Iron Porphyrin Catalyzed Insertion Reaction of N-Tosylhydrazone-Derived Carbenes into X-H (X = Si, Sn, Ge) Bonds

Article abstract of DOI:10.1021/acs.orglett.8b01931

An efficient Fe(TPP)Cl catalyzed insertion reaction of in situ generated benzylic carbenes from N-tosylhydrazones into X-H (X = Si, Sn, Ge) was developed. Silanes bearing tertiary, secondary, and primary (3°, 2°, and 1°) Si-H bonds all reacted well to afford insertion products in moderate to high yields (up to 97%), and the reaction time could be significantly shortened to 1 h under microwave irradiation. A programmable stepwise double insertion strategy was developed for the synthesis of unsymmetrical tetrasubstituted silanes.

Full text of DOI:10.1021/acs.orglett.8b01931

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Iron Porphyrin Catalyzed Insertion Reaction of N‑Tosylhydrazone-
Derived Carbenes into X−H (X = Si, Sn, Ge) Bonds
En-Hui Wang,† Yuan-Ji Ping,‡ Zong-Rui Li,‡ Hongling Qin,‡ Zhen-Jiang Xu,*,‡
and Chi-Ming Che*,‡,§
†School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, P. R. China
‡Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, 354 Feng Lin Road,
Shanghai 200032, P. R. China
§Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong
Kong, P. R. China
S
* Supporting Information
ABSTRACT: An efficient Fe(TPP)Cl catalyzed insertion reaction of in situ generated benzylic carbenes from N-
tosylhydrazones into X−H (X = Si, Sn, Ge) was developed. Silanes bearing tertiary, secondary, and primary (3°, 2°, and
1°) Si−H bonds all reacted well to afford insertion products in moderate to high yields (up to 97%), and the reaction time
could be significantly shortened to 1 h under microwave irradiation. A programmable stepwise double insertion strategy was
developed for the synthesis of unsymmetrical tetrasubstituted silanes.
transition metal catalyzed carbene insertion reaction to
sulfonylhydrazones would be beneficial.10 An elegant AgOTf
AX−H bonds is a straightforward and appealing strategy prompted carbene insertion reaction into a tertiary Si−H bond
was reported by Bi and co-workers in 2017.11 N-Nosylhy-
drazones derived from aldehydes and ketones were successfully
used as the carbene precursor, and the corresponding insertion
products were isolated in moderate to high yields. Unfortu-
nately, the more commonly used N-tosylhydrazone gave a low
yield under the same reaction conditions, and 30 mol %
AgOTf was necessary for achieving a high yield of the insertion
product. Recently, Xiao and Lin reported the iron porphyrin
catalyzed insertion reaction into a tertiary Si−H bond with tri-
and difluoromethylcarbene generated in situ from sulfonium
salts, in which the fluorinated carbon chain was essential for
the reaction.12 Metal porphyrins are robust catalysts in carbene
transfer reactions.9a,13 We have previously reported the
isolation of reactive iron porphyrin carbene intemediates
which may undergo C−H insertion14 and found iridium
porphyrin could efficiently catalyze asymmetric Si−H insertion
with a donor−acceptor diazo compound as the carbene
source.7b Herein, we would like to report our work on iron
for the construction of C−X bonds.1 In particular, the metal
catalyzed carbene insertion reaction into the Si−H bond of
simple silanes has emerged as an efficient and convenient
method for the preparation of functionalized organosilicon
compounds.2 Due to the versatile application of organosilicon
compounds in organic synthesis3 and material science4 as well
as the abundance of simple silanes, much effort has been
devoted to metal complexes catalyzing selective carbene
insertion reactions to Si−H bonds. Transition metals such as
Rh,5 Cu,6 Ir,7 and Ru8 have been reported to catalyze the
decomposition of diazo compounds for generation of carbene
intermediates and insertion to Si−H bonds with high
efficiency. It is noteworthy that, recently, iron catalysts were
also reported to catalyze the carbene insertion reaction of Si−
H bonds with α-diazo compounds as the carbene source.9
Despite the fact that much progress has been achieved in
transition metal catalyzed Si−H insertion reactions with diazo
compounds as the carbene source, the toxicity and potential
explosive character of diazo compounds restrict their
application in organic synthesis. In this regard, generation of
diazo compounds in situ from a stable precursor such as N-
Received: June 21, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01931
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
porphyrin catalyzed selective carbene insertion into X−H
bonds with readily available N-tosylhydrazones as the carbene
source. Not only tertiary, but also secondary and primary Si−H
bonds, could be efficiently inserted under mild reaction
conditions. Consequently, a programmable stepwise insertion
sequence was developed, through which unsymmetrical
tetrasubstituted silanes could be easily accessed. In addition,
the insertion reaction of Sn−H and Ge−H bonds could also be
efficiently catalyzed to afford the insertion products in high
yields.
The catalytic carbene insertion reaction into a Si−H bond
was initially investigated using triethylsilane 1a as the model
substrate and N-tosylhydrazone 2a as the carbene source, in
the presence of various catalysts including iron porphyrins
(Figure 1) with K2CO3 as a base in toluene at 80 °C. The
Table 1. Optimization of the Reaction Conditions
b
entry
solvent
toluene
DCM
CHCl3
DCE
THF
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
base
temp (°C)
yield (%)
1
2
3
4
5
6
7
8
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
80
80
80
80
80
80
60
110
80
80
80
80
80
80
80
80
80
76
69
42
76
51
60
NP
38
5
4
34
2
90
85
75
90
92
9
10
11
12
DBU
KH2PO4
Na2CO3
NaH
NaH
NaH
c
13
cd
,
14
15
16
17
ce
,
cf
,
NaH
NaH
cg
,
Figure 1. Structure of iron porphyrin catalysts.
a
Unless otherwise specified, reaction conditions were as follows: 1a
(0.2 mmol), 2a (0.4 mmol, 2 equiv), cat. (2 mol %), and
corresponding base (0.4 mmol, 2 equiv) were reacted in specified
reactions catalyzed by copper salts were complicated, and the
desired Si−H insertion product 3a was formed in only 16−
25% yields (entries 1−4, Table S1 in the Supporting
Information). Subsequently, some rhodium and cobalt
porphyrins were investigated as the catalyst in the reaction
(entries 5−10, Table S1), and Rh(TPP)Cl showed higher
activity to afford 3a in 50% yield (entry 6, Table S1). To our
delight, when various iron porphyrins (Figure 1) were
employed as the catalyst (entries 11−15, Table S1), the
readily available iron porphyrin Fe(TPP)Cl sufficiently
promoted the Si−H insertion reaction to afford 3a in a
much higher yield of 62% (entry 12, Table S1). Extension of
the reaction time to 14 h further improved the reaction, and 3a
was isolated in 76% yield (entry 15, Table S1).
b
solvent (2 mL) at the specified temperature for 14 h. Isolated yield.
c
d
e
f
1.2 equiv of NaH were used. 1 mol % cat. 0.5 mol % cat. 5 mol %
g
cat. 4 equiv of Et3SiH were used.
N-tosylhydrazones into Et3SiH was investigated; the corre-
sponding products are depicted in Scheme 1. A series of N-
a b
,
Scheme 1. Scope of N-Tosylhydrazones
With Fe(TPP)Cl as the catalyst, the reaction conditions
were further optimized (Table 1). The reaction was tolerant to
a number of common solvents such as DCM, CHCl3, DCE,
THF, and 1,4-dioxane, and 3a was obtained in moderate to
good yields. Toluene and DCE led to the highest yield of 76%
(Table 1, entries 1−6). Either lowering or raising the reaction
temperature led to a lower yield of 3a, which may due to the
insufficient conversion of N-tosylhydrazones to the diazo
compound at 60 °C and more competitive side reactions at
110 °C (Table 1, entries 7−8). It is noteworthy that the base
played an important role for achieving a high yield of 3a.
Organic bases such as Et3N and DBU were not strong enough
to convert N-tosylhydrazones 2a to the corresponding diazo
compound, and only a trace amount of 3a was formed (Table
1, entries 9−10). Stronger inorganic bases gave better results,
and NaH proved to be the best to afford 3a in 90% yield
(Table 1, entries 11−13). Lowering the catalyst loading to 1
and 0.5 mol % led to slightly lower yields of 85% and 75%,
respectively (Table 1, entries 14−15), while increasing the
catalyst loading to 5 mol % did not improve the reaction
(Table 1, entry 16). Increasing the amount of Et3SiH to 4
equiv slightly improved the yield (Table 1, entry 17).
a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), Fe(TPP)Cl (2
mol %), and NaH (0.24 mmol) were reacted in toluene (2 mL) at 80
°C for 14 h. Isolated yield. K2CO3 (2 equiv) was used. 42% 2-
naphthylethylene was formed.
b
c
d
tosylhydrazones derived from different substituted benzalde-
hydes were well tolerant of the optimized reaction conditions.
The insertion products were generally obtained in moderate to
excellent yields, regardless of the electronic nature and position
of the substituents in the phenyl ring (3b−o). N-Tosylhy-
drazone 1p derived from β-naphthaldehyde also underwent the
reaction well to afford the insertion product 3p in 76% yield.
The α,β-unsaturated aldehyde derived N-tosylhydrazone 1q
With the optimized reaction conditions and employing 2
mol % Fe(TPP)Cl as catalyst, the insertion reaction of various
B
DOI: 10.1021/acs.orglett.8b01931
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
could also be converted to the corresponding insertion product
3q in 28% yield. N-Tosylhydrazones derived from ketones
were subsequently investigated. When the N-tosylhydrazone
derived from 2-acetonaphthone 1r was treated under the
optimized reaction conditions, 42% of 2-naphthylethylene
derived from 1,2-hydride migration was formed instead of the
desired insertion product 3r. Changing the base from NaH to
K2CO3 improved the reaction and 3r was afforded in 26%
yield. When benzophenone derived N-tosylhydrazone 1s was
employed as the substrate, 1,2-hydride migration dominated
and 3s was not detected. When N-tosylhydrazone 1t and 1u
derived from ketones without an α-hydride were attempted,
alkenes derived from the dimerization side reaction dominated
and no desired insertion products were detected.
Scheme 3. Synthesis of Tetrasubstituted Silanes
a
b
c
Reactions were run with 0.2 mmol silane. Isolated yield. Mono Si−
H insertion product 4i was isolated in 38% yield.
Subsequently we explored the scope of silanes, and the
results are summarized in Scheme 2. Tributyl silane and
silanes 5b−5d were obtained in moderate to good yields, thus
providing an efficient programmable method for the
preparation of tetrasubstituted silanes.
a b
,
Scheme 2. Scope of Silanes
The insertion reactions of N-tosylhydrazones into Sn−H
and Ge−H bonds were also explored with the same reaction
conditions (Scheme 4). N-Tosylhydrazones derived from both
Scheme 4. Scope of Fe(TPP)Cl Catalyzed Carbene
a b
,
Insertion into Sn/Ge−H Bonds
a
Reaction conditions: 1 (0.2 mmol), 6 (0.4 mmol), Fe(TPP)Cl (2
mol %), and NaH (0.24 mmol) were reacted in toluene (2 mL) at 80
°C for 14 h. Isolated yield.
a
b
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), Fe(TPP)Cl (2
mol %), and NaH (0.24 mmol) were reacted in toluene (2 mL) at 80
°C for 14 h. Isolated yield.
b
aldehydes and benzophenone reacted with tributylstannane
hydride and triphenylstannane hydride to afford 7a−7d in
moderate to good yields. Similarly, the insertion into the Ge−
H bond was also applicable to afford 7e−7h in moderate to
high yields.
To demonstrate the utility of this novel iron porphyrin
catalyzed insertion reaction, a gram-scale reaction of Fe(TPP)
Cl catalyzed N-tosylhydrazone 2a derived carbene insertion
into the secondary Si−H bond of methylphenylsilane was
conducted, and the desired insertion product 4i was isolated in
64% yield (Scheme 5, equation a). Moreover, the insertion
reaction could be carried out under microwave irradiation
conditions at 80 °C and no precaution related to moisture and
oxygen was needed. The reaction time was greatly shortened to
1 h, and the corresponding insertion products were afforded in
moderate to good yields. And the reaction even worked at 60
°C, albeit with a lower yield (Scheme 5, equation b).
In conclusion, we successfully developed a practical and
efficient iron porphyrin catalyzed carbene insertion into X−H
(X = Si, Sn, and Ge) bonds with readily available N-
tosylhydrazones as the carbene source. With as low as 2 mol %
Fe(TPP)Cl as the catalyst, a series of different substituted N-
tosylhydrazones derived from benzaldehydes sufficiently
reacted with silanes bearing tertiary, secondary, and primary
Si−H bonds under mild reaction conditions to afford the
triphenyl silane afforded the corresponding insertion products
4a−4d in moderate to good yields. tert-Butyldimethylsilane
was also a suitable substrate for this reaction albeit with a
relatively low yield, presumably due to the steric hindrance of
the tert-butyl group. To our delight, silanes with secondary Si−
H bonds could also be employed in the reaction. The insertion
reaction of both methylphenylsilane and diphenylsilane
proceeded smoothly with a variety of different substituted N-
tosylhydrazones under the optimized reaction conditions, and
the insertion products 4g−4q were obtained in moderate to
good yields. It is noteworthy that the insertion into the primary
Si−H bond of phenylsilane was also applicable to give the
corresponding insertion products 4r−4t in relatively low yield.
As insertion into secondary Si−H bonds could be efficiently
catalyzed by Fe(TPP)Cl, a novel method for the preparation of
tetrasubstituted silanes was further developed (Scheme 3).
When methylphenylsilane was treated with excess 2a (5
equiv), the one-pot double Si−H insertion reaction occurred
to afford the desired tetrasubstituted silane 5a in 60% yield,
and the mono Si−H insertion product 4i was obtained in 38%
yield. Alternatively, when mono Si−H insertion product 4i was
treated with an excess of different N-tosylhydrazones with the
optimized reaction conditions, unsymmetrical tetrasubstituted
C
DOI: 10.1021/acs.orglett.8b01931
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Organic Letters
Letter
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a
Reaction was conducted at 60 °C for 1 h.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b01931.
■
S
Synthesis and analytical data, NMR spectra (PDF)
́
J.; Valdes, C. Angew. Chem., Int. Ed. 2011, 50, 7486. (e) Fulton, J. R.;
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AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: xuzhenjiang@sioc.ac.cn.
*E-mail: cmche@hku.hk.
ORCID
Zhen-Jiang Xu: 0000-0003-3574-917X
Chi-Ming Che: 0000-0002-2554-7219
Notes
The authors declare no competing financial interest.
(14) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.; Che, C.-M.; You, X.-Z. J. Am.
Chem. Soc. 2002, 124, 13185.
ACKNOWLEDGMENTS
■
We sincerely thank the National Natural Science Foundation
of China (NSFC 21472216), the CAS-Croucher Funding
Scheme for Joint Laboratories and Hong Kong Research
Grants Council General Research Fund (17306714, 17303815,
17301817) for financial support.
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DOI: 10.1021/acs.orglett.8b01931
Org. Lett. XXXX, XXX, XXX−XXX