Anti-markovnikov hydroamination of aromatic alkenes with secondary amines catalyzed by easily accessible yttrium complexes

Article abstract of DOI:10.1002/cctc.201402012

Binaphthylamido alkyl yttrium complexes have been proven to promote the anti-Markovnikov addition between various styrene derivatives and secondary amines efficiently. Although the reaction has to be performed at high temperature, it is realized advantage

Full text of DOI:10.1002/cctc.201402012

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DOI: 10.1002/cctc.201402012
Anti-Markovnikov Hydroamination of Aromatic Alkenes
with Secondary Amines Catalyzed by Easily Accessible
Yttrium Complexes
Stꢀphane Germain,[a] Emmanuelle Schulz,*[a, b] and Jꢀrꢁme Hannedouche*[a, b]
Binaphthylamido alkyl yttrium complexes have been proven to
promote the anti-Markovnikov addition between various sty-
rene derivatives and secondary amines efficiently. Although
the reaction has to be performed at high temperature, it is re-
alized advantageously with a 1:2 amine/alkene molar ratio to
deliver the hydroamination product in a satisfactory isolated
yield. Furthermore, the reaction with 2-vinylpyridine proceeds
at room temperature within a few minutes with a low catalyst
loading of 1 mol%. The procedure has been extended to
a tandem intermolecular anti-Markovnikov–intramolecular Mar-
kovnikov hydroamination for which the chiral precatalyst deliv-
ered the targeted product in up to 85% yield and 48% enan-
tiomeric excess.
Introduction
The direct addition reaction of the amine across a C=C bond,
the so-called hydroamination reaction, is one of the more ele-
gant and most atom economical methods for the formation of
value-added N-containing compounds from relatively inexpen-
sive and ubiquitous amines and alkenes.[1] Over the years, con-
siderable effort has been devoted to the development of cata-
lytic systems mainly for the selective intra-[2] or intermolecular[3]
Markovnikov hydroamination reaction of alkenes and signifi-
cant progress has been achieved in terms of activities, stereo-
selectivities, and scope of applications.[4] Conversely, and de-
spite the industrial relevance of the products formed,[1] little
work deals with catalytic systems that exhibit anti-Markovnikov
regioselectivity.[5,6] Only a few metal systems based on either
alkali,[6a,b] alkaline,[6c–f] rare-earth,[6g,h] or late transition met-
als[6i–m] or to a lower extent some metal-free systems[6n] have
sporadically demonstrated such a regioselectivity with the
scope of alkenes limited to vinylarene derivatives, such as sty-
rene. To the best of our knowledge, there is no report of the
direct anti-Markovnikov addition of amines on simple aliphatic
alkenes.[7] This underlines the challenge related to the develop-
ment of catalytic systems that display anti-Markovnikov reac-
tivity.
Figure 1. Chiral binaphthylamido alkyl yttrium complexes.
1 (Figure 1), and their successful use as highly active precata-
lysts for the intramolecular, enantioselective Markovnikov hy-
droamination of primary and secondary amines.[8] In this paper,
we disclose our studies towards the applications of these sys-
tems in the more challenging intermolecular hydroamination
reaction of alkenes. The reaction development and exploration
of the substrate scope, described herein, demonstrate the effi-
ciency of 1 as precatalysts for the highly selective, intermolecu-
lar anti-Markovnikov hydroamination of styrene derivatives and
2-vinylpyridine with secondary amines. Complex 1 has also the
ability to catalytically promote a tandem[9] intermolecular anti-
Markovnikov–intramolecular Markovnikov hydroamination re-
action sequence. This work completes the rare contributions of
rare-earth-based catalysts that display intermolecular anti-Mar-
kovnikov selectivity.[6g,h]
Our group has recently reported the in situ preparation of
chiral binaphthylamido alkyl yttrium complexes, such as
[a] S. Germain, Dr. E. Schulz, Dr. J. Hannedouche
Equipe de Catalyse Molꢀculaire
Universitꢀ Paris-Sud, ICMMO, UMR 8182
Orsay, 91405 (France)
Results and Discussion
Fax: (+33)169154680
E-mail: emmanuelle.schulz@u-psud.fr
jerome.hannedouche@u-psud.fr
Preliminary experiments were conducted to investigate the re-
action between primary amines and simple aliphatic alkenes.
Catalyst 1a was thus engaged (10 mol%, 0.1m) to test its abili-
ty to promote the intermolecular hydroamination of alkenes
(pent-1-ene, hept-1-ene, and oct-1-ene) with benzylamine. The
amine was first introduced in the catalyst solution followed by
[b] Dr. E. Schulz, Dr. J. Hannedouche
CNRS
Orsay, 91405 (France)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402012.
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the alkene in a 15-fold excess, and the mixture was heated to
1308C in deuterated toluene using ferrocene as an internal
standard to follow the course of the reaction by NMR spectros-
copy. In each case, precipitation occurred after 10 to 15 min of
reaction time and no traces of any hydroamination product
could be detected, even after prolonged reaction time (up to
120 h). Similar results were obtained if cyclopentylamine was
used as the substrate under the same conditions. A control ex-
periment was thus performed to evaluate the catalyst integrity
under these reaction conditions. 2,2-Diphenylhex-4-enylamine
was added in the same amount as benzylamine to 15 equiva-
lents (equiv.) of pent-1-ene and
nene in the presence of 10 mol% 1a at 1308C, but no hydro-
amination activity was observed. Nevertheless no precipitation
occurred in these cases, which demonstrates that catalyst de-
activation was negligible and could thus be ascribed conceiv-
ably to the presence of the primary amine. Delightfully, howev-
er, the reaction of N-methylbenzylamine with styrene
(10 equiv.) delivered the expected benzylmethylphenethyl-
amine (2a) with an almost complete conversion after 18 h. The
only byproduct observed was polystyrene, the amount of
which could be estimated by comparison with the ferrocene
standard (Table 1, entry 1). The amine/alkene molar ratio could
allowed to react with 1a
Table 1. Intermolecular anti-Markovnikov hydroamination reaction of styrene with secondary amines catalyzed
by 1a.
(6 mol%) at 1308C. Again, no hy-
droamination product that arises
from an intermolecular process
could be detected, but 2-ethyl-
Entry[a] Amine
Amine/alkene Product
molar ratio
t
Conversion to hydroami- Conversion to
[h] nation product [%][b,c]
polymer [%][b]
4,4-diphenylpyrrolidine
was
5
80
10
25
–
5
20
–
1
1:10
formed in only 49% yield (NMR).
A complete conversion for the
intramolecular hydroamination
product should be expected
under these conditions,[8] which
indicates, therefore, that a partial
catalyst deactivation occurred
that led to its precipitation to
a large extent. Other catalytic
tests towards an intermolecular
procedure were conducted in
the presence of slightly activated
alkenes such as norbornene or
cyclohexa-1,3-diene. These al-
kenes were engaged in a 10-fold
excess with benzylamine in the
catalysis at 1308C with 1a for
a prolonged reaction time with-
out delivery of the expected
products. Some hydroamination
activity was, however, detected
18 95
60
5
2
3
1:2
1:1
24 80
48 95 (91)
5
24 56
88 91
38
–
–
24 38
48 49 (41)
13
18
4
5
6
1:2
1:2
1:2
2.5 63
5
–
–
92 (67)
24 50
48 63
5
9
[a] Reactions were performed in C7D8 at 1308C under Ar with 10 mol% of catalyst unless otherwise stated.
[b] Determined by in situ 1H NMR spectroscopy using ferrocene (0.4 equiv.) as internal standard. [c] Isolated
yield in brackets.
with the use of styrene as an activated alkene, for which the
anti-Markovnikov product, benzylphenethylamine, could be
detected as traces in the NMR spectrum. The major compound
formed under these conditions issued from styrene polymeri-
zation. However, the reversal of the order of the introduction
of the reagents on the catalyst influenced the course of the
transformation greatly. If styrene was mixed firstly in the pres-
ence of the precatalyst before the introduction of the amine,
the expected hydroamination product could be recovered in
up to 50% yield (NMR). Unfortunately, these results remained
not easily reproducible, and the formation of the product was
always accompanied by a large amount of polymer formation
and catalyst precipitation.
be decreased to 1:1 with these substrates (Table 1, entries 2
and 3), which allowed the preparation of the targeted product
in a nearly quantitative yield free of any polystyrene after 88 h.
Such an equimolar ratio between both hydroamination part-
ners is a noticeable result in the field of catalysis promoted by
rare-earth elements, which demonstrates the high activity of
1a under these conditions. It was further checked by control
experiments that the presence of the catalyst did not impact
the styrene polymerization rate, which only occurred because
of the high reaction temperature. For the rest of the study an
amine/alkene ratio of 1:2 was chosen as the best compromise
for a high yield of the recovered product in a reasonable time
(Table 1, entry 2).
In an attempt to improve these results, more nucleophilic
amines were then introduced and the use of secondary amines
was privileged in this study. Accordingly, N-methylbenzylamine
was reacted under the same conditions as those described for
the use of primary amines with either pent-1-ene or norbor-
Other secondary amines were tested in this intermolecular
hydroamination reaction in an attempt to widen its scope.
1-Phenethylpyrrolidine (2b) could be prepared from styrene in
a 1:2 ratio, but the conversion reached only 49% after two
days. The amount of polystyrene also remained limited in this
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case (Table 1, entry 4). The reactivity of piperazine de-
rivatives was also investigated as these substrates re-
mained resistant to hydroamination with Rh-promot-
ed catalysis by inhibition of the metal active sites.[10]
The formation of 1-methyl-4-phenethylpiperazine
(2c) was achieved readily in a short reaction time
starting from 1-methylpiperazine (Table 1, entry 5),
whereas the use of unprotected piperazine or mor-
pholine led to the formation of a precipitate, and the
expected products could not be quantified correctly.
N-Methylcyclohexylmethylamine also reacted with
styrene (Table 1, entry 6) to afford 2d, but steric hin-
drance in close proximity to the N atom affected the
course of the reaction dramatically. No hydroamina-
tion product could be detected on using either
N-ethylbenzylamine or diethylamine even after a very
long reaction time. Contrary to the observations
made during the use of primary amines, the order of
introduction of the reagents had no influence on the
hydroamination yield.
Table 2. Intermolecular anti-Markovnikov hydroamination reaction of styrene deriva-
tives with N-methylbenzylamine or pyrrolidine catalyzed by 1a.[a]
Conversion [%]
Entry
Amine:
R2, R3
Styrene
derivative: R1
Product
t
[h]
Hydroamination
product[b,c]
Polymer[b]
1
2
3
4
Bn, Me
o-Cl
m-Cl
p-Cl
3a
3b
3c
3d
24
24
48
3
73 (67)
28
33
19
34
49
–
o-OMe
85
10
3
48
3
48
5
48
5
>98 (77)
58
93 (79)
0
15
62
>98 (88)
70
99 (63)
43
10
–
16
–
17
–
12
–
5
6
7
8
9
m-OMe
p-OMe
o-Me
3e
3 f
3g
3h
3i
m-Me
p-Me
48
5
16
–
48
24
24
48
48
48
48
48
48
48
93 (90)
98 (52)
51 (47)
75 (47)
85 (41)
76 (52)
n.d.
74 (57)
70 (32)
53 (32)
23
11
16
23
32
12
n.d.
11
16
7
10
11
12
13
14
15
16
17
18
À(CH2)4À
o-Cl
m-Cl
p-Cl
o-OMe
m-OMe
p-OMe
o-Me
m-Me
p-Me
4a
4b
4c
4d
4e
4 f
4g
4h
4i
N-Methylbenzylamine and pyrrolidine were further
tested to examine the intermolecular hydroamination
with various styrene derivatives that bear different
substituents (i.e., ÀCl, ÀOMe, ÀMe) in either the
ortho, meta, or para position (Scheme 1 and Table 2).
All expected hydroamination products were obtained
in a moderate to high yield, except for pyrrolidine
and 1-methoxy-4-vinylbenzene, which did not deliver
any hydroamination product (Table 2, entry 15). Some
[a] Reactions were performed in C7D8 at 1308C under Ar with 10 mol% of catalyst,
amine (1 equiv.), and alkene (2 equiv.) unless otherwise stated. [b] Determined by
1
in situ H NMR spectroscopy using ferrocene (0.4 equiv.) as internal standard. [c] Isolat-
ed yield in brackets.
N-methylbenzylamine (Table 2, entries 1–3 versus Table 1,
entry 2). Contrarily, the substitution on styrene led predomi-
nantly to better results in terms of conversion compared to
the transformation with unmodified styrene for pyrrolidine
(Table 2, entries 10–18 versus Table 1, entry 4). If we regard the
chloride derivatives, the conversion could reach up to 98% for
the reaction with 1-chloro-2-vinylbenzene to 4a in only one
day, accompanied with a low amount of residual styrene poly-
merization (Table 2, entry 10). Another noticeable result is the
formation of 1-[2-(2-methoxyphenyl)ethyl]pyrrolidine (4d) in
85% yield (NMR; Table 2, entry 13).
Scheme 1. Intramolecular anti-Markovnikov hydroamination reaction of sty-
rene derivatives.
general trends may be deduced from the results given in
Table 2, in which the presence of electron-donating groups
seems to provide the targeted products with improved yields
in comparison with unsubstituted styrene, which is even more
significant if a substitution in the ortho position allows a sup-
plementary coordination to the Y atom. Benzyl-[2-(2-methoxy-
phenyl)ethyl]methylamine (3d) was indeed obtained with
a complete conversion in only 10 h (Table 2, entry 4), whereas
the introduction of the para-OMe group on the styrene led to
a drastic decrease of the reaction rate to yield 3 f (Table 2,
entry 6), probably because of an important participation of the
methoxy substituent to the coordination, which upset the nec-
essary contribution of the double bond. Similarly high yields
were obtained in the presence of the methyl-substituted sty-
rene derivatives (Table 2, entries 7–9), but the introduction of
a Cl atom on the styrene backbone reduces the reactivity with
The scope of the transformation was then studied in an at-
tempt to react other derivatives based on the styrene core
(Figure 2) with both amines. 2-Vinylnaphthalene (5) and 9-vi-
Figure 2. Styrene derivatives used in this study.
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nylanthracene (6) were active substrates, although a poor reac-
tion yield was recorded for 5 (Table 3, entries 1–2). If the
amine/alkene ratio was maintained at 1:2, the polymerization
of 5 could not be avoided, and the intermolecular hydroamina-
tion product reached only 16% in the case of benzylmethyl-(2-
naphthalen-2-ylethyl)amine (3j; Table 3, entry 1), whereas pyr-
rolidine was slightly more active and delivered the hydroami-
nation product 4j in up to 33% yield (NMR; entry 10). No poly-
merization of 6 occurred under these reaction conditions, and
the hydroamination products 3k and 4k were recovered in
isolated yields of 83 and 45%, respectively (Table 3, entries 2
and 11). All hydroamination products produced by this new in-
termolecular procedure issued from an anti-Markovnikov regio-
selectivity. To gain a deeper insight into the selectivity of the
transformation, isopropenylbenzene (7), propenylbenzene (8),
and cis- and trans-stilbene (9) were investigated as alkene sub-
strates. Unfortunately, none of them were reactive with either
N-methylbenzylamine or pyrrolidine, even after 10 days of re-
action at 1308C (Table 3, entries 3–5 and 12–14).
As further coordination of the olefinic substrate was shown
to accelerate the reaction rate, the reactivity of vinylpyridines
10 and 11 was investigated in this reaction. 4-Vinylpyridine
(11) was proven to be unreactive to organolanthanide catalysis
by Marks and co-workers and led to instantaneous catalyst pre-
cipitation,[2r] and, as far as we know, no report describes any in-
termolecular hydroamination with rare-earth elements for
these substrates.[11] Beller and co-workers investigated the Rh-
catalyzed hydroamination of vinylpyridines that occurred con-
currently with oxidative amination in the presence of secon-
dary amines.[12] Reactions were conducted in THF heated to
reflux with an excess of the alkene (4:1), which led to different
ratios of enamine to alkylamine depending on the substrate
and the reaction conditions. Hartwig et al. studied the anti-
Markovnikov Rh-catalyzed hydroamination on vinylarenes, and
in this case, 2-vinylpyridine (10) reacted with dimethylamine to
deliver the hydroamination product in a 9:1 ratio together
with the enamine adduct.[6i] More recently, cation-exchange
resins (Amberlyst-15) were demonstrated to catalyze the hy-
droamination of vinylpyridines with aliphatic or aromatic pri-
mary or secondary amines in ethanol heated to reflux.[13] These
substrates were also considered by the group of Maurya and
Pessoa, in the course of their studies towards the use of poly-
mer-bound VIV and VV complexes.[14] In this case, however, a per-
fect regioselectivity towards the anti-Markovnikov products
was not observed. Finally, these substrates were also treated
with a combination of Cu and Ag salts but this catalysis was
not successful (for 11) or poorly effective (16% yield for 10) in
the presence of tosylamines.[15] Contrarily, catalyst 1a is highly
efficient to promote the reaction of N-methylbenzylamine with
10 at room temperature as benzylmethyl-(2-pyridin-2-ylethyl)-
amine (3o) was produced in 58% yield (NMR) in only 5 min
(Table 3, entry 6). If the catalyst quantity was diminished to
only 1 mol%, the targeted product was delivered in a 91%
yield (NMR; entry 7). Furthermore, the reaction could be con-
ducted with an equimolar mixture of amine and
alkene with the low amount of catalyst kept con-
stant, and the hydroamination compound was pro-
duced again instantaneously in a 68% yield (NMR;
entry 8).[16]
Table 3. Intermolecular anti-Markovnikov hydroamination reaction of aromatic al-
kenes 5–11 with N-methylbenzylamine or pyrrolidine catalyzed by 1a.[a]
Conversion [%]
Under these conditions, the polymerization of 10
competes strongly for the hydroamination, and the
yield of the resulting polymer was evaluated to be
approximately 32% (entry 8).[17] Pyrrolidine could also
be successfully added to 10 with this catalyst, and
2-(2-pyrrolidin-1-ylethyl)pyridine (4o) was produced
quantitatively under very mild conditions (room tem-
perature, 1 mol% of catalyst, amine/alkene=1:1,
5 min) free of any traces of poly(vinylpyridine)
(Table 3, entries 15–16). The location of the coordinat-
ing N atom in the ortho position of the reacting
alkene is of utmost importance as 11 delivered only
poly(vinylpyridine) and not a hydroamination product
with any of the amines tested (Table 3, entries 9 and
17).
Entry
Amine:
R2, R3
Alkene
Product
t
[h]
Hydroamination Polymer[b]
product[b,f]
1
2
Bn, Me
5
6
3j
24
72
24
10
16
52
69
74
–
3k
48
82
–
120
240
240
240
0.08
0.08
0.08
0.08
24
91 (83)
–
–
–
58
91 (82)
68
0
3
4
5
7
8
3l
3m
–
–
–
71
55
32
100
68
72
–
cis- or trans-9 3n
10
6[c]
7[c,d]
8[c,d,e]
9[c,d]
10
3o
11
5
3 p
4j
À(CH2)4À
14
33
29
72
24
11
6
4k
48
41
–
In a previous study, we demonstrated that chiral Y
complexes 1a–e were also efficient catalysts for the
enantioselective cyclohydroamination of C-(1-allylcy-
clohexyl)methylamine (12) at room temperature,
which led to the spiropyrrolidine 14 in high yields
(>95%) and moderate enantiomeric excess (ee; 5–
75%).[8b] To further extend the scope of the applica-
tion of theses complexes, we next examined their
ability to catalytically promote the tandem inter- and
intramolecular reaction of 10 and 12 (Scheme 2).[18] In
120
240
240
240
0.08
0.08
0.08
63 (45)
–
–
–
82
>98 (84)
0
12
13
14
15[c]
16[c,d,e]
17[c,d]
7
8
4l
4m
–
–
–
59
0
100
cis- or trans-9 4n
10
11
4o
4 p
[a] Reactions were performed in C7D8 at 1308C under Ar with 10 mol% of catalyst,
amine (1 equiv.), and alkene (2 equiv.) unless otherwise stated. [b] Determined by
in situ 1H NMR spectroscopy using ferrocene (0.4 equiv.) as internal standard. [c] C6D6,
RT. [d] 1 mol% of catalyst. [e] amine/alkene=1:1. [f] Isolated yield in brackets.
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temperature, the reaction of 13 only affords 25% of tandem
product 15 after 2.5 h with no trace of the intramolecular
product 14 (entry 3). However, further heating of the reaction
mixture led to the appearance of 14, the yield of which was
determined to be 58% at the end of the reaction time
(entry 4). The tandem product 15 was formed in 42% yield
(entry 4). The same reactions conducted with the isolated
tandem product 15 furnish 45% yield of 14 at 1008C (en-
tries 5–6). These experiments underline that, under this
tandem process, 14 may arise from three distinct pathways. It
can either emanate from 12 by classical intramolecular hydro-
amination, from 15 by direct retrohydroamination, or from 13
by a sequence of retrohydroamination and cyclohydroamina-
tion. The latter two routes, which are only promoted at higher
temperatures, are the predominant pathways under these cat-
alytic conditions (3 mol% of 1a, 1008C) and drive the forma-
tion of 14 as the main product (entry 2). The use of catalyst 1e
does not alter the outcome of the tandem process as the
major product 14 is obtained in 65% yield and 15 in 14%
yield, despite a better ee for the tandem product (entry 8).
However, the use of catalysts 1b–d, which bear bulkier sub-
stituents on the phenyl ring of the ligand, affords a better cata-
lyst control over the selectivity of the tandem reaction as, in
these cases, 15 is the sole product of the reaction with no sub-
stantial trace of 13 or 14 (<5%; entries 9–10, 12-15). Notably,
in the case of 1b, the selectivity in favor of the tandem prod-
uct is temperature dependent as further heating the reaction
mixture at 1008C affords 15 in only 41% yield but with 14 in
55% (entry 11).[20] Nevertheless, despite these high selectivities,
the enantioinduction was lower than that achieved with 1e
(entry 8 versus entries 11, 13, and 15).
Scheme 2. Tandem intermolecular anti-Markovnikov–intramolecular Markov-
nikov hydroamination reaction with 10 and 12.
the presence of 3 mol% of 1a at room temperature, the reac-
tion of 10 (1.5 equiv.) and 12 (1 equiv.) provides a complete
conversion (>95%) after 2.5 h and the formation of the inter-
molecular product 13, the intramolecular product 14, and the
tandem product 15 in 26, 28, and 42% yields respectively
(Scheme 2 and Table 4, entry 1). To our surprise, subsequent
heating of the resulting reaction mixture at 1008C for 2.5 h
leads to the complete consumption of 13 and the recovery of
14 and 15 in 67 and 14% yields, respectively, with an ee of
10% for 15 (entry 2). The formation of 14 in 67% yield from
a mixture of products 13, 14, and 15 in a ratio of 26:28:42 sug-
gests that a retrohydroamination[19] reaction may occur at high
temperature under these catalytic conditions. To gain more in-
sight into this hypothetical pathway, the intermolecular prod-
uct 13 and the tandem product 15 were isolated and treated
independently with 3 mol% of 1a firstly at room temperature
for 2.5 h then at 1008C for over 2.5 h (entries 3–6). At room
Conclusions
Table 4. Tandem intermolecular anti-Markovnikov–intramolecular Mar-
kovnikov hydroamination reaction with 10 and 12 catalyzed by 1.[a]
We have demonstrated that chiral binaphthylamido alkyl yttri-
um complex 1a is an active precatalyst for the highly selective,
intermolecular anti-Markovnikov hydroamination of secondary
amines with styrene derivatives and 2-vinylpyridine at 1308C
and room temperature, respectively. The reaction development
and exploration of the substrate scope highlight that the reac-
tivity, reaction rate, and yield of anti-Markovnikov hydroamina-
tion products are highly substrate dependent. As a general
trend, the introduction of a coordinating group at the ortho
position of the vinyl group on styrene or the use of 2-vinylpyri-
dine increase the addition rate and yield of the hydroamina-
tion product significantly. The use of bulky secondary amines
or disubstituted alkenes lead to no catalytic activity as does
the presence of a coordinating group at the para position of
the styrene vinyl group. We have also established that chiral
binaphthylamido alkyl yttrium complexes 1a–e have the ability
to catalytically promote the tandem intermolecular anti-Mar-
kovnikov hydroamination–intramolecular Markovnikov hydro-
amination reaction of 2-vinylpyridine and C-(1-allylcyclohexyl)-
methylamine to give the tandem product in up to 85% yield
and with an enantiomeric excess up to 48%. This work has
brought to light that a retrohydroamination process might
occur during this tandem reaction at high temperature, the
Entry
Catalyst
Step
Yield [%]
ee (15)[c]
[%]
13[b,h]
14[b]
15[b,h]
1
2
1a
1a
1a
1e
1b
1
2
1
2
1
2
1
2
26
0
75
0
0
0
28
67
0
58
0
45
10
65
0
0
55
0
0
0
42
14
25
42
100
55
19
14
18
88 (85)
41
–
10
–
–
–
3[d]
4[d]
5[e]
6[e]
7
–
–
66 (32)
8
9
0
79
0
0
50
0
48
–
29
25
–
31
–
15
1
10
11
12
13
14
15
2[f]
2[g]
1
1c
59
82
47
79
2
1
2
1d
53
3
5
[a] Reactions were performed in C6D6 under Ar with 3 mol% of catalyst,
10 (1.5 equiv.), and 12 (1 equiv.) at RT (20–258C) for 2.5 h (step 1) then
heated at 1008C for 2.5 h (step 2), 100% conversion, unless otherwise
stated. [b] Determined by in situ 1H NMR spectroscopy using ferrocene
(0.4 equiv.) as internal standard. [c] Determined by chiral SFC. [d] Reaction
performed with isolated 13. [e] Reaction performed with isolated 15.
[f] Reaction performed at 508C. [g] 20 h, 1008C. [h] Isolated yield in brack-
ets.
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spectra are in total accordance with the data described in the liter-
ature.[6a]
extent of which relies upon the nature of the substituents on
the catalyst N atoms.
1-Methyl-4-phenethylpiperazine (2c): (Table 1, entry 5) Rf =0.09
(pentane/EtOAc 75:25); yellow oil (62 mg, 0.30 mmol, 67%);
1H NMR (300 MHz, CDCl3, 294 K): d=2.35 (s, 3H), 2.47–2.76 (m,
10H), 2.78–2.87 (m, 2H), 7.16–7.33 ppm (m, 5H); 13C{1H} NMR
(75 MHz, CDCl3, 294 K): d=33.7, 46.0, 53.0, 55.1, 60.5, 126.3, 128.6,
128.9, 140.3 ppm; MS (EI): m/z (%): 113.0 (100), 70.0 (88); HRMS
(ESI): m/z: calcd for C13H21N2 (205.1699): [M+H]+; found 205.1705.
Experimental Section
General
All manipulations were performed under an Ar atmosphere by
using standard Schlenk or glovebox techniques. [D8]Toluene and
[D6]benzene were dried with sodium benzophenone ketyl, trans-
ferred under vacuum, and stored over activated 3 ꢃ molecular
sieves. Complexes 1a–e were prepared from [Li(THF)4]
[Y(CH2SiMe3)4][21] and the appropriate ligand according to a reported
procedure.[8] Compound 12 was prepared as reported.[22] All
amines, styrene derivatives, and vinylpyridines were dried with cal-
cium hydride and transferred under vacuum. 2-Vinylnaphthalene
(5) and 9-vinylanthracene (6) were dried under vacuum. All amines
and alkene derivatives were further dried for at least 2 h with 3 ꢃ
molecular sieves with a few drops of [D8]toluene or [D6]benzene
prior to use. Bruker AM250, AV300, AV360, and DRX400 NMR spec-
trometers operating at 250, 300, 360, and 400 MHz, respectively,
N-Benzyl-2-(2-chlorophenyl)-N-methylethanamine (3a): (Table 2,
entry 1) Rf =0.50 (pentane/EtOAc 75:25); yellow oil (69 mg,
1
0.27 mmol, 67%); H NMR (360 MHz, CDCl3, 294 K): d=2.35 (s, 3H),
2.67–2.74 (m, 2H), 2.96–3.04 (m, 2H), 3.63 (s, 2H), 7.11–7.37 ppm
(m, 9H); 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=31.6, 42.3, 57.3,
62.2, 126.9, 127.2, 127.7, 128.4, 129.2, 129.6, 131.0, 134.3, 138.3,
139.1 ppm; MS (EI): m/z (%): 134.0 (79), 90.9 (100); HRMS (ESI): m/z:
calcd for C16H19ClN (260.1201): [M+H]+; found 260.1202.
N-Benzyl-2-(2-methoxyphenyl)-N-methylethanamine
(3d):
(Table 2, entry 4) Rf =0.52 (pentane/EtOAc 75:25); yellow oil
1
(88 mg, 0.34 mmol, 77%); H NMR (360 MHz, CDCl3, 294 K): d=2.36
1
were used to record the H NMR spectra. Chemical shifts were ref-
(s, 3H), 2.62–2.75 (m, 2H), 2.86–2.97 (m, 2H), 3.64 (s, 2H), 3.82 (s,
3H), 6.83–6.98 (m, 2H), 7.16–7.43 ppm (m, 7H); 13C{1H} NMR
(90 MHz, CDCl3, 294 K): d=28.3, 42.3, 55.4, 57.5, 62.1, 110.5, 120.6,
127.0, 127.4, 128.3, 129.1, 129.2, 130.5, 139.4, 157.8 ppm; MS (EI):
m/z (%): 134.0 (89), 90.9 (100); HRMS (ESI): m/z: calcd for C17H22NO
(256.1696): [M+H]+; found 256.1692. The spectra are in total ac-
cordance with the data described in the literature.[23]
erenced internally according to the Me4Si resonance. Mass spectra
were recorded by using a Finnigan MAT 95 S spectrometer. Enan-
tiomeric excesses of the product 15 were determined by supercriti-
cal fluid chromatography (SFC; Chiralpak AD-H (250ꢄ4.6 mm),
PCO =100 bar, 4 mLminÀ1, T=308C, 3% MeOH as modifier).
2
Anti-Markovnikov hydroamination of styrene derivatives
N-Benzyl-2-(3-methoxyphenyl)-N-methylethanamine
(3e):
(Table 2, entry 5) Rf =0.48 (pentane/EtOAc 75:25); yellow oil
(91 mg, 0.36 mmol, 79%); H NMR (300 MHz, CDCl3, 294 K): d=2.33
with N-methylbenzylamine or pyrrolidine
1
General procedure: In
[Y(CH2SiMe3)4] (73 mg, 0.10 mmol) in C7D8 (500 mL) was added into
solution of (R)-2,2’-dibenzyl-1,1’-binaphthyldiamine ligand
a glovebox, a solution of [Li(THF)4]
(s, 3H), 2.64–2.74 (m, 2H), 2.82–2.91 (m, 2H), 3.62 (s, 2H), 3.82, (s,
3H), 6.73–6.86 (m, 3H), 7.17–7.40 ppm (m, 6H); 13C{1H} NMR
(75 MHz, CDCl3, 294 K): d=34.1, 42.3, 55.3, 59.2, 62.3, 111.4, 114.6,
121.3, 127.1, 128.4, 129.2, 129.4, 139.0, 142.3, 159.8 ppm; MS (EI):
m/z (%): 134.0 (93), 90.9 (100); HRMS (ESI): m/z: calcd for C17H22NO
(256.1696) [M+H]+; found 256.1694.
a
(46 mg, 0.10 mmol) in C7D8 (500 mL) at RT. The clear reaction mix-
ture turned to a deep yellow colored solution. The homogeneous
reaction solution was then allowed to stir 2 min at RT and an ali-
quot (450 mL) was transferred to a vial containing the appropriate
secondary amine (0.45 mmol), the styrene derivative (0.90 mmol)
and ferrocene (0.18 mmol). The reaction mixture was then intro-
duced into a screw-tap or a J. Young-tap NMR tube and the prog-
N-Benzyl-N-methyl-2-o-tolylethanamine (3g): (Table 2, entry 7)
Rf =0.56 (pentane/EtOAc 75:25); yellow oil (95 mg, 0.40 mmol,
88%); 1H NMR (250 MHz, CDCl3, 294 K): d=2.35 (s, 3H), 2.41 (s,
3H), 2.59–2.72 (m, 2H), 2.84–2.97 (m, 2H), 3.66 (s, 2H), 7.19 (s, 4H),
7.25–7.94 ppm (m, 5H); 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=
19.4, 31.5, 42.4, 58.0, 62.5, 126.1, 126.3, 127.2, 128.4, 129.2, 129.5,
130.4, 136.2, 138.8, 139.2 ppm; MS (EI): m/z (%): 134.0 (82), 90.9
(100); HRMS (ESI): m/z: calcd for C17H22N (240.1747): [M+H]+; found
240.1747.
1
ress of the reaction was monitored by H NMR spectroscopy using
ferrocene as internal standard. The reaction mixture was quenched
with ethanol and dried under vacuum after addition of silica gel.
The product was extracted from silica gel with ethanol and purified
on a preparative TLC plate.
N-Benzyl-N-methyl-2-phenylethanamine (2a): (Table 1, entry 2)
Rf =0.48 (pentane/EtOAc 75:25); colorless oil (92 mg, 0.41 mmol,
N-Benzyl-N-methyl-2-m-tolylethanamine (3h): (Table 2, entry 8)
Rf =0.61 (pentane/EtOAc 75:25); yellow oil (68 mg, 0.28 mmol,
63%); 1H NMR (250 MHz, CDCl3, 294 K): d=2.34 (s, 3H), 2.38 (s,
3H), 2.65–2.78 (m, 2H), 2.78–2.92 (m, 2H), 3.62 (s, 2H), 6.66–7.09
(m, 3H), 7.13–7.39 ppm (m, 6H); 13C{1H} NMR (90 MHz, CDCl3,
294 K): d=21.6, 34.0, 42.3, 59.4, 62.4, 125.9, 126.9, 127.2, 128.4,
129.2, 129.7, 138.0, 139.1, 140.6 ppm; MS (EI): m/z (%): 134.0 (97),
90.9 (100); HRMS (ESI): m/z: calcd for C17H22N (240.1747): [M+H]+;
found 240.1750.
1
91%); H NMR (300 MHz, CDCl3, 294 K): d=2.34 (s, 3H), 2.64–2.77
(m, 2H), 2.83–2.95 (m, 2H), 3.62 (s, 2H), 7.20–7.39 ppm (m, 10H);
13C{1H} NMR (75 MHz, CDCl3, 294 K): d=34.1, 42.3, 59.4, 62.3, 126.1,
127.1, 128.4, 128.5, 128.9, 129.2, 139.1, 140.7 ppm; MS (EI): m/z (%):
134.0 (78), 90.9 (100); HRMS (ESI): m/z: calcd for C16H20N (226.1590):
[M+H]+; found 226.1587. The spectra are in total accordance with
the data described in the literature.[6a]
1-Phenethylpyrrolidine (2b): (Table 1, entry 4) Rf =0.09 (pentane/
EtOAc 75:25); yellow oil (29 mg, 0.17 mmol, 41%); 1H NMR
(300 MHz, CDCl3, 294 K): d=1.75–1.94 (m, 4H), 2.55–2.68 (m, 4H),
2.68–2.78 (m, 2H), 2.83–2.91 (m, 2H), 7.16–7.37 ppm (m, 5H);
13C{1H} NMR (90 MHz, CDCl3, 294 K): d=23.7, 35.9, 54.4, 58.5, 126.3,
128.6, 128.8, 140.5 ppm; MS (EI): m/z (%): 83.9 (100); HRMS (ESI):
m/z: calcd for C12H18N (176.1434): [M+H]+; found 176.1433. The
N-Benzyl-N-methyl-2-p-tolylethanamine (3i): (Table 2, entry 9) Rf =
0.61 (pentane/EtOAc 75:25); yellow oil (100 mg, 0.42 mmol, 90%);
1H NMR (250 MHz, CDCl3, 294 K): d=2.33 (s, 3H), 2.37 (s, 3H), 2.60–
2.78 (m, 2H), 2.78–2.91 (m, 2H), 3.62 (s, 2H), 7.14 (s, 4H), 7.22–
7.41 ppm (m, 5H); 13C{1H} NMR (63 MHz, CDCl3, 294 K): d=21.2,
33.6, 42.3, 59.5, 62.4, 127.1, 128.4, 128.8, 129.2, 135.5, 137.6,
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139.1 ppm; MS (EI): m/z (%): 134.0 (88), 90.9 (100); HRMS (ESI): m/z:
calcd for C17H22N (240.1747): [M+H]+; found 240.1745.
1-(4-Methylphenethyl)pyrrolidine (4i): (Table 2, entry 18) Rf =0.14
(pentane/EtOAc 75:25); yellow oil (27 mg, 0.15 mmol, 32%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.75–1.89 (m, 4H), 2.33 (s, 3H),
2.53–2.63 (m, 4H), 2.64–2.74 (m, 2H), 2.78–2.88 (m, 2H), 7.07–
7.15 ppm (m, 4H); 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=21.2,
23.7, 35.5, 54.4, 58.7, 128.7, 129.2, 135.6, 137.6 ppm; MS (EI) m/z
(%) 84.0 (100); HRMS (ESI): m/z: calcd for C13H20N (190.1590):
[M+H]+; found 190.1587.
1-(2-Chlorophenethyl)pyrrolidine (4a): (Table 2, entry 10) Rf =0.09
(pentane/EtOAc 75:25); yellow oil (49 mg, 0.23 mmol, 52%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.76–1.87 (m, 4H), 2.58–2.78
(m, 6H), 2.96–3.04 (m, 2H), 7.10–7.22 (m, 2H), 7.26 (dd, J=7.3 Hz,
1.9 Hz, 1H), 7.33 ppm (dd, J=7.6 Hz, 1.3 Hz, 1H); 13C{1H} NMR
(90 MHz, CDCl3, 294 K): d=23.7, 33.4, 54.3, 56.3, 127.0, 127.8, 129.6,
130.9, 134.2, 138.1 ppm; MS (EI): m/z (%): 84.0 (100); HRMS (ESI):
m/z: calcd for C12H17ClN (210.1044): [M+H]+; found 210.1047.
2-(Anthracen-9-yl)-N-benzyl-N-methylethanamine (3k): (Table 3,
entry 2) Rf =0.60 (pentane/EtOAc 75:25); yellow oil (122 mg,
1
0.37 mmol, 83%); H NMR (360 MHz, CDCl3, 294 K): d=2.58 (s, 3H),
1-(3-Chlorophenethyl)pyrrolidine (4b): (Table 2, entry 11) Rf =0.09
(pentane/EtOAc 75:25); yellow oil (44 mg, 0.21 mmol, 47%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.76–1.91 (m, 4H), 2.58–2.70
(m, 4H), 2.70–2.78 (m, 2H), 2.81–2.90 (m, 2H), 7.06–7.14 (m, 1H),
7.14–7.25 ppm (m, 3H). 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=
23.7, 35.2, 54.3, 57.9, 126.5, 127.0, 128.9, 129.8, 134.3, 142.3 ppm;
MS (EI): m/z (%): 84.0 (100); HRMS (ESI): m/z: calcd for C12H17ClN
(210.1044): [M+H]+; found 210.1044.
2.82–2.95 (m, 2H), 3.76 (s, 2H), 3.81–3.93 (m, 2H), 7.28–7.57 (m,
9H), 8.02 (dd, J=7.4 Hz, 1.8 Hz, 2H), 8.24 (d, J=8.2 Hz, 2H),
8.36 ppm (s, 1H); 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=26.3,
42.7, 57.8, 62.5 124.4, 125.0, 125.8, 126.1, 127.3, 128.5, 129.3, 129.4,
130.0, 131.8, 132.5, 139.2 ppm; MS (EI): m/z (%): 191.1 (6), 134.0
(100), 90.9 (74); HRMS (ESI): m/z: calcd for C24H24N (326.1903):
[M+H]+; found 326.1901.
1-[2-(Anthracen-9-yl)ethyl]pyrrolidine (4k): (Table 3, entry 11) Rf =
0.16 (pentane/EtOAc 75:25); yellow oil (55 mg, 0.20 mmol, 45%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.84–2.00 (m, 4H), 2.71–2.93
(m, 6H), 3.82–3.95 (m, 2H), 7.42–7.58 (m, 4H), 8.02 (d, J=8.7 Hz,
2H), 8.33 (d, J=9.9 Hz, 2H), 8.35 ppm (s, 1H); 13C{1H} NMR
(90 MHz, CDCl3, 294 K): d=23.8, 28.0, 54.5, 57.0, 124.4, 125.0, 125.9,
126.2, 129.4, 130.0, 131.8, 132.3 ppm; MS (EI): m/z (%): 204.1 (26),
191.1 (27), 98.0 (38), 84.0 (100), 71.0 (25); HRMS (ESI): m/z: calcd for
C20H22N (276.1747): [M+H]+: found 276.1743.
1-(4-Chlorophenethyl)pyrrolidine (4c): (Table 2, entry 12) Rf =0.09
(pentane/EtOAc 75:25); yellow oil (44 mg, 0.21 mmol, 47%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.82–1.97 (m, 4H), 2.65–2.87
(m, 6H), 2.87–2.97 (m, 2H), 7.15 (d, J=8.3 Hz, 2H), 7.26 ppm (m,
J=8.5 Hz, 2H); 13C{1H} NMR (90 MHz, CDCl3, 294 K): d=23.7, 34.5,
54.3, 57.9, 128.8, 130.2, 132.3, 138.2 ppm; MS (EI): m/z (%): 83.9
(100); HRMS (ESI): m/z: calcd for C12H17ClN (210.1044): [M+H]+;
found 210.1042. The spectra are in total accordance with the data
described in the literature.[6f]
1-(2-Methoxyphenethyl)pyrrolidine (4d): (Table 2, entry 13) Rf =
0.08 (pentane/EtOAc 75:25); yellow oil (38 mg, 0.19 mmol, 41%);
1H NMR (400 MHz, CDCl3, 294 K): d=1.76–1.88 (m, 4H), 2.55–2.76
(m, 6H), 2.81–2.91 (m, 2H), 3.82 (s, 3H), 6.80–6.92 (m, 2H), 7.13–
7.22 ppm (m, 2H); 13C{1H} NMR (100 MHz, CDCl3, 294 K): d=23.6,
30.2, 54.3, 55.4, 56.7, 110.4, 120.6, 127.5, 128.9, 130.3, 157.6 ppm;
MS (EI): m/z (%): 83.9 (100); HRMS (ESI): m/z: calcd for C13H20NO
(206.1539): [M+H]+; found 206.1543.
Anti-Markovnikov hydroamination of 2-vinylpyridine (10)
with N-methylbenzylamine or pyrrolidine
General procedure: In
[Y(CH2SiMe3)4] (12 mg, 0.025 mmol) in C6D6 (125 mL) was added to
solution of (R)-2,2’-dibenzyl-1,1’-binaphthyldiamine ligand
a glovebox, a solution of [Li(THF)4]
a
(18 mg, 0.025 mmol) in C6D6 (125 mL) at RT. The clear reaction mix-
ture turned to a deep yellow solution. The homogeneous reaction
solution was then allowed to stir for 2 min at RT, and an aliquot
(45 mL) was transferred to a vial under stirring that contained
a C6D6 solution (450 mL) of the secondary amine (0.45 mmol), 10
(0.675 mmol), and ferrocene (0.18 mmol). The reaction mixture was
then introduced into a screw-tap or a J. Young-tap NMR tube, and
1-(3-Methoxyphenethyl)pyrrolidine (4e): (Table 2, entry 14) Rf =
0.14 (pentane/EtOAc 75:25); yellow oil (48 mg, 0.23 mmol, 52%);
1H NMR (300 MHz, CDCl3, 294 K): d=1.77–1.87 (m, 4H), 2.56–2.65
(m, 4H), 2.67–2.77 (m, 2H), 2.78–2.88 (m, 2H), 3.79 (s, 3H), 6.68–
6.85 (m, 3H), 7.2 ppm (dd, J=7.8 Hz, 7.8 Hz, 1H); 13C{1H} NMR
(75 MHz, CDCl3, 294 K): d=23.6, 35.9, 54.3, 55.3, 58.3, 111.5, 114.6,
121.2, 129.5, 142.1, 159.8 ppm; MS (EI): m/z (%): 83.9 (100); HRMS
(ESI): m/z: calcd for C13H20NO (206.1539): [M+H]+; found 206.1544.
1
the progress of the reaction was monitored by H NMR spectrosco-
py using ferrocene as an internal standard. The reaction mixture
was quenched with ethanol and dried under vacuum after the ad-
dition of silica gel. The product was extracted from silica gel with
ethanol and purified on a preparative TLC plate.
1-(2-Methylphenethyl)pyrrolidine (4g): (Table 2, entry 16) Rf =0.19
(pentane/EtOAc 75:25); yellow oil (48 mg, 0.25 mmol, 57%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.81–2.01 (m, 4H), 2.35 (s, 3H),
2.70–2.90 (m, 6H), 2.92–3.01 (m, 2H), 7.07–7.23 ppm (m, 4H);
13C{1H} NMR (90 MHz, CDCl3, 294 K): d=19.5, 23.7, 32.3, 54.2, 56.9,
126.3, 126.7,129.4, 130.5, 136.3, 137.6 ppm; MS (EI): m/z (%): 83.9
(100); HRMS (ESI): m/z: calcd for C13H20N (190.1590): [M+H]+; found
190.1594.
N-Benzyl-N-methyl-2-(pyridin-2-yl)ethanamine (3o): (Table 3,
entry 7) Rf =0.48 (CH2Cl2/MeOH 90:10); colorless oil (84 mg,
0.37 mmol, 82%; contaminated with 9% of the hydroaminoalkyla-
tion product; see Supporting Information); 1H NMR (300 MHz,
CDCl3, 294 K): d=2.29 (s, 3H), 2.78–2.88 (m, 2H), 2.97–3.07 (m, 2H),
3.57 (s, 2H), 7.02–7.36 (m, 7H), 7.58 (td, J=7.7 Hz, 1.9 Hz, 1H),
8.52 ppm (d, J=4.9 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3, 294 K):
d=36.4, 42.2, 57.5, 62.4, 121.2, 123.4, 127.1, 128.3, 129.1, 136.3,
139.2, 149.4, 160.8 ppm; MS (EI): m/z (%): 134.0 (92), 90.9 (100);
HRMS (ESI): m/z: calcd for C15H19N2 (227.1543): [M+H]+; found
227.1539.
1-(3-Methylphenethyl)pyrrolidine (4h): (Table 2, entry 17) Rf =0.11
(pentane/EtOAc 75:25); yellow oil (28 mg, 0.15 mmol, 32%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.76–1.99 (m, 4H), 2.34 (s, 3H),
2.54–2.65 (m, 4H), 2.66–2.77 (m, 2H), 2.78–2.87 (m, 2H), 6.99–7.06
(m, 3H), 7.18 ppm (dd, J=7.3 Hz, 7.3 Hz, 1H); 13C{1H} NMR (75 MHz,
CDCl3, 294 K): d=21.5, 23.7, 35.9, 54.4, 58.6, 125.8, 126.9, 128.4,
129.6, 138.0, 140.6 ppm; MS (EI): m/z (%): 84.0 (100); HRMS (ESI):
m/z: calcd for C13H20N (190.1590): [M+H]+: found 190.1589.
2-[2-(Pyrrolidin-1-yl)ethyl]pyridine (4o): (Table 3, entry 16) Rf =
0.51 (CH2Cl2/MeOH 90:10); colorless oil (67 mg, 0.38 mmol, 84%);
1H NMR (360 MHz, CDCl3, 294 K): d=1.72–1.83 (m, 4H), 2.54–2.67
(m, 4H), 2.80–2.92 (m, 2H), 2.94–3.09 (m, 2H), 7.09 (dd, J=7.4 Hz,
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5.2 Hz, 1H), 7.18 (d, J=7.7 Hz, 1H), 7.57 (ddd, J=7.7 Hz, 7.7 Hz,
1.9 Hz, 1H), 8.51 ppm (d, J=5.0 Hz, 1H); 13C{1H} NMR (90 MHz,
CDCl3, 294 K): d=23.7, 38.2, 54.4, 56.4, 121.3, 123.3, 136.5, 149.4,
160.6 ppm; MS (EI): m/z (%): 105.0 (20), 83.9 (100), 79.0 (19); HRMS
(ESI): m/z: calcd for C11H17N2 (177.1386): [M+H]+; found 177.1389.
Tandem reaction of 2-vinylpyridine (10) and C-(1-allylcyclo-
hexyl)-methylamine (12)
In
a glovebox, a solution of [Li(THF)4][Y(CH2SiMe3)4] (12 mg,
0.024 mmol) in C6D6 (500 mL) was added to a solution of (R)-2,2’-
disubstituted-1,1’-binaphthyldiamine ligand (0.024 mmol) in C6D6
(500 mL) at RT. The homogeneous reaction solution was then al-
lowed to stir for 10 min at RT, and an aliquot (300 mL) was intro-
duced quickly under stirring to a vial that contained a C6D6 solu-
tion (450 mL) of 12 (0.24 mmol), 10 (0.36 mmol), and ferrocene
(0.096 mmol). The reaction mixture was then introduced into
a screw-tap NMR tube, kept at RT for 2.5 h, then heated at 1008C
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hydroamination: a) A. L. Reznichenko, T. J. Emge, S. Audçrsch, E. G.
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1
for 2.5 h. The progress of the reaction was monitored by H NMR
spectroscopy using ferrocene as an internal standard. The reaction
mixture was quenched with ethanol and dried under vacuum after
the addition of silica gel. The product was extracted from silica gel
with ethanol and purified on a preparative TLC plate.
N-[(1-Allylcyclohexyl)methyl]-2-(pyridin-2-yl)ethanamine
(13):
(Table 4, entry 7) Rf =0.54 (CH2Cl2/MeOH/Et3N 90:10:1); white
1
powder (20 mg, 0.08 mmol, 32%); H NMR (360 MHz, CDCl3, 294 K):
d=1.35–1.65 (m, 10H), 2.36 (d, J=7.5 Hz, 2H), 2.89 (bs, 2H), 3.37–
3.55 (m, 4H), 5.10–5.22 (m, 2H), 5.83 (ddt, J=17.0 Hz, 10.1 Hz,
7.5 Hz, 1H), 7.18–7.26 (m, 2H), 7.69 (ddd, J=7.7 Hz, 7.7 Hz, 1.8 Hz,
1H), 8.39 ppm (d, J=4.9 Hz, 1H); 13C{1H} NMR (90 MHz, CDCl3,
294 K): d=21.4, 25.9, 31.1, 33.5, 36.4, 39.5, 49.1, 54.9, 119.7, 122.7,
124.1, 132.9, 137.9, 148.2, 159.2 ppm; MS (EI): m/z (%): 134.9 (100),
106.0 (28); HRMS (ESI): m/z: calcd for C17H27N2 (269.2169) [M+H]+;
found 269.2175.
3-Methyl-2-[2-(pyridin-2-yl)ethyl]-2-azaspiro[4.5]decane
(15):
(Table 4, entry 10) Rf =0.44 (CH2Cl2/MeOH/Et3N 90:10:1); yellow oil
1
(53 mg, 0.20 mmol, 85%); H NMR (300 MHz, CDCl3, 294 K): d=1.08
(d, J=6.0 Hz, 3H), 1.19–1.51 (m, 11H), 1.74 (dd, J=12.4 Hz, 6.5 Hz,
1H), 2.05 (d, J=9.4 Hz, 1H), 2.34–2.52 (m, 2H), 2.91–3.04 (m, 2H),
3.07–3.23 (m, 2H), 7.10 (ddd, J=7.5 Hz, 4.9 Hz, 1.0 Hz, 1H), 7.20 (d,
J=7.7 Hz, 1H), 7.58 (ddd, J=7.7 Hz, 7.7 Hz, 1.9 Hz, 1H), 8.52 ppm
(d, J=4.9 Hz, 1H); 13C{1H} NMR (63 MHz, CDCl3, 294 K): d=19.1,
23.8, 23.9, 26.2, 37.4, 38.9, 39.6, 47.3, 54.2, 59.6, 66.8, 121.2, 123.4,
136.4, 149.4, 161.0 ppm; MS (EI): m/z (%): 166.1 (100), 106.0 (32);
HRMS (ESI): m/z: calcd for C17H27N2 (259.2169) [M+H]+; found
259.2166.
Acknowledgements
This work has been supported by MENSR, CNRS, and the Groupe
de Recherche International (GDRI) “Homogeneous Catalysis for
Sustainable Development”.
Keywords: amines · enantioselectivity · hydroamination · rare
earths · yttrium
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Received: February 5, 2014
Revised: March 13, 2014
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ChemCatChem 2014, 6, 2065 – 2073 2073