A novel one-pot reductive amination of aldehydes and ketones with lithium perchlorate and zirconium borohydride-piperazine complexes

Article abstract of DOI:10.1016/j.tet.2007.02.026

A novel, one-pot reductive mono-alkylation method of amines (primary and secondary), 1,2-phenylenediamine, O-trimethylsilylhydroxylamine, and N,N-dimethylhydrazine was developed using LiClO₄ (5 mol %) as a source for in situ generation of imine

Full text of DOI:10.1016/j.tet.2007.02.026

Tetrahedron 63 (2007) 3363–3366
A novel one-pot reductive amination of aldehydes and ketones with
lithium perchlorate and zirconium borohydride–piperazine
complexes
a,*
a
Akbar Heydari, Samad Khaksar, Maryam Esfandyari and Mahmoud Tajbakhsh
a
b
a
Chemistry Department, Tarbiat Modarres University, PO Box 14155-4838, Tehran, Iran
b
Chemistry Department, Mazandaran University, Babol Sar, Iran
Received 1 November 2006; revised 20 January 2007; accepted 8 February 2007
Available online 13 February 2007
This paper is dedicated to Morteza Nilforoushan for his contribution in Iranian pharmaceutical industry
Abstract—A novel, one-pot reductive mono-alkylation method of amines (primary and secondary), 1,2-phenylenediamine, O-trimethylsilyl-
hydroxylamine, and N,N-dimethylhydrazine was developed using LiClO (5 mol %) as a source for in situ generation of imine, iminium ion,
4
oxime, and hydrazone, and zirconium borohydride–piperazine complex as reducing agent. This condition is especially useful for situations in
which it is not practical to use the amine in excess (as is typically the case under acid-catalyzed conditions) or for acid-sensitive compounds.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
reducible functional groups such as double and triple bonds,
nitro, cyano, and furyl groups. NaBH , which is used for
8
4
1
9
The direct reductive amination, which allows the conver-
sion of carbonyl functionality to structurally diverse pri-
mary, secondary, and tertiary amines, is an important
reductive amination requires harsh reaction conditions.
Cyanoborohydride and tin hydride reagents are highly toxic
1
0
and generate toxic by-products such as HCN, NaCN, or
upon workup, organotin compounds. NaBH(OAc) is flam-
2
method in organic synthesis. The overall process involves
3
the formation of an imine or iminium ion intermediate
upon reaction of a carbonyl compound with ammonia, pri-
mary or secondary amine, followed by in situ reduction to
an alkylated amine of higher order in a single operation.
This reaction offers compelling advantages over amine syn-
thesis, including brevity, wide commercial availability of
substrates, and generally mild reaction conditions. Several
reagents, which effect reductive amination have been
recently developed, including the following: catalytic
mable, water-reactive, and poorly soluble in most of the
commonly used organic solvents. Pyridine–BH is unstable
3
to heat and must be handled with extreme care. Other
hydrides such as zinc borohydride and nickel boride are
not suitable for use in chemoselective reduction of imines
1
1
having ketone, ester, and amide groups. However, since
carbonyl compounds themselves are also reduced under
the conditions used, many of these reactions require an ex-
cess amount of the amines to obtain good yields of products.
In addition, in some cases, some correlations between reac-
tion time and reactivity of the amine species have been
observed. For example, secondary alkylamines give moder-
3
4
5
hydrogenation, Zn–AcOH, Et SiH–CF CO H, Bu SnH–
2
3
3
3
6
DMF. In addition, various modified borohydride deriva-
tives, which effect direct and indirect reductive amination,
have been developed including the following: NaBH CN,
7
a
12
ate yields, as compared to primary alkylamines. Reductive
3
7
b
7c
7d
NaBH(OAc) , pyridine–BH , ZnCl –NaBH , silica gel–
3
amination of conjugated carbonyl compounds has been ad-
dressed in detail in many of the reported methods; only
two examples use sodium triacetoxyborohydride and silica
3
2
4
7
e
7f
7g
Zn(BH ) , Ti(O-i-Pr) –NaBH , and NiCl –NaBH .
2
4
2
4
4
4
7
a
However, in terms of functional group tolerance, side reac-
tions and reaction conditions, most of these reagents may
have one or more drawbacks. For example, catalytic hydro-
genation is incompatible with compounds containing other
7
e
gel–zinc borohydride procedures. Furthermore, while the
literature abounds with heterogenous reductive amination
3
,13
processes,
little attention has been paid to the use of
1
4
homogenous catalysts. Direct reductive amination is per-
formed in anhydrous conditions in order to avoid the decom-
position of the reducing agents or catalysts, and to enhance
the generation of the intermediate imines or iminium ions.
As a result, the selection of the reagent is crucial. If one
4
Keywords: Direct reductive amination; LiClO ; Zirconium borohydride–
piperazine complex; Imine; Iminium ion; Oxime; Hydrazone.
*
0
Corresponding author. Fax: +98 21 88006544; e-mail: akbar.heydari@
gmx.de
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.026

3364
A. Heydari et al. / Tetrahedron 63 (2007) 3363–3366
could perform the direct reductive amination of carbonyl
compounds in air and in the presence of moisture, it should
be of considerable interest. Thus, it is challenging to develop
such an effective catalyst or reagent.
Next, we turned our attention to the direct mono-N-alkyl-
ation of a symmetrical primary diamine. In the presence of
a catalytic amount of LiClO (5 mol %) and TMSCl (stoi-
4
chiometric), 1,2-diaminobenzene underwent mono-N-alkyl-
ation under the usual one-pot aminoreduction conditions in
high yield. Di-alkylation was not detected. Under our
standard conditions, direct reductive amination of p-nitro-
and p-cyano benzaldehydes with primary amines proceeded
smoothly with full conversion of aldehydes and good yields
of the desired alkylated amines (Scheme 1, entries i and j).
With these results in hand, we next studied the regioselective
one-pot reductive amination of trans-cinnamaldehyde with
Our recent endeavor of selective reduction of various impor-
tant functionalities with zirconium borohydride–piperazine
1
5
complex prompted us to initiate a systematic study of
this useful air and thermally stable reducing agent. In this pa-
per, we report our results on the development of a highly
practical method for the synthesis of amine derivatives by
the direct reductive amination of carbonyl compounds in
the presence of lithium perchlorate (5 mol %) as a Lewis
acid and zirconium borohydride–piperazine complex as a
reducing agent in reagent grade dichloromethane (DCM).
Varieties of aldehydes were subjected to direct reductive
amination by this procedure. The results appear in Scheme 1.
The acyclic and conjugated carbonyl compounds under-
went successful reductive amination with diethylamine to
produce the corresponding tertiary amines in good to excel-
aniline in the presence of LiClO (5 mol %)/TMSCl (stoi-
4
chiometric) and zirconium borohydride–piperazine complex
as the reducing agent in DCM. It afforded the expected
substituted cinnamyl amine in 92% isolated yields. The
result is interesting since acetophenone has been shown to
be an inert or difficult substrate in some reported reductive
1
8
aminations, the use of our procedure also enabled the
reductive amination of ketones.
lent yields. Without LiClO , the process of using carbonyl
4
compounds with amines, in the presence of zirconium
borohydride–piperazine complex, does not smoothly lead to
reductive amination, but is generally accompanied by reduc-
tive products of the carbonyl compounds.
The substrate versatility of this direct reductive amination
method was further demonstrated by the successful prepara-
tion of several N- and O-substituted primary amines. Thus,
the reductive amination of 4-chlorobenzaldehyde and trans-
cinnamaldehyde with O-trimethylsilylhydroxylamine and
N,N-dimethylhydrazine resulted in the corresponding mono-
alkylated products as showed in Scheme 1. In both entries,
no overalkylations were detected.
R2
LiClO / (TMSCl)
O
H
N
4
3
4
R4
+
R1
R2 R3
R1
R4
R4
(Ppyz)Zr(BH ) Cl
N
4 2
2
1
2
5
6
R3
In summary, we have established a lithium perchlorate/
zirconium borohydride–piperazine complex promoted di-
rect reductive N-alkylation methodology, which is selective
and efficient. High selectivity of the converting primary
amine and symmetrical diamine, mono-N-alkylations has
been clearly demonstrated, and use of protecting groups
has been eliminated. This methodology proves to be a
general protocol for the syntheses of the N-alkylated hydr-
oxylamines and hydrazines, offering a wide variety of
applications.
R1
R2
R3
6%
a
b
c
d
e
f
i-Propyl
n-Propyl
H
H
H
H
H
H
H
H
H
H
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
H
87
90
75
80
82
90
95
92
90
90
95
84
89
4-Br-Phenyl
4-Pyridyl
trans-Cinnamyl
4-Cl-Phenyl
4-Cl-Phenyl
trans-Cinnamyl
4-NO2-Phenyl
4-NC-Phenyl
Benzyl
Phenyl
4-Cl-Phenyl
trans-Cinnamyl
2-NH2Phenyl
Phenyl
g
h
i
H
Phenyl
H
Phenyl
H
j
Phenyl
H
k
l
Me Phenyl
Me Phenyl
H
H
m
n
H
H
O-TMSi
H
H
NMe 80
2
2. Experimental section
2.1. General procedure
Scheme 1.
Although many of the reported protocols for reductive ami-
nations work well for the preparation of tertiary amines, in
many cases the synthesis of secondary amines is compro-
2.1.1. Preparation of N-mono-alkylation of amines and
amine derivatives. To a suspension containing LiClO4
(11 mg, 5 mol %) in reagent grade DCM (8 mL), carbonyl
compound (2 mmol) and diethylamine (2.2 mmol) were
added and the mixture vigorously stirred for 15 min at
1
6
mised of overalkylation reactions. However, because of
their potential as robust pharmacophores and as useful syn-
thetic intermediates, the synthesis of these amines has long
ꢀ
40 C. After this time, zirconium borohydride–piperazine
1
7
been of interest. To test the synthetic feasibility of our ap-
proach, we studied the direct reductive amination of an alde-
hyde with aniline. Thus, treatment of 4-chlorobenzaldehyde
complex (104 mg, 3 mmol, 1.5 equiv) was added, the mix-
ture was stirred for an additional 3 h. The reaction mixture
was washed with water followed by brine solution and
then extracted with CH Cl , dried over Na SO , concen-
with aniline in DCM in the presence of LiClO (5 mol %)
4
2
2
2
4
and a stoichiometric amount of TMSCl as activator, afforded
the corresponding iminium salt that was reduced with zirco-
nium borohydride–piperazine complex to give N-(4-chloro-
phenyl) aniline in 90% isolated yield. To obtain good yields,
the use of TMSCl was important in this reaction. In contrast,
reaction with primary amines gave the corresponding
trated under vacuum, and the crude mixture was purified
by column chromatography on silica gel (hexane:ethylace-
tate, 2:1) to afford pure products. When aniline, O-trimethyl-
silylhydroxylamine, and N,N-dimethylhydrazine were used
as the amine compound, the procedure was the same, but
2.0 mmol of trimethylsilyl chloride was used before reduc-
tion. All products were identified by comparing their NMR
1
imines, as determined by H NMR of the crude reaction
mixtures.
7
b,11,19–21
and IR values with those of authentic samples.

A. Heydari et al. / Tetrahedron 63 (2007) 3363–3366
3365
1
9
ꢁ1
1
Compound 6a. Oil; IR: 2930, 2850, 2700, 1490 cm ; H
NMR (90 MHz, CDCl ): d 0.87 (d, J¼7.9 Hz, 6H), 1.4 (t,
118.27 (CH), 128.931 (CH), 129.43 (CH), 130.21 (CH),
140.62 (C), 143.00 (C), 157.44 (C).
3
J¼7.6 Hz, 6H), 1.8 (m, 1H), 2.3 (d, J¼8.1 Hz, 2H), 2.6 (q,
1
3
11
J¼7.6 Hz, 4H); C NMR (22.5 MHz, CDCl ): d 20.68
Compound 6j. IR: 3330, 2940, 2850, 2210, 1610,
3
ꢁ
1530 cm ; H NMR (500 MHz, CDCl ): d 4.2 (s, 1H),
3
1 1
(
CH ), 25.02 (CH ), 29.43 (CH), 53.33 (CH ), 66.79 (CH ).
3
3
2
2
4
.47 (s, 2H), 6.6 (m, 2H), 6.7–6.8 (m, 1H), 7.2 (d,
1
9
ꢁ1
1
13
Compound 6b. Oil; IR: 2930, 2840, 2700, 1490 cm ; H
NMR (90 MHz, CDCl ): d 0.87–0.98 (t, J¼8.3 Hz, 3H), 1.1–
J¼8.4 Hz, 2H), 7.45 (m, 2H), 7.6 (d, J¼8.4 Hz, 2H); C
NMR (22.5 MHz, CDCl ): d 47.55 (CH ), 110.99 (C),
113.02 (CH), 117.95 (CH), 118.27 (CN), 128.93 (CH),
129.54 (CH), 130.21 (CH), 145.62 (C), 147.60 (C).
3
3
2
1
.3 (m, 4H), 1.4–1.8 (t, J¼7.8 Hz, 6H), 2.3 (q, J¼7.8 Hz,
1
3
4
d 10.27 (CH ), 13.79 (CH ), 20.55 (CH ), 28.82 (CH ),
H), 2.6 (t, 7.8 Hz, 2H); C NMR (22.5 MHz, CDCl ):
3
3
3
2
2
7
b
5
3.21 (CH ), 58.41 (CH ).
2
Compound 6k.
1503 cm ;
Oil; IR: 3411, 3055, 2926, 1602,
H NMR (90 MHz, CDCl ): d 1.1 (d,
2
ꢁ1
1
3
1
9
Compound 6c. Oil; IR: 2958, 2880, 2800, 1620, 1500, 740,
J¼6.7 Hz, 3H), 2.7 (d, J¼7.9 Hz, 2H), 3.4 (m, 1H), 3.7 (br
ꢁ
1
1
13
7
6
2
00 cm ; H NMR (90 MHz, CDCl ): d 1.3 (t, J¼7.3 Hz,
s, 1H), 6.8 (m, 4H), 7.3 (m, 6H); C NMR (22.5 MHz,
CDCl ): d 22.10 (CH ), 44.21 (CH ), 48.29 (CH), 114.11
3
H), 2.7 (q, J¼7.3 Hz, 4H), 3.5 (s, 2H), 7.4 (d, J¼7.8 Hz,
3
3
2
1
3
H), 7.5 (d, J¼7.8 Hz, 2H);
C NMR (22.5 MHz,
(CH), 116.10 (CH), 126.00 (CH), 128.90 (CH), 131.20
(CH), 132.00 (CH), 140.25 (C), 147.32 (C).
CDCl ): d 11.25 (CH ), 46.42 (CH ), 56.60 (CH ), 119.24
3
3
2
2
(
C), 128.41 (CH), 130.64 (CH), 139.23 (C).
1
1
Compound 6l.
1503 cm ;
Oil; IR: 3411, 3055, 2926, 1602,
H NMR (500 MHz, CDCl ): d 1.58 (d,
1
9
ꢁ1
1
Compound 6d.
1
Oil; IR: 3055, 2926, 2850, 1602,
H NMR (90 MHz, CDCl ): d 1.3 (t,
3
ꢁ
1
1
503 cm
;
J¼6.8 Hz, 3H), 4.45 (q, J¼6.8 Hz, 1H), 4.11 (br s, 1H),
13
3
J¼7.8 Hz, 6H), 2.7 (q, J¼7.8 Hz, 4H), 3.5 (s, 2H), 6.75 (d,
6.6 (m, 2H), 6.7–6.8 (m, 2H), 7.2 (m, 2H), 7.45–7.6 (m,
4H); C NMR (22.5 MHz, CDCl ): d 24.73 (CH ), 53.26
1
3
J¼7.8 Hz, 2H), 8.6 (d, J¼7.8 Hz, 2H);
C NMR
22.5 MHz, CDCl ): d 11.24 (CH ), 46.10 (CH ), 56.60
CH ), 121.30 (CH), 149.24 (CH), 151.91 (C).
2
3
3
(
(
(CH), 112.91 (CH), 118.27 (CH), 125.03 (CH), 126.01
(CH), 129.43 (CH), 130.21 (CH), 145.62 (C), 147.00 (C).
3
3
2
1
9
19
Compound 6e. Oil; IR: 3057, 3030, 2940, 2817, 1597,
1
Compound 6m. The TMS group was removed after hydro-
lysis. Oil; IR: 3410, 2905, 1648, 1478, 1401, 1046, 1021,
ꢁ
1
1
494, 967 cm ; H NMR (90 MHz, CDCl ): d 1.3 (t,
3
ꢁ1 1
J¼7.8 Hz, 6H), 2.7 (q, J¼7.8 Hz, 4H), 3.5 (d, J¼6.3 Hz,
818, 756, 621 cm ; H NMR (90 MHz, CDCl ): d 4.3 (s,
3
1
3
2
NMR (22.5 MHz, CDCl ): d 11.24 (CH ), 46.42 (CH ),
H), 6.4 (m, 1H), 6.6 (d, J¼6.3 Hz, 1H), 7.6 (m, 5H);
C
2H), 8.21 (s, 1H), 7.5–7.7 (m, 1H), 7.1 (d, J¼7.36 Hz,
1
3
2H), 7.3 (d, J¼7.36 Hz, 2H); C NMR (22.5 MHz,
3
3
2
5
5.20 (CH ), 120.1 (CH), 124.1 (CH), 127.1 (CH), 128.2
2
CDCl ): d 51.10 (CH ), 127.95 (CH), 128.93 (CH), 129.31
3
2
(
CH), 134.41 (CH), 135.64 (C).
(CH), 138.48 (C).
1
9
19
Compound 6f. Oil; IR: 3415, 2920, 1593, 1494, 1319,
1265, 1086, 1008, 808, 743, 690 cm ; H NMR (90 MHz,
CDCl ): d 4.3 (s, 2H), 3.6 (br s, 3H), 6.5–6.8 (m, 4H), 7.1–
Compound 6n. Oil; IR: 3410, 2945, 1685, 1662, 1577,
1472, 1085, 877, 818, 726, 623, 514 cm ; H NMR
ꢁ1
1
ꢁ1
1
(90 MHz, CDCl ): d 2.3 (s, 6H), 3.6 (d, J¼6.3 Hz, 2H),
3
3
1
3
13
7
.8 (m, 4H); C NMR (22.5 MHz, CDCl ): d 47.36
3
3.3 (s, 1H), 6.0 (m, 1H), 6.7 (m, 2H), 7.4 (m, 5H);
C
(
CH ), 113.02 (CH), 117.95 (CH), 128.93 (CH), 129.31
2
NMR (22.5 MHz, CDCl ): d 32.3 (CH ), 42.47 (CH ),
3 2 3
(
1
CH), 130.21 (CH), 131.11 (CH), 132.22 (C), 135.40 (C),
38.48 (C), 148.12 (C).
119.24 (CH), 125.40 (CH), 127.20 (CH), 128.41 (CH),
129.64 (C), 135.40 (CH).
2
0
Compound 6g. Oil; IR: 3415, 2920, 1593, 1494, 1319,
1265, 1086, 1008, 808, 743, 690 cm ; H NMR (90 MHz,
CDCl ): d 4.3 (s, 2H), 3.6 (br s, 1H), 6.5–6.8 (m, 5H), 7.1–
ꢁ1 1
Acknowledgements
3
1
3
7
.8 (m, 4H); C NMR (22.5 MHz, CDCl ): d 47.36
3
Research supported by the National research Council of I. R.
Iran as a National Research project under the number 984.
(
CH ), 113.02 (CH), 117.95 (CH), 128.93 (CH), 129.31
2
(
CH), 130.21 (CH), 131.11 (C), 132.22 (C), 138.48 (C).
2
1
Compound 6h. Oil; IR: 3315, 3057, 3025, 2930, 2817,
H NMR
References and notes
ꢁ1
1
1
597, 1494, 1447, 967, 779, 692 cm
;
(
2
500 MHz, CDCl ): d 3.9 (br s, 1H), 4.1 (d, J¼6.4 Hz,
1. The indirect reaction is a stepwise one, which involves produc-
tion of the amine from the reduction of the imine derivatives
isolated in a separate step.
3
1
3
H), 6.5–6.8 (m, 7H), 7.1–7.8 (m, 5H);
C NMR
(
(
(
22.5 MHz, CDCl ): d 47.36 (CH ), 113.02 (CH), 117.95
3 2
CH), 128.93 (CH), 129.31 (CH), 130.21 (CH), 131.11
CH), 132.22 (CH), 138.48 (CH), 142.12 (C), 148 (C).
2. For reviews on reductive amination see: Hutchins, R. O.;
Hutchins, M. K. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 8,
p 25; Baxter, E. W.; Reitz, A. B. Organic Reactions; Wiley:
New York, NY, 2002; Vol. 59, p 1; Hudlicky, M. Reductions
in Organic Chemistry, 2nd ed.; ACS Monograph 188;
American Chemical Society: Washington, DC, 1996; p 187.
3. Tarasevich, V. A.; Kozlov, N. G. Russ. Chem. Rev. 1999, 68, 55.
1
1
Compound 6i. IR: 3440, 3060, 2935, 1634, 1519, 1352,
1
4
J¼8.1 Hz, 2H), 7.45 (m, 2H), 7.6 (d, J¼8.1 Hz, 2H); C
NMR (22.5 MHz, CDCl ): d 47.204 (CH ), 112.91 (CH),
ꢁ
1 1
139 cm ; H NMR (500 MHz, CDCl ): d 4.2 (s, 1H),
3
.47 (s, 2H), 6.6 (m, 2H), 6.7–6.8 (m, 1H), 7.2 (d,
1
3
3
2

3366
A. Heydari et al. / Tetrahedron 63 (2007) 3363–3366
4
5
6
7
. Micovic, I. V.; Ivanovic, M. D.; Piatak, D. M.; Bojic, V. D. 13. Ikenaga, T.; Matsushita, K.; Shinozawa, J.; Yada, S.; Takagi, Y.
Synthesis 1991, 1043.
Tetrahedron 2005, 61, 2105; Heinen, A. W.; Peters, J. A.; van
Bekkum, H. Eur. J. Org. Chem. 2000, 2501; Birtill, J. J.;
Chamberlain, M.; Hall, J.; Wilson, R.; Costello, I. Catalysis
of Organic Reactions; Herkes, F. E., Ed.; Dekker: New York,
NY, 1998; p 255.
. Chen, B.-C.; Sundeen, J. E.; Guo, P.; Bednarz, M. S.; Znao, R.
Tetrahedron Lett. 2001, 42, 1245.
. Suwa, T.; Sugiyama, E.; Shibata, I.; Baba, A. Synthesis 2000,
6, 789.
. (a) Lane, C. F. Synthesis 1975, 135; (b) Abdel-Magid, A. F.;
Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D.
J. Org. Chem. 1996, 61, 3849; (c) Bomann, M. D.; Guch,
I. C.; Dimare, M. J. Org. Chem. 1995, 60, 5995; (d)
Bhattacharyya, S. Synth. Commun. 1997, 27, 4265; (e) Ranu,
B. C.; Majee, A.; Sarkar, A. J. Org. Chem. 1998, 63, 370; (f)
Bhattacharyya, S.; Neidigh, K. A.; Avery, M. A.; Williamson,
J. C. Synlett 1999, 1781; (g) Saxena, I.; Borah, R.; Sarma,
J. C. J. Chem. Soc., Perkin Trans. 1 2000, 503.
14. Gross, T.; Seayad, A. M.; Ahmad, M.; Beller, M. Org. Lett.
2002, 4, 2055; Kadyrov, R.; Riermeier, T. H.; Dingerdissen,
U.; Tararov, V.; Boerner, A. J. Org. Chem. 2003, 68, 4067;
Imao, D.; Fujihara, S.; Yamamoto, T.; Ohta, T.; Ito, Y.
Tetrahedron 2005, 61, 6988; Chi, Y.; Zhou, Y.-U.; Zhang, X.
J. Org. Chem. 2003, 68, 4120; Tararov, V. I.; Kadyrov, R.;
Riermeier, T. H.; Boerner, A. Chem. Commun. 2000, 1867.
15. Tajbakhsh, M.; Lakowraj, M. M.; Shirini, F.; Habibzadeh, S.;
Nikdoost, A. Tetrahedron Lett. 2004, 45, 3295.
8
. Rylabder, P. N. Hydrogenation Methods; Academic: New York,
NY, 1985.
16. Mattson, R. J.; Pham, K. M.; Leuck, D. J.; Cowen, K. A. J. Org.
Chem. 1990, 55, 2552.
9
. Weis, A. L.; Bakos, T.; Alferiev, I.; Chang, X.; Chao, B.;
Kinney, W. A. Tetrahedron Lett. 1999, 40, 4863.
0. Care must be taken to control pH. For a successful reductive
17. Merla, B.; Risch, N. Synthesis 2002, 1365; Gordon, E. M.;
Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A.
J. Med. Chem. 1994, 37, 1385.
1
amination, it should bew6. Moreover, at pH 3–4 it reduces al-
dehyde and ketone to alcohol. Borch, R. F.; Bernstein, M. D.;
Durst, H. D. J. Am. Chem. Soc. 1971, 39, 2897.
18. Apodaca, R.; Xiao, W. Org. Lett. 2001, 3, 1745.
19. Heydari, A.; Tavakol, H.; Aslanzadeh, S.; Azarnia, J.; Ahmadi,
N. Synthesis 2005, 4, 627.
1
1
1. Cho, B. T.; Kang, S. K. Tetrahedron 2005, 61, 5725.
2. Kangasmetsa, J. J.; Johnson, T. Org. Lett. 2005, 7, 5653.
20. Varma, R. S.; Dahiya, R. Tetrahedron 1998, 54, 6293.
21. Cho, B. T.; Kang, S. K. Synlett 2004, 1484.