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
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 3833 – 3837