Four-component radical-dual-difunctionalization (RDD) and decarbonylative alkylative peroxidation of two different alkenes with aliphatic aldehydes and TBHP

Article abstract of DOI:10.1039/c9cc05764a

From difunctionalization of a single alkene to radical-dual-difunctionalization of two different alkenes! Abundant aliphatic aldehydes were readily decarbonylated into alkyl radicals for the cascade construction of C(sp³)-C(sp³), C(sp³)-C(sp³) and C(sp³)-O bonds via double radical addition and radical-radical coupling, following the intrinsic nucleophilic/electrophilic reactivity of both the radicals and alkenes.

Full text of DOI:10.1039/c9cc05764a

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Four-component radical-dual-difunctionalization (RDD) and
decarbonylative alkylative peroxidation of two different alkenes
with aliphatic aldehydes and TBHP
Received 00th January 20xx,
Accepted 00th January 20xx
a
a,b
a
a,
Ren-Xiang Liu, Feng Zhang, Yong Peng and Luo Yang *
DOI: 10.1039/x0xx00000x
www.rsc.org/
From difunctionalization of a single alkene to radical-dual- carbon–carbon double bond of another alkene (b), to form the
difunctionalization of two different alkenes! Abundant aliphatic carbon-centered radical (II), which then terminates similarly as
t
aldehydes were readily decarbonylated into alkyl radicals for the radical (I) via radical-radical coupling with the BuOO∙ radical, to
3
3
3
3
3
cascade construction of C(sp )-C(sp ), C(sp )-C(sp ) and C(sp )-O enable the radical-dual-difunctionalization (RDD) and alkylative
bonds via double radical addition and radical-radical coupling, peroxidation of two different alkenes (Scheme 1b).
following the intrinsic nucleophilic/electrophilic reactivity of both
the radicals and alkenes.
a) Our previous results: alkylative peroxidation of single alkene
OOtBu
alkene a:
alkene b:
R1
R2
R1
tBuOO•
•
R
R
R•
R1
R1
The peroxy entity is a privileged structural motif not only found
in many important natural products and pharmaceutical
I
b) This work: RDD and alkylative peroxidation of two different alkenes
R1
R1 R2
R1
•
R2
•
tBuOO•
1
applications, but also served as key potential intermediate in
R
R
R
R•
R1
R2
t
OO Bu
organic synthesis, due to their readily conversion into alcohols,
ketones and epoxy compounds. In recent years, the direct
radical type difunctionalization of alkenes has become a
powerful strategy in organic synthesis, which has also been
I
II
2
Scheme 1. Radical difunctionalization vs radical dual-difunctionalization for the
alkylative peroxidation alkenes
To put this radical-dual-difunctionalization (RDD) of alkenes
applied to the preparation of peroxides, to enable the direct into practice, the selectivity of radical addition to carbon–
installation of a peroxy group and the introduction of other carbon double bond is crucial: 1) for the first radical addition,
functionalities across the C=C bond in a single procedure to the initiating radical (R∙) prefers alkene a, but not alkene b; 2)
3
increase molecular complexity. In this context, elegant studies for the second time radical addition, the radical intermediate (I)
4
involving
trifluoromethylative
peroxidation,
silylative prefers alkene b, but not alkene a itself to produce oligomers;
5
6
7
peroxidation, acylative peroxidation, arylative peroxidation,
alkylative peroxidation and others have been realized.
3) the regio-selectivity of the dual radical addition (head to tail)
to realize the ordered-assembly of two alkenes; 4) the radical
8
9
As our continuous interest on the oxidative decarbonylation intermediate (II) is stable enough and quenched in time to
of aldehydes,10 a decarbonylative alkylative peroxidation of suppress further co-polymerization oligomers. The former two
alkenes with aliphatic aldehydes and tert-butyl hydroperoxide requirements on chemo-selectivity might be achieved by the
1
0i
(TBHP) has recently been established under mild conditions.
intrinsic nucleophilic/electrophilic reactivity of radicals and
Mechanistically, this radical type alkylative peroxidation of alkenes, as exhibited by Ryu and co-workers in the multi-
alkenes is initiated by addition of the carbon radical (obtained compound cascade reactions of alkyl radicals with carbon
1
2a
by oxidative decarbonylation of aliphatic aldehydes) to the monoxide and alkenes, and Cheng et. al. in the radical polar
1
2b
carbon–carbon double bond of alkene a (Scheme 1a) to produce crossover reaction of dioxolanes with two alkenes. The regio-
t
a new radical (I), which was directly trapped by BuOO∙ radical selectivity of the dual radical addition could be controlled by the
1
via radical-radical coupling (Scheme 1a). By careful design, one steric difference between terminal and internal carbon of
might speculate that the new generated carbon-centered alkenes. The fourth challenge might be realized by generating a
radical (I), might undergo the second radical addition to the persistent radical (II) for radical-radical coupling with another
1
3
transient radical, following the “persistent radical effect”, as
revealed by the decarbonylative alkylative peroxidation of
1
0i
a. Key Laboratory for Green Organic Synthesis and Application of Hunan Province,
College of Chemistry, Xiangtan University, Hunan, 411105, PR China,
E-mail: yangluo@xtu.edu.cn
single alkene. Herein, we report a novel four-component
radical-dual-difunctionalization (RDD) and alkylative
peroxidation of two different alkenes with aliphatic aldehydes
b
College of Science, Hunan Agricultural University, Hunan, 410128, China.
and TBHP.
Electronic Supplementary Information (ESI) available: experimental details and
characterization of products. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Based on our studies on the decarbonylative alkylative supported that the salen-cobalt complex acted as a promoter
View Article Online
1
0i
DOI: 10.1039/C9CC05764A
peroxidation of single alkene
and the above speculation, for this cascade reaction.
pivaldehyde (1a), methyl acrylate (2a), styrene (3a) and tert-
The generality of this decarbonylative RDD on styrene
TBHP was chosen as model substrates to test this radical-dual- analogs, electron-deficient alkenes and aliphatic aldehydes was
difunctionalization strategy (Table 1). The oxidative subsequently investigated. The effect of substituents on the
decarbonylation of pivaldehyde (1a) produces a tert-butyl styrene moiety is listed in Table 2. Various styrene derivatives
radical, which is nucleophilic and prefers addition onto the bearing electron donating or withdrawing substituents on the
electro-deficient and terminal carbon–carbon double bond of phenyl moiety (3a-3l) smoothly underwent this four-
1
2
methyl acrylate (2a), to produce another carbon-centered component decarbonylative cascade reaction to afford the
radical (I-a). In contrast, radical (I-a) is electrophilic due to its - desired alkylated ketones (4a-4l) in moderate yields after the
1
2
electron withdrawing group (an ester group), so it favors the Kornblum−DeLaMare rearrangement, such as methyl (3b), tert-
subsequent radical addition to electro-rich styrene (3a) butyl (3c), methoxy (3d), halo (3e-3h) and tirfluoromethyl (3i)
alternatively, to provide a metastable benzyl radical (II-a), which groups. Besides substituted styrenes, 2-vinylnaphthalene (3j)
t
would further be trapped by the BuOO∙ via radical-radical and alkenes (3p and 3q) containing pyridine and thiophene
coupling to yield the peroxide 4a’. The model reaction did yield heterocycles, could underwent this cascade reaction similarly to
the expected RDD product in the presence of a cobalt salt (Table produce the RDD products (4j-4l), respectively. At the same
1
, entry 1). Since part of (around 5%) the peroxide 4a’ would time, 1-ocetene (3m) and cyclohexene (3n) as the
1
4
undergo Kornblum−DeLaMare rearrangement automatically representatives of aliphatic alkenes, were also tested for this
and be transformed into the aromatic ketone 4a even without RDD, but turned out to be unsuccessful, which might imply that
adding any base, the subsequent optimization was valued after generating a metastable benzyl radical (II) during the second
one-pot conversion of the peroxide 4a’ to the corresponding radical addition was essential for this RDD reaction.
aromatic ketone 4a.
Table 2. Scope and limitation of the styrenes
- CO
) 2 mol% Co-1
CH CN, 90 oC, 12 h
Table 1. Optimization of reaction conditions a
Me
O
1

O
-
CO
O
Me
O
3
O
1) x mol% Cat.
+
CO Me +
+
TBHP
2
Ar
tBu
O
CH3CN, 90 oC, 12 h
O
tBu
H
2) 1.5 equiv DBU
CH3CN, 70 oC, 8 h
O
Ar
+
CO2Me +
Ph
3a
+
TBHP
tBu
2a
tBu
2) 1.5 equiv DBU
CH3CN, 70 oC, 8 h
1a
3a-3l
4a-4l
H
Ph
1a
2a
4a
3
3c
3e
3g
a
styrene
4-tert-butylstyrene
4-fluorostyrene
3b
3d
3f
3h
3j
4-methylstyrene
Me
O
4-methoxylstyrene
4-chlorostyrene
3-boromostyrene
2-vinylnaphthalene
2-vinylthiophene
cyclohexene
O
OMe
O
OMe
O
tBuOO•
OO Bu
t
3a
via:
tBu
tBu
•
tBu
•
4-boromostyrene
Ph
Ph
3
3
3
i
k
m
4-trifluoromethylstyrene
2-vinylpyridine
1-octene
I-a
II-a
4a'
3l
3n
entry
Cat.
Yield (%)
29
36
21
48
30
22
40
70
.
.
.
1
2
3
4
5
6
7
8
9
Co(OAc)
Co(OAc)
Co(OAc)
Co-1 (5 mol%)
Co-2 (5 mol%)
Co-3 (5 mol%)
Fe-1 (5 mol%)
Co-1 (2 mol%)
--
2
2
2
4H
4H
4H
2
2
2
O (5 mol%)
O/dipy (5 mol%)
O/phen (5 mol%)
Me
Me
O
Me
O
O
O
O
O
O
O
O
tBu
tBu
tBu
Me
tBu
4
a, 62%
4b, 67%
4c, 70%
Me
Me
Me
O
O
O
O
O
O
O
O
22
O
tBu
tBu
tBu
N
O
N
N
O
N
O
N
O
N
O
OMe
F
Cl
Co
Co
N
O
N
O
Fe
tBu
tBu
4d, 62%
4e, 64%
4f, 58%
O
Co
tBu
tBu
Me
Me
Me
tBu
tBu
Co-1
Co-2
Co-3 t
Fe-1
O
O
O
O
O
O
O
O
tBu
O
Bu
tBu
tBu
tBu
tBu
tBu
Br
a
Conditions: 1a (0.8 mmol, 4.0 equiv), 2a (0.2 mmol, 1.0 equiv), 3a (0.4 mmol, 2.0
equiv), TBHP (70% in H O, 1.0 mmol, 5.0 equiv), Cat. (x mol %) in CH CN (1 mL,
prepared solution), stirred at 90 °C for 12 h and then DBU (1.5 equiv) was added
and stirred at 70 °C for another 8 h. GC yield.
Br
CF3
2
3
4g, 63%
4h, 55%
4i, 41%
Me
Me
Me
O
O
O
O
O
O
O
O
O
tBu
N
tBu
S
When this RDD was promoted by a catalytic amount of
4j, 64%
4k, 46%
4l, 34%
Co(OAc) .
4H O, the alkylated ketone 4a was obtained in a 29%
2 2
Me
Me
O
O
O
O
O
O
yield. Subsequent optimization revealed that the nitrogen-
containing ligands showed marked influence on this alkylative
peroxidation, thus 2,2’-dibipyridine, 1,10-phenathroline and
several salen ligands were tested (entries 2-6). Among them,
the Co-1 complex derived from ethylenediamine provided the
best results, while a similar salen-iron complex (Fe-1) showed
inferior activities. Unexpectedly, decreasing on the loading of
this salen-cobalt complex (Co-1) from 5 mol% to 2 mol%,
resulted in a rise from 48% to 70% on the yield of the desired
product 4a (entries 4 and 8). It should be noted that this
alkylative peroxidation still worked in the absence of cobalt salt,
providing the alkylated ketone 4a in a lower yield of 22%, which
tBu
(
)5
4m, 0
4n, 0
Isolated yields listed.
Then, the scope and limitation of electron-deficient alkenes
for this radical dual-difunctionalization were tested (Table 3).
Besides methyl acrylate (2a), similar ,-unsaturated esters
such as n-butyl acrylate (2b), benzyl acrylate (2c), cyclohexyl
acrylate (2d), 4-hydroxybutyl acrylate (2e), N,N-dimethyl
acrylamide (2f), N-methyl-N-phenyl acrylamide (2g),
acrylonitrile (2h), ethyl vinyl ketone (2i), diethyl
vinylphosphonate (2j) and dimethyl maleate (2k) all underwent
this cascade reaction with pivaldehyde (1a), styrene (3a) and
2
| J. Name., 2012, 00, 1-3
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TBHP to yield the targeted ketones (5b-5k) successfully under didn’t undergo decarbonylation at all and afforded the acylative
View Article Online
DOI: 10.1039/C9CC05764A
the optimized conditions. It’s encouraged that this alkylative product (9i) exclusively.
peroxidation cascade reaction could incorporate the un-
protected hydroxyl group, ester, amide, nitrile, ketone and
phosphonate moieties into the product directly, which should
facilitate further potential application of this method.
Me
O
O
O
3 equiv BHT
mol% Co-1
O
a)
H
+
CO2Me +
Ph + TBHP
tBu
2
Ph
6c, not detected
CH3CN, 90 oC, 12 h
1c
2a
3a
O
tBu
10, isolated and characterized
Table 3. Scope of electron-deficient alkenes for the RDD

-
CO
Me
O
x mol% Cat
1
) 2 mol% Co-1
O
CH3CN, 90 o
O
OBn
O
C
O
CH3CN, 90 oC, 12 h
+
+
TBHP
O
b)
+
CO2Bn
2c
Ph
tBu
+
CO2Me +
Ph + TBHP
tBu
tBu
H
:
2c 3a
•
tBu
1
H
2) 1.5 equiv DBU
CH3CN, 70 oC, 8 h
= 1:1
Ph
1a
3a
I-c
a
2b-2k
3a
5b-5k
Bn
t
O
O
OO Bu
t
nBu
Bn
Cyclohex
OO Bu
OO Bu
t
tBu
O
O
O
O
O
O
Bn
+
tBu
+
tBu
O
O
O
O
Ph
Ph
tBu
O
tBu
tBu
Ph
Ph
Cat. = 2 mol% Co-1, 0.5 h 7, 37%
Cat. = 5 mol% FeCl2, 4 h 7, 8.0%
without any catalyst, 12 h 7, 2.3%
5c', 44%
5c', 37%
5c', 13%
8, 21%
8, 21%
8, 5.4%
Ph
Ph
5b, 63%
5c, 60%
5d, 64%
Ph
KCo-1 = k1 / k2 = (7 + 5c') / 8 = 3.8
KFeCl2 = k1 / k2 = (7 + 5c') / 8 = 2.1
KFeCl2 = k1 / k2 = (7 + 5c') / 8 = 2.8
O
O
O
NMe2
O
NMe
O
O
OH
O
O
tBu
tBu
5f, 65%
tBu
Ph
Ph
Ph
5e, 54%
5g, 60%
Scheme 2. Mechanistic experiments.
OEt
O
Et
O
OEt
CN
O
P
O
Several mechanistic experiments were carried out to
understand this radical dual-difunctionalization. First, the The
RDD between 2-ethylbutanal (1c) and two alkenes was
completely inhibited in the presence of di-tert-
butylhydroxytoluene (BHT), and instead, the decarbonylated
alkyl radical was captured as 2,6-di-tert-butyl-4-methyl-4-
tBu
tBu
5i, 43%
tBu
Ph
Ph
Ph
5h, 49%
5j, 36%
Me
O
O
O
tBu
O
OMe
5k, 47%
Isolated yields listed.
(
pentan-3-yl)cyclohexa-2,5-dien-1-one (10), which confirmed
Table 4. Scope and limitation of the aliphatic aldehydes
the radical-type decarbonylation mechanism (Scheme 2a).
Second, by shortening the reaction time, overriding the DBU-
promoted Kornblum−DeLaMare rearrangement step at the
same time) and carefully isolating the reaction mixture, three
main-products (7, 5c’ and 8) were obtained and characterized
-
CO
) 2 mol% Co-1
CH CN, 90 oC, 12 h
Me
O
1
O
O
3
O
+
CO2Me +
+
TBHP
Ph
2) 1.5 equiv DBU
R
R
H
Ph
2a
3a
CH3CN, 70 oC, 8 h
1b-1i
6b-6i
1
1
1
1
b
d
f
isobutyraldehyde
cyclohexanecarbaldehyde
2-methylpentanal
1c
1e
1g
1i
2-ethylbutanal
2-methylbutanal
2-ethylhexanal
benzaldehyde
(Scheme 2b), which verified the generation of radical
intermediates I and II produced via radical addition to alkenes
h
cyclamen aldehyde
t
(
captured by the BuOO∙ radical to form 7and 5c’, respectively).
Me
Me
O
Me
O
O
O
O
O
1
O
O
O
Furthermore, their yields were determined by the H NMR using
the nitromethane as the internal standard. These results
supported our speculation (Scheme 1) that the radical cascade
reaction was initiated by the decarbonylated alkyl radical, which
not only was able to add onto the carbon-carbon double bond
of benzyl acrylate (2c) to produce radical intermediate I-c, but
also reacted with the styrene (3a) similarly. Under the reduced
reaction time and in the absence of DBU, the Kornblum−
DeLaMare rearrangement of these peroxides to the ketones
Ph
Ph
Ph
6b, 53%
6c, 56%
6d, 45%
Me
Me
Me
O
O
O
O
O
O
O
O
O
Ph
e, 56%
Ph
Ph
6
6f, 57%
6g, 58%
Me
O
Me
O
Me
O
O
O
O
O
O
O
O
Ph
Ph
Ph Ph
i, not detected
Isolated yields listed., d.r.=1:1 for 6e-6h.
Ph
6h, 53%
6
9i, 55%
Co-1
was almost negligible, so the relative reaction rate (K ) for
After investigating the scope of the two different alkenes of
RDD, we next tested the generality of this reaction for various
aliphatic aldehydes (1b-1h) under the optimized conditions
addition of tert-butyl radical to benzyl acrylate (2c) and that of
styrene (3a) could be approximatively calculated as dividing the
total yield of 7 and 5c’ by the yield of 8, to provide a value of
(Table 4). While the -di-substituted pivaldehyde (1a) provided
3
.8, when promoted by Co-1. In contrast, when promoted by
a tertiary carbon radical after decarbonylation, the -mono-
substituted aliphatic aldehydes including isobutyraldehyde
FeCl or in the absence of any metal catalyst, the RDD became
2
slower and at the same time, the relative reaction rate (K) was
much smaller, revealed that the salen-Co complex effectively
improved both the rate and chemo-selectivity for the radical
addition to the two different alkenes. The Co-complex might be
able to coordinate to the carbonyl of methyl acrylate to increase
its electrophilicity, thus improves the chemo-selectivity for the
radical addition. These results on relative reacting rates agreed
(1b), 2-ethylbutanal (1c), cyclohexanecarbaldehyde (1d), 2-
methylbutanal (1e), 2-methylpentanal (1f), 2-ethylhexanal (1g),
and cyclamen aldehyde (1h) would provide secondary carbon
radicals. Gratifyingly, all of these aliphatic aldehydes underwent
alkylative peroxidation with methyl acrylate (2a), styrene (3a)
and tert-butyl hydroperoxide (TBHP) to smoothly yield the
targeted ketones (6b-6h) after the one-pot manipulation. It’s a
pity that the secondary aliphatic aldehydes led to lower yields
for this RDD, companied by the generation of the un-
decarbonylated counterparts; while the aromatic aldehyde (1i)
15
well with the literature reports, and effectively supported our
speculation on radical dual-difunctionalization of two different
alkenes.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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Journal Name
Based on the above mechanistic experiments, our previous
studies10 and literature reports, a possible reaction pathway
on this radical dual-difunctionalization of two different alkenes
is depicted in Scheme 3, with the reaction of pivaldehyde (1a),
methyl acrylate (2a) and styrene (3a) as an example. First,
Notes and references
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11
DOI: 10.1039/C9CC05764A
1
Z. Rappoport, The Chemistry of Peroxides; Wiley and Sons:
New York, 2006.
2
3
M. Klussmann, Chem. Eur. J., 2018, 24, 4480.
For selected reviews, see: (a) X. Wang and A. Studer, Acc.
Chem. Res., 2017, 50, 1712; (b) X.-W. Lan, N.-X. Wang and Y.
Xing, Eur. J. Org. Chem., 2017, 5821; (c) H. Yi, G. Zhang, H.
Wang, Z. Huang, J. Wang, A. K. Singh and A. Lei, Chem. Rev.,
2017, 117, 9016.
II
reduction of TBHP by Co -complex produces tert-butoxy radical
t
III
II
(
2
BuO•) and Co (OH)X (while in the absence of Co , the
homolytic cleavage of TBHP occurs at elevated temperature).
Subsequent intermolecular hydrogen atom abstraction of the
4
5
6
(a) H.-Y. Zhang, C. Ge, J. Zhao and Y. Zhang; Org. Lett., 2017,
1
9, 5260; (b) E. Shi, J. Liu, C. Liu, Y. Shao, H. Wang, Y. Lv, M. Ji,
t
pivaldehyde (1a) by BuO• and spontaneous decarbonylation
X. Bao and X. Wan, J. Org. Chem., 2016, 81, 5878.
generates tert-butyl radical, which is a nucleophilic carbon
radical thus preferentially adds to the electron-deficient and
less-hindered -carbon of methyl acrylate (2a) to produce
radical intermediate (I-a). In turn, this new formed carbon
radical (I-a) becomes electrophilic due to its -electron
withdrawing group (an ester group), so it favors the subsequent
addition to electron-rich and less-hindered -carbon of styrene
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Yang, Org. Lett., 2019, 21, 6117.
(
3a) selectively, to provide a metastable benzyl radical (II-a),
t
which would further be trapped by the BuOO∙ (or its precursor)
via radical-radical coupling to yield the peroxide 4a’. On the
7
8
(a) T. Taniguchi, H. Zaimoku and H. Ishibashi, Chem. Eur. J.,
III
other hand, reaction of Co (OH)X
2
with TBHP provides the
2
011, 17, 4307; (b) Y.-H. Chen, M. Lee, Y.-Z. Lin and D. Leow,
t
II
BuOO• (and water) to regenerate the Co complex.
Chem. Asian J., 2015, 10, 1618; (c) S. Kindt, H. Jasch and M. R.
Heinrich, Chem. Eur. J., 2014, 20, 6251.
Me
O
O
(a) B. Schweitzer-Chaput, J. Demaerel, H. Engler and M.
Klussmann, Angew. Chem. Int. Ed., 2014, 53, 8737; (b) S. Lu, L.
Qi and Z. Li, Asian. J. Org. Chem., 2017, 6, 313; (c) J.-K. Cheng
and T.-P. Loh, J. Am. Chem. Soc., 2015, 137, 42; (d) J. Jiang, J.
Liu, L. Yang, Y. Shao, J. Cheng, X. Bao and X. Wan, Chem.
Commun., 2015, 51, 14728; (e) A. Banerjee, S. K. Santra, N.
Khatun, W. Ali and B. K. Patel., Chem. Commun., 2015, 51,
15422; (f) A. Banerjee, S. K. Santra, A. Mishra, N. Khatun and
B. K. Patel, Org. Biomol. Chem., 2015, 13, 1307; (g) Y. Lan, C.
Yang, Y.-H. Xu and T.-P. Loh, Org. Chem. Front., 2017, 4, 1411.
Y. Chen, Y. Chen, S. Lu and Z. Li, Org. Chem. Front., 2018, 5,
DBU
t
OO Bu
II
Co X2
4a
tBuOOH
tBu
Ph
4
a'
tBuOO
H2O
+
CO2Me
CoIII(OH)X2
t
tBu
tBuOOH
+ BuO
Ph
O
II-a
tBu
H
1a
Ph
a
tBuOH
3
O
tBu
tBu
CO
CO2Me
I-a
tBu
9
1
CO2Me 2a
9
72.
Scheme 3. Proposed mechanism
0 (a) R. -J. Tang, Q. He and L. Yang, Chem. Commun., 2015, 51,
5925; (b) R. -J. Tang, L. Kang and L. Yang, Adv. Synth. Catal.,
In conclusion, we have developed a convenient salen-Co
promoted four-component radical-dual-difunctionalization and
alkylative peroxidation of two different alkenes with aldehydes
and TBHP to provide ketones via one-pot procedure. Radical
difunctionalization of alkenes was famous for its ability to
synthesize complex molecules from structurally simple and
readily available alkenes; this radical-dual-difunctionalization of
two different alkenes has amplified this advantage by realizing
the difunctionalization and ordered-assembly of two different
alkenes, to incorporate multi-functionalities and elongated alkyl
chain into the products, with TBHP playing a triple role of radical
initiator, terminal oxidant and radical coupling partner. The
application of abundant aliphatic aldehydes as alkyl source,
convenient operation for carbon radical generation, readily
available styrene analogs/electron-deficient alkenes and
versatile synthetic utilities of the cascade reaction products,
would render this radical-dual-difunctionalization attractive for
organic synthesis and medicinal chemistry.
2
015, 357, 2055; (c) L. Yang, W. Lu, W. Zhou and F. Zhang,
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Acknowledgements
This work was supported by the National Natural Science
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team of the Ministry of Education (IRT_17R90).
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