Highly efficient metal-free cross-coupling by C-H activation between allylic and active methylenic compounds promoted by DDQ

Article abstract of DOI:10.1002/adsc.200800085

A metal-free very highly efficient and concise oxidative-coupling reaction promoted by 2,3-dichloro-5,6-dicyanoquinone (DDQ)between diarylallylic sp ³ C-H and active methylenic sp³ C-H bonds is reported. The corresponding products are obtained in good to excellent yields.

Full text of DOI:10.1002/adsc.200800085

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DOI: 10.1002/adsc.200800085
À
Highly Efficient Metal-Free Cross-Coupling by C H Activation
between Allylic and Active Methylenic Compounds Promoted by
DDQ
Dongping Chenga,b and Weiliang Baoa,*
a
Department of Chemistry, Zhejiang University (Xixi Campus), Hangzhou 310028, Peopleꢀs Republic of China
Phone/fax: (+86)-571-8827-3814
E-mail: wlbao@css.zju.edu.cn
b
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, Peopleꢀs Republic of China
Received: February 8, 2008; Revised: February 29, 2008; Published online: May 9, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A metal-free very highly efficient and
concise oxidative-coupling reaction promoted by
the fact that the nitrogen or oxygen atom activates
the adjacent sp C H bond and further stabilizes the
3
À
À
2,3-dichloro-5,6-dicyanoquinone (DDQ)between
in situ formed intermediates. The C H activation of
the sp C H bond at the a-position of an aromatic
3
3
diarylallylic sp3 C H and active methylenic sp
À
À
C H bonds is reported. The corresponding products
ring or a vinyl group was also re
ported.[6a,d] For exam-
ple, the allylic sp C H bond of cyclohexene was cou-
pled with the methylenic sp C H bond via catalysis
by copper(I)bromide and cobalt(II)chloride. Very
recently, coupling of cyclohexane with methylene
À
3
À
are obtained in good to excellent yields.
3
À
Keywords: active methylenic compounds; allylic
À
À
compounds; C C bond formation; C H activation;
cross-coupling; DDQ; 2,3-dichloro-5,6-dicyanoqui-
none
compounds catalyzed by the system of FeCl /
2 ACHTREUNG(t-
Bu)2O2 was re
AHCTREUNG
À
excellent results about C C bond formation through
À
C H activation, examples of the reactions under
metal-free condition are rare.
The palladium-catalyzed allylic alkylation (the
The formation of carbon-carbon bonds is one of the Tsuji–Trost coupling reaction), usually employing an
most useful and fundamental reactions since it repre- allylic acetate or its derivatives as the starting materi-
sents a key step in the synthesis of complex mole- al, which have to be synthesized in several steps, rep-
cules.[1] Metal-mediated cross-coupling of two pre- resents one of the most common C C bond formation
À
functionalized substrates is one of the most important methodologies in organic synthesis.[10] Progress has
synthetic tools for constructing the carbon-carbon been made by the direct use of allylic alcohols and
bond.[2] With the emergence of the concepts of “atom the overall process of allylation has become highly ef-
economy”[3] and “green chemistry”,[4] the cross-cou- ficient and atom economical.[11] In fact, Trostꢀs group
À
pling reaction for C C bond formation by transition tried to make an allylic alkylation directly from an al-
metal-catalyzed C H activation of one partner has at- lylic sp3 C H by palladating an olefin in the late
À
À
tracted great interest because of its conciseness and 1970s.[12] Recently, Liꢀs group has reported a first cata-
atom economy and a number of excellent results have lytic allylic alkylation reaction directly from allylic sp3
been obtained.[5] As a more challenging subject, oxi- C H and methylenic sp C H bonds using Cu(I)/
3
À
À
dative intermolecular C C bond formation by using Co(II)and t-BuOOH as the catalyst-system.[6d]
À
À
two different C H bonds was also developed, such as
Herein, we report that 2,3-dichloro-5,6-dicyanoqui-
none (DDQ)mediates a very highly efficient and con-
3
3
[6]
2
2
À
À
À
(i) sp C H with sp C H, (ii) sp C H with sp
C H, (iii) sp C H with sp C H, and (iv) sp3 cise oxidative-coupling reaction between diarylallylic
[7]
3
2
[8]
À
À
À
[9]
3
3
À
À
À
À
C H with sp C H. In these transformations, both of sp C H and active methylenic sp C H bonds with-
the starting materials could be used directly in the out any metal catalyst.
À
C H form without pre-functionalization. Among
DDQ is a well-known oxidation reagent for organic
them, sp C H bonds that undergo the cross-coupling synthesis.[13] The coupling reactions between some nu-
reaction are usually located at the a-position to a ni- cleophiles and benzylic substrates bearing a hetero
trogen or oxygen atom. The reason for this may lie in atom at the a-position were reported in the presence
3
À
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1263

Dongping Cheng and Weiliang Bao
Table 1. Screening of reaction conditions.[a]
COMMUNICATIONS
of DDQ.[14] In this paper, we initially examined the
oxidative-coupling of 1a and 2a with DDQ in the ab-
sence of metal and solvent at room temperature. To
our delight, the desired coupling product 3a was ob-
tained in 75% yield after an hour (Table 1, entry 1). It
seemed that the reaction was not sensitive to temper-
ature, since the results of the reaction did not change
obviously when the temperature was raised to 50 8C
or 90 8C (entries 2 and 3). Then a number of solvents
were surveyed. No desired coupling product was ob-
served when the reaction was carried out in NMP or
hexane (entries 4 and 5). The reaction could proceed
in THF, CHCl3, CH2Cl2, DCE, CCl4, MeNO2, MeCN
and dioxane (entries 6–13). However, considerable
amounts of undesired products were formed in THF
or dioxane and the rate of the reaction became
slower when CHCl3, CCl4 or MeNO2 were used as the
solvents. Interestingly, the speed and yield of the reac-
tion in DCE were comparable with those in CH2Cl2.
Based on the above investigation, CH2Cl2 was pre-
ferred as the reaction media from the practical point
of view. As for the influence of DDQ dosage on the
reaction, it was found that decreasing the amount of
the DDQ resulted in reduced yield, while increasing
the amount to 1.5 equiv. did not make the reaction
system complex and the yield was just a little lower.
With the optimized reaction conditions established,
various substrates were subjected to this cross-cou-
pling reaction (Table 2). The electronic effect of the
Entry
Solvent
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
neat
neat
neat
NMP
hexane
THF
CHCl3
CH2Cl2
DCE
r.t.
50
90
75[c]
74[c]
68[c]
nd
nd
53
61
88
82
71
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
9
10
11
12
13
14
CCl4
MeNO2
dioxane
CH2Cl2
CH2Cl2
70
42
73[d]
80[e]
[a]
0.5 mmol of 1a, 0.6 mmol of 2a, 1.2 mL of solvent,
0.6 mmol of DDQ, 1 hour.
Isolated yield.
0.5 mmol of 1a, 4 mmol of 2a, and 0.6 mmol of DDQ.
0.5 mmol of DDQ.
0.75 mmol of DDQ.
[b]
[c]
[d]
[e]
Table 2. Allylation of active methylenic compounds.[a]
Entry
R1, R2
R3, R4
Time [h]
Product
Yield [%][b]
1
2
3
4
5
6
7
8
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
C6H5, C6H5
4-CH3C6H4, C6H5
4-CNC6H4, C6H5
1
0.5
2
0.5
4
0.5
0.5
0.5
0.5
0.5
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
88
79
84
96
40
84
98
93
90
60
70
75
92
72
95
71
2-CH3C6H4, C6H5
3-ClC6H4, C6H5
3-CH3OC6H4, C6H5
4-ClC6H4, C6H5
4-CH3OC6H4, C6H5
thienyl, C6H5
furanyl, C6H5
C6H5, CH3
CH3, CH3
CH3, OEt
-(CH2)4-, OEt
C6H5, C6H5
C6H5, C6H5
9
10
11[c]
12[c]
13
14
15
16
3
2.5
3.5
2.5
3
CH3, CH3
C6H5, C6H5
4-CH3OC6H4, 4-CH3OC6H4
4-CH3OC6H4, 4-CH3OC6H4
[a]
0.5 mmol of 1, 0.6 mmol of 2, 0.6 mmol of DDQ, and 1.2 mL of CH2Cl2 unless noted.
Isolated yields.
0.5 mmol of 1, 4 mmol of 2, 0.6 mmol of DDQ, 908C.
[b]
[c]
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Adv. Synth. Catal. 2008, 350, 1263 – 1266

À
Highly Efficient Metal-Free Cross-Coupling by C H Activation
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Scheme 1. Possible reaction mechanism.
substituents on aromatic ring of 1 was observed. For without a metal catalyst and additional reagent and
example, the substrates bearing an electron-donating (ii)it gives the products in good to excellent yields in
group on the aromatic ring (entries 2, 4, and 6)react-
ed rapidly and 79–96% yields were obtained, while
that bearing a chloro group on the para-position re-
a short time.
acted a little more slowly and a moderate yield was Experimental Section
obtained (entry 5). Heteroaryl species such as furanyl,
thienyl were compatible with the present procedure General Procedure
and excellent results were obtained (entries 7 and 8).
A 10-mL, two-necked, round-bottom flask was charged with
a mixture of the methylene compound (0.5 mmol)and the
Acetylacetone and benzoylacetone were also suitable
substrates here (entries 9 and 10). Reactions of acyclic
and cyclic b-keto esters were comparatively sluggish,
so the reaction temperature was raised to 90 8C (en-
tries 11 and 12). To expand the scope of the sub-
strates, we further examined the mono- and disubsti-
tuted 1,3-diarylpropenes (entries 13–16)and obtained
the expected products in satisfactory yields.
1,3-diarylpropene (0.6 mmol)in CH Cl2 (1.2 mL)and DDQ
2
(0.6 mmol)was added. The resulting mixture was stirred for
the indicated time at room temperature. Purification was
done by column chromatography on silica gel (200–300
mesh)with petroleum ether and ethyl acetate as the eluent
to give the pure product. For more details, see Supporting
Information.
A possible mechanism for this coupling reaction
may involve a single-electron transfer process in the
first step.[6e,14a,15] But we cannot ascertain if DDQ ab-
stracts an electron firstly from the arylallylic com-
pound or the active methylene compound. When a so-
lution of 2a was combined with DDQ, we observed
the immediate formation of a deep green color that is
likely a charge-transfer complex A, whereas when a
solution of 1a was combined with DDQ, no obvious
Acknowledgements
This work was financially supported by the Specialized Re-
search Fund for the Doctoral Program of Higher Education
of China (20060335036).
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À
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Adv. Synth. Catal. 2008, 350, 1263 – 1266
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asc.wiley-vch.de
1265

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Adv. Synth. Catal. 2008, 350, 1263 – 1266