Chemoselective reductive amination of aldehydes and ketones by dibutylchlorotin hydride-HMPA complex

Article abstract of DOI:10.1055/s-2000-6273

Reductive amination of various aldehydes and ketones has been performed effectively by pentacoordinate chloro-substituted tin hydride complex, Bu₂SnClH-HMPA. The tin reagent worked particularly well for the case using weakly basic aromatic amines as starting substrates. Stoichiometric amounts of a substrate and a reducing agent were adequate for the reaction. The Sn-Cl bond in the complex plays an important role for both steps of imine formation and subsequent reduction. Highly chemoselective reduction of carbonyls could be achieved regardless of other functionalities such as halogen, carbon- carbon double bond and hydroxyl groups in the starting carbonyls and amines.

Full text of DOI:10.1055/s-2000-6273

PAPER
789
Chemoselective Reductive Amination of Aldehydes and Ketones by
Dibutylchlorotin Hydride-HMPA Complex
Toshihiro Suwa, Erika Sugiyama, Ikuya Shibata, Akio Baba*
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
Fax +81(6)8797387; E-mail: shibata@ap.chem.eng.osaka-u.ac.jp
Received 22 December 1999; revised 31 January 2000
O
O
Abstract: Reductive amination of various aldehydes and ketones
has been performed effectively by pentacoordinate chloro-substitut-
ed tin hydride complex, Bu2SnClH-HMPA. The tin reagent worked
particularly well for the case using weakly basic aromatic amines as
starting substrates. Stoichiometric amounts of a substrate and a re-
ducing agent were adequate for the reaction. The Sn-Cl bond in the
complex plays an important role for both steps of imine formation
and subsequent reduction. Highly chemoselective reduction of car-
bonyls could be achieved regardless of other functionalities such as
halogen, carbon-carbon double bond and hydroxyl groups in the
starting carbonyls and amines.
n-Bu2SnClH-HMPA
Ph
Ph
Ph
Ph
rt, 20h, 73%
NPh
NHPh
Scheme 1
In order to explore this high imine reduction selectivity of
Bu2SnClH-HMPA, we investigated the details of reduc-
tive amination of various aldehydes and ketones to give a
variety of secondary and tertiary amines under mild and
neutral conditions (Scheme 2).10 The characteristic fea-
tures of the reduction with Bu2SnClH-HMPA are as fol-
lows: (1) weakly basic aromatic amines 2 are effectively
employed; (2) stoichiometric amounts of substrates and
the reductant are adequate; and (3) presence of other re-
ducible functionalities is allowed in the starting carbonyls
1 and amines 2.
Key words: reductive amination, aldehydes, ketones, amines, tin
hydride, highly coordination
The reductive amination of aldehydes and ketones is one
of the most useful route to secondary amines, in which the
three components – carbonyl, amine and reductant – are
treated in one portion.1 A particular advantage of this pro-
cedure is that no isolation of unstable intermediate imines
is necessary. The choice of the reductant is very critical
since undesirable reduction of starting carbonyls must be
suppressed for the predominant formation of intermediate
imines. Catalytic hydrogenation is one of the classical
methods for carrying out this transformation.2 However,
these reaction conditions are not compatible with a num-
ber of otherwise reducible functional groups such as nitro,
cyano and carbon-carbon double and triple bonds. Among
the hydride reagents used to effect this transformation, so-
dium cyanoborohydride (NaBH3CN) has been used be-
cause of its wide applicability.3 However, there reactions
require excess amounts of amines and are not applicable
to aromatic amines. To solve these problems, modified
borohydrides such as NaBH(OAc)3,4a NaBH3CN-Ti(OPr-
i)4,4b-f NaBH3CN-Mg(ClO4)2,4g BH3∑pyridine,4h and
Zn(BH4)2-ZnCl2 have been developed.4i Among them, bo-
rane-pyridine (BH3∑Py) works well for the reaction using
aromatic amines.4h However, the reaction must be per-
formed under acidic conditions. Beside borohydride de-
rivatives, alternative metal hydride reagents such as Zn-
AcOH5a and Cl3SiH5b have also been developed. We have
already provided a set of organotin hydrides to achieve
highly chemoselective reductions of functionalized sub-
strates.6 In particular, pentacoordinated tin hydride,
Bu2SnClH-HMPA,7 formed in situ by simple mixing of
Bu2SnClH8 and HMPA, has been revealed to be a selec-
tive reductant of imines even in the presence of carbonyls
(Scheme 1).9
R2
R1
R1
R2
n-Bu2SnClH-HMPA
+
R3NH2
NHR3
O
Scheme 2
Table 1 summarizes the effects of various tin hydride sys-
tems in the reductive aminations of benzadehyde (1a)
with aniline (2a). With the sole use of non-halogentated
tributytin hydride, Bu3SnH, the reaction scarcely proceed-
ed (Table 1, Entry 1). We have already reported that the
combination of Bu3SnH with HMPA induced the effec-
tive reduction of simple aldehydes.6a The use of Bu3SnH-
HMPA resulted in the prior reduction of benzaldehyde
(1a) to the formation of the imine, where no desired amine
3a was obtained (Table 1, Entry 2). For reductive amina-
tion, it is necessary to introduce halogen substituents on
the tin center. Using Bu2SnClH gave the desired amine 3a
in 85% yield (Table 1, Entry 3). The reaction with penta-
coordinate tin, Bu2SnClH-HMPA afforded a quantitative
yield (Table 1, Entry 4). Iodo-substituted tin hydride,
Bu2SnIH-HMPA, also induced reductive amination to
give 3a in 90% yield (Table 1, Entry 5). However,
Bu2SnFH-HMPA gave a lower yield of 3a together with
the direct reduction of 1a to benzyl alcohol (3a’) (Table 1,
Entry 6). As a result, Bu2SnClH-HMPA was the choice
for the reductant among the tin examined hydride sys-
tems. The efficiency of Bu2SnClH-HMPA is especially
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

790
T. Suwa et al.
PAPER
Table 1 Reductive Amination of Benzaldehyde 1a with Aniline 2aa
ical pathways.11 These facts suggest that Bu2SnClH-
HMPA provides an ionic reaction as we have postulated
for the trialkyltin hydride-base systems.6 In the reaction of
1e, the acidic hydroxy group on the aromatic ring did not
affect the amination at all (Table 2, Entry 5). Cyano and
nitro groups on aromatic rings tolerated the reduction con-
ditions (Table 2, Entries 6 and 7), while these functional-
ities were reduced under catalytic hydrogenation
conditions.2 2-Furylaldehyde (1h) also gave the amine 3h
(Table 2, Entry 8). Unsaturated aldehydes, 1i and 1j, were
converted to N-allyl phenylamines 3i and 3j, respectively
by the regioselective 1,2-addition to the intermediate un-
saturated imines (Table 2, Entries 9 and 10). Halogen
functions on vinyl carbons were not reduced during the
amination (Table 2, Entries 11 and 12). The reactions of
aliphatic aldehydes such as 1m and 1n also proceeded to
give N-alkyl phenylamines, 3m and 3n, in 70% and 99%
yields, respectively (Table 2, Entries 13 and 14).
+
PhNH2
PhCHO
1a
2a
+
NHPh
Ph
Ph
OH
3a
3a'
Entry
Tin Hydride System
Yield
Yield
3a (%)b
3a’ (%)b
1
2
3
4
5
6
Bu3 SnH
Bu3SnH-HMPA
Bu2SnClH
Bu2SnClH-HMPA
Bu2SnIH-HMPA
Bu2SnFH-HMPA
0
0
85
99
90
86
6
27
0
0
0
13
a Tin hydride (1 mmol), 1a (1 mmol), 2a (1 mmol), THF (1 mL), 0°C,
1 h.
b Isolated yields.
Table 3 shows the results using various amines other than
aniline (2a). Thus reductive amination was carried out
with aromatic amine 2b to give 4a in an excellent yield
(Table 3, Entry 1). Although the yield was decreased to
48%, product 4b which contains a hydroxy group was ob-
tained selectively (Table 3, Entry 2). Aliphatic aldehyde
1m was reactive against an aromatic amine, giving 4c in a
quantitative yield (Table 3, Entry 3). Thus, in all cases us-
ing aromatic amines, no side reactions such as direct re-
duction of starting aldehydes and over-alkylation of the
produced amines were observed. In contrast, more basic
clear in the reactions using ketones, for which results are
shown later. In this case, stoichiometric amounts of
Bu2SnClH-HMPA, benzaldehyde (1a) and aniline (2a)
were successively mixed in THF. Therefore the condi-
tions offer very clean conversions of all substrates afford-
ing only the desired amines without over-alkylation of the
produced amine. Preformation of imines prior to the addi-
tion of the reductant is not necessary. Promoters such as
acids and dehydrating agents5b to accerelate the imine for-
mation are not necessary.
Table 2 shows the formation of amines from various alde- aliphatic amines gave less than 40% yield. For example,
hydes 1 and aniline (2a) by using Bu2SnClH-HMPA as a the reaction of PhCHO (1a) with PrNH2 (2d) afforded
reductant. As in the case of 1a, various aromatic alde- only 37% yield of 4c (Table 3, Entry 4). Other aliphatic
hydes gave high yields of secondary amines. In entries 3 amines such as i-Pr, Bn, allyl and secondary alkyl amines,
and 4, Bu2SnClH-HMPA did not affect halogen functions 2e-i, were also the cases of low yields, although no direct
in 1c and 1d, which are generally reducible by conven- reduction of aldehydes was observed in all cases (Table 3,
tional tin hydride systems such as Bu3SnH-AIBN via rad- Entries 5-10). Thus the low yields for aliphatic amines
seems to be the limitation of the present method with
Bu2SnClH-HMPA. Preheating of aldehydes with these al-
iphatic amines to accelerate the imine formation prior to
Table 2 Reductive Amination of Aldehydes 1 with Aniline (2a)a
the addition of the reductant did not improve the yields. In
contrast, the reactions of amino ester 2j and amino alcohol
2k afforded better yields of 4k and 4l, where heating of al-
dehydes and amines prior to the addition of the tin reduc-
tant was effective for the higher yields (Table 3, Entries
11 and 12). In particular, the effective amination from
amino alcohols was noteworthy since it is difficult to iso-
late the imines because of their instability.12 Functional-
ized aromatic aldehydes, 1c and 1e, gave the
corresponding amines, 4m-o, selectively (Table 3, En-
tries 13-15).
Entry
R1
Starting
Aldehyde
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
81
89
83
87
99
99
99
78
96
81
83
67c
70d
99
p-MeOC6H4
p-ClC6H4
o-BrC6H4
o-HOC6H4
p-NCC6H4
p-NO2C6H4
furyl
PhCH=CH
EtCH=CH
PhCH=CCl
PhCH=CBr
Bn
In the reactions of dicarbonyl compounds, 1o and 1p, cy-
clic amines 5a-c were obtained by the use of 2 equiva-
lents of Bu2SnClH-HMPA, where two consecutive
reductive amination took place as shown in Scheme 3.
i-Pr
a Bu2SnClH-HMPA (1 mmol), 1 (1 mmol), 2a (1 mmol), THF (1 mL),
Next, we explored to use ketones as starting materials
(Table 4), which were less reactive in reductive amination
0°C, 1 h.
b Isolated yields.
c 0°C, 6.5 h.
d -78°C to r.t., 23 h.
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemoselective Reductive Amination of Aldehydes and Ketones
791
Table 3 Reductive Amination of Aldehydes with Various Aminesa
Entry
R1
Starting
Aldehyde
R3
Starting
Amine
Reaction
Conditions
Product
Yieldb
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph
Ph
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Ph
Ph
p-ClC6H4
o-HOC6H4
o-HOC6H4
1a
1a
1m
1a
1a
1a
1a
1a
1a
1a
1a
1a
1c
1e
1e
p-ClC6H4
p-HOC6H4
p-ClC6H4
Pr
i-Pr
Bn
allyl
(CH2)4
Et2
Pr
i-Pr(CO2Me)CH
Ph(CH2OH)CH
Ph(CH2OH)CH
Ph(CH2OH)CH
i-Pr(CO2Me)CH
2b
2c
2b
2d
2e
2f
2g
2h
2i
2d
2j
2k
2k
2k
2j
0°C, 1 h
0°C, 1 h
0°C, 1 h
−78°C, 1 h
−78°C, 1 h
0°C, 1 h
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
99
48
99
37
26
25
14
39
3
33
56c
77c
90c
70c
84c
0°C, 3 h
0°C, 1 h
−78°C, 2 h
−78°C to r.t., 23 h
0°C, 1 h
0°C, 2.5 h
0°C, 2.5 h
0°C,1 h
0°C,1 h
a Bu2SnClH-HMPA (1 mmol), 1 (1 mmol), 2 (1 mmol), THF (1 mL).
b Isolated yields.
c Amine and aldehyde were preheated to 65°C for 4 h before the addition of Bu2SnClH-HMPA.
4, Entry 3). The use of Bu2SnClH without complexation
with HMPA resulted in a lower yield of 7a (16%) (Table
4, Entry 4). Weakly basic aromatic amine 2b could also be
used to give 7b, where halogen function on the aromatic
ring was not affected (Table 4, Entry 5). Halogen func-
tionality in ketone 6c was not reduced (Table 4, Entry 9).
The reactions with aliphatic amines gave only lower
yields of 7c and 7d (Table 4, Entries 6 and 7). The reaction
of cyclic ketones 6d and 6e with aniline (2a) gave 7g and
7h respectively, in good yields (Table 4, Entries 10 and
11). The reaction using 2-methylcyclohexanone (6e) gave
cis-selectivity (cis:trans = 91:9) (Table 4, entry 11). This
result could be explained by an equatorial attack of hy-
dride to the intermediate cyclic imine (Scheme 4).13 Thus
cis-selectivity of 7h indicates that Bu2SnClH-HMPA acts
as a more hindered reductant than the conventional ones
such as BH3•Py which affords a lower selectivity
(cis:trans = 66:34) in the same reaction.4h
CHO
CHO
2 n-Bu2SnClH-HMPA
N
R
+
RNH2
0°C, 1.5 h
1o
R = Ph 5a 74%
Ph
Sn
NR
35%
5b
Me
CHO
CHO
2 n-Bu2SnClH-HMPA
+
PhNH2
N Ph
0°C, 1.5 h
CHO
1p
2a
5c
63%
Scheme 3
compared with aldehydes.1-4 Even with most effective re-
ductants such as NaBH(OAc)3, one of the most serious
problems is the low reactivity of aromatic ketones, and
particularly in the case with weakly basic aromatic
amines.4a Due to the difficult reductive amination of ace-
tophenone (6a) with aniline (2a), as far as we know, the
effective reagent is limited to BH3•Py complex.4h Since
Bu2SnClH-HMPA complex was suitable for aromatic
amines (Table 2), we initially examined the reaction of ar-
omatic ketones with aromatic amines. The yield of desired
aromatic secondary amine 7a, however, was somewhat
low for 1 equiv of Bu2SnClH-HMPA. The use of 2 equiv-
alents of Bu2SnClH-HMPA increased the yield of 7a up to
61% (Table 4, Entry 1). Here Bu2SnClH-HMPA was also
revealed to be the best choice for the reductive amination
of ketones. Iodotin hydride complex, Bu2SnIH-HMPA,
did not give any products (Table 4, Entry 2). Fluorotin hy-
dride complex, Bu2SnFH-HMPA6c afforded no reductive
amination, and only reduced the starting ketone 6a (Table
Sn
PhN
NPh
Me
n-Bu2SnClH-HMPA
H
Me
Scheme 4
The reactions with acyclic ketones 6f, 6g and 6h afforded
acceptable yields of desired amines 7i-n (Table 4, Entries
12-17). Although the yield of 7o from 6i was not satisfac-
tory, no side reactions through the ring opening of the cy-
clopropane took place (Table 4, Entry 18). This fact
clearly indicates that the reaction with Bu2SnClH-HMPA
proceeds via ionic process, because a tin radical has been
widely recognized to promote the ring opening of cyclo-
propanes (Scheme 5).14
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

792
T. Suwa et al.
PAPER
Table 4 Reductive Amination of Ketones 6 with Amines
Entry R1
R2
Starting R3
Ketone
Starting
Amine
SnH
(equiv)
Reaction
Conditions
Product
Yield
(%)
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
6a
6a
6a
6a
6a
6a
6a
Ph
Ph
Ph
Ph
p-ClC6H4
Pr
PhMeCH
2a
2a
2a
2a
2b
2d
2m
2
2
2
2
2
2
2
0°C, 3 h
0°C, 3 h
0°C, 3 h
0°C, 3 h
0°C to rt, 24 h
0°C, 3 h
7a
7a
7a
7a
7b
7c
7d
61
trc
tr (51)d
16e
69
tr
35
60°C, 6 h
and 0°C, 1h
0°C to r.t., 16 h
0°C to r.t., 16 h
0°C, 1 h
(threo/erythro =88:12)
8
9
10
11
p-Tol
p-ClC6H4
Me
Me
-(CH2)5-
6b
6c
6d
Ph
Ph
Ph
Ph
2a
2a
2a
2a
2
2
1
1
7e
49
7f
7g
7h
62
>99
57
2-methylcyclohexanone 6e
−78°C, 3 h
(cis:trans = 91:9)
12
13
14
15
16
17
18
19
20
21
22
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
Pr
Me
Me
Me
Me
Pr
6f
6f
6f
6f
6g
6h
6i
6j
6k
6l
Ph
p-ClC6H4
p-HOC6H4
p-MeC6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2a
2b
2c
2h
2a
2a
2a
2a
2a
2a
2a
1
1
1
1
1
2
2
2
2
2
2
0°C to r.t., 4 h
0°C to r.t., 8 h
r.t., 1 h
0°C to r.t., 3 h
0°C, 1 h
0°C to r.t., 6 h
0°C to r.t., 6 h
−78°C to r.t., 20 h
0°C to r.t., 22 h
0°C, 6.5 h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
91
81
51
81
56
54
37
60
73
58
99
i-Pr
c-Pr
Me
Me
(E)-PhCH=CH Me
MeO2CCH2
MeO2C
Me
Me
benzalacetone oxide
6m
0°C, 3 h
(major/minor = 70:30)
a Bu2SnClH-HMPA (1 or 2 mmol), 6 (1 mmol), 2 (1 mmol), THF (1 mL).
b Isolated yields.
c Bu2SnIH-HMPA was used.
d Yield of 2-phenethyl alcohol by using Bu2SnFH-HMPA.
e Bu2SnClH was used.
HMPA, however, with its lower nucleophilicity, lead to
reductive amination of carbonyls without prior epoxide
ring opening.
.
AIBN
+
.
n-Bu3Sn
O
Bu3Sn
O
HMPA
.
H+
I
SnBu2H
n-Bu3SnH
- n-Bu3Sn
n-Bu2SnIH-HMPA
O
R2
O
R1
.
OSnBu3
R1
R2
OSnBu3
O
O
I
O
Scheme 5
R1
R2
H+
R2
OH
R1
H
O
O
O
Reductive amination of enones is difficult, and only one
example using an aliphatic amine and NaBH(OAc)3 is
known.4a When Bu2SnClH-HMPA was employed in the
reaction of enone 6j with 2a, allylic amine 7p was formed
in 60% yield (Table 4, Entry 19). In the reaction of func-
tionalized ketones such as 6k and 6l, the reductive amina-
tion of ketone moieties took place selectively to give 7q
and 7r respectively, without reducing ester moieties (Ta-
ble 4, Entries 20 and 21). Epoxy ketone 6m gave the ep-
oxy amine 7s with an excess of one diastereoisomer (70%
selectivity) (Table 4, Entry 22). On the other hand, iodo-
substituted tin, Bu2SnIH-HMPA, induces the ring opening
of epoxides due to the high nucleophilicity of the Sn-I
bond (Scheme 6).6d The tin-chlorine bond in Bu2SnClH-
Bu2Sn
HMPA
Scheme 6
It is not clear why the reductive aminations proceed effec-
tively even for weakly basic aromatic amines. The effec-
tive formation of imines by Bu2SnCl2 catalyst has been
reported.15 Because imine formation was not completed
by simple mixing of acetophenone and aniline at room
temperature, the presence of the tin reductant would play
an important role in the formation of imine intermediate
prior to the reduction step. In the reduction step, the high
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemoselective Reductive Amination of Aldehydes and Ketones
793
for 10 min. IR spectra showed the change from n = 1800 to 1851
cm-1, which indicate the formation of Bu2SnClH by the redistribu-
tion between Bu2SnCl2 and Bu2SnH2. The addition of HMPA gave
pentacoordinate tin hydride Bu2SnClH-HMPA which was indicated
by the Sn-H absoption at 1862 cm-1. To the solution were added
benzaldehyde (1a; 106 mg, 1 mmol) and aniline (2a; 0.093 g, 1
mmol), and the mixture was stirred at 0 °C until the Sn-H absorp-
tion disappeared. After quenching with MeOH (5 mL), volatiles
were removed under reduced pressure. The residue was subjected to
column chromatography (Fuji-gel FL100DX) eluting with hexane/
EtOAc (9:1) to give pure product 3a. Tin residue and HMPA were
removed by this treatment. Further purification was performed by
Kugelrohr distillation. Amine 3a was identified with the authentic
spectral data which we have reported previously.7
imine selectivity is explainable in terms of the formation
of iminium salts by the tin chloride reductant as shown in
Scheme 7.
Cl
Bu
Sn
O
H
Bu
R2
R3
R1
R3NH2
- H2O
R1
R2
R2
P(NMe2)3
N
O
6
R2
Cl-
R1
R1
+
N
N-(4-Methoxybenzyl)aniline (3b)
R3
R3
N
H
Yield: 0.187 g (89%); colorless liquid, purified by Kugelrohr distil-
R2
R1
H+
lation at 80 °C/0.09 Torr (Lit.18 mp 63-64 °C).
Bu
Bu
Bu
Bu
Sn
O
Sn
O
Cl
H
NH
HRMS: m/z calcd for C14H15NO 213.1155, found 213.1156.
R3
N-(4-Chlorobenzyl)aniline (3c)
7
P(NMe2)3
P(NMe2)3
Yield: 0.18 g (83%); colorless liquid, purified by Kugelrohr distil-
lation at 100 °C/0.09 Torr (Lit.18 mp 51-52 °C).
Scheme 7
HRMS: m/z calcd for C13H12ClN 217.0660, found 217.0664.
N-(2-Bromobenzyl)aniline (3d)
We have already shown by 119Sn NMR investigation that Yield: 0.18 g (87%); colorless liquid purified by column chroma-
tography eluting with hexane/EtOAc (9:1) (Lit.19 bp 184-189 °C/7
Bu2SnClH-HMPA has a trigonal bipyramid (TBP) struc-
ture in which the Sn-H and Sn-C bonds occupy equato-
rial positions and the remaining Sn-Cl bond is located in
Torr).
N-(2-Hydroxybenzyl)aniline (3e)
the apical positions.7 In pentacoordinate tin complexes,
Yield: 0.20 g (99%); white solid purified by column chromatogra-
phy eluting with hexane-EtOAc (9:1), mp 114 °C (lit.20 mp 111-
the apical Sn-Cl bond is longer as compared to that in tet-
112 °C).
racoordinate tins.16 The prolonged Sn-Cl bond makes it
easy to form iminium salts with imines. The electrophilic
iminium ion is more reducible than carbonyl moieties.
The ionic character of the tin hydride and characteristic
activation of imine moieties allowed the predominance of
the reductive amination over other functionalities.
N-(4-Cyanobenzyl)aniline (3f)
Yield: 0.21 g (99%); white solid purified by column chromatogra-
phy eluting with hexane-EtOAc (9:1), mp 86-87 °C.
Anal. calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45; found C,
80.86; H, 5.90; N, 13.36.
N-[(4 -Nitrophenyl)methyl]aniline (3g)
In summary, compared with conventional borohydride re-
Yield: 0.23 g (99%); yellow liquid purified by Kugelrohr distilla-
tion at 130 °C/0.09 Torr (Lit.20 mp 67-69 °C).
ductants such as NaBH3CN and NaBH(OAc)3, the present
tin system, Bu2SnClH-HMPA, is especially useful in the
reaction using weakly basic aromatic amines. In all cases,
highly chemoselective reactions are achieved even in the
coexistence of aryl halides, vinyl halides, hydroxyl group,
carbon-carbon double bonds and epoxide functionalities.
The effective preparation of various functionalized
amines are demonstrated in one-pot procedure.
N-Furfurylaniline (3h)
Yield: 0.14 g (78%); colorless liquid purified by Kugelrohr distilla-
tion at 65 °C/0.09 Torr.
HRMS: m/z calcd for C11H11NO 173.0841, found 173.0835.
N-Cinnamylaniline (3i)
Yield: 0.20 g (96%); colorless liquid purified by Kugelrohr distilla-
tion at 85 °C/0.09 Torr.
HRMS: m/z calcd for C15H15N 209.1206, found 209.1193.
IR spectra were recorded as thin films on a Hitachi 260-30 spec-
N-2-Pentenylaniline (3j)
Yield: 0.13 g (81%); colorless liquid purified by Kugelrohr distilla-
tion at 45 °C/0.09 Torr.
1
trometer. H, 13C and 119Sn NMR spectra were recorded with a
JEOL JNM-GSX-270 (270, 67.9 and 100 MHz, respectively). Mass
spectra were recorded on a JEOL JMS-DS303 or a Shimadzu
GCMS-QP2000A spectrometer. Column chromatography was per-
formed by using Fuji Davison silica gel FL-100DX. Preparative
TLC was carried out on Wakogel B-5F silica gel.
Bu2SnH2 was prepared by the reduction of Bu2SnCl2 with LiAlH4.17
Bu2SnClH was synthesized in situ by the reaction of Bu2SnH2 and
Bu2SnCl2.8 THF was freshly distilled over sodium benzophenone
ketyl and HMPA was distilled from finely powdered CaH2. All re-
actions were carried out under dry N2.
HRMS: m/z calcd for C11H15N 161.1206, found 161.1216.
N-[(2Z)-2-Chloro-3-phenylprop-2-enyl]aniline (3k)
Yield: 0.20 g (0.83 mmol, 83%); colorless liquid purified by Kugel-
rohr distillation at 110 °C/0.09 Torr.
HRMS calcd for C15H14ClN 243.0816, found 243.0824.
N-[(2Z)-2-Bromo-3-phenylprop-2-enyl]aniline (3l)
Yield: 0.19 g (0.67, 67%); colorless liquid purified by Kugelrohr
distillation at 90 °C/0.09 Torr.
HRMS: m/z calcd for C15H14BrN 287.0510, found 287.0304.
Reductive Amination; N-Benzylamine (3a); Typical Procedure
To a solution of Bu2SnH2 (0.117 g, 0.5 mmol) in THF (1 mL) was
added Bu2SnCl2 (0.152 g, 0.5 mmol). The mixture was stirred at r.t.
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

794
T. Suwa et al.
PAPER
Table 5 Spectral Data of Compounds 3 Prepared
Prod- IR
uct
1H HMR (CDCl3/TMS)
d, J (Hz)
13C HMR (CDCl3/TMS)
d
n (cm-1)
3b
3400 (N−H), 3000,
1610, 1510, 1250,
1040 (C−OMe)
3.80 (s, 3 H, OCH3), 3.94 (br s, 1 H, NH), 4.25 (s, 47.8 (1 C, CH2), 55.3 (1 C, OCH3), 112.8 (2 C, arom CH),
2 H, CH2), 6.22 (d, 2 H, J = 7.7, o-NHarom-H),
6.73 (t, 1 H, J =7.8, p-NHarom-H), 6.90 (d, 2 H,
114.2 (2 C, arom CH), 117.5 (1 C, arom CH), 128.8 (2 C,
arom CH), 129.2 (2 C, arom CH), 130.5 (1 C, arom C),
148.2, (1 C, arom CNH), 155.6 (1 C, arom COMe)
J = 7.7, o-MeO arom-H ) 6.62−7.38 (m, 4 Harom
)
3c
3e
3380 (N-H), 1600, 4.03 (br s, 1 H, NH), 4.29 (s, 2 H, CH2), 6.58 (d,
47.6 (1 C, CH2), 112.8 (2 C, arom CH), 117.8 (1 C, arom
1490, 1320 (C-N), 2 H, J = 7.7, o-NHarom-H), 6.72 (t, 1 H, J = 7.8, CH), 128.7 (2 C, arom CH), 128.7 (2 C, arom CH), 129.3
1095
p-NHarom-H), 7.13−7.29 (m, 6 Harom
)
(2 C, arom CH), 133.0 (1 C, arom CCl), 138.0 (1 C, arom
C), 147.8 (1 C, arom CNH)
3500 (O-H), 3264
3.94 (br s, 1 H, NH), 4.41 (d, 2 H, J = 4.9, CH2),
(N-H), 3052 (C-H, 6.83−7.27 (m, 9 Harom), 8.42 (br s, 1 H, OH)
48.7 (1 C, CH2), 115.9 (2 C, arom CH), 116.6 (1 C, arom
CH), 120.0 (1 C, arom CH), 120.8 (1 C, arom CH), 122.9
(1 C, arom CH), 128.7 (1 C, arom CH), 129.2 (1 C, arom
CH), 129.3 (2 C, arom CH), 147.2 (1 C, arom CNH), 156.7
(1 C, arom COH)
ar), 2854, 1594,
1498, 1459
3f
3425 (N-H), 3047
(C-H, ar), 2218,
(CN), 1600, 1508,
1450
4.22 (br s, 1 H, NH), 4.41 (s, 2 H, CH2), 6.56 (d,
2 H, J = 7.7, o-NHarom-H), 6.73 (t, 1 H, J = 7.8, CH), 118.0 (1 C, arom CH), 118.8 (1 C, arom CN), 127.6
47.7 (1 C, CH2), 110.8 (1 C, arom CCN), 112.8 (2 C, arom
p-NHarom-H), 7.16−7.61 (m, 6 Harom
)
(2 C, arom CH), 129.3, (2 C, arom CH), 132.3 (2 C, arom
CH), 145.3 (1 C, arom C), 147.3 (1 C, arom CNH)
3g
3h
3i
3421(N-H), 3047
(C-H, ar), 2846,
4.26 (br s, 1 H, NH), 4.77 (s, 2 H, CH2), 6.57 (d,
2 H, J = 7.8, o-NHarom-H), 6.75 (t, 1 H, J = 7.8, CH), 123.8 (2 C, arom CH), 127.6 (2 C, arom CH), 129.3
47.5 (1 C, CH2), 112.8 (2 C, arom CH), 118.1 (1 C, arom
1604, 1512 (N=O), p-NHarom-H), 7.15-20 (m, 6 Harom
)
(2 C, arom CH), 147.3 (1 C, arom C), 147.5 (1 C, arom
CNO2), 157.3 (1 C, arom CNH)
1346, 844
3380 (N-H), 3000
(C-H, ar), 1600,
1500
3.99 (br s, 1 H, NH), 4.30 (s, 2 H, CH2), 6.21-6.30 41.4 (1 C, CH2), 106.9 (1 C, C=CH), 110.3 (1 C, C=CH),
(m, 2 H, furyl-H), 6.68 (d, 2 H, J = 7.8, o-NHarom- 113.1 (2 C, arom CH), 118.0 (1 C, arom CH), 129.2 (2 C,
H), 6.75 (t, 1 H, J =7.8, p-NHarom-H), 7.15−7.60 arom CH), 141.8 (1 C, arom CNH), 147.6 (1 C, CHO),
(m, 3 Harom
)
152.7 (1 C, OC=C)
3400(N-H), 3010
(C-H, ar), 1605,
1500
3.84 (br s, 1 H, NH), 3.93 (d, 2 H, J = 5.9, CH2),
46.2 (1 C, CH2), 113.0 (2 C, arom CH), 117.6 (1 C, arom
6.33 (dt, 1 H, J = 15.6, 5.9, CHCH2), 6.62 (d, 1 H, CH), 126.3 (2 C, arom CH), 127.0 (1 C, PhCH=CH), 127.5
J = 15.6, CHPh), 6.60 (d, 2 H, J = 7.8, o-NHarom- (1 C, arom CH), 128.6 (2 C, arom CH), 129.3 (2 C, arom
H), 6.72 (t, 1 H, J = 7.8, p-NHarom-H), 7.10−7.38 CH), 131.5 (1 C, PhCH=CH), 136.9 (1 C, arom C), 148.0
(m, 7 Harom
)
(1 C, arom CNH)
3j
3390 (N-H), 2950
(C-H, ar), 1600,
1500
0.99 (t, 3 H, J = 7.3, CH3), 2.00−2.11 (m, 2 H, CH2), 13.5 (1 C, CH3), 25.3 (1 C, CH2), 46.1 (1 C, CH2), 113.0
3.68 (br s, 1 H, NH), 3.69 (d, 2 H, J = 5.9, CH2NH), (2 C, arom CH), 117.3 (1 C, arom CH), 125.8 (1 C, CHEt),
5.56 (td, 1 H, J = 5.9, 15.1, CHEt), 5.75 (td, 1 H, J 129.2 (2 C, arom CH), 134.9 (1 C, CH2CH=), 148.3 (1 C,
= 6.8, 15.1, CHCH2NH), 6.65 (d, 2 H, J = 7.8, o- arom CNH)
NHarom-H), 6.72 (t, 1 H, J = 7.8, p-NHarom-H),
7.14−7.25 (m, 2 Harom
)
3k
3l
3400 (N-H), 3020
(C-H, ar), 1600,
1500, 1450
4.08 (s, 2 H, CH2), 4.56 (br s, 1 H, NH), 6.70 (d, 2 52.2 (1 C, CH2), 113.3 (2 C, arom CH), 118.5 (1 C, PhCH),
H, J = 7.8, o-NHarom-H), 6.75 (t, 1 H, J = 7.8, p- 124.7 (1 C, arom CH), 127.9 (1 C, arom CH), 128.2 (2 C,
NHarom-H), 7.15−7.65 (m, 8 H, PhCH and arom) arom CH), 129.1 (2 C, arom CH), 129.3 (2 C, arom CH),
130.9 (1 C, CCl), 134.3 (1 C, arom C), 146.7 (1 C, arom
CNH)
3400 (N-H), 3020
(C-H, ar), 1600,
1500, 1450
4.17 (s, 2 H, CH2), 4.27 (br s, 1 H, NH), 6.65 (d, 2 53.9 (1 C, CH2), 113.0 (2 C, arom CH), 118.2 (1 C, arom
H, J = 7.8, o-NHarom-H), 6.75 (t, 1 H, J = 7.8, p- CH), 124.2 (1 C, PhCH), 126.3 (1 C, CBr), 127.9 (1 C,
NHarom-H), 7.05−7.63 (m, 8 H, PhCH and arom) arom CH), 128.1 (2 C, arom CH), 129.0 (2 C, arom CH),
129.3 (2 C, arom CH), 135.3 (1 C, arom C), 146.9 (1 C,
arom CNH).
3m
3n
3400 (N-H), 3050
(C-H, ar), 1615,
1510, 1190
2.90 (t, 2 H, J = 6.8, CH2), 3.39 (t, 2 H, J = 6.8,
CH2), 3.65 (br s, 1 H, NH), 6.62 (d, 2 H, J = 7.8, o- 117.4 (1 C, arom CH), 126.3 (1 C, arom CH), 128.5 (2 C,
NHarom-H), 6.70 (t, 1 H, J = 7.8, p-NHarom-H), arom CH), 128.7 (2 C, arom CH), 129.2 (2 C, arom CH),
35.5 (1 C, CH2), 45.0 (1 C, CH2,), 112.9 (2 C, arom CH),
7.14−7.34 (m, 7 H)
139.3 (1 C, arom C), 148.0 ( 1C, arom CNH)
3400 (N-H), 3050
(C-H, ar), 1615,
1510, 1190
0.98 (d, 6 H, J = 6.4, CH3), 1.81−1.96 (m, 1 H,
20.4 (2 C, CH3), 28.0 (1 C, CH), 51.8 (1 C, CH2), 112.6, (2
CHMe2), 2.92 (d, 2 H, J = 6.8, CH2), 3.66 (br s, 1 C, arom CH) 116.9 (1 C, arom CH), 129.2 (2 C, arom CH),
H, NH), 6.58 (d, 2 H, J = 7.8, o-NHarom-H), 6.70 148.6 (1 C, arom C)
(t, 1 H, J = 7.8, p-NHarom-H), 7.13−7.19 (m, 2
Harom
)
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemoselective Reductive Amination of Aldehydes and Ketones
795
Table 6 Compounds 4 Prepared
Prod- IR (film)
uct
1H HMR (CDCl3/TMS)
d, J (Hz)
13C HMR (CDCl3/TMS)
d
n (cm−1)
4a
3425 (N-H), 3062
(C-H, ar), 2839,
1597, 1504, 818
4.06 (br s, 1 H, NH), 4.30 (s, 2 H, CH2), 6.54 (d,
2 H, J = 8.8, o-NHarom-H), 7.10 (d, 2 H, J = 8.8, CCl), 127.3, (1 C, arom CH), 127.4 (2 C, arom CH), 128.7
48.3 (1 C, CH2), 113.9 (2 C, arom CH), 122.03 (1 C, arom
p-NHarom-H), 7.25-7.35 (m, 5 Harom
)
(2 C, arom CH), 129.0 (2 C, arom CH), 138.92 (1 C, arom
C), 146.6 (1 C, arom CNH)
4b
4c
3675 (N-H), 3317
(C-H, ar), 3031
(C-H, ar), 2881,
1600, 1516, 1485
1.75 (br s, 1 H, OH), 2.14 (br s, 1 H, NH), 4.23 (s, 49.3 (1 C, CH2), 114.4 (2 C, arom CH), 116.2 (2 C, arom
2 H, CH2), 6.55 (d, 2 H, J = 8.8, o-NHarom-H), CH), 127.2 (1 C, arom CH), 127.6 (2 C, arom CH), 128.6
6.68 (d, 2 H, J = 8.8, o-HOarom-H), 7.24-7.35 (m, (2 C, arom CH), 139.5 (1 C, arom C), 142.3 (1 C, arom
5 Harom CNH), 147.8 (2 C, arom CH)
)
3410 (N-H), 3024
(C-H, ar), 2931,
1597, 1504, 1088,
817
2.90 (t, 2 H, J = 6.8, CH2), 3.37 (t, 2 H, J = 6.8 Hz, 35.3 (1 C, CH2), 45.1 (1 C, CH2), 114.0 (2 C, arom CH),
CH2), 3.68 (br s, 1 H, NH), 6.52 (d, 2 H, J = 8.8, 122.0 (1 C, arom CCl), 126.5 (1 C, arom CH), 128.6 (2 C,
o-NHarom-H), 7.11 (d, 2 H, J = 8.8, m-NHarom- arom CH), 128.7 (2 C, arom CH), 129.1 (2 C, arom CH),
H), 7.19-7.35 (m, 5 Harom
)
139.0 (1 C, arom C), 146.5 (1 C, arom CNH)
4d
4h
4j
3305 (N-H), 3027
(C-H, ar), 2931,
1604, 1492, 1454
0.92 (t, 3 H, J = 7.3, CH3), 1.47-1.60 (m, 2 H,
CH2), 1.57 (br s, 1 H, NH), 2.60 (t, 2 H, J = 7.3,
CH2), 3.78 (s, 2 H, CH2Ph), 7.22-7.33 (m, 5 H)
11.7 (1 C, CH3,), 23.1 (1 C, CH2,), 51.3 (1 C, CH2), 54.0
(1 C, CH2), 126.8 (1 C, arom CH), 128.1 (2 C, arom CH),
128.3 (2 C, arom CH), 140.5 (1 C, arom C)
3028 (C-H, ar),
2966, 2784, 1492,
1454
1.72-1.85 (m, 4 H, CH2), 2.48-2.54 (m, 4 H,
NCH2), 3.61 (s, 2 H, CH2Ph), 7.21-7.35 (m,
23.4 (2 C, CH2), 54.2 (2 C, CH2N), 60.7 (1 C, CH2Ph),
126.8 (1 C, arom CH), 128.2 (2 C, arom CH), 128.9 (2 C,
arom CH), 139.4 (1 C, arom C)
5 Harom
)
3317 (N-H), 3027
(C-H, ar), 2931,
1604, 1496, 1454
0.89 (t, 3 H, J = 7.3, CH3), 1.43-1.54 (m, 2 H,
CH2), 1.77 (br s, 1 H, NH), 2.60 (t, 2 H, J = 7.3,
CH2), 2.82 (t, 2 H, J = 5.4, CH2), 2.89 (t, 2 H, J = C, arom CH), 128.7 (2 C, arom CH), 140.0 (1 C, arom C)
5.4, CH2), 7.20-7.33 (m, 5 H)
11.7 (1 C, CH3), 23.0 (1 C, CH2), 36.2 (1 C, CH2), 51.6 (1
C, CH2), 51.7 (1 C, CH2), 126.1 (1 C, arom CH), 128.4 (2
4k
4l
3340 (N-H), 3028
(C-H, ar), 2962,
1735, 1604, 1496,
1457, 1195
0.94 (d, 6 H, J = 6.4, CH3), 1.77 (br s, 1 H, NH),
1.86-1.98 (m, 1 H, CHMe2), 3.02 (d, 1 H, J = 5.9, (1 C, OCH3), 52.5 (1 C, CH2Ph,), 66.6 (1 C, CHCO),
CHCO), 3.58 (d, 1 H, J = 13.2, CH2Ph), 3.72 (s, 127.01 (1 C, arom CH), 128.2 (2 C, arom CH), 128.3 (2 C,
3 H, OCH3), 3.83 (d, 1 H, J = 13.2, CH2Ph), 7.23- arom CH), 140.1 (1 C, arom C), 175.8 (1 C, CO)
7.35 (m, 5 Harom
18.6 (1 C, CH3), 19.3 (1 C, CH3,), 31.7 (1 C, CHMe2), 51.4
)
3247 (N-H), 3139
(C-H, ar), 3032,
2915, 2846, 1488,
1450
2.26 (br s, 2 H, NH and OH), 3.56 (dd, 1 H, J = 8.8, 51.2 (1 C, CH2Ph), 63.8 (1 C, CHPh), 66.7 (1 C, CH2OH),
10.8, CH2OH), 3.59 (d, 1 H, J = 13.2, CH2Ph), 3.70 127.1 (1 C, arom CH), 127.3 (2 C, arom CH), 127.7 (1 C,
(dd, 1 H, J = 10.8, 4.4, CH2OH), 3.76 (d, 1 H, J = arom CH), 128.2 (2 C, arom CH), 128.4 (2 C, arom CH),
13.2, CH2Ph), 3.81 (dd, 1 H, J = 4.4, 8.8, CHPh), 128.7 (2 C, arom CH), 140.0 (1 C, arom C), 140.5 (1 C,
7.25-7.40 (m, 10 Harom
)
arom C)
4m
4n
3247 (N-H), 3139
(C-H, ar), 3032,
2915, 2846, 1488,
1450
2.62 (br s, 2 H, NH and OH), 3.53-3.81 (m, 5 H, 50.3 (1 C, CH2Ph), 63.7 (1 C, CHPh), 66.6 (1 C, CH2OH),
CH2 and CH), 7.19-7.37 (m, 9 Harom
)
127.3 (2 C, arom CH), 127.8 (1 C, arom CH), 128.5 (2 C,
arom CH), 128.7 (2 C, arom CH), 129.6 (2 C, arom CH),
132.8 (1 C, arom CCl), 140.0 (1 C, arom C), 140.5 (1 C,
arom C)
3298, (O-H) 3170
3.71 (d, 1 H, J = 13.7, CH2Ar), 3.74-3.85 (m, 3 H, 50.1 (1 C, CH2Ar), 63.8 (1 C, CHPh), 66.5 (1 C, CH2OH),
(N-H), 3028 (C-H, CH2OH and CHPh), 3.95 (d, 1 H, J = 13.7, CH2Ar), 116.4 (1 C, arom CH), 119.2 (1 C, arom CH), 122.6 (1 C,
ar), 2924, 1608,
1493, 1458
4.84 (br s, 3 H, NH and OH), 6.74 (t, 1 Harom, J = arom CH), 127.4 (2 C, arom CH), 128.2 (1 C, arom CH),
7.3), 6.84 (d, 1 Harom, J = 7.3), 6.89 (d, 1 Harom, J = 128.4 (1 C, arom CH), 128.7 (1 C, arom CH), 128.8 (1 C,
7.3), 7.15 (t, 1 Harom, J = 7.3), 7.29-7.41 (m, 5
Harom
arom CH), 129.0 (2 C, arom CH), 138.5,(1 C, arom C)
157.8 (1 C, arom COH)
)
4o
3309 (N-H), 3170
(C-H, ar), 2962,
1736, 1619, 1589,
1492
0.96 (d, 3 H, J = 6.8, CH3), 0.99 (d, 3 H, J = 6.8,
CH3), 1.96-2.06 (m, 1 H, CHMe2), 2.19-2.31 (br (1 C, CHMe2), 51.8, 65.9 (1 C, CHCO), 116.3 (1 C, arom
s, 1 H, NH), 3.16 (dd, 1 H, J = 5.9, 11.7, CHCO), CH), 119.2 (1 C, arom CH), 122.3 (1 C, arom C), 128.6 (1
18.2 (1 C, CH3), 19.3 (1 C, CH3), 31.3 (1 C, OCH3), 51.5
3.69 (dd, 1 H, J = 6.8, 13.7 Hz, CH2Ph), 3.78 (s,
C, arom CH), 129.0 (1 C, arom CH), 157.8 (1 C, arom
3 H, OCH3), 4.05 (dd, 1 H, J = 4.9, 13.7, CH2Ph), COH), 174.1 (1 C, CO)
6.75-7.26 (m, 4 Harom), 10.39 (br s, 1 H, OH)
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

796
T. Suwa et al.
PAPER
Table 7 Compounds 7 Prepared
Product
IR
1H HMR (CDCl3/TMS)
d, J (Hz)
13C HMR (CDCl3/TMS)
d
n (cm−1)
7b
3420 (N-H), 1600, 1.50 (d, 3 H, J = 6.8, CH3), 4.04 (s, 1 H, NH), 25.0 (1 C, CH3), 53.6 (1 C, CH), 114.3 (2 C, arom CH),
1500, 1320
4.42 (q, 1 H, J = 6.8, CHMe), 6.41 (d, 2 H, J = 121.8 (1 C, arom CCl), 125.7 (2 C, arom CH), 127.0
8.79, o-NHarom-H), 7.01 (d, 2 H, J = 8.79
o-Clarom-H), 7.19-7.32 (m, 5 Harom
(1 C, arom CH), 128.7 (2 C, arom CH), 128.9 (2 C, arom
CH), 144.7 (1 C, arom C), 145.7 (1 C, arom CNH)
)
erythro-7d
threo-7d
7e
3200 (N-H), 3050
(C-H, ar), 1450,
1130
1.35 (d, 6 H, J = 6.8, CH3), 3.76 (q, 2 H, J = 23.1 (2 C, CH3), 55.0 (2 C, CH), 126.8 (4 C, arom CH),
6.8, CHMe), 2.61 (s, 1 H, NH), 7.20-7.49 (m, 126.6 (2 C, arom CH), 128.2 (4 C, arom CH), 145.9
10 Harom
)
(2 C, arom C)
3200 (N-H), 3050
(C-H, ar), 1450,
1130
1.27 (d, 6 H, J = 6.8, CH3), 3.49 (q, 2 H, J = 24.9 (2 C, CH3), 55.0 (2 C, CH), 126.7 (4 C, arom CH),
6.8, CHMe), 2.61 (s, 2, NH), 7.20-7.49 (m, 10 126.6 (2 C, arom CH), 128.3 (4 C, arom CH), 145.8
Harom
)
(2 C, arom C)
3400 (N-H), 3045
(C-H, ar), 2970,
1600, 1500, 1320,
1095
1.49 (d, 3 H, J = 6.8, CH3), 2.32 (s, 3 H,
21.0 (1 C, CH3Ar), 24.97 (1 C, CH3), 53.13 (1 C, CH),
CH3Ar), 3.99 (br s, 1 H, NH), 4.45 (q, 1 H, J = 113.26 (1 C, arom CH), 117.1 (1 C, arom CH), 125.7
6.8, CHMe), 6.50 (d, 2 H, J= 7.8, o-NHarom- (2 C, arom CH), 129.1 (2 C, arom CH), 129.3 (2 C, arom
H), 6.63 (t, 1 H, J=7.8, p-NHarom-H), 7.05- CH), 136.4 (1 C, arom C), 142.2 (1 C, arom C), 147.3
7.27 (m, 6 H)
(1 C, arom CNH)
7f
3410 (N-H), 3050
(C-H, ar), 2970,
1600, 1500, 1320,
1095
1.48 (d, 3 H, J = 6.8, CH3), 3.99 (br s, 1 H,
NH), 4.44 (q, 1 H, J = 6.8, CHMe), 6.47 (d,
2 H, J= 7.8, o-NHarom-H), 6.65 (t, 1 H, J=7.8, (2 C, arom CH), 129.11 (2 C, arom CH), 132.41 (1 C,
25.1 (1 C, CH3), 53.0 (1 C, CH), 113.31 (2 C, arom CH),
117.5,1 (1 C, arom CH) 127.21 (2 C, arom CH), 128.81
p-NHarom-H), 7.06-7.43 (m, 6 Harom
)
arom CCl), 143.81 (1 C, arom C), 147.01 (1 C, arom
CNH)
trans-7h
3417 (N-H), 3054
(C-H, ar), 2927,
1600, 1500
1.00 (d, 3 H, J = 6.4, CH3), 1.26-1.70 (m, 8 H, 19.6 (1 C, CH3), 25.5 (1 C, CH2), 25.9 (1 C, CH2), 30.2
CH2), 2.14 (qdd, 1 H, J = 6.4, 3.9, 7.8, CHMe), (1 C, CH2), 33.5 (1 C, CH2), 34.8 (1 C, CHMe), 58.0
2.86 (ddd, 1 H, J = 10.3, 10.3, 3.9, CHN), 3.61 (1 C, CHN), 112.8 (2 C, arom CH), 116.4 (1 C, arom
(br s, 1 H, NH), 6.56 (d, 2 H, J = 7.8, o-
NHarom-H), 6.63 (t, 1 H, J = 7.8, p-NHarom-
H), 7.13 (dd, 2 Harom, J = 8.8, 7.3)
CH), 128.8 (2 C, arom CH), 147.8 (1 C, arom CNH)
cis-7h
3417 (N-H), 3054
(C-H, ar), 2927,
1600, 1500
0.91 (d, 3 H, J = 6.8, CH3), 1.35-1.70 (m, 8H, 15.5 (1 C, CH3), 22.8 (1 C, CH2), 23.0 (1 C, CH2), 28.7
CH2), 2.01 (qdd, 1 H, J = 6.8, 6.8, 2.9, CHMe), (1 C, CH2), 30.3 (1 C, CH2), 33.1 (1 C, CHHMe), 53.1
3.49 (ddd, 1 H, J = 3.4, 3.4, 2.9, CHN), 3.61 (1 C, CHN), 113.1 (2 C, arom CH), 116.5 (1 C, arom
(br s, 1 H, NH), 6.60 (d, 2 H, J = 7.8, o-
NHarom-H), 6.63 (t, 1 H, J = 7.8, p-NHarom-
H), 7.14 (dd, 2 Harom, J = 7.8, 7.3)
CH), 129.2 (2 C, arom CH), 147.8 (1 C, arom CNH)
7i
3402 (N-H), 3023
(C-H, ar), 2962,
1604, 1504
1.21 (d, 3 H, J = 6.4, CH3), 1.69-1.94 (m, 2 H, 20.8 (1 C, CH3), 32.5 (1 C, CH2), 38.8 (1 C, CH2), 47.9
CH2), 2.72 (t, 2 H, J = 7.8, CH2Ph), 3.42 (br s, (1 C, CH), 113.2 (2 C, arom CH), 116.9 (1 C, arom CH),
1 H, NH), 3.48 (tq, 1 H, J = 6.4, 6.4, CHMe), 125.8 (1 C, arom CH), 128.4 (2 C, arom CH), 128.4
6.50 (d, 2 H, J = 7.8, o-NHarom-H), 6.65 (t, (2 C, arom CH), 129.3 (2 C, arom CH), 142.0 (1 C, arom
1 H, J = 7.8, p-NHarom-H), 7.10-7.29 (m, 7 C), 147.6 (1 C, arom CNH)
Harom
)
7j
3410 (N-H), 3024
(C-H, ar), 2962,
1600, 1500, 1454,
1091
1.12 (d, 3 H, J = 4.9, CH3), 1.66-1.79 (m, 2 H, 20.7 (1 C, CH3), 32.4 (1 C, CH2), 38.6 (1 C, CH2), 48.0
CH2), 2.64 (t, 2 H, J = 7.8, CH2Ar), 3.34 (br s, (1 C, CH), 114.2 (2 C, arom CH), 121.4 (1 C, arom CCl),
1 H, NH), 3.27-3.38 (m, 1 H, CHMe), 6.50 (d, 125.9 (1 C, arom CH), 128.4 (2 C, arom CH), 128.4
2 H, J =6.8, o-NHarom-H), 6.65 (d, 2 H, J = (2 C, arom CH), 129.1 (2 C, arom CH), 141.8 (1 C, arom
6.8, o-Clarom-H), 7,15-7.31 (m, 5 Harom
)
C), 146.1 (1 C, arom CNH)
7k
3420 (O-H), 3282
1.19 (d, 3 H, J = 6.9, CH3), 1.67-1.95 (m, 2 H, 20.7 (1 C, CH3), 32.4 (1 C, CH2), 38.6 (1 C, CH2), 49.3
(N-H), 3028 (C-H, CH2), 2.71 (t, 2 H, J = 7.8, CH2Ar), 3.30-3.45 (1 C, CH2), 115.3 (2 C, arom CH), 116.2 (2 C, arom CH),
ar), 2939, 1600,
1520, 1496
(m, 1 H, CH), 3.82 (br s, 2 H NH and OH),
125.8 (1 C, arom CH), 128.4 (2 C, arom CH), 128.4
6.50 (d, 2 H, J = 8.1, o-NHarom-H), 6.65 (d, (2 C, arom CH), 141.3 (1 C, arom C). 142.0 (1 C, arom
2 H, J = 8.1, o-OHarom-H), 7.15-7.31 (m, 5H, CNH), 147.7 (1 C, arom COH)
arom)
7l
3406 (N-H), 3024
(C-H, ar), 2918,
1619, 1520, 1454
1.20 (d, 3 H, J = 6.4, CH3), 1.67-1.94 (m, 2 H, 20.3 (1 C, CH3), 20.8 (1 C, CH3), 32.5 (1 C, CH2), 38.8
CH2), 2.23 (s, 3 H, CH3Ar, 2.72 (t, 2 H, J = 7.8, (1 C, CH2), 48.2 (1 C, CH), 113.4 (2 C, arom CH), 125.8
CH2Ph), 3.27 (br s, 1 H, NH), 3.39-3.51 (m, (1 C, arom CH), 126.1 (1 C, arom CMe), 128.3 (2 C,
1 H, CHMe), 6.45 (d, 2 H, J = 8.1, o-NHarom- arom CH), 128.4 (2 C, arom CH), 129.7 (2 C, arom CH),
H), 6.96 (d, 2 H, J = 8.1, o-Me arom-H), 7.15– 142.0, (1 C, arom C) 145.2 (1 C, arom CNH)
7.30 (m, 5H)
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemoselective Reductive Amination of Aldehydes and Ketones
797
Table 7 (continued)
Product
IR
1H HMR (CDCl3/TMS)
d, J (Hz)
13C HMR (CDCl3/TMS)
d
n (cm−1)
7m
3406 (N-H), 3050
(C-H, ar), 2958,
1600, 1504, 1461
0.91 (t, 6 H, J = 6.8, CH3), 1.26-1.55 (m, 8 H, 14.2 (2 C, CH3), 19.12 (2 C, CH2), 37.3 (2 C, CH2), 52.3
CH2), 3.36 (m, 2 H, NH and CH), 6.56 (d, 2 H, (1 C, CH), 112.8 (2 C, arom CH), 116.4 (1 C, arom CH),
J = 7.8, o-NHarom-H), 6.63 (t, 1 H, J = 7.8, 129.2 (2 C, arom CH), 148.2 (1 C, arom C)
p-NHarom-H), 7.10-7.17 (m, 2 H)
7n
7o
3406 (N-H), 3051
(C-H, ar), 2962,
1600, 1504, 1462
0.91 (d, 3 H, J = 6.8, CH3), 0.97 (d, 3 H, J = 16.6 (1 C, CH3), 17.5 (1 C, CH3), 19.2 (1 C, CH3), 32.2
6.8, CH3), 1.09 (d, 3 H, J = 6.8, CH3), 1.78- (1 C, CHMe2), 53.4 (1 C, CHN), 113.0 (2 C, arom CH),
1.90 (m, 1 H, CHMe2), 3.27-3.39 (m, 1 H,
116.6 (1 C, arom CH), 129.2 (2 C, arom CH), 147.8
CHN), 3.45 (br s, 1 H, NH), 6.55 (d, 2 H, J = (1 C, arom CNH)
7.8, o-NHarom-H), 6.65 (t, 1 H, J = 7.8,
p-NHarom-H), 7.10-7.18 (m, 2 Harom
)
3406 (N-H), 3051
(C-H, ar), 2970,
1600, 1504, 1454
0.22-0.43 (m, 2 H, CH2), 0.45-0.54 (m, 2 H, 2.55 (1 C, CH2), 3.03 (1 C, CH2), 17.9 (1 C, CH), 20.2
CH2), 0.86-0.98 (m, 1 H, CH), 1.22 (d, 3 H, (1 C, CH3), 52.4 (1 C, CHMe), 113.2 (2 C, arom CH),
J = 6.4, CH3), 2.93-3.03 (m, 1 H, CHMe),
116.9 (1 C, arom CH), 129.2 (2 C, arom CH), 147.9
3.64 (br s, 1 H, NH), 6.58 (d, 2 H, J = 7.8, o- (1 C, arom CNH)
NHarom-H), 6.60 (t, 1 H, J = 7.8, p-NHarom-
H), 7.10-7.18 (m, 2 Harom
)
7p
7q
3406 (N-H), 3024
(C-H, ar), 2966,
1601, 1504, 1450
1.40 (d, 3 H, J = 6.8, CH3), 3.69 (br s, 1 H,
NH), 4.09-4.18 (m, 1 H, CHMe), 6.21 (dd,
1 H, J = 5.9, 16.1, CHC=), 6.57 (d, 1 H, J =
22.1 (1 C, CH3), 50.8 (1 C, CH), 113.4 (1 C, CH=), 113.4
(2 C, arom CH), 117.3 (1 C, PhCH=), 126.3 (2 C, arom
CH), 127.3 (1 C, arom CH), 128.5 (2 C, arom CH),
16.1, CHPh), 6.60-6.71 (m, 3 H, arom), 7.12- 129.2 (2 C, arom CH), 133.2 (1 C, arom CH), 137.0
7.36 (m, 7 Harom (1 C, arom CH), 147.4 (1 C, arom CNH)
)
3394 (N-H), 3050
(C-H, ar), 2973,
1731, 1604, 1508,
1434, 1195
1.28 (d, 3 H, J = 6.8, CH3), 2.42 (dd, 1 H, J = 20.6 (1 C, CH3), 40.7 (1 C, CH2), 45.9 (1 C, CH), 51.6
15.1, 6.8, CH2CO), 2.65 (dd, 1 H, J = 15.1, 5.4, (1 C, OCH3), 113.6 (2 C, arom CH), 117.7 (1 C, arom
CH2CO), 3.68 (s, 3 H, OCH3), 3.74 (br s, 1 H, CH), 129.3 (2 C, arom CH), 146.7 (1 C, arom CH), 172.3
NH), 3.89-4.01 (m, 1 H, CHMe), 6.62 (d,
2 H, J = 7.8, o-NHarom-H), 6.71 (t, 1 H, J =
(1 C, CO)
7.8, p-NHarom-H), 7.14-7.21 (m, 2 Harom
1.46 (d, 3 H, J = 5.9, CH3), 3.72 (s, 3 H,
OCH3), 4.15 (q, 1 H, J = 5.9, CHMe), 4.15 (br (2 C, arom CH), 118.3 (1 C, arom CH), 129.3 (2 C, arom
s, 1 H, NH), 6.59 (d, 2 H, J = 8.3, o-NHarom- CH), 146.5 (1 C, arom CNH), 175.0 (1 C, CO).
H), 6.73 (t, 1 H, J = 7.3, p-NHarom-H), 7.12
)
7r
7s
3350 (N-H), 3000
(C-H, ar), 1740,
1600, 1500
18.9 (1 C, CH3), 51.9 (1 C, OCH3), 52.1 (1 C, CH), 113.3
(dd, 2 Harom, J = 8.3, 7.3)
3394 (N-H), 3055
(C-H, ar), 2915,
2846, 1604, 1504,
1458
Major isomer: 1.39 (d, 3 H, J = 6.4, CH3), 3.08 Major isomer: 18.3 (1 C, CH3), 47.8 (1 C, CHMe), 56.3
(dd, 1 H, J = 2.5, 2.0, CHO), 3.67 (br s, 1 H, (1 C, CHO), 65.6 (1 C, CHPh), 113.0 (2 C, arom CH),
NH), 3.80 (d, 1 H, J = 2.5, CHPh), 3.82 (qd, 117.6 (1 C, arom CH), 125.5 (2 C, arom CH), 128.1
1 H, J = 6.4, 2.0, CHMe), 6.66 (d, 2 H, J = 7.8, (1 C, arom CH), 128.4 (2 C, arom CH), 129.4 (2 C, arom
o-NHarom-H), 6.72 (t, 1 H, J = 7.8, p-
NHarom-H), 7.167.36 (m, 7 Harom
CH), 137.1 (1 C, arom C), 147.1 (1 C, arom CNH)
Minor isomer: 17.3 (1 C, CH3), 49.5 (1 C, CHMe), 57.5
)
Minor isomer: 1.33 (d, 3 H, J = 5.9, CH3), 3.02 (1 C, CHO), 65.6 (1 C, CHPh), 113.7 (2 C, arom CH),
(dd, 1 H, J = 3.9, 2.0, CHO), 3.67 (br s, 1 H, 118.0 (1 C, arom CH), 125.5 (2 C, arom CH), 128.1
NH), 3.70 (qd, 1 H, J = 5.9, 3.9, CHMe), 3.87 (1 C, arom CH), 128.4 (2 C, arom CH), 129.3 (2 C, arom
(d, 1 H, J = 2.0, CHPh), 6.66 (d, 2 H, J = 7.8, CH), 137.0 (1 C, arom C), 147.0 (1 C, arom CNH)
o-NHarom-H), 6.72 (t, 1 H, J = 7.8, p-
NHarom-H), 7.16-7.36 (m, 7 Harom
)
N-(2-Phenylethyl)aniline (3m)
N-Benzyl-4-chloroaniline (4a)
Yield: 0.14 g (70%);colorless liquid purified by Kugelrohr distilla-
Yield: 0.215 g (99%); colorless liquid purified by Kugelrohr distil-
tion at 108 °C/0.09 Torr (Lit.21 bp 120-125 °C/0.025 Torr).
lation at 100 °C/0.09 Torr (Lit.18 mp 43-45 °C).
HRMS: m/z calcd for C14H15N 197.1206, found 197.1198.
N-Benzyl-4-hydroxyaniline (4b)
Yield: 0.095g (48%); white solid purified by column chromatogra-
N-(2-Methylpropyl)aniline (3n)
Yield: 0.147 g (99%); colorless liquid purified by Kugelrohr distil-
lation at 60 °C/0.09 Torr.
phy eluting with EtOAc; mp 89 °C (Lit.22 mp 89 °C).
N-(2-Phenylethyl)-4-chloroaniline (4c)
Yield: 0.229g (99%); colorless liquid purified by Kugelrohr distil-
HRMS: m/z calcd for C10H15N 149.1206, found 149.1223.
lation at 105 °C/0.09 Torr (Lit.23 bp 126-128 °C/0.15 Torr).
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

798
T. Suwa et al.
PAPER
N-Benzyl-1-propylamine (4d)
IR (neat): n = 3027 (C-H, ar), 2971, 2769, 1492, 1452 cm- 1
1H NMR (CDCl3): d = 1.49 (d, 3 H, J = 6.3 Hz, CH3), 3.63 (q, 1 H,
J = 6.3 Hz, CH), 3.79 (d, 2 H, J = 11.2 Hz, CH2), 3.94 (d, 2 H,
J = 11.2 Hz, CH2), 7.16-7.44 (m, 9 Harom).
.
Yield: 0.055g (37%); colorless liquid purified by Kugelrohr distil-
lation at 80 °C/0.09 Torr (Lit.24 bp 129 °C/100 Torr).
HRMS calcd for C10H15N 149.1206, found 149.1221.
N-Benzylpyrrolidine (4h)
Yield: 0.062g (39%); colorless liquid purified by Kugelrohr distil-
lation at 50 °C/5 Torr.
13C NMR (CDCl3): d = 23.3 (1 C, CH3), 58.0 (2 C, CH2), 65.4 (1 C,
CH), 122.3 (2 C, arom CH), 126.6 (2 C, arom CH), 127.1 (1 C, arom
CH), 127.3 (2 C, arom CH), 128.5 (2 C, arom CH), 140.1 (2 C, arom
C), 145.3 (1 C, arom C).
Anal. calcd for C11H15N: C, 81.94; H, 9.38; N, 8.69, found C, 81.54;
H, 9.35; N, 8.60.
HRMS: m/z calcd for C16H17N 223.1362, found 223.1357.
N-(2-Phenylethyl)propylamine (4j)
N-1-Phenylethyl-4-chloroaniline (7b)
Yield: 0.054g (33%); colorless liquid purified by column chroma-
tography eluting with hexane/EtOAc (9:1).
Yield: 0.16g (69%);colorless liquid purified by Kugelrohr distilla-
tion at 105 °C/0.09 Torr.
HRMS: m/z calcd for C11H17N 163.1361, found 163.1363.
HRMS: m/z calcd for C14H14ClN 231.0816, found 231.0824.
erythro-N-(1-Phenylethyl)-1-phenylethylamine (erythro-7d)
N-Benzylvaline Methyl Ester (4k); Typical Procedure
Colorless liquid purified by Kugelrohr distillation at 87 °C/0.09
Torr.
This reaction was performed by preheating the starting aldehyde
and amine to 65 °C. A solution of Bu2SnCl2 (0.152 g, 0.5 mmol) in
THF (1 mL) was added to a mixture of 1a (0.106 g, 1 mmol) and 2j
(0.131 g, 1mmol). The mixture was heated at 65 °C for 4 h. After
cooling to 0 °C, Bu2SnH2 (0.117 g, 0.5 mmol) was added, and the
mixture was stirred at 0 °C until the Sn-H absorption (1862 cm-1)
had disappeared. After quenching with MeOH (5 mL), volatiles
were removed under reduced pressure. The residue was subjected to
silica gel column chromatography (Fuji-gel FL100DX) eluting with
hexane/EtOAc (9:1) to give the pure product 4k. Further purifica-
tion was performed by Kugelrohr distilation at 75 °C/0.09 Torr;
yield: 0.123g (56%); colorless liquid.
HRMS: m/z calcd for C16H19N 225.1519, found 225.1513.
threo-N-(1-Phenylethyl)-1-phenylethylamine (threo-7d)
This compound was identified with commercially available sample.
Colorless liquid purified by Kugelrohr distillation at 87 °C/0.09
Torr.
HRMS: m/z calcd for C16H19N 225.1519, found 225.1513.
N-(1-p -Tolylethyl)aniline (7e)
Yield: 0.103g (49%); colorless liquid purified by Kugelrohr distil-
lation at 105 °C/0.09 Torr.
HRMS: m/z calcd for C13H19NO2 221.3019, found 221.1408.
IR (neat): n = 3400 (N-H), 3045 (C-H, ar), 2970, 1600, 1500,
1320, 1095 cm- 1
.
Anal. calcd for C13H19NO2: C 70,54, H 8.66, N 6.33. Found C 70.74,
H 8.69, N 6.10.
1H NMR (CDCl3): d = 1.49 (d, 3 H, J = 6.8 Hz, CH3), 2.32 (s, 3 H,
CH3Ar), 3.99 (br s, 1 H, NH), 4.45 (q, 1 H, J = 6.8 Hz, CHMe), 6.50
(d, 2 H, J = 7.8 Hz, o-NHarom-H), 6.63 (t, 1 H, J = 7.8 Hz, p-
NHarom-H), 7.05-7.27 (m, 6 H).
13C NMR (CDCl3): d = 21.0 (1 C, CH3Ar), 24.97 (1 C, CH3), 53.13
(1 C, CH), 113.26 (1 C, arom CH), 117.1 (1 C, arom CH), 125.7 (2
C, arom CH), 129.1 (2 C, arom CH), 129.3 (2 C, arom CH), 136.4
(1 C, arom C), 142.2 (1 C, arom C), 147.3 (1 C, arom CNH).
2-(Benzylamino)-2-phenylethanol (4l)
The preparation of 4l was analogous to that described for the syn-
thesis of 4k. White solid purified by column chromatography elut-
ing with hexane/EtOAc (9:1), mp 99 °C (Lit.25 100-102 °C); yield:
0.176g (77%);
HRMS: m/z calcd for C15H17NO CI+ 227.1311, found 228.1388 (M
+ 1).
HRMS: m/z calcd for C15H17N 211.1362, found 211.1368.
2-(4-Chlorophenylmethylamino)-2-phenylethanol (4m)
The preparation of 4m was analogous to that described for the syn-
thesis of 4k. Colorless liquid purified by Kugelrohr distillation at
170 °C/0.09 Torr; yield: 0.236g (90%).
HRMS: m/z calcd for C15H16ClNO CI+ 261.0922, found 262.0983
(M + 1).
N-(1-p-Chlorophenyl)aniline (7f)
Yield: 0.143g (0.62 mmol, 62%); colorless liquid purified by
Kugelrohr distillation at 105 °C/0.09 Torr.
HRMS: m/z calcd for C14H14ClN 231.0816, Found 231.0814.
trans-N-(2-Methylcyclohexyl)aniline (7h)
2-(2-Hydroxyphenylmethylamino)-2-phenylethanol (4n)
The preparation of 4n was analogous to that described for the syn-
thesis of 4k. white solid purified by column chromatography eluting
with EtOAc; mp 116 °C; yield: 0.167g (70%);
Colorless liquid purified by Kugelrohr distillation at 115 °C/5 Torr.
HRMS: m/z calcd for C13H19N 189.1519, found 189.1519.
cis-N-(2-Methylcyclohexyl)aniline (7h)
Colorless liquid purified by Kugelrohr distillation at 115 °C/5 Torr.
Anal. calcd for C16H17NO: C 74.05, H 7.04, N5.76. Found C 73.71,
H 6.98, N 5.62.
HRMS: m/z calcd for C13H19N 189.1519, found 189.1519.
N-2-(4-Phenylbutyl)aniline (7i)
Yield: 0.204g (91%); colorless liquid purified by Kugelrohr distil-
lation at 115 °C/0.09 Torr.
N-[(2-Hydroxyphenyl)methyl]valine Methyl Ester (4o)
The preparation of 4o was analogous to that described for the
synthesis of 4k. Colorless liquid purified by Kugelrohr distillation
at 78 °C/0.09 Torr; yield: 0.199g (84%).
HRMS calcd for C16H19N 225.1519, found 225.1515.
Anal. calcd for C13H19NO3: C, 65.80; H, 8.07; N, 5.90, found C,
65.50; H, 8.06; N, 5.94.
N-2-(4-Phenylbutyl)-p-chloroaniline (7j)
Yield: 0.209g (81%); colorless liquid purified by Kugelrohr distil-
lation at 105 °C/0.09 Torr.
2-Phenylisoindoline (5a)
Yield: 0.135g (74%); white solid purified by column chromatogra-
HRMS: m/z calcd for C16H18ClN 259.7736, found 259.1137.
phy eluting with hexane/EtOAc (9:1) mp164 °C (Lit.26 mp 165 °C).
N-2-(4-Phenylbutyl)-p-hydroxyaniline (7k)
Yield: 0.122g (51%); white solid purified by column chromatogra-
phy eluting with EtOAc; mp 114 °C.
N-1- Phenetylisoindoline (5b)
Yield: 0.08g (36%); colorless liquid purified by Kugelrohr distilla-
tion at 110 °C/0.09 Torr.
Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Chemoselective Reductive Amination of Aldehydes and Ketones
799
HRMS: m/z calcd for C16H19NO 241.1467, found 241.14618.
References
N-2-(4-Phenylbutyl)-p-methylaniline (7l)
Yield: 0.193g (81%); colorless liquid purified by Kugelrohr distil-
lation at 105 °C/0.09 Torr.
(1) Hutchins, R. O.; Hutchins, M. K. In Comprehensive Organic
Synthesis, Vol. 8; Trost, B. M.; Fleming, I., Ed.; Pergamon:
New York, 1991; p 25.
(2) (a)Roe, A.; Montgomery, J. A. J. Am. Chem. Soc. 1953, 75,
910.
(b) Rylander, P. N. In Catalytic Hydrogenation over Platinum
Metals; Academic: New York, 1967; p 218.
(3) (a) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem.
Soc. 1971, 93, 2897.
HRMS: m/z calcd for C17H21N 239.1674, found 239.1678.
Anal. calcd for C17H21N : C, 85.30; H, 8.84; N, 5.85, Found C,
85.04; H, 8.87; N, 5.95.
N-4-Heptylaniline (7m)
Yield: 0.107g (56%); colorless liquid purified by Kugelrohr distil-
lation at 50 °C/0.09 Torr.
(b) Borch, R. F.; Hassid, A. I. J. Org. Chem. 1972, 37, 1673.
(c) Marchini, P.; Liso, G.; Reho, A.; Liberatone, F.; Moracci,
F. M. J. Org. Chem. 1975, 40, 3453.
HRMS: m/z calcd for C13H21N: 191.1674, found 191.1688.
Anal. calcd for C13H21N: C, 81.61; H, 11.06; N, 7.32, Found C,
81.67; H, 11.18; N, 7.37.
(d) Lane, C. F. Synthesis 1975, 135.
(4) NaBH(OAc)3:
N-2-(3-Methylbutyl)aniline (7n)
Yield. 0.209g (54%); colorless liquid purified by Kugelrohr distil-
lation at 70 °C/5 Torr.
(a) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849.
NaBH3CN-Ti(Oi Pr)4:
(b) Mattson, R. J.; Pham, K. M.; Leuck, D. J.; Cowen, K. A. J.
Org. Chem. 1990, 55, 2552.
(c) Bhattacharyya, S. Synlett 1994, 1029.
(d) Bhattacharyya, S.; Chatterjee, A.; Williamson, J. S. Synlett
1995, 1079.
(e) Bhattacharyya, S. J. Org. Chem. 1995, 60, 4928.
(f) Neidigh, K. A.; Avery, M. A.; Williamson, J. S.;
Bhattacharyya, S. J. Chem. Soc., Perkin Trans 1 1998, 2527.
NaBH3CN-Mg(ClO4)2:
HRMS: m/z calcd for C11H17N: 163.1361, found 163.1365.
Anal. Calcd for C11H17N: C, 80.93; H, 10.50; N, 8.58, Found C,
80.67; H, 10.46; N, 8.64.
N-(1-Cyclopropylethyl)aniline (7o)
0.06g (37%); colorless liquid purified by Kugelrohr distillation at
85 °C/5 Torr.
HRMS: m/z calcd for C11H15N 161.1205, found 161.1201.
Anal. calcd for C11H15N: C, 81.94; H, 9.38; N, 8.69, found C, 81.77;
H, 9.41; N, 8.86.
(g) Brussee, J.; van Benthem R. A. T. M.; Kruse, C. G.; van
der Gen, A. Tetrahedron: Asymmetry 1990, 1, 163.
BH3•pyridine:
(h) Pelter, A.; Rosser, R. M.; Mills, S. J. Chem. Soc., Perkin
Trans. 1 1984, 717.
Zn(BH4)2-ZnCl2:
(i) Bhattacharyya, S.; Chatterjee, A.; Duttachowdhury, K. J.
Chem. Soc., Perkin Trans 1 1994, 1.
N-2-(4-Phenylprop-3-enyl)aniline (7p)
Yield: 0.133g (60%); white solid purified by column chromatogra-
phy eluting with EtOAc; mp 49 °C (Lit.27 mp 49-50 °C).
HRMS calcd for C16H17N 223.1361, found 223.1367.
Methyl 3-(N-Phenylamino)butyrate (7q)
Yield: 0.140g (73%); colorless liquid purified by Kugelrohr distil-
lation at 73 °C/0.09 Torr.
(5) (a) Micovic, I. V.; Ivanovic, M. D, Piatak, D. M.; Bojic, V. D.
Synthesis 1991, 1043.
(b) Kobayashi, S.; Yasuda, M.; Hachiya, I. Chem. Lett. 1996,
407.
(6) (a) Shibata, I.; Yoshida, T.; Baba, A.; Matsuda, H. Chem. Lett.
1989, 619.
HRMS: m/z calcd for C11H15NO2: 193.1103, found 193.1107.
Anal. calcd for C11H15NO2: C, 68.37; H, 7.82; N, 7.25. found: C,
68.08; H, 7.77; N, 7.27.
(b) Shibata, I.; Yoshida, T.; Kawakami, T.; Baba, A.;
Matsuda, H. J. Org. Chem. 1992, 57, 4049.
(c) Kawakami, T.; Shibata, I.; Baba, A.; Matsuda, H. J. Org.
Chem. 1993, 58, 7608.
(d) Kawakami, T.; Shibata, I.; Baba, A. J. Org. Chem. 1996,
61, 82.
Methyl 2-(N-Phenylamino)propionate (7r)
Colorless solid purified by Kugelrohr distillation at 75 °C/0.09
Torr; yield: 0.103g (58%);
HRMS: m/z calcd for C10H13NO2 179.0947, found. 179.0948.
trans-1,2-Epoxy-1-phenyl-(3-phenylamino)butane (major iso-
(e) Kawakami, T.; Miyatake, M.; Shibata, I.; Baba, A.;
Matsuda, H. J. Org. Chem. 1996, 61, 376.
(7) Kawakami, T.; Sugimoto, T.; Shibata, I.; Baba, A.; Matsuda,
H.; Sonoda, N. J. Org. Chem. 1995, 60, 2677.
(8) Neumann, W. P.; Pedain, J. Tetrahedron Lett. 1964, 5, 2461.
(9) Shibata, I; Suwa, T.; Moriuchi-Kawakami, T.; Tanizawa, D.;
Sugiyama, E.; Matsuda, H.; Baba, A. J. Org. Chem. 1998, 63,
383.
(10) Shibata, I, Suwa, T.; Sugiyama, E. Synlett 1998, 1081.
(11) Tin hydride, review, Pereyre, M.; Quintard, J.-P.; Rahm, A.
Tin in Organic Synthesis; Butterworths: London, 1987.
(12) Eleveld, M. B.; Hogeveen, H.; Schudde, E. P. J. Org. Chem.
1986, 51, 3635.
mer) (7s)
Colorless liquid purified by Kugelrohr distillation at 75 °C/0.09
Torr.
HRMS: m/z calcd for C16H17NO 239.1311, found 239.1296.
trans-1,2-Epoxy-1-phenyl-(3-phenylamino)butane (minor iso-
mer) (7s)
Colorless liquid purified by Kugelrohr distillation at 75 °C/0.09
Torr.
HRMS: m/z calcd for C16H17NO 239.1311, found 239.1296.
Acknowledgement
(a) Wrobel, J. E.; Ganem, B. Tetrahedron Lett. 1981, 22,
3447.
(b) Hutchins, R. O.; Adams, J.; Rutledge, M. C. J. Org. Chem.
1995, 60, 7396.
This work was financially supported by the Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Science and Culture,
and JSPS Research Fellowships for Young Scientists. Thanks are
due to Mr. H. Moriguchi, Faculty of Engineering, Osaka University,
for assistance in obtaining HRMS spectra.
(14) Pereyre, M.; Godet, J. Y. Tetrahedron Lett. 1970, 3653.
(15) Stetin, C.; Jeso, de B.; Pommier, J. C. Synth. Commun. 1982,
496.
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Article Identifier:
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Synthesis 2000, No. 6, 789–800 ISSN 0039-7881 © Thieme Stuttgart · New York