Primary-tertiary diamine/Bronsted acid catalyzed C-C coupling between para-vinylanilines and aldehydes

Article abstract of DOI:10.1002/chem.201300995

Aromatic enamines: para-Vinylanilines were identified as unique nucleophiles, closely resembling enamines, to undergo C-C coupling with aldehydes catalyzed by a simple primary-tertiary diamine/Bronsted acid. The resulting bis(allylic) adducts, which have potential as functional materials, were obtained in high yields under rather mild conditions (see scheme). Copyright

Full text of DOI:10.1002/chem.201300995

COMMUNICATION
DOI: 10.1002/chem.201300995
Primary–Tertiary Diamine/Brønsted Acid Catalyzed C–C Coupling between
para-Vinylanilines and Aldehydes
Lingyun Cui, Yunbo Zhu, Sanzhong Luo,* and Jin-Pei Cheng[a]
Vinylation of carbonyls or iminines represents one of the
most straightforward approaches for the synthesis of versa-
tile allylic compounds.[1] Traditionally, stoichiometric
amounts of vinyl metal reagent, either preformed or gener-
ated in situ, are employed in the reactions (Scheme 1a).[2–7]
In this context, direct vinylation of carbonyl compounds
nocatalytic direct vinylation reactions are rare and have not
yet been reported.
Recently we found that para-vinylanilines (e.g. 1a) are
unique nucleophiles in reacting with aldehydes, furnishing
vinylation-type products under mild organocatalytic condi-
tions (Scheme 1c). Mechanistically, the remote para-amino
group enhances the nucleophilicity of the olefin bond by
electron-delocalization via the conjugated phenyl ring.[12]
The para-vinylanilines, endowed with a nucleophilic termi-
nal carbon atom, in a manner, closely resemble the well-
known enamine intermediates, and may be regarded as aro-
matics intervened enamine (aromatic enamine). Surprising-
ly, these seemingly well-known structural moieties have not
À
been well explored as synthons in C C bond formation re-
actions, not to mention their synthetic potentials in many
catalytic systems. Provided with the now quite well-estab-
À
À
lished strategies for C N and C H transformations of ani-
line derivatives,[13] direct vinylation reactions with para-vi-
nylanilines would deliver versatile synthetic pathways for
multifunctional conjugate molecules, that are of significant
potential in organic electronics. In fact, the parent vinylani-
lines serve as important building blocks for a number of
leuco dyes.[14–18] Herein, we report an effective aminocatalyt-
À
ic C C coupling reaction between para-vinylanilies and al-
dehydes, formulating a rare example of an organocatalytic
direct vinylation reaction.
Preliminary studies started with the examination of the
nucleophilic addition of vinylaniline 1a to benzaldehyde.
Previously, the coupling of vinylaniline 1a and aldehyde has
been disclosed in patents to react under rather harsh condi-
tions (reflux in the presence of excess acid).[19] The resulting
Scheme 1. Vinylation reactions.
À
with alkenes by C H functionalization would be highly de-
sirable as handling sensitive vinyl organomatellic species can
be avoided and such a process is also highly atom-economic
with readily available alkenes as the feed stocks.[8] To this
end, novel catalytic strategies have been developed and the
successes so far have been mainly achieved with transition-
metal catalysts, such as Pd, Rh, and Ni.[9–11] However, orga-
bisACTHNUGRTENUNG(allylic) adducts (e.g. 3a) can be used as charge control
agents in electroreprographic toners and as colour formers,
particularly in transfer imaging, pressure sensitive and ther-
mal-responsive carbonless duplicating systems.[19] In our
studies, it was found that a catalytic amount of Brønsted
acid, such as benzoic acid or TfOH, demonstrated rather
low activity at room temperature (Table 1, entries 2 and 3).
In contrast, the combined use of Brønsted acids and a pri-
mary amine, such as N,N-dimethylethylene diamine 4a, a
proved biomimetic aminocatalytic motif,[20] was found to be
[a] L. Cui, Y. Zhu, Prof. Dr. S. Luo, Prof. Dr. J.-P. Cheng
Beijing National Laboratory for Molecular Sciences (BNLMS)
CAS Key Laboratory of Molecular Recognition
and Function Institute of Chemistry, Chinese Academy of Sciences
Beijing 100190 (P.R.China)
an effective catalyst for the reaction to furnish a bisACHTUNGTRENNUNG(allylic)
adduct 3a (entry 7).[21] In this regard, a range of acidic addi-
tive has been screened with 4a as the initial aminocatalyst
and the strongest acid TfOH gave the optimal results (en-
tries 4–9). The acid/base catalytic feature is reminiscent of
Fax : (+86)10-62554449
E-mail: luosz@iccas.ac.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300995.
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Table 2. Scope of aldehydes.
Entry[a]
R1
Product
t [h]
Yield [%][b]
1
2
3
4
5
6
7
Ph
4-ClPh
4-CF3Ph
2-BrPh
3a
3b
3c
3d
3e
3 f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
17
48
24
32
32
24
24
22
88
97
98
80
50
63
97
98
90
97
71 (70)
96
95
88 (91)
90
85
82
95
52
98
89
75
82
70
67
86
the typical iminium-based Knoevenagel reaction. To seek
the optimal amine catalysts, a number of amines including
both primary and secondary amines have been screened and
the simple primary–tertiary diamine 4a turned out to be the
preferred aminocatalyst in this reaction (Table 1, entries 9–
14). Similar diamines, such as tertiary–tertiary diamine 4c
and secondary–secondary diamine 4d, gave much lower ac-
tivity (entries 11 and 12). These results together with the ob-
servation of virtually inactive secondary amines, such as pyr-
rolidine 4e and diethylamine 4 f (entries 13 and 14) highlight
the critical role of the primary amine moiety in the cataly-
sis.[20] In a further optimization of the reactions, ethanol was
identified as the favourable solvent (entries 15–20) and the
reaction gave 88% yield in 17 h with 10 mol% of 4a/TfOH
(entry 19).
4-OHPh
3-CH3Ph
3-NO2Ph
2-NO2Ph
4-FPh
2-FPh
4-N,N-dimethylPh
4-BrPh
4-NO2Ph
4-MeOPh
2-Br-5-ClPh
3,4-dimethoxylPh
2-F-4-CF3Ph
2-F-4-BrPh
2-F-4-MeOPh
2-F-3-Cl-4-CF3Ph
2-thiophene
2-furan
8[c]
9
24
22
10[d]
11[e]
12[g]
13[h]
14
15
16
17
18
19
20
21[i]
22
23[d]
24[d]
25
26[d]
12 (36)[f]
32
32
32 (36)[f]
22
40
17
29
29
5
10
36
30
3s
3t
Under the optimized conditions (10 mol% of 4a/TfOH in
EtOH, RT), we next probed the scope of the vinylation re-
action for a variety of aldehydes and the results were pre-
sented in Table 2. The scope of aldehyde is quite general.
Aromatic aldehydes bearing either electron-donating or
-withdrawing groups are equally applicable in the reactions
3u
3v
3w
3x
3y
3z
nPr
ipr
nBu
PhCH2CH2
30
4 days
30
[a] General conditions: 1a (53.2 mg, 0.2 mmol), aldehyde (0.12 mmol),
solvent (0.8 mL), catalyst (10 mol%), RT. [b] Isolated yield. [c] Catalyst
loading was 40 mol%. [d] Catalyst loading was 20 mol%. [e] At 408C.
[f] 1a (5 mmol), aldehyde (3 mmol), solvent (20 mL), catalyst (4 mol%),
408C. [g] 1a (5 mmol), aldehyde (3 mmol), solvent (20 mL), catalyst
(20 mol%), 408C. [h] 1a (2 mmol), aldehyde (1.2 mmol), solvent (8 mL),
catalyst (20 mol%), 408C. [i] At 808C.
Table 1. Screening of different catalysts and solvents for the reaction of
aromatic enamines and benzaldehyde.
Entry[a]
Catalyst[b]
Solvent
t [h]
Yield [%][c]
1
2
3
4
5
6
7
8
none
PhCOOH
TfOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH2Cl2
DMF
11
11
11
11
11
11
11
11
11
11
11
11
11
11
17
17
17
17
17
17
none
<5
<5
<5
<5
<5
65
49
85
57
<5
7
with the latter generally favoured. Ortho-substituted benzal-
dehydes reacted much slower than their para and meta de-
rivatives (Table 2, entry 7 versus 8; entry 9 versus 10), which
indicates the presence of steric effects in these cases, and
good yields were obtained by increasing the loading of cata-
lyst or raising the reaction temperature. The reactions with
heterocyclic aldehydes, such as 2-furan-carbaldehyde and 2-
thiophene-carbaldehyde also worked very well to afford the
4a
4a/AcOH
4a/PhCOOH
4a/TFA
4a/TsOH
4a/TfOH
4b/TfOH
4c/TfOH
4d/TfOH
4e/TfOH
4 f/TfOH
4a/TfOH
4a/TfOH
4a/TfOH
4a/TfOH
4a/TfOH
4a/TfOH
9
10
11
12
13
14
15
16
17
18
19
20
desired bisACTHNUTRGNEUG(N allylic) adducts in high yields (entries 21 and 22).
Notably, aliphatic aldehydes also served as reactive sub-
strates for the reactions, affording the products 3w–z in
moderate to good yields (entries 23–26). The crystal struc-
ture of 3w has been determined, showing unequivocally the
10
5
84
31
85
81
Et2O
bis
(aldehyde), 1,4-phthalaldehyde, has also been examined in
reacting with excess vinylaniline 1a and tetra-allylated
adduct 3a’ was isolated in moderate 26% yield
ACHTUNGTERN(NGNU allylic) motif (Figure 1). The reaction with a bis-
PhCH3
EtOH
CH3CN
AHCTUNGTRENNUNG
94 (88)[d]
80
a
[a] General conditions: 1a (26.6 mg, 0.1 mmol), benzaldehyde
(0.06 mmol), solvent (0.4 mL), catalyst (10 mol%), RT. [b] TfOH: tri-
fluoromethanesulfonic acid; TsOH: benzenesulfonic acid; TFA: trifluoro-
acetic acid. [c] NMR spectroscopic yield. [d] Isolated yield.
(Scheme 2). The use of activated ketones, such as trifuoro-
methyl ketones, has also been tested, showing no reaction
under the present conditions.
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Primary-Amine-Catalyzed C–C Coupling
COMMUNICATION
Figure 1. X-ray crystal structure of adduct 3w (H atoms are omitted for
clarity).
Scheme 2. Coupling of 1,4-phthalaldehyde with vinylaniline 1a.
The scope of the para-vinylanilies was next explored.
Alkyl substitutes on the para-amino group, such as in 2b
and 2c are tolerated and the corresponding adducts 3b’–3e’
can be obtained with moderate to good yields (Scheme 3).
Unfortunately, the triarylamine 2d was found to be inert,
likely as a result of its unfavoured electronic delocalization.
Replacement of the dialkylamino group with a methoxyl
group also depletes the reactivity as observed with 2e
(Scheme 3). The impact of the olefinic substitution has also
been examined. In this regard, no reactions were observed
with terminal substituted 2 f or replacing one aniline moiety
with H or methyl substitute, as in 2g and 2h, respectively.
Interestingly, vinyl aniline 2i, of which one aniline moiety is
replaced with a phenyl ring, demonstrated moderate activity
Scheme 3. Scope of vinylanilines.
tive for the reaction (Table 1, entry 11), suggests that the
acid catalysis, if present, should be minor under the current
conditions. In addition, ESI-MS analysis of the reaction mix-
ture showed m/z bands at 177 and 355, consistent with imini-
um intermediates I and IV (see the Supporting Informa-
tion), respectively, adding further support to the proposed
mechanism.
to give the bisACHTUNGTRENNUNG(allylic) adduct 3 f’ in 45% yield (Scheme 3).
On the basis of the above experimental observations, we
propose an iminium-based cata-
lytic cycle as shown in
Scheme 4. The reaction is ini-
tialized by the nucleophilic ad-
dition of 1a to iminium ion I.
The resulting iminium ion II
undergoes an iminiu–enamine-
type tautomerization, followed
by elimination of diamine 4a
and then affords a highly conju-
gated iminium IV, which reacts
readily with the second mole-
cule of nucleophilic 1a to give
the desired bisACHTUNGTRENNUNG(allylic) adduct.
Though pure acid catalysis
cannot be completely ruled out,
the fact that 4c, a dimethylated
derivative of 4a, is nearly inac- Scheme 4. Proposed catalytic cycle.
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In conclusion, we have uncovered para-vinylanilines as a
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ines. A simple primary amine in concert with TfOH has
À
been found to promote effectively C C coupling of para-vi-
nylanilines and aldehydes, affording bis
A
potential organic electronic materials in high yields under
rather mild conditions. Further explorations of the nucleo-
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Experimental Section
General procedure for the coupling of 1a and aldehyde: Compounds 2a
(12.7 mg, 0.12 mmol) and 1a (53.2 mg, 0.2 mmol) were added to a solu-
tion of N,N-dimethylethylenediamine/TfOH (2.4 mg, 10 mol%) in EtOH
(0.8 mL). The resulting solution was stirred at room temperature for
17 h. After complete conversion as indicated by TLC analysis, the prod-
uct was purified by silica gel column chromatography (EtOAc/PE 1:10)
to give product 3a as a white solid (yield: 88%).
Acknowledgements
This project was supported by the Natural Science Foundation of China
(NSFC 20972163 and 21025208) and the Ministry of Science and Technol-
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MS analysis.
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À
Keywords: C C bond formation · enamines · iminium
activation · organocatalysis · primary amines
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Received: March 15, 2013
Published online: && &&, 0000
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Primary-Amine-Catalyzed C–C Coupling
COMMUNICATION
Organocatalysis
L. Cui, Y. Zhu, S. Luo,*
J.-P. Cheng .................... &&&& — &&&&
Primary–Tertiary Diamine/Brønsted
Acid Catalyzed C–C Coupling between
para-Vinylanilines and Aldehydes
Aromatic enamines: para-Vinylanilines
were identified as unique nucleophiles,
closely resembling enamines, to
diamine/Brønsted acid. The resulting
bis(allylic) adducts, which have poten-
tial as functional materials, were
obtained in high yields under rather
mild conditions (see scheme).
AHCTUNGTRENNUNG
À
undergo C C coupling with aldehydes
catalyzed by a simple primary-tertiary
Chem. Eur. J. 2013, 00, 0 – 0
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www.chemeurj.org
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