Highly enantioselective intermolecular carbene insertion to C-H and Si-H bonds catalyzed by a chiral iridium(iii) complex of a D4-symmetric Halterman porphyrin ligand

Article abstract of DOI:10.1039/c2cc30441d

The chiral iridium porphyrin [Ir((-)-D₄-Por*)(Me)(EtOH)] displays excellent reactivity and stereoselectivity towards carbene insertion to C-H and Si-H bonds, affording corresponding products in high yields (up to 96%) and high enantioselectivities (up to 98% ee). The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc30441d

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COMMUNICATION
Highly enantioselective intermolecular carbene insertion to C–H and
Si–H bonds catalyzed by a chiral iridium(III) complex of a D4-symmetric
Halterman porphyrin ligandwz
Jing-Cui Wang,a Zhen-Jiang Xu,a Zhen Guo,b Qing-Hai Deng,a Cong-Ying Zhou,b
Xiao-Long Wana and Chi-Ming Che*ab
Received 19th January 2012, Accepted 9th March 2012
DOI: 10.1039/c2cc30441d
The chiral iridium porphyrin [Ir((ꢀ)-D4-Por*)(Me)(EtOH)] displays
excellent reactivity and stereoselectivity towards carbene insertion to
C–H and Si–H bonds, affording corresponding products in high
yields (up to 96%) and high enantioselectivities (up to 98% ee).
transfer reactions giving products with high stereoselectivity and
high product turnovers under mild conditions.5 However, only few
metalloporphyrin complexes are known to catalyse carbene C–H
insertion with high enantioselectivity.4 Very recently, Suematsu
and Katsuki reported a chiral iridium(III) Schiff-base complex
which can catalyze carbene C–H insertion with diazo esters in high
enantioselectivity at low temperature.6 Herein, we report the first
chiral iridium porphyrin-catalyzed enantioselective carbene C–H
and Si–H bond insertion reactions featuring high enantio- and
diastereo-selectivity and high product turnovers.
Direct functionalization of C–H bonds is an appealing strategy
for C–C, C–N and C–O bond formation due to the abundance of
C–H bonds in organic compounds and the high atom-economy
of this methodology.1 In these endeavours, much attention has
been devoted to develop transition metal-catalyzed carbene
insertion to C–H bonds.2 Chiral rhodium carboxamidates and
carboxylates have been proven to be effective catalysts for highly
enantioselective intramolecular carbene C–H bond insertion
reactions.2 However, the asymmetric intermolecular version
remains a formidable challenge as facile formation of dimer
product(s) from a metal–carbene moiety and low chemo- and
regioselectivity are usually encountered. A notable achievement
in this area is the rhodium prolinate complex [Rh2(DOSP)4]-
catalyzed carbene C–H insertion with aryl- or vinyldiazoacetates
to give products in high enantioselectivity.3 Recently, we reported
a chiral rhodium complex bearing the D4-symmetric Halterman
porphyrin ligand to achieve a highly enantioselective carbene
C–H insertion of alkanes with methyl phenyldiazoacetate.4 Apart
from rhodium complexes, few transition metal complexes are
known to efficiently catalyze intermolecular carbene C–H insertion
with high enantioselectivity.
Complex 1 [Ir(TTP)(Me)(L)] (L = solvent molecule, H2O)
was synthesized in 50% yield by heating [Ir(COD)Cl]2 with
tetrakis(p-tolyl)porphyrin (TTP) in 1,2,4-trichlorobenzene at
190 1C, followed by treatment with NaBH4 and MeI.7 The
complex [Ir((ꢀ)-D4-Por*)(Me)(L)] (L = solvent molecule,
H2O) bearing the D4-symmetric Halterman porphyrin ligand
(H2(D4-Por*) = meso-tetrakis-{(1R,4S,5S,8R)-1,2,3,4,5,6,7,8-
octahydro-1,4:5,8-dimethano-anthracen-9-yl}porphyrin) was
prepared in 64% yield via a similar procedure. Recrystallisation
in a THF/EtOH mixture gave [Ir((ꢀ)-D4-Por*)(Me)(EtOH)] 2,
the structure of which has been determined by X-ray crystal
analysis (Fig. 1).
With complexes 1 and 2, we examined their reactivity towards
intermolecular carbene C–H insertion of 1,4-cyclohexadiene 4 with
methyl phenyldiazoacetate 3a (Table 1). Treatment of 4 with 3a in
the presence of 1 mol% [Ir(TTP)(CO)Cl] at room temperature for
24 h gave the C–H insertion product 5a in 35% isolated yield and
61% substrate conversion (entry 1). [Ir(TTP)(Me)(L)] displayed a
much higher activity than [Ir(TTP)(CO)Cl] with the reaction
reaching completion in 5 min giving 5a in 90% yield under the
Metalloporphyrin complexes of ruthenium, iron, rhodium,
osmium and cobalt are known to catalyze a variety of carbene
a Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis,
Shanghai Institute of Organic Chemistry, 354 Feng Lin Road,
Shanghai, China
b Department of Chemistry, State Key Laboratory of Synthetic
Chemistry, and Open Laboratory of Chemical Biology of the
Institute of Molecular Technology for Drug Discovery and Synthesis,
The University of Hong Kong, Pokfulam Road, Hong Kong, China.
E-mail: cmche@hku.hk; Fax: +852 2857-1586;
Tel: +8522859-2154
w This article is part of the ChemComm ‘Porphyrins and phthalo-
cyanines’ web themed issue.
z Electronic supplementary information (ESI) available: Experimental
procedures and compound characterization. CCDC 790901. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2cc30441d
Fig. 1 Structure of [Ir((ꢀ)-D4-Por*)(Me)(EtOH)] 2.
Chem. Commun., 2012, 48, 4299–4301 4299
c
This journal is The Royal Society of Chemistry 2012

Table 1 C–H insertion reactions of 1,4-cyclohexadiene with methyl
phenyldiazoacetate catalyzed by iridium porphyrins
Scheme 1
be scaled up. Slow addition of a solution of 3a (2 g, 11.4 mmol) in
4 (1 mL) to a mixture of 2 (0.01 mol%) and 4 (2 mL) for 1 h at
0 1C afforded C–H insertion products in 96% isolated yield and
96% ee with a product turnover number of 9600 (Scheme 1).
The 2-catalyzed C–H bond insertion of THF with methyl
aryldiazoacetate was also examined. With 1 mol% 2 as catalyst,
the one-pot reaction of THF with methyl phenyldiazoacetate
proceeded smoothly in DCM at ꢀ40 1C giving C–H insertion
products anti-6a and syn-6a in overall 82% yield with an anti/syn
ratio of 10 : 1, the enantiomeric excess of the major isomer anti-6a
was determined to be 90% (Table 3, entry 1). In most cases, all of
the other aryl substituted diazo compounds 3 reacted with THF
efficiently at ꢀ40 1C to give C–H insertion products in good to
high yields with high diastereoselectivities (up to anti/syn = 20:1)
and excellent enantioselectivities (up to 97% ee). Electron-
donating group MeO led to low product yield and diastereo-
selectivity, but retained high enantio-induction for anti-isomer
(entry 5). It is noteworthy that the syn-selectivity is favorable
in the similar reaction catalyzed by rhodium carboxylates and
iridium(III) Schiff-base complexes,3,6 thus the chiral iridium(III)
porphyrin 2 catalyzed carbene C–H insertion provides the first
efficient method for the enantioselective synthesis of anti-isomer 6.
No reaction was observed with [Ru(D4-Por*)(CO)(EtOH)] as
catalyst under the same conditions.
Entrya Catalyst
Temp./1C Time/h Yieldb (%) eec (%)
1
2
3
4
5
[Ir(TTP)(CO)Cl]
23
23
24
o0.1
o0.1
16
35
90
90
90
90
1
2
2
2
23
ꢀ40
91
95
93
ꢀ78
24
a
Reaction conditions: 4 (4 mmol), 3a (0.4 mmol), catalyst (0.004 mmol),
b
DCM (4 mL). Isolated yield. Determined by chiral HPLC.
c
same conditions (entry 2). When [Ir((ꢀ)-D4-Por*)(Me)(EtOH)] 2
was used, 5a was obtained in 90% yield and 91% ee (entry 3).
Lowering the reaction temperature to ꢀ40 1C extended the reaction
time to 16 h and led to 5a in 95% ee (entry 4). When the reaction
was performed at ꢀ78 1C 5a was obtained in 93% ee (entry 5).
It is noteworthy that the 2-catalyzed carbene C–H insertion was
performed in a one-pot fashion; neither a dimer nor a cyclopropa-
nation product was found in the reaction mixture.
With the optimized conditions, we examined the substituent
effect of methyl aryldiazoacetates on the reaction. As shown in
Table 2, both electron donating and electron withdrawing groups
on the phenyl ring led to C–H insertion products in high yields and
excellent enantioselectivities (Table 2, entries 1–4). Moreover, all of
the reactions were accomplished in a one-pot manner without the
need of slow addition of diazo compounds. Probably due to the
steric hindrance of an o-substituted chloro group, no reaction of
methyl o-Cl-phenyldiazoacetate with 4 was observed (entry 5).
Changing a phenyl to naphthyl group did not affect neither the
reaction yield nor enantioselectivity (entry 6). It is noteworthy that
2 also efficiently catalyzed the C–H insertion of 4 with a-thienyl
substituted diazoacetate in high enantioselectivity (entry 7).
Under the same reaction conditions, the ruthenium analogue
[Ru(D4-Por*)(CO)(EtOH)] failed to effect similar carbene
C–H insertion. The 2-catalyzed C–H insertion protocol can
The Si–H bond insertion catalyzed by 2 was also investigated.8
As shown in Table 4, 2 catalyzed carbene Si–H bond insertion
with various diazo compounds even at ꢀ80 1C to give products
in high yields and good to high enantioselectivities. Among the
diazo compounds examined, methyl p-bromophenyldiazoacetate
was proven to be the most effective giving products in 93% yield
and 91% ee (Table 4, entries 2 and 5).
We also examined the reactivity and stereoselectivity of
2-catalysed cyclopropanation of styrene with EDA. With as low
Table 3 C–H insertion reactions of THF with methyl aryldiazoacetate
catalyzed by 2
Table 2 C–H insertion reactions of 1,4-cyclohexadiene with methyl
aryldiazoacetate catalyzed by 2
Entrya
Ar
Yieldb (%)
anti : sync
eed (%)
Entrya
Ar
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
Ph
6a, 82
6b, 96
6c, 86
6d, 74
6e, 22
6f, 86
6g, 76
6h, 23
10 : 1
90
97
97
96
92
81
92
91
1
2
3
4
5
6
7
p-MeO–C6H4
p-Br–C6H4
p-Cl–C6H4
m-Cl–C6H4
o-Cl–C6H4
2-Naphthyl
3-Thienyl
5b, 94
5c, 91
5d, 82
5e, 90
NR
96
96
98
86
—
95
96
p-Br–C6H4
p-Cl–C6H4
p-Me–C6H4
p-MeO–C6H4
m-Cl–C6H4
2-Naphthyl
3-Thienyl
420 : 1
16.9 : 1
14.6 : 1
2.5 : 1
13.7 : 1
9.3 : 1
5f, 85
5g, 62
420 : 1
a
a
Reaction conditions: 4 (4 mmol), 3 (0.4 mmol), 2 (0.004 mmol),
Reaction conditions: 3 (0.4 mmol), THF (4 mmol), 2 (0.004 mmol),
b
b
c
c
DCM (4 mL), ꢀ40 1C. Isolated yield. Determined by chiral HPLC,
the absolute configuration of the products is determined to be R by
comparing the optical rotation with the literature.
DCM (4 mL), ꢀ40 1C. Isolated yield. Determined by analysis of
the crude reaction mixture, with 1H NMR spectroscopy. Determined
by chiral HPLC.
d
c
4300 Chem. Commun., 2012, 48, 4299–4301
This journal is The Royal Society of Chemistry 2012

Table 4 Si–H insertion reaction with methyl aryl-diazoacetate cata-
lyzed by 2
Entrya
Ar
X
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
Ph
PhMe2Si
PhMe2Si
PhMe2Si
Et3Si
Et3Si
Et3Si
Et3Si
8a, 92
8b, 93
8c, 75
8d, 75
8e, 93
8f, 94
8g, 92
72
91
78
75
91
82
75
p-Br–C6H4
p-Cl–C6H4
Ph
p-Br–C6H4
p-Cl–C6H4
2-Naphthyl
a
Reaction conditions: 3 (0.4 mmol), X–H substrate (0.48 mmol), 2
c
b
(0.004 mmol), DCM (4 mL), ꢀ80 1C, 24 h. Isolated yield. Deter-
mined by chiral HPLC.
Scheme 3 The calculated potential energy surfaces of intermolecular
carbene insertion reaction pathway of I and II to the 1,4-cyclo-
hexadiene at the B3LYP/6-31G(d):LAN2DZ level.
as 0.01 mol% 2 as catalyst, the reaction proceeded smoothly in
DCM at ꢀ78 1C to afford the trans cyclopropyl ester 9 as the
major product in 80% yield with 88% ee and a TON of 8000
(Scheme 2). Upon comparing this result with that catalyzed by
[Ru(D4-Por*)(CO)(EtOH)]9 which effected styrene cyclopro-
panation at room temperature, the change from ruthenium(II)
to iridium(III) greatly speeds up the catalysis.
J.-C. Wang thanks the Croucher Foundation of Hong Kong
for a postgraduate studentship.
Notes and references
1 (a) Activation and Functionalization of C–H Bonds, ed.
K. I. Goldberg and A. S. Goldman, American Chemical Society,
USA, 2004; (b) Handbook of C–H Transformations: Applications in
Organic Synthesis, ed. G. Dyker, Wiley-VCH, Weinheim, 2005;
(c) C–H Activation, Top. Curr. Chem., J.-Q. Yu and Z. Shi, Spring-
er-Verlag, Berlin, 2010vol. 292.
2 Review: (a) T. Ye and M. A. Mckervey, Chem. Rev., 1994, 94, 1091;
(b) M. P. Doyle and D. C. Forbes, Chem. Rev., 1998, 98, 911;
(c) M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds, John Wiley
and Sons, New York, 1998; (d) H. M. L. Davis and R. E.
J. Beckwith, Chem. Rev., 2003, 103, 2861; (e) H. M. L. Davies
and J. R. Denton, Chem. Soc. Rev., 2009, 38, 3061; (f) M. P. Doyle,
R. Duffy, M. Ratnikov and L. Zhou, Chem. Rev., 2010, 110, 704.
3 (a) H. M. L. Davies and D. Morton, Chem. Soc. Rev., 2011,
40, 1857; (b) H. M. L. Davis, T. Hansen and M. R. Churchill,
J. Am. Chem. Soc., 2000, 122, 3063; (c) H. M. L. Davis and
T. Hansen, J. Am. Chem. Soc., 1997, 119, 9075.
We performed DFT calculation on [Ir(TPP)(Me)]-catalyzed
carbene C–H insertion of 4 with 3a via two potential intermediates
I and II as shown in Scheme 3. The transformation of intermediate
I to III via transition state TSI–III requires 19.9 kcal molꢀ1 and this
process is endergonic by 10.6 kcal molꢀ1. Whereas carbene
insertion to 4 from intermediate II has an overall activation barrier
of only 16.2 kcal molꢀ1 via TSII–IV, which is 3.7 kcal molꢀ1
lower than the energy required in the intermediate I pathway.
The formation of product IV is significantly exothermic by
43.9 kcal molꢀ1. Intermediate II has a longer Ir–C(carbene) bond
length than I, (2.06 A vs. 1.90 A for II vs. I), revealing that II is
more facile to undergo the C–H insertion.
To get further information on the reaction mechanism, we
monitored the [Ir(TTP)(Me)(L)] 1-catalyzed carbene C–H insertion
of 4 with 3a by UV-visible absorption and 1H NMR spectro-
scopies. When 3a was added to a CH2Cl2 solution of 1, a shift of
the Soret band from 407 nm to 419 nm was observed. Upon
addition of 4, the Soret band shifted back to 407 nm. By 1H NMR
spectroscopy, addition of 3a to a CDCl3 solution of 1 caused a
downfield shift of the ligated methyl group from ꢀ6.30 ppm to
ꢀ5.71 ppm. The signal then shifted to ꢀ6.45 ppm upon addition of
excess 4. These findings revealed that 1 catalyzed carbene C–H
insertion proceeded through a short-lived intermediate.
4 H.-Y. Thu, G. S.-M. Tong, J.-S. Huang, S. L.-F. Chan, Q.-H. Deng
and C.-M. Che, Angew. Chem., Int. Ed., 2008, 47, 9747.
5 Review: (a) K. M. Kadish, K. M. Smith and R. Guilard, The
Porphyrin Handbook, Academic Press, San Diego, CA, 2000–2003,
vol. 1–20; (b) C.-Y. Zhou, J.-S. Huang and C.-M. Che, Synlett,
2010, 2681; (c) G. Simonneaux and P. Le Maux, Coord. Chem. Rev.,
2002, 228, 43; (d) C.-M. Che and J.-S. Huang, Coord. Chem. Rev.,
2002, 231, 151; (e) G. Maas, Chem. Soc. Rev., 2004, 33, 183;
(f) G. Simonneaux, P. Le Maux, Y. Ferrand and J. Rault-Berthelot,
Coord. Chem. Rev., 2006, 250, 2212.
6 H. Suematsu and T. Katsuki, J. Am. Chem. Soc., 2009, 131, 14218.
7 For recent synthesis and application of iridium porphyrin, see:
(a) H. Kanemitsu, R. Harada and S. Ogo, Chem. Commun., 2010,
46, 3083; (b) S. K. Yeung and K. S. Chan, Organometallics, 2005,
24, 6426; (c) M. Yanagisawa, K. Tashiro, M. Yamasaki and
T. Aida, J. Am. Chem. Soc., 2007, 129, 11912.
We acknowledge the support from The University of
Hong Kong (University Development Fund), Hong Kong
Research Grants Council (HKU 1/CRF/08), CAS-GJHZ200816
and CAS-Croucher Funding Scheme for Joint Laboratory.
8 For recent metal catalyzed Si–H insertion, see: (a) Y.-Z. Zhang,
S.-F. Zhu, L.-X. Wang and Q.-L. Zhou, Angew. Chem., Int. Ed.,
2008, 47, 8496; (b) Y. Yasutomi, H. Suematsu and T. Katsuki,
J. Am. Chem. Soc., 2010, 132, 4510.
9 C.-M. Che, J.-S. Huang, F.-W. Lee, Y. Li, T.-S. Lai, H.-L. Kwong,
P.-F. Teng, W.-S. Lee, W.-C. Lo, S.-M. Peng and Z.-Y. Zhou,
J. Am. Chem. Soc., 2001, 123, 4119.
Scheme 2
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 4299–4301 4301