Titanium-catalyzed intermolecular hydroaminoalkylation of conjugated dienes

Article abstract of DOI:10.1002/chem.201203693

Ti me kangaroo down: Conjugated dienes undergo intermolecular hydroaminoalkylation in the presence of Ti catalyst [Ind₂TiMe ₂] (Ind=η⁵-indenyl). This new reaction offers a highly atom-efficient approach to homoallylic amines from 1,3-butadienes. Copyright

Full text of DOI:10.1002/chem.201203693

COMMUNICATION
DOI: 10.1002/chem.201203693
Titanium-Catalyzed Intermolecular Hydroaminoalkylation of Conjugated
Dienes
Till Preuß, Wolfgang Saak, and Sven Doye*[a]
The catalytic hydroaminoalkylation of alkenes is a highly
the reaction.[6g] However, neither Group 5 metal catalysts
nor titanium catalysts have been successfully used for hydro-
aminoalkylation reactions of conjugated 1,3-dienes to date.
This limitation can easily be explained by the fact that most
of these hydroaminoalkylation catalysts require high reac-
tion temperatures (130–1708C). Under these conditions,
many 1,3-dienes decompose or undergo dimerization or pol-
ymerization reactions.[7] To the best of our knowledge, the
only example of a transition-metal-catalyzed hydroaminoal-
kylation of a 1,3-diene is the reaction of 1-phenyl-1,3-buta-
diene with 2-(ethylamino)pyridine, which was performed at
858C or 958C in the presence of an iridium catalyst.[3] As
mentioned above, the severe drawback of this catalyst is the
fact that the reaction can only be achieved with 2-(alkylami-
no)pyridine derivatives. Herein, we report the first examples
of titanium-catalyzed intermolecular hydroaminoalkylation
reactions of 1-aryl- and 1-alkyl-substituted 1,3-dienes with
N-methylanilines, which give access to synthetically useful 2-
substituted homoallylic amines.
Owing to the electronic similarities between 1,3-dienes
and styrene derivatives and the fact that [Ind2TiMe2] (Ind=
h5-indenyl) has already been identified to efficiently catalyze
the hydroaminoalkylation reactions of styrenes at a temper-
ature of only 1058C,[6d] we used this catalyst in our initial hy-
droaminoalkylation experiments between 1-phenyl-1,3-buta-
diene (1) and N-methylaniline (2) as model substrates. Thus,
a solution of one equivalent of the amine (2), 1.5 equivalents
of the diene (1) and 10 mol% of [Ind2TiMe2] in n-octane[8]
was heated at 1058C. After a reaction time of 96 h, GC
analysis of the crude reaction mixture revealed that both
starting materials had been almost completely consumed
and that the branched (3a) and linear hydroaminoalkylation
products (3b) had been formed in a ratio of 66:34 (Table 1,
entry 1). Unsurprisingly, two additional products, which
were detected in minor quantities, were identified by GC/
MS analysis as dimerization products (m/z 260) of the diene
(1).[9] Finally, we isolated the hydroaminoalkylation products
(3a and 3b) in a combined 84% yield by flash column chro-
matography on silica gel. However, notably, the branched
isomer (3a) was obtained in its pure form (51% yield),
whereas the linear product (3b) was only isolated with small
impurities of the branched isomer (3a). Interestingly, we did
not detect or isolate any products that were generated by
the hydroaminoalkylation of the internal double bond of
diene 1. This lack of reactivity of the internal alkene moiety
is in good agreement with the previous identification of 1,2-
À
atom-efficient reaction that allows the addition of a-C H
À
bonds of primary or secondary amines to C C double bonds
in a single step (Scheme 1).[1] This reaction, which involves a
Scheme 1. Catalytic intermolecular hydroaminoalkylation of alkenes.
3
À
C H activation at an sp center in the a position to a nitro-
gen atom can be achieved in the presence of ruthenium,[2]
iridium,[3] Group 5 metal,[4] zirconium,[5] or titanium cata-
lysts.[6] Unfortunately, a number of limitations exist, which
impede the synthetic applicability of the reaction. For exam-
ple, the use of ruthenium and iridium catalysts is limited to
amine substrates that possess a directing 2-pyridinyl sub-
stituent on the nitrogen atom[2,3] and zirconium catalysts can
only be used for intramolecular hydroaminoalkylation reac-
tions of primary aminoalkenes.[5] On the other hand,
Group 5 metal and titanium catalysts also offer the possibili-
ty of performing intermolecular hydroaminoalkylation reac-
tions with more simple secondary amines, such as N-alkyla-
nilines or dialkylamines.[4,6] However, in these cases, the
number of suitable alkenes is limited. For example, Group-
5-metal-catalyzed hydroaminoalkylation reactions tolerate
many 1-alkenes, as well as selected 1,1- and 1,2-disubstituted
alkenes, as substrates, whereas the corresponding reactions
of styrenes are extremely rare.[4i] An interesting feature of
all Group 5 metal catalysts is that the branched hydroami-
noalkylation product is always formed exclusively. In con-
trast, titanium catalysts also offer the possibility of perform-
ing hydroaminoalkylation reactions of many styrenes[6c,d,g]
and, depending on the structure of the catalyst, it is also
possible to obtain the linear isomer as the major product of
[a] T. Preuß, W. Saak, Prof. Dr. S. Doye
Institut fꢀr Reine und Angewandte Chemie
Universitꢁt Oldenburg
Carl-von-Ossietzky-Straße 9–11, 26111 Oldenburg (Germany)
Fax : (+49)441-798-3329
E-mail: doye@uni-oldenburg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203693.
Chem. Eur. J. 2013, 19, 3833 – 3837
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3833

Table 1. Hydroaminoalkylation of 1-phenyl-1,3-butadiene (1) with N-
methylaniline (2).
entries 6–11), revealed that these catalysts did not promote
the successful hydroaminoalkylation reactions between 1-
phenyl-1,3-butadiene (1) and N-methylaniline (2) at temper-
atures between 1058C and 1608C. Although, in each case,
the consumption of diene 1 was observed by GC, we did not
detect or isolate any hydroaminoalkylation products. This
finding again confirms that undesired side-reactions of the
1,3-diene (1) readily take place under these reaction condi-
tions. The assumption that this behavior is caused by the
well-known propensity of 1,3-dienes to undergo facile dime-
rization or polymerization[7] is strongly supported by the de-
tection of large quantities of the dimerization products of
diene 1 by GC/MS analysis of the crude reaction mixtures.
As shown in Table 1, the regioselectivities of the hydroami-
noalkylation reactions, in favor of the branched product
(3a), are relatively low (approximately 2:1). This observa-
tion, in combination with the fact that regioselectivities of
>99:1 are typical for [Ind2TiMe2]-catalyzed hydroaminoal-
kylation reactions of simple alkyl-substituted alkenes, like 1-
octene,[6d] strongly support the expectation that conjugated
1,3-diene 1 does not behave like a simple 1-alkene in hydro-
aminoalkylation reactions. However, in this context, it must
be noted that, under comparable conditions, the hydroami-
noalkylation of styrene with compound 2 also gave signifi-
cantly higher regioselectivity (85:15)[6d] than the reaction of
diene 1. Clearly, the electronic similarities between styrene
and 1-phenyl-substituted 1,3-diene 1 in hydroaminoalkyla-
tion chemistry are not as strong as expected.
Entry
Ti catalyst
T [8C] t [h] Yield
3a+3b
Selectivity
3a/3b[b]
[%][a]
1
2
3
4
5
6
7
8
[Ind2TiMe2]
[Ind2TiMe2]
[Ind2TiMe2]
[Ind2TiMe2]
[Ind2TiMe2]
105
105
105
130
160
105
160
105
160
96
24
144
96
96
96
96
96
96
96
96
84[c]
83
66:34
68:32
69:31
69:31
85[d]
80[d]
65[d]
–
71:29
[Ti
[Ti(NMe2)4]
[TiBn4]
[TiBn4]
A
–
–
–
–
–
–
[d]
N
–
G
–
–
–
–
[d]
[d]
9
10
11
ACHTUNGTRENNUNG
[Ti
[TiACHTUNGTRENNUNG
ACHTUNGTRENNUNG
(NMe2)4]/2-MeAP-H[e] 105
[a] Reaction conditions: amine (2.0 mmol), diene (3.0 mmol), Ti catalyst
(0.2 mmol, 10 mol%), n-octane (1 mL). Yields are of isolated mixtures of
compounds 3a and 3b. [b] GC analysis prior to chromatography. [c] A
corresponding reaction that was performed on a 15 mmol scale gave a
yield of 83%. [d] 100% Conversion of the diene. [e] 2-MeAP-H=2-
(methylamino)pyridine.
disubstituted alkenes as poor substrates for Ti-catalyzed hy-
droaminoalkylation reactions.[6] Two additional experiments
with longer (144 h) and shorter reaction times (24 h), which
gave almost identical yields and selectivities (Table 1, en-
tries 2 and 3), clearly confirmed that longer reaction times
did not necessarily lead to improved results. On the other
hand, very interesting behavior was observed at elevated
temperatures (Table 1, entries 4 and 5). First, we found that,
at 1308C, compounds 3a and 3b were still formed in good
yield (80%). However, GC/MS analysis of the crude reac-
tion mixture revealed a significantly increased formation of
the dimerization products of diene 1. Particularly interesting
was the result at 1608C. In that case, even larger amounts of
the dimers were observed and, in addition, in contrast to the
reactions that were performed at 1058C and 1308C, the re-
action mixture still contained significant amounts of uncon-
sumed N-methylaniline (2) after a reaction time of 96 h.
This result clearly indicates that, at elevated temperatures,
the consumption of the diene through undesired side-reac-
tions, such as dimerization, becomes so fast that, after a cer-
tain point in the reaction, no more diene is present in the re-
action mixture to react with the remaining N-methylaniline.
As the result, the reaction at 1608C gave the desired prod-
ucts (3a and 3b) in a significantly lower yield of only 65%.
As a consequence, it is not advisable to perform [In-
d2TiMe2]-catalyzed hydroaminoalkylation reactions of 1,3-
dienes at temperatures above 105–1308C. Additional experi-
ments that were performed with the established hydroami-
To investigate the scope and limitations of this new reac-
tion, we performed the reactions of a number of 1-aryl-sub-
stituted 1,3-butadienes (1, 4–11) with N-methylanilines (2,
12–15) under our standard conditions at 1058C (Table 2).
Although the reaction time was initially chosen to be 96 h,
selected reactions were also performed for a shorter length
of time (24 h). First of all, we recognized that the regioselec-
tivity of the reaction was not strongly influenced by the
steric bulk of the phenyl substituent of the diene. Conse-
quently, similar regioselectivities between 62:38 and 75:25 in
favor of the branched products were obtained with ortho-,
meta- and para-tolyl-substituted 1,3-dienes 4–6 (Table 2, en-
tries 3–7). In addition, the reactivities of these three dienes
did not differ dramatically and modest-to-good yields were
obtained in all cases. Both of these observations can be un-
derstood by the remote position of the tolyl substituent rela-
tive to the reaction double bond. Owing to their better sepa-
ration from unreacted N-methylaniline, occasionally, the hy-
droaminoalkylation products were isolated after conversion
into their corresponding acetamides (AcCl, CH2Cl2, room
temperature). An additional advantage of this procedure
was the crystalline nature of product 16a, which gave us the
opportunity to unambiguously verify the structure of the
branched hydroaminoalkylation product by X-ray crystal-
structure analysis (Figure 1).[10]
Additional reactions of 1-(methoxyphenyl)-substituted
1,3-butadienes 7 and 8 with N-methylaniline (2; Table 2, en-
tries 8 and 9) also gave their expected products in moder-
ate-to-good yields (44–89%) and, in both cases, the
noalkylation catalysts, [Ti
ACHTUNGTRENNUNG
(NMe2)4],[6b] [TiBn4],[6c] and [Ti-
ACHTUNGTRENNUNG
3834
www.chemeurj.org
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3833 – 3837

Intermolecular Hydroaminoalkylation of Conjugated Dienes
Table 2. Hydroaminoalkylation of 1-aryl-substituted 1,3-butadienes.
COMMUNICATION
change the reactivity of the diene or the regioselec-
tivity of the reaction. On the other hand, the pres-
ence of electron-withdrawing chloro or trifluoro-
methyl substituents on the phenyl group of the
diene led to dramatically lower yields of only 8–
23% (Table 2, entries 10–13), although the regiose-
lectivity of the reaction did not seem to be influ-
enced significantly by these substituents. The po-
tential negative influence of halide substituents
was strongly underlined by the fact that 1-(m-bro-
mophenyl)-1,3-butadiene did not undergo the de-
sired reaction at all. Unfortunately, 1-(o-nitrophen-
Entry
Ar (diene)
R (amine)
t [h] Yield a+b [%][a] Selectivity a/b[b]
1
2
3
4
5
6
7
8
Ph (1)
Ph (1)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
96
24
96
24
96
24
96
96
96
96
24
96
24
96
24
96
96
84 (3a/b)[c]
66:34
68:32
75:25
75:25
62:38
62:38
70:30
67:33
73:27
66:34
66:34
65:35
66:34
55:45
55:45
67:33
65:35
60:40
71:29
67:33
83 (3a/b)[c]
o-Me-C6H4 (4)
o-Me-C6H4 (4)
m-Me-C6H4 (5)
m-Me-C6H4 (5)
p-Me-C6H4 (6)
m-MeO-C6H4 (7)
p-MeO-C6H4 (8)
p-Cl-C6H4 (9)
p-Cl-C6H4 (9)
m-CF3-C6H4 (10)
m-CF3-C6H4 (10)
2-thiophenyl (11)
2-thiophenyl (11)
Ph (1)
89 (16a/b)[c,d]
85 (16a/b)[c,d]
73 (17a/b)[c,d]
47 (17a/b)[d]
61 (18a/b)[c]
44 (19a/b)[c,d]
87 (20a/b)[c,d]
12 (21a/b)[c,d,e]
8 (21a/b)[d,e,f]
23 (22a/b)[c,d]
14 (22a/b)[d]
44 (23a/b)[c,d]
35 (23a/b)[d]
73 (24a/b)[c,d]
85 (25a/b)[c,d]
23 (26a/b)[d,g]
6 (27a/b)
yl)-1,3-butadiene,
1-(2-naphthyl)-1,3-butadiene,
and 1-(2-furyl)-1,3-butadiene did not give any hy-
droaminoalkylation products either. However, the
2-furyl- and 2-naphtyl-subtituted dienes turned out
to be too unstable under the reaction conditions.
In both cases, both dimerization and decomposi-
tion of the diene were observed.[7] In contrast, the
more stable thiophenyl-substituted diene 11 under-
went a successful reaction to give the desired prod-
ucts (23a/23b) in moderate yields of 35–44%
(Table 2, entries 14 and 15). To investigate the lack
of reactivity of 1-(m-bromophenyl)-1,3-butadiene
and 1-(o-nitrophenyl)-1,3-butadiene, we performed
three additional hydroaminoalkylation experiments
under the conditions given in Table 2, entry 1, in
which we tried to react diene 1 with N-methylani-
line (2) in the presence of one equivalent (relative
to diene 1) of either 1-(m-bromophenyl)-1,3-buta-
diene, bromobenzene, or nitrobenzene. The fact
that all three of these reactions did not lead to any
9
10
11
12
13
14
15
16
17
18
19
20
m-Me (12)
p-Me (13)
p-MeO (14) 96
p-Cl (15)
p-Me (13)
Ph (1)
Ph (1)
Ph (1)
96
96
m-Me-C6H4 (5)
78 (28a/b)[c,d]
[a] Reaction conditions: amine (2.0 mmol), diene (3.0 mmol), [Ind2TiMe2] (0.2 mmol,
10 mol%), n-octane (1 mL), 1058C, 24 or 96 h. Yields are of isolated mixtures of prod-
ucts a and b. [b] GC analysis prior to chromatography. [c] According to GC analysis,
>90% conversion of the diene. [d] The products were isolated after conversion into
the corresponding acetamides. [e] No separation of regioisomers a and b could be ach-
ieved by chromatography. [f] Owing to the low yield, the product could not be isolated
in its pure form. [g] The non-acetylated amine products are not stable on silica gel.
formation of the desired products (3a/3b) clearly indicated
that the bromo and nitro groups inhibited the [Ind2TiMe2]-
catalyzed hydroaminoalkylation reaction. Additional reac-
tions between 1-phenyl-1,3-butadiene (1) and N-methylani-
line derivatives 12–15 (Table 2, entries 16–19) revealed that
good yields (73–85%) could only be obtained with the tolyl
derivatives, that is, N-methyl-m-toluidine (12) and N-
methyl-p-toluidine (13; Table 2, entries 16 and 17). In both
cases, a regioselectivity of approximately 2:1 in favor of the
branched product was observed. Interestingly, the sterically
more hindered analogue N-methyl-o-toluidine did not un-
dergo the reaction at all, which was also true for N-methyl-
p-trifluoromethylaniline. In addition, poor yields of only
23% and 6% were obtained with N-methyl-p-methoxyani-
line (14) and N-methyl-p-chloroaniline (15), respectively
(Table 2, entries 18 and 19), and no successful reactions took
place with 1,2,3,4-tetrahydroquinoline or dialkylamines (N-
methylcyclohexylamine, N-methylbenzylamine, and 1,2,3,4-
tetrahydroisoquinoline). These latter results are in good
agreement with the already reported lack of reactivity of di-
alkylamines in [Ind2TiMe2]-catalyzed hydroaminoalkylation
reactions.[6d] However, the observation that relatively un-
functionalized conjugated dienes and N-methylaniline deriv-
atives were good substrates for the [Ind2TiMe2]-catalyzed
hydroaminoalkylation reaction was strongly supported by
Figure 1. X-ray crystal structure of branched acetamide 16a. Thermal el-
lipsoids are set at 50% probability. Selected bond lengths [ꢃ] and angles
À
À
À
À
[8]: C14 C13 1.4734(9), C13 C12 1.3321(8), C12 C10 1.4979(8), C11
À
À
À
C10 1.5355(9), C10 C9 1.5355(8), C9 N1 1.4668(7), N1 C3 1.4341(7),
À
À
À
N1 C1 1.3615(8), C1 C2 1.5055(9), C1 O1 1.2319(7); C14-C13-C12
124.89(6), C13-C12-C10 125.63(6), C12-C10-C11 110.16(5), C12-C10-C9
111.24(5), C11-C10-C9 108.09(5), C9-N1-C3 117.07(5), C9-N1-C1
120.00(5), C3-N1-C1 122.39(5).[10]
branched product was again obtained as the major product
with a regioselectivity of ꢀ67:33. These results, which are
comparable to those that were obtained with the 1-phenyl-
and 1-tolyl-substituted 1,3-butadienes, indicate that the pres-
ence of electron-donating groups on the benzene ring of the
1-phenyl-1,3-butadiene substrate does not significantly
Chem. Eur. J. 2013, 19, 3833 – 3837
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3835

S. Doye et al.
had cooled to room temperature, EtOAc (65 mL) was added and the re-
gioselectivity of the reaction was determined by GC (branched/linear,
the good yield (78%) that was obtained for the reaction be-
tween 1-(m-tolyl)-1,3-butadiene (5) and N-methyl-p-tolui-
dine (13, Table 2, entry 20).
Finally, some preliminary reactions between 1-alkyl-sub-
stituted 1,3-butadienes 29–31 and N-methylanilines 2 and 13
gave access to the desired hydroaminoalkylation products in
moderate-to-good yields (Table 3). In particular, interesting-
73:27). Then,
a solution of acetyl chloride in CH2Cl2 (1m, 4.0 mL,
4.0 mmol) was added and the mixture was stirred overnight at room tem-
perature. Finally, the solvents were removed under reduced pressure in
the presence of Celite and the residue was purified by flash column chro-
matography on silica gel (n-hexane/EtOAc, 2:1) to give three fractions of
compounds 20a and 20b (total: 540 mg, 1.74 mmol, 87% yield) as yellow
oils. Fraction 1 contained the branched product (20a, 260 mg, 0.84 mmol,
42% yield) in high purity, fraction 2 contained a mixture of the branched
and linear products (180 mg, 0.58 mmol, 29% yield), and fraction 3 con-
tained the linear product (20b, 100 mg, 0.32 mmol, 16% yield) as the
major component.
Table 3. Hydroaminoalkylation of 1-alkyl-substituted 1,3-butadienes.
Acknowledgements
Entry
R1 (diene)
R2 (amine) t [h] Yield a+b
Selectivity
[%][a]
a/b[b]
We thank the Deutsche Forschungsgemeinschaft for financial support of
our research. We also thank Jessica Reimer and Kristin Petersen for their
great help with the experiments.
1
2
3
4
5
6
7
8
n-C6H13 (29)
n-C6H13 (29)
Ph-(CH2)2 (30)
Ph-(CH2)2 (30)
Cy (31)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
H (2)
96
24
96
24
96
24
48
49 (32a/b)[c,d] >99:1
13 (32a/b)[c,d] >99:1
72 (33a/b)
74 (33a/b)
84 (34a/b)
–
90:10
90:10
92:8
–
À
Keywords: alkenes
homogeneous catalysis · titanium
·
amines
·
C H activation
·
Cy (31)
Cy (31)
Cy (31)
74 (34a/b)
72 (35a/b)
92:8
92:8
p-Me (13) 96
[a] Reaction conditions: amine (2.0 mmol), diene (3.0 mmol), [Ind2TiMe2]
(0.2 mmol, 10 mol%), n-octane (1 mL), 1058C, 24–96 h. Yields are of iso-
lated mixtures of products a and b. [b] GC analysis prior to chromatogra-
phy. [c] The reaction was performed on a 1.0 mmol scale. [d] According
to 1H NMR and GC/MS analysis, the product was contaminated with
trace amounts of unidentified isomerization products.
[1] For a review on the hydroaminoalkylation of alkenes, see: P. W.
Roesky, Angew. Chem. 2009, 121, 4988–4991; Angew. Chem. Int.
Ed. 2009, 48, 4892–4894.
[2] For ruthenium catalysts, see: a) C.-H. Jun, D.-C. Hwang, S.-J. Na,
Chem. Commun. 1998, 1405–1406; b) N. Chatani, T. Asaumi, S. Yor-
imitsu, T. Ikeda, F. Kakiuchi, S. Murai, J. Am. Chem. Soc. 2001, 123,
10935–10941.
[3] For iridium catalysts, see: S. Pan, K. Endo, T. Shibata, Org. Lett.
2011, 13, 4692–4695.
ly, in comparison with the results that were obtained with 1-
aryl-substituted 1,3-butadienes, the regioselectivities of the
reactions were much higher (ꢀ90:10). A comparable differ-
ence between aryl-substituted and alkyl-substituted 1-al-
kenes has already been observed during [Ind2TiMe2]-cata-
lyzed hydroaminoalkylation reactions.[6d]
In summary, we have shown for the first time that the in-
termolecular hydroaminoalkylation reactions of 1-aryl- and
1-alkyl-substituted 1,3-butadienes can be achieved in the
presence of a titanium catalyst. Although the scope of this
[Ind2TiMe2]-catalyzed reaction is still limited, these results
will hopefully initiate further studies towards an optimiza-
tion of this new and highly atom-efficient process for the
synthesis of homoallylic amines from readily available 1,3-
butadienes.
[4] For Group 5 metal catalysts, see: a) M. G. Clerici, F. Maspero, Syn-
thesis 1980, 305–306; b) W. A. Nugent, D. W. Ovenall, S. J. Holmes,
Organometallics 1983, 2, 161–162; c) S. B. Herzon, J. F. Hartwig, J.
Am. Chem. Soc. 2007, 129, 6690–6691; d) S. B. Herzon, J. F. Hart-
wig, J. Am. Chem. Soc. 2008, 130, 14940–14941; e) P. Eisenberger,
R. O. Ayinla, J. M. P. Lauzon, L. L. Schafer, Angew. Chem. 2009,
121, 8511–8515; Angew. Chem. Int. Ed. 2009, 48, 8361–8365; f) P.
Eisenberger, L. L. Schafer, Pure Appl. Chem. 2010, 82, 1503–1515;
g) G. Zi, F. Zhang, H. Song, Chem. Commun. 2010, 46, 6296–6298;
h) A. L. Reznichenko, T. J. Emge, S. Audçrsch, E. G. Klauber, K. C.
Hultzsch, B. Schmidt, Organometallics 2011, 30, 921–924; i) A. L.
Reznichenko, K. C. Hultzsch, J. Am. Chem. Soc. 2012, 134, 3300–
3311.
[5] For zirconium catalysts, see: J. A. Bexrud, P. Eisenberger, D. C.
Leitch, P. R. Payne, L. L. Schafer, J. Am. Chem. Soc. 2009, 131,
2116–2118.
[6] For titanium catalysts, see: a) C. Mꢀller, W. Saak, S. Doye, Eur. J.
Org. Chem. 2008, 2731–2739; b) R. Kubiak, I. Prochnow, S. Doye,
Angew. Chem. 2009, 121, 1173–1176; Angew. Chem. Int. Ed. 2009,
48, 1153–1156; c) I. Prochnow, R. Kubiak, O. N. Frey, R. Beckhaus,
S. Doye, ChemCatChem 2009, 1, 162–172; d) R. Kubiak, I. Proch-
now, S. Doye, Angew. Chem. 2010, 122, 2683–2686; Angew. Chem.
Int. Ed. 2010, 49, 2626–2629; e) I. Prochnow, P. Zark, T. Mꢀller, S.
Doye, Angew. Chem. 2011, 123, 6525–6529; Angew. Chem. Int. Ed.
2011, 50, 6401–6405; f) D. Jaspers, W. Saak, S. Doye, Synlett 2012,
23, 2098–2102; g) J. Dçrfler, S. Doye, Angew. Chem. 2013, 125,
1851–1854; Angew. Chem. Int. Ed. 2013, 52, 1806–1809.
[7] a) D. Mundal, K. Lutz, R. Thomson, Org. Lett. 2009, 11, 465–468;
b) J. A. Berson, P. B. Dervan, R. Malherbe, J. A. Jenkins, J. Am.
Chem. Soc. 1976, 98, 5937–5968; c) J. Mulzer, U. Kꢀhl, G. Huttner,
K. Evertz, Chem. Ber. 1988, 121, 2231–2238.
Experimental Section
General procedure for the hydroaminoalkylation reaction, as exemplified
by the reaction of compound 8 with compound 2 (Table 2, entry 9): An
oven-dried Schlenk tube that was equipped with a Teflon stopcock and a
magnetic stirrer bar was transferred into a nitrogen-filled glove box and
charged with [Ind2TiMe2] (62 mg, 0.20 mmol, 10 mol%), (E)-1-(para-me-
thoxyphenyl)butadiene (8, 481 mg, 3.0 mmol), N-methylaniline (2,
214 mg, 2.0 mmol), and dry n-octane (1 mL). Then, the tube was sealed
and the resulting mixture was heated at 1058C for 96 h. After the mixture
3836
www.chemeurj.org
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3833 – 3837

Intermolecular Hydroaminoalkylation of Conjugated Dienes
COMMUNICATION
[8] The reaction could also be performed in toluene or in the absence
of a solvent. In these cases, no significant changes in terms of the
yield or regioselectivity were observed.
[9] We isolated a mixture of the two dimerization products by HPLC.
According to GC/MS and 1H and 13C NMR analysis, this mixture
consisted of the two stereoisomeric Diels–Alder products, cis- and
trans-3-phenyl-4-[(E)-styryl]-1-cyclohexene, in an approximately 1:1
ratio. These compounds have previously been synthesized from com-
pound 1 by thermal [4+2] cycloaddition (see Ref. [7c]).
[10] CCDC-904794 (16a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.a-
c.uk/data_request/cif.
Received: October 16, 2012
Revised: January 18, 2013
Published online: February 20, 2013
Chem. Eur. J. 2013, 19, 3833 – 3837
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3837