: irodrigu@ual.es
Received: 10.05.2012; Accepted after revision: 23.08.2012
um(III) porphyrin complex,41 there are no examples on the
use of iridium porphyrins, or related complexes, for this
type of cyclization. In addition, the use of iridium com-
plexes can be competitive towards rhodium complexes
Abstract: Octaethylporphyrin and tetraphenylporphyrin Ir(I) and
Ir(III) complexes are useful catalysts for intramolecular C–H inser-
tion processes of stabilized diazo compounds. While the Ir(I) com-
plex TPP[Ir(CO)3]2 is the most efficient and selective catalyst, the
others afford mixtures of cyclization and dimerization products. due to its lower price, and also has a potential in green
chemistry if water-soluble iridium porphyrins42,43 could
The effect of the solvent polarity on the selectivity of the reaction is
also presented.
be developed as catalysts.
Key words: iridium complexes, porphyrins, diazo compounds, car-
In this study, we report a convenient strategy to obtain ox-
bene complexes, intramolecular C–H insertion
ygenated five-membered rings through intramolecular C–
H insertion reaction using diazo compounds as starting
materials and iridium catalysts. We present also a compar-
Iridium complexes are excellent catalysts for a large
ative study of Ir(I) towards Ir(III) in this cyclization pro-
group of reactions in organic synthesis, like hydrogena-
cess. The method can be used for the preparation of the
dihydrobenzo[b]furan moiety present in numerous natural
products.
tion processes,1–3 oxidations,4 allylic substitutions and re-
lated reactions,5–7 cycloadditions and cycloisomerizations,8
alkylations and carbonylations,9 aldol condensations,10
In our initial studies, we explored the reaction of 2-(2-ben-
zyloxyphenyl)-2-diazoacetate (1)44,45 with several com-
mercial iridium catalysts (Table 1, Scheme 1).46
and cross-coupling reactions.11 The intramolecular C–H
insertion processes are among the best ways to form new
3
C–C bonds in cyclization processes.12 The Csp –H inser-
tion by carbenoid transfer reaction is a useful tool in or-
ganic synthesis13,14 because it is an atom efficient catalytic
method, which usually offers high yields and has a poten-
tial asymmetric version. Excellent applications have been
described, based on the use of rhodium,15–17 ruthenium,18
silver,19–21 iron,22,23 copper21 and gold24 complexes. The
mechanism of the C–H insertion process by treatment of
diazo compounds with rhodium complexes has been stud-
ied.25 Recently, iridium complexes have also proved to be
able to convert diazo compounds into useful carbenoids.
Thus, iridium(III)–salen complexes have been used by
O
CO2Me
OBn
CO2Me
2
iridium catalyst
solvent
+
1
N2
CO2Me
OBn
BnO
MeO2C
3
Katsuki and co-workers in intermolecular Csp –H26 and
3
Si–H27 insertions by decomposition of α-diazoacetates,
and for the intramolecular benzylic amination through in-
sertion of nitrenes into C–H bonds.28
Scheme 1 Preparation of dihydrobenzo[b]furan 2 and dimer 3 from
diazoacetate 1
The use of porphyrins as ligands in transition metal com-
plexes has emerged as a new source of metal catalysts for
Csp –H insertion reactions through carbenoids prepared
Table 1 C–H Insertion with Several Commercial Iridium Catalysts
3
Entry Catalyst
Ir
Solvent Product
Yield (%)
from diazo reagents.22,23,29–31 The intramolecular version
of these reactions is useful for the preparation of carbo-
and heterocycles which are frequently found as the core
part of important bioactive natural products. Furthermore,
although the activation of C–H bonds by iridium(I) com-
plexes have been extensively studied,32–40 as well as the
intermolecular carbene insertion to C–H by a chiral iridi-
1
2
3
4
5
Ir4(CO)12
0
0
I
toluenea degradation
–
Ir4(CO)12
THFa
degradation
–
[Ir(CO)3Cl]2
[Ir(CO)3Cl]2
[Ir(cod)Cl]2
toluenea
THFa
3
17
46
I
3
I
THFa
2 + 3
21 (2)
42 (3)
SYNLETT 2012, 23, 2469–2472
Advanced online publication: 21.09.2012
DOI: 10.1055/s-0032-1317296; Art ID: ST-2012-D0406-L
© Georg Thieme Verlag Stuttgart · New York
6
7
Ir(acac)3
Ir(acac)3
III
III
THFa
s.m.c
–
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
tolueneb
2
30
a The reaction was performed at room temperature.
b The reaction was carried out at reflux.
c The starting material was recovered.

2470
C. López-Sánchez et al.
LETTER
While the iridium(0) complex gave no results (entries 1 fast and clean reaction, which can be completed in few
and 2), all the iridium(I) complexes gave the dimerization minutes even at low temperatures (Table 2, entry 5). How-
product 3 (entries 3–5).47 In addition, [Ir(cod)Cl]2 gave ever, with this catalyst, no diastereoselectivity was ob-
also the desired cyclization product, the 2,3-dihydroben- served, as the cis/trans ratio was 50:50, possibly due to the
zo[b]furan 2,45 although as the minor component of a mix- fact that its high catalytic activity makes the energy pro-
ture with the dimer 3. Moreover, although the iridium(III) files of both pathways very similar and advantageous to-
complex Ir(acac)3 did not promote any reaction at room wards the intermolecular dimerization. The Ir(III)
temperature in any solvent, when the conditions were porphyrin complexes 6 and 7 proved to have a lower cat-
forced (refluxing toluene; Table 1, entry 7) the cyclized alytic ability, needing higher temperatures and longer re-
product was formed, although in poor yields. These re- action times. In addition, mixtures of cyclized product 2
sults prompted us to prepare new iridium complexes to and dimer 3 were formed (Table 2, entries 6–10). Finally,
3
study their ability to promote this intramolecular Csp –H the Ir(III)–salen complex also promoted the cyclization at
insertion reaction. Complexes presented in Figure 1 were room temperature, although with low conversion rates
prepared48 and spectroscopically characterized.49 14N even with long reaction times, resulting in reduced yields
NMR was measured in all the porphyrin complexes. A by formation of decomposition side products (entry 11).
significant shielding is observed when compared with the High temperatures and long reaction times increased the
free porphyrin (i.e. δ = 265.90 ppm in TPPH2 vs. δ = conversion degree, but in this case, dimerization was also
264.08 ppm in 5). Thus, the iridium porphyrins complexes observed (Table 2, entries 12–14).
4–7 were obtained using the methodology reported by
Yoshida et al.50,51 while the iridium (III)–salen complex 8
Table 2 C–H Insertion in Compound 1 with Iridium Porphyrins and
Salen Complexesa
was prepared following a Schrock52 modified procedure.53
Entry Complex
Temp Time Ratio Yield dr of 2
(%)b
(cis/trans)
CO
Ir
(°C)
2/3
CO
Ir
OC
CO
OC
N
CO
N
1
OEP[Ir(CO)3]2
25
40
25
0
1 h
5 h
–
–
–
Et
Et
Ph
Ph
Et
Et
2
98:2 95
30:70
50:50
50:50
50:50
–
N
N
N
Et
Et
N
3
TPP[Ir(CO)3]2
0.5 h 100:0 98
N
N
Ph
Et
Ph
4
1 h
1 h
1 h
5 h
–
100:0 98
100:0 98
Et
Ir
Ir
OC
OC
5
–50
CO
CO
OC
OC
6
OEP[Ir(CO)Cl] 25
40
–
–
OEP[Ir(CO)3]2 (4)
TPP[Ir(CO)3]2 (5)
7
89:11 85
30:70
–
8
TPP[Ir(CO)Cl]
25
40
50
–
–
Et
Ph
Et
9
117 h 52:48 46
27 h 40:60 40
20 h 100:0 12
58:42
67:33
50:50
50:50
50:50
50:50
Et
Et
N
N
N
N
CO N
Ir
Cl
CO N
Ir
10
11
12
13
14
Ph
Ph
Ir[salen][toluene] 25
N
N
Cl
Et
Et
40
50
60
4 d
2 d
50:50 26
55:45 40
Et
OEP[Ir(CO)Cl] (6)
Et
Ph
TPP[Ir(CO)Cl] (7)
31 h 52:48 52
Figure 1 Iridium–porphyrin complexes
a Reaction solvent was THF.
b Yields are for isolated products after column chromatography.
With all these complexes in hand, we could check their
ability to catalyze the intramolecular C–H insertion reac-
tion from compound 1, under the reaction conditions
shown in Table 2.
The influence of the solvent was also studied using com-
plex 5 (Table 3). While less polar solvents afforded only
the cyclized product in excellent yield (entries 1–3), more
polar solvents promoted also the formation of the dimer 3.
In DMSO, the dimerization product was formed exclu-
sively. These results suggest that the reaction transition
state leading to the cyclized product is much less polar
than the transition state leading to the dimer. It is worth
mentioning that, in contrast to the previously reported
iridium complexes catalyzed C–H activation reactions,26
The octaethylporphyrin tricarbonyl iridium(I) complex
(4) did not promote the reaction at room temperature, but
at 40 °C (Table 2, entry 2) gave, in almost quantitative
yield, both isomers of the cyclized product 2, with the
trans diastereomer being the major one. A small amount
of the dimer 3 was also formed. To our delight, the other
prepared Ir(I) complex, tetraphenylporphyrin tricarbonyl
iridium(I) (5) gave exclusively the cyclized product in a
Synlett 2012, 23, 2469–2472
© Georg Thieme Verlag Stuttgart · New York

LETTER
Efficient Intramolecular C–H Insertion
2471
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no intermolecular solvent reaction products were detected
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Table 3 C–H Insertion with TPP[Ir(CO)3]2 (5) with Different Sol-
vents and Temperatures
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Entry Solvent
T
(°C)
Time
2/3
Yield
(%)
dr of 2
(cis/trans)
1
2
3
4
5
6
toluene
CH2Cl2
THF
25 30 min 100:0
25 45 min 100:0
25 60 min 100:0
99
97
98
97
98
99
54:45
38:61
50:50
33:67
50:50
–
CHCl3
MeCN
DMSO
45 3 d
70 5 d
65 7 d
60:40
50:50
0:100
In conclusion, the use of iridium porphyrins, mainly the
Ir(I) complex TPP[Ir(CO)3]2, has proved to be a conve-
nient approach to synthesize dihydrobenzo[b]furans
3
through intramolecular Csp –H insertion in high yields.
No intermolecular C–H insertion with the solvent was ob-
served. No derivatives of the porphyrin nucleus due to re-
action with carbenoids were formed. The oxidation state,
the nature of side ligands and the stereoelectronic nature
of the porphyrin have a strong influence on the catalytic
activity. The reactions with the tetraphenylporphyrin
complex 5 were faster than those with the other complex-
es used. We are currently exploring the preparation of chi-
ral porphyrin ligands to be used in the asymmetric version
of the reaction. A water-soluble porphyrin complex is also
being explored.
Acknowledgment
We wish to acknowledge the Spanish Ministerio de Ciencia e Inno-
vación for financial support (Project CTQ2010-17115), and the
Universidad de Almería for a scholarship to C. López-Sánchez.
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Chem. Soc. 1983, 105, 7190.
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(46) Procedure for Intramolecular Csp3–H Insertion
Reaction: The catalyst (5% mmol) was added to a solution
of diazo compound 1 (0.2 mmol) in anhyd solvent (10
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2469–2472

2472
C. López-Sánchez et al.
LETTER
mL/mmol) under a nitrogen atmosphere. The reaction was
monitored by TLC until completion. Next, the solvent was
removed at reduced pressure and the residue was chromatog-
raphed (SiO2), eluting with a mixture of hexane–Et2O (98:2).
Compounds 2 and 3 were obtained in different relations and
yields (see Table 1).
8:2, 6:4 and 1:1) affording a red solid which was identified
as the iridium(I) complex 5.
(49) Spectroscopic data of OEP[Ir(CO)3]2 (4) have been
described previously.50 14N NMR (36.15 MHz, CDCl3): δ =
263.92. Spectroscopic data of TPP[Ir(CO)3]2 (5): IR (film):
2923, 2852, 2052, 1982, 1596, 1441, 1357, 1073, 1017 cm–
1. HRMS (FAB): m/z [M + H]+ calcd for C50H28N4O6Ir2:
1166.1267; found: 1166.3176. 1H NMR (300 MHz, CDCl3):
δ = 7.81 (m, 3 H, H3′, H4′, H5′), 8.15 (m, 2 H, H2′, H6′), 8.90
(br s, 2 H, Hβ). 13C NMR (75 MHz, CDCl3): δ = 123.18 (C,
Cmeso), 124.35 (CH, C3′, C4′, C5′), 124.72 (CH, C2′, C6′),
(47) Spectroscopic Data of Dimethyl 2,3-Bis[2-(benzyloxy)-
phenyl]maleate (3): IR(film): 1010, 1110, 1273, 1595, 1664,
1737, 2851, 2920 cm–1. 1H NMR (300 MHz, CDCl3): δ =
3.35 (s, 3 H, CO2Me), 5.11 (s, 2 H, OCH2Ph), 7.08 (m, 2 H,
H6, H4), 7.55 (m, 5 H, H2′–H6′), 7.61 (dt, 3J = 7.5 Hz, 4J =
1.9 Hz, 1 H, H5), 7.93 (dd, 3J = 7.8 Hz, 4J = 1.9 Hz, 1 H, H3).
13C NMR (75 MHz, CDCl3): δ = 51.84 (Me, CO2Me), 71.18
(OCH2Ph), 112.65 (CH, C6), 121.43 (CH, C4), 122.68 (C,
C2), 128.47–128.66 (CH, C2′,C3′,C4′), 130.91 (CH, C3),
133.98 (C, C=C), 135.10 (C, C1′), 136.32 (CH, C5), 159.41
(C, C1), 165.41 (CO2Me).
(48) Representative Procedure of the Synthesis of Iridium
Porphyrin Complexes:50 A mixture of (TPP)H2 (39 mg,
0.06 mmol) and [Ir(CO)3Cl]2 (20 mg, 0.06 mmol) in xylene
(3 mL) was stirred at reflux temperature for 15 h under a N2
atmosphere. The resulting solution was evaporated at
reduced pressure and the residue was chromatographed on a
silica gel column with several solvent mixtures to afford
three fractions. The first one (hexane–Et2O, 9:1), was non-
reacted tetraphenylporphyrin, which could be recycled. The
second fraction (toluene–acetone, 3:1) was a brown-red
solid, and the third fraction a purple solid. This was
129.32 (CH, Cβ), 135.59 (C, C1′), 201.53 (C, C=O). 14
NMR (36.15 MHz, CDCl3): δ = 264.08. Spectroscopic data
of OEP[Ir(CO)Cl] (6) have been described previously.50 14
N
N
NMR (36.15 MHz, CDCl3): δ = 264.01. Spectroscopic data
of TPP[Ir(CO)Cl] (7): IR (film): 2962, 2059, 1259, 1173,
1017, 870 cm–1. HRMS (FAB): m/z [M + H]+ calcd for
C45H29N4OClIr: 869.1654, found: 869.1622. 1H NMR (300
MHz, CDCl3): δ = 7.78 (m, 3 H, H3′, H4′, H5′), 8.21 (m, 2
H, H2′, H6′), 8.82 (br s, 2 H, Hβ). 13C NMR (75 MHz,
CDCl3): δ = 118.14 (C, Cmeso), 124.72 (CH, C3′, C4′, C5′),
125.75 (CH, C2′, C6′), 132.48 (CH, Cβ), 140.43 (C, C1′).
14N NMR (36.15 MHz, CDCl3): δ = 264.2.
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recrystallized in EtOH to afford the iridium(III) complex 7.
The second fraction (brown-red solid) was recromatographed
with different mixtures of toluene and acetone (100:0, 95:5,
Synlett 2012, 23, 2469–2472
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