Fe(II)-Catalyzed alkenylation of benzylic C-H bonds with diazo compounds

Article abstract of DOI:10.1039/c9cc01060b

We report herein an alkenylation of benzylic C(sp³)-H bonds with diazo compounds via carbon cation intermediates with DDQ as the oxidant in the presence of a catalytic amount of Fe(ii). Diphenylmethane, toluene, benzyl methyl sulfide and their derivatives could be applied as substrates to afford the tetra-substituted olefin products, which may serve as useful building blocks in organic synthesis.

Full text of DOI:10.1039/c9cc01060b

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DOI: 10.1039/C9CC01060B
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Fe(II)-Catalyzed Alkenylation of Benzylic C-H Bonds with Diazo
Compounds†
Jiang-Ling Shi,a Qinyu Luo,a Weizhi Yu,a Bo Wang,a Zhang-Jie Shib and Jianbo Wanga*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
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We report herein an alkenylation of benzylic C(sp3)-H bonds with
diazo compounds via carbon cation intermediates with DDQ as the
oxidant in the presence of catalytic amount of Fe(II).
Diphenylmethane, toluene, benzyl methyl sulfide and their
derivatives could be applied as the substrates to afford the tetra-
substituted olefin products, which may be served as useful
building blocks in organic synthesis.
Transition-metal-catalyzed oxidative transformation of C(sp3)-H
bonds has emerged as one of the important tools in synthetic
organic chemistry.1-4 In particular, Fe(II)-catalyzed oxidative
coupling of benzylic C(sp3)-H bonds have attracted considerable
attentions.5,6 The general pathway of this type of transformations is
shown in Scheme 1a. In the presence of oxidant and Fe(II) catalyst,
benzylic cation is generated through hydrogen abstraction followed
by single electron oxidation of the generated benzylic radical
species. The benzylic cation is then trapped by a nucleophile to
deliver the product. With Fe(II)/2,3-dichloro-5,6-dicyanoquinone
(DDQ) reaction system, various nucleophiles have been explored in
the benzylic C(sp3)-H bond functionalizations.5-11 For examples, Shi
et al. reported an oxidative coupling of C(sp3)–H bonds with arenes,
vinyl acetates with Fe(II) catalyst and DDQ as the oxidant.8,9 Jiao et
al. explored azides as the nucleophiles in the amidation reaction of
diphenylmethane through benzylic C(sp3)-H bond cleavage and
Schmidt rearrangement.10 In 2015, Song et al. used 1,3-dicarbonyl
compounds as the nucleophiles in the similar reaction system with
arylmethanes.11 While significant progresses have been made in
this arena, the scope of this type of transformations is still limited.
Thus, further exploration of other nucleophiles is highly desirable.
On the other hand, diazo compounds have found wide
applications as carbene precursors in transition-metal-catalyzed
Scheme 1 Fe(II)-Catalyzed Oxidative Coupling of Benzylic C(sp3)-H Bonds.
reactions.12 Diazo compounds have also been as nucleophiles in
various transformations.13 In particular, the reaction of diazo
compounds with carbon cations is well-known in the literature.14
We thus conceived that for the above-mentioned Fe(II)-catalyzed
oxidative cleavage of benzylic C(sp3)-H bonds, it might be possible
to apply diazo compounds as the nucleophiles to trap the benzylic
carbon cation. The reaction is expected to generate diazonium
intermediates, followed by dinitrogen extrusion to afford olefin
products (Scheme 1b). We report herein the study along this line,
namely the FeCl2-catalyzed alkenylation of benzylic C(sp3)-H bonds
with diazoesters in the presence of DDQ as the oxidant.
To begin with, we have evaluated the compatibility of the diazo
compounds under the reaction conditions with FeCl2 catalyst and
DDQ oxidant (Scheme 2). Diphenylmethane 1a was chosen as the
substrate to investigate the benzylic C(sp3)-H bonds transformation
with diazo compounds. We first tested the reaction between 1a (0.4
mmol) and phenyldiazoacetate 2a (0.2 mmol) with 10 mol% FeCl2
and DDQ (0.5 mmol) in 1,2-dichloroethane (DCE, 1.0 mL) at 90 oC
for 24 h. Gratifyingly, the expected methyl 2,3,3-triphenylacrylate
product was obtained, albeit in a low yield. However, with methyl
2-diazopropanoate 2b as the nucleophile, the reaction failed to
afford the expected olefin product. Similarly, the reaction with
(diazomethylene)dibenzene 2c also gave no olefin product. The low
a. Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China. E-mail:
wangjb@pku.edu.cn
b. Department of Chemistry, Fudan University, Shanghai 200433, China
† Electronic supplementary information (ESI) available: Experimental details,
Characterization data. See DOI: 10.1039/x0xx00000x
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yields or no product with the diazo substrate 2a-c were attributed
to the side reactions of the diazo substrates under the reaction
conditions, mainly the dimerization and oxidation of the diazo
compounds. We then turned our attention to dimethyl 2-
diazomalonate 2d, which was known to be the diazo compound
with relatively high stability. As expected, dimethyl 2-
diazomalonate 2d was compatible with the reaction conditions and
afforded the olefin product in 88% yield. Furthermore, control
experiments showed that no C-H bond insertion product could be
detected in the absence of DDQ. However, in the absence of FeCl2
catalyst, the olefin product could be obtained in 30% yield.
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DOI: 10.1039/C9CC01060B
Scheme 2 Evaluation of the Compatibility of Diazo Compounds.
With dimethyl 2-diazomalonate 2d as the nucleophile, we then Scheme 3 Evaluation of Substrates Scope of the Diphenylmethanes.
investigated the scope of a series of substituted diphenylmethanes
1a-p (Scheme 3). The substrates with electron-withdrawing and conditions (6e-g). Benzyl methyl sulfoxide failed to afford the
electron-donating groups on the ortho position of the phenyl ring alkenylation products, presumably due to its oxidation to sulfone. It
both afforded the corresponding products 3a-d in good yields. The is worth mentioning that alkenyl sulfides are valuable building
results indicated that steric effect did not affect the reaction blocks widely used as enolate surrogates, Michael acceptors, or
efficiency. The substrates with electron-rich or weakly electron intermediates in organic synthesis.15
deficient substituents on meta position of the phenyl ring could also
smoothly participate the reaction (3e, 3h). In addition, substituted
groups with various electronic properties on para phenyl ring were
also tolerated (3g-k). The reaction with others diphenylmethane
derivatives, such as symmetrical and unsymmetrical disubstituted
derivatives, could be also afforded the corresponding products 3l-p
in moderate to good yields under the standard conditions.
Next, we have examined the substrate scope of the diazo
compounds (Scheme 3). The reactions with diethyl 2-diazomalonate
2e and diisopropyl 2-diazomalonate 2f afforded the products in
similar yields (4a, 4b). Notably, for the reaction with methyl
phenyldiazoacetate 2a, when the diazo substrate was added with
syringe pump over a period of 30 min the corresponding product 4c
could be obtained in 72% yield. Slow addition of diazo substrate is
necessary in this case for avoiding the oxidation of diazo substrate. Scheme 4 Reaction with Benzyl Sulfide Derivatives.
Other aryldiazoacetates were also subjected to the reaction under
Interestingly, when toluene 7a was submitted to the reaction
under slightly modified conditions (20 mol% FeCl2 and 1.0 mmol
DDQ in 1.0 mL DCE at 90 oC for 24 h), the benzylic cation
intermediate first underwent Friedel-Crafts reaction with the
substrate to give diphenylmethane, which was further followed by
an alkenylation with diazo substrate 1d to deliver the products 8a
and 8b in 1:1 ratio. The toluene substrates bearing substituents 7b-
e were also examined. The reaction with these substrates all
worked similarly, affording products 9a,b, 10a,b and 11a,b,
respectively. The regioselectivity was found relevant to the position
and steric bulk of the substituents (Scheme 5).
the same conditions, however, the reactions only offered
complicated mixtures.
Furthermore, we have explored the reactivity of other benzylic
C(sp3)-H bonds under the identical conditions. We have found that
the reaction with benzyl methyl sulfide 5a could also afford the
alkenylation product 6a in 70% yield. We then evaluated the scope
of a series of benzyl sulfide derivatives 5a-h (Scheme 4). The
substrates with different substituents on sulfur, such as ethyl,
phenyl, p-tolyl and p-FC6H4-, could afford the corresponding
alkenylation products in moderate yields (6b-d, 6h). The
substituents on the benzyl aromatic ring also tolerated the reaction
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In summary, we have developed the first alkenylation of
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DOI: 10.1039/C9CC01060B
benzylic C(sp )-H bonds with diazo compounds under FeCl2/DDQ
reaction system. The oxidative reaction conditions are compatible
with wide range of diazo substrates. The reaction provides an
efficient and unique method for the synthesis of substituted olefins.
The project is supported by 973 Program (No. 2015CB856600) and
NSFC (Grant 21871010).
Conflicts of interest
There are no conflicts to declare.
Notes and references
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Scheme 5 Reaction with Toluene and Its Derivatives.
7
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Based on the previous reports, We have proposed a plausible
reaction mechanism, as shown in Scheme 5.5-11 First, radical A is
generated through hydrogen abstraction from the substrate 1a by
FeCl2 and DDQ. In this process, the hydrogen is reduced to proton
through single electron transfer to Fe(II)/DDQ, generating Fe(III)
intermediate B. Subsequently, single electron transfer (SET) from A
to B forms carbon cation C, which reacts with nucleophilic diazo
substrate 2d to form D. From D deprotonation and elimination of N2
occur to deliver the product 3a, with regeneration of Fe(II) and 2,3-
dichloro-5,6-dicyanohydroquinone E.
8
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Scheme 6 The proposed reaction mechanism
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