Simple Metal-Free Direct Reductive Amination Using Hydrosilatrane to Form Secondary and Tertiary Amines

Article abstract of DOI:10.1002/adsc.201700079

This work describes the use of cheap, safe, and easy-to-handle hydrosilatrane as the reductant in direct reductive amination reactions. This efficient method enables a facile, metal-free access to secondary and tertiary amines from a wide range of aldehydes and ketones, with the synthesis of tertiary amines requiring no additives at all. This reaction demonstrates excellent functional group tolerance, chemoselectivity, and scalability. (Figure presented.).

Full text of DOI:10.1002/adsc.201700079

Title: Simple Metal-Free Direct Reductive Amination Using
Hydrosilatrane to Form Secondary and Tertiary Amines
Authors: Sami Varjosaari, Vladislav Skrypai, Paolo Suating, Joseph
Hurley, Ashley DeLio, and Thomas Gilbert
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700079
Link to VoR: http://dx.doi.org/10.1002/adsc.201700079

10.1002/adsc.201700079
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Simple Metal-Free Direct Reductive Amination Using
Hydrosilatrane to Form Secondary and Tertiary Amines
Sami E. Varjosaari,+a Vladislav Skrypai,+a Paolo Suating,a Joseph J. M. Hurley,a Ashley
M. De Lio,a Thomas M. Gilbert,a and Marc J. Adlera,b*
a
Department of Chemistry & Biochemistry, Northern Illinois University, 1425 W. Lincoln Hwy., DeKalb, IL, 60115,
USA, E-mail: mjadler@niu.edu
Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4,
b
Canada, E-mail: marc.adler@uoit.ca
These authors contributed equally to this work.
+
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. This work describes the use of cheap, safe, and
easy-to-handle hydrosilatrane as the reductant in direct
reductive amination reactions. This efficient method enables
facile, metal-free access to secondary and tertiary amines
from a wide range of aldehydes and ketones, with the
synthesis of tertiary amines requiring no additives at all. This
reaction demonstrates excellent functional group tolerance,
chemoselectivity, and scalability.
Keywords: Direct reductive amination • solvent free •
green • 1-Hydrosilatrane • metal free
is effective on a large scale but tends not to tolerate
unsaturated substituents on the reactants.[9]
Introduction
The most commonly used reducing agents for DRA
[10]
are NaBH3CN[4] and NaBH(OAc)3
due to their
Due to the ubiquity of amines in important
biologically active molecules in nature, and in a wide
range of applications from pharmaceuticals to fine
chemicals, effective syntheses are of paramount
importance.[1]
wide availability, simplicity of use, chemoselectivity,
and mild reaction condition requirements. However,
NaBH3CN is toxic, forms toxic byproducts during
work-up, and tends to require large excesses of amine,
whilst NaBH(OAc)3 is not compatible with most
aromatic ketones, or with aromatic secondary
amines.[1b,10,11] Other borohydride derivatives
overcome these issues but require more complex
purification techniques.[3a,12]
Although various methods are known,[2] direct
reductive amination (DRA) is considered the most
practical method for the synthesis of amines, and
therefore is the most widely used.[3] DRA involves a
reaction between an amine and an aldehyde, or
ketone, to form an imine or iminium ion in situ,
which is then converted by a reducing agent to the
corresponding amine.[4] While several methods exist
for the formation of secondary amines,[3] there are
few studies of direct reductive aminations that form
tertiary amines due to the steric influence on
enamine/iminium ion formation at equilibrium.[5]
Additionally, DRA using secondary arylamines to
form aromatic tertiary amines has been described as
challenging,[6] and only a handful of procedures are
known.[5,7]
Organosilanes have been reported as efficient
alternatives to borohydrides for DRA, as they require
simpler purification methods due to their good
solubility in organic solvents.[12] PMHS has been the
silane of choice due to its non-toxicity, low price, and
inertness in the absence of an activator.[13] However,
PMHS and other organosilanes require activating
catalysts for reduction to occur.[11a,14] These catalysts
all have their drawbacks. For example, trifluoroacetic
acid
cannot
be
used
with
acid–labile
functionalities,[15] Bu2SnCl2, SnCl2, and BiCl3 are
toxic,[5,16] and InCl3 is expensive and a known
teratogen.[17]
For DRA, choosing a chemoselective reducing agent
is crucial: the reductant must be able to reduce the
imine or iminium ion but not the parent carbonyl
compound (or other functionalities present).[8] For
example, catalytic hydrogenation with metal catalysts
1-Hydrosilatrane 1 (Figure 1, also called silatrane)
has largely been overlooked as a reducing agent since
it was first synthesized by Frye et al. in 1961.[18] 1 has
a cage structure with a lone pair of electrons on
1
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10.1002/adsc.201700079
Advanced Synthesis & Catalysis
nitrogen oriented towards the silicon, rendering it
effectively pentacoordinate. This has the potential to
make silatrane a good reducing agent because the
increase in electron density at the hypervalent silicon
center should make the hydride more hydridic.[19]
Furthermore, the hypervalent silicon should be more
Lewis acidic and therefore more likely to further
coordinate reducible Lewis base functionalities such
as carbonyls.[20] As an air- and moisture-stable solid,
1 is easy to synthesize (cheaply) and handle.[21]
Scheme 2. Comparative effectiveness of different silanes
using optimized method. [a] Yield determined by GCMS.
[b] Isolated yields.
Table 1 demonstrates the broad applicability of this
method for the reaction of secondary amines with
aldehydes to form tertiary amines. Benzaldehyde
reacted with secondary amines to give products 4-7.
A clear pattern is seen relating the steric bulk of the
amine and the resulting isolated yield (compare 4 and
3 to 5 and 8, for example): this discrepancy is not
related to the reaction itself, but rather due to the
method of purification (acid extraction) as inspection
by GCMS prior to workup indicated quantitative
conversion. The reaction works well with both
electron rich (3, 9-11, 13-15, 19-20, 22, 24) and
electron poor (16-18, 21, 23) aromatic aldehydes.
Both aldehydes of teraphthdialdehyde were readily
aminated to give bis-tertiary amine 25.
Our previous work has shown that 1 is good reducing
[22]
[23]
agent for aldehydes
and ketones
in the
presence of a Lewis base (Figure 2), but does not
readily reduce nitro, vinyl or arylhalide functional
groups. To the best of our knowledge 1 has not
previously been considered as a reducing agent for
direct reductive aminations. We describe here our
successes in accomplishing this.
N
The α,β-unsaturated cinnamaldehyde gave high yields
of the tertiary amines 26-28 with no reduction of the
double bond observed. DRA of 1-naphthaldehyde
gave high yields of 29 and 31 with diethylamine and
pyrrolidine respectively; the relatively low isolated
yield of 30 (using dibenzylamine) was due to the low
solubility of the product complicating work up. The
reaction is not limited to aromatic aldehydes, as the
O
Si
O
O
H
1
Figure 1. 1-Hydrosilatrane
Previous work:
aliphatic
cyclohexylcarboxaldehyde
and
1
O
OH
isovaleraldehyde produced 32 and 33 in excellent
yields. Picolinaldehyde formed 34 but the isolation
was difficult due to enhanced solubility of the
product in water. Very good functional group
tolerance is observed, as reducible groups such as
nitro (18), cyano (21), olefin (26-28), and ester (28)
along with common protecting groups such as benzyl
(24) and triisopropylsilyl (35-36) remain unaffected.
With respect to the amines, high yields are obtained
with acyclic and cyclic aliphatic secondary amines, as
well as the far less nucleophilic aromatic amines.
However, the reaction was not successful with N-Boc
protected amine 12, as it does not form the required
iminium ion under our conditions.
R1 R2
R1 R2
Lewis base
R1= alkyl, aryl; R2= H, alkyl, aryl
This work:
R4 R3
N
R4
1
O
HN
R3
R1 R2
R1 R2
no additive
R1,R3 = alkyl, aryl; R2 = H, alkyl, aryl; R4 = H, alkyl
Scheme 1. 1-Hydrosilatrane as a reducing agent.
We further desired to extend this method to the
formation of secondary amines, however under neat
conditions propylamine with para-tolualdehyde only
gave the corresponding imine in quantitative yield
with no observed reduction.[24] We postulated that
protonation of the imine would allow its reduction by
1. Using acetic acid as the solvent, reductive
amination of a series of aldehydes was observed at
room temperature within 1 hour (Table 2). The
reaction works well with both electron rich (38-42)
and electron poor (44) aldehydes, as well as α,β-
unsaturated aldehydes (45) and aliphatic aldehydes
(46). O-protected amino acids can be used as an
amine source as well, as no reduction of the ester is
observed (43). Both aliphatic and aromatic amines
give excellent yields.
Results and Discussion
After optimization,[24] DRA was conducted by
combining 1, aldehyde 2, and secondary amine in a
vial, which was heated at 70°C overnight to give
corresponding amine 3 product in high yields. As can
be seen in Scheme 2, exchanging PMHS for 1 under
neat conditions gave a much lower yield of product,
while no reaction was observed when triethylsilane
was used as the reductant.
O
silane (2 equiv.),
Et2NH (1 equiv.)
N
H
70oC, 20h
3
2
silane = 1
99%[a] (84%)[b]
PMHS 48%[a] (32%)[b]
Et3SiH no reaction
2
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10.1002/adsc.201700079
Advanced Synthesis & Catalysis
Table 1. Scope of aldehydes and secondary amines for DRA to form tertiary amines[d]
O
R2
R2
1 (2 equiv.)
R1
HN
R3
N
R3
R1
H
R3
Et
R3
R3
R3
N
R4
N
N
R4
N
R4
N
R4
Et
Cl
O2N
MeO
4 R3,R4 = Et 80%[c]
5 R3,R4 = iPr 59%[c]
6 R3,R4 = Bn 62%[b]
7 R3,4 = -(CH2)4- 99%[c]
3 R3,R4 = Et 81%[c]
8 R3,R4 = iPr 60%[a]
9 R3,R4 = Bn 92%[c]
10 R3 = Me, R4 = Ph 78%[c]
11 R3,4 = -(CH2)4- 91%[c]
12 R3 = Bn, R4 = Boc n.r.[a]
13 R3,R4 = Et 88%[a]
14 R3, R4 = Bn 97%[c]
15 R3 = Me, R4 = Ph 84%[c]
16 R3,R4 = Et 95%[b]
17 R3,R4 = Bn 61%[b]
18 74%[a]
Et
N
Et
N
Et
N
MeO
Et
F
Et
N
N
Et
Et
Et
Et
Et
tBu
Ph
NC
19 92%[a]
20 84%[a]
21 84%[b]
22 62%[a]
23 83%[a]
O
O
Et
N
Et
Et
N
Et
N
N
N
N
Et
Et
Et
O
BnO
Et
24 83%[b]
25 93%[a]
26 98%[a]
27 70%[a]
28 78%[a]
iPr
N
Et
N
iPr
O
R3
R3
N
Si
iPr
N
R4
Bn
Bn
N
N
Et
R4
Bn
32 99%[a]
Bn
29 R3,R4 = Et 98%[c]
30 R3,R4 = Bn 59%[c]
31 R3,4 = -(CH2)4- 99%[c]
33 90%[c]
34 35%[a]
35 R3,R4 = Et 76%[c]
36 R3 = Me, R4 = Ph 87%[c]
[a] CHCl3 as solvent, 60°C, 2 equivalents of amine. [b] MeCN as solvent, 70°C, 1.2 equivalents of aldehyde. [c] No
solvent, 70°C, 2 equivalents of aldehyde. [d] Isolated yields, reaction ran overnight, monitored by GC until completion.
Table 2. Scope of aldehydes and primary amines for DRA
Reaction ran overnight. [d] Isolated yields, reaction time
1h unless otherwise stated.
to form secondary amines[d]
O
R2
1 (2 equiv.)
R2
Having explored the scope of tertiary and
secondary amine synthesis via aldehydes, we decided
to further study the possibility of reductive
aminations with ketones. Formation of the enamine
was observed when the reactions were attempted neat,
but was avoided when small amounts of solvent were
used, suggesting the importance of having silatrane
available in solution as the iminium is formed.
Overall, DRA involving a range of ketones and
amines was observed (Table 3).
Dimethylamine, pyrollidine and morpholine
reacted with acetophenone to form the corresponding
tertiary amines 48, 49 and 50. In contrast,
diethylamine did not react with acetophenone(47) nor
with the more active nitroacetophenone (52).
R1
H3N
N
R1
H
H
AcOH, r.t.
Pr
Bn
N
Ph
N
N
H
H
H
38 88%[a]
39 72%[b][c]
40 96%
Bn
Bn
Bn
N
N
NH
Ph
H
H
OMe
Me2N
MeO
42 99%[b][c]
O
41 93%
43 93%
Bn
Bn
N
N
H
N
H
H
F
This seemed to be due to the inability of diethylamine
to form the required iminium ion. Potentially
reducible nitro 51 and allyloxy 53 groups remained
intact indicating some functional group tolerance.
The steric effect of the bulkier isopropyl group in the
44 90%[b][c]
45 80%
46 98%
[a] In the absence of acetic acid, corresponding imine was
isolated in quantitative yield. [b] Reactions ran at 70°C. [c]
3
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10.1002/adsc.201700079
Advanced Synthesis & Catalysis
reaction forming 54 did not seem to have a great
negative effect on the yield. Both cyclic (55) and
acyclic (56) aliphatic ketones gave good yields.
yield of 58. Both cyclic and acyclic aliphatic ketones
reacted well with both benzylic (59, 60) and aromatic
amines (61).
DRA of ketones and aldehydes with ammonium
salts were unsuccesful mainly due to overalkylation.
Similar obstacles have been recently noted in
literature.[25]
Table 3. Scope of ketones and secondary amines for DRA
to form tertiary amines.[d]
R2
O
To study the chemoselectivity of the DRAs we ran
R3
R3
1 (2 equiv.)
R1
N
HN
R4
R1 R2
several
competition
reactions
with
4-
R4
acetylbenzaldehyde 62 (Scheme 3). Under neat
conditions, the aldehyde is reduced preferentially
over the ketone by both N-methyl aniline to form 63
and diethylamine to form 64 with good and very good
isolated yields. Aminoalcohol 65 was formed in one
pot through reduction of in situ generated 64 by 1.
R3
N
N
N
R4
O
47 R3,R4 = Et n.r.[a]
48 R3,R4 = Me 74%[b]
49 85%[a]
50 83%[b]
R3
N
N
R4
N
1, MeNHPh
70oC, 16h
O
O
O2N
51 R3,4 = -(CH2)4- 91%[a]
52 R3,R4 = Et n.r.[a]
53 37%[a][c]
63 66%
O
N
1, HNEt2
H
O
N
O
70oC, 16h
N
N
64 83%
62
54 68%[a]
55 75%[a]
56 80%[a]
a) 1, HNEt2
70oC, 16h
N
HO
b) tBuOK, DMF
r.t., 30 min
[a] CHCl3 as solvent, 60°C, 2 equivalents of amine. [b]
MeCN as solvent, 70°C, 1.2 equivalents of aldehyde. [c]
Unable to fully purify product. [d] Isolated yields, reaction
ran overnight, monitored by GC until completion.
.
65 76%
Scheme 3. Chemoselectivity of DRA with 1-hydrosilatrane.
To test the utility and safety of this reaction, we
performed the reaction on a multigram scale to
produce 10, as demonstrated in Scheme 4. It must be
noted that PMHS and other alkoxysilanes would not
be suitable for a scaled up reaction as volatile and
pyrophoric active species are potentially formed
during the reaction.[26] Although a stoichiometric
amount of 1-hydrosilatrane is required, it is
inexpensive to synthesize[24] and upon aqueous work-
up silatrane is hydrolysed into silicon dioxide and
triethanolamine, which are environmentally benign
and potentially recyclable waste products.
Table 4. Scope of ketones and primary amines for DRA to
form secondary amines[a]
R2
O
R1 R2
R3
1 (2 equiv.)
R3
R1
H2N
N
H
AcOH, 70oC
H
N
Bn
Ph
N
N
Bn
H
H
57 50%
58 98%
59 76%
Ph
Bn
O
N
N
H
1 (3.3g)[c]
H
N
H
HN
70oC, 32h
60 92%
61 72%
2 (2.2g)[a]
66 (1.0g)[b]
10 90%, (1.77g)
Scheme 4. Gram scale reaction using 1-hydrosilatrane
under solvent free conditions.[d] [a] 18.6 mmol (2 equiv.).
[b] 9.3 mmol (1 equiv.). [c] 18.6 mmol (2 equiv.). [d]
Isolated yield.
[a] Isolated yields, reaction ran overnight, monitored by
GC until completion.
.
Primary amines also reacted with ketones, albeit
much more slowly than with the aldehydes, requiring
higher temperatures and longer reaction times (Table
4). Acetophenone reacted with benzylamine to give
57 in modest yield whilst aniline gave a much higher
Many significant pharmaceutically relevant
compounds are alkaloids, and for this reason the
synthesis of amines is of great practical interest in
this field. To highlight this application, we applied
4
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10.1002/adsc.201700079
Advanced Synthesis & Catalysis
our described method for reductive amination using 1
in the synthesis of two 2-substituted isoindoline
derivatives of alpha-amino acids. (Scheme 5)
Compounds 68 and 69 are selective COX-2 and
COX-1 inhibitors, respectively, of which 68 has been
singled out for further study as an anti-inflammatory
agent.[27] Both compounds have also shown moderate
antiproliferative activity towards HeLa cells.[28] To
form the isoindoline structure, one aldehyde of an
ortho-dialdehyde arene would have to undergo
intermolecular reductive amination, whereupon the
other aldehyde function would have to undergo
intramolecular reductive amination. Phthaldialdehyde
67 reacted with the two corresponding amino acid
methyl esters to give the isoindoline products 68 and
69 in one step, in very good yield. (Scheme 5)
being a stable, cheap, easy to handle, and versatile
reducing agent.
Experimental Section
General Consideration
All chemicals were obtained from commercial sources and
used without further purification. Column chromatography
was performed using silica gel from Macherey-Nagel (60
M, 0.04–0.063 mm). 1H NMR, and 13C NMR were
recorded on either a 300 or 500 MHz Bruker Avance III
spectrometer. Chemical shifts were reported in ppm with
the solvent resonance as internal standard (1H NMR CDCl3
δ = 7.28, 13C NMR CDCl3 δ = 77.01). IR spectra were
acquired using an ATI Mattson FTIR spectrophotometer
on neat samples. Melting Points were obtained using a
Mel-temp capillary heating apparatus. MS data were
obtained with a Shimadzu GCMS QC2010S spectrometer
at 275°C.
R
R
H
H
1 (4 equiv.)
O
O
H2N
N
+
General procedure for synthesis of tertiary amines
from aldehydes
AcOH, r.t., 20 min
O
O
MeO
MeO
67
68 R = H 73%
69 R = OH 75%
In a 5 dram vial containing 1-hydrosilatrane (2 mmol)
was added aldehyde (1.5 mmol) and secondary amine (1
mmol). The vial was sealed and heated at 70°C overnight.
Resulting residue was dissolved in dichloromethane and
extracted with 1M HCl three times. Aqueous extract was
neutralized with 4M NaOH and extracted with
dichloromethane three times. Organic phase was dried over
anhydrous sodium sulfate and the solvent was removed
under low pressure. Resulting residue was analyzed with
no further purification unless otherwise stated. See
supporting information for characterization details.
Scheme 5. Synthesis of biologically active compounds of
interest.[a] [a] Isolated yields.
Mechanistically, the data preliminarily suggests
that iminium ion formation is required for the
reaction to proceed. Secondary amines and aldehydes
are readily reduced by 1, whilst primary amines and
aldehydes form imines without reduction. However,
in the presence of acetic acid, the imine can be
protonated to the iminium ion, and reduction occurs
to the amine. Based on our current understanding of 1
General procedure for synthesis of secondary amines
from aldehydes
To a 5 dram vial containing aldehyde (1 mmol),
primary amine (1.2 mmol) and acetic acid (1 mL) was
added 1-hydrosilatrane (2 mmol). Reaction mixture was
stirred using a magnetic stir bar for 1.5 hours upon which
the reaction was neutralized using 1M NaOH and extracted
using dichloromethane three times. Organic phase was
dried over anhydrous sodium sulfate and the solvent was
removed under low pressure. Resulting residue was
analyzed with no further purification unless otherwise
stated. See supporting information for characterization
details.
as a reducing reagent (i.e. that it requires a
nucleophilic activator to transfer the hydride),
[22,23]
a
Lewis base formed in situ may act as the activator.
Alternatively, iminiums are significantly more
electrophilic than either aldehydes of ketones,[29] so 1
may be able to reduce such reactive compounds in the
absence of an activator. Further mechanistic studies
are currently ongoing.
General procedure for synthesis of tertiary amines
from ketones
Conclusion
We have demonstrated 1 as an efficient reducing
agent in the direct reductive amination of aldehydes
and ketones to form secondary and tertiary amines.
This is a reasonably green procedure, as tertiary
amines form readily without any solvent, catalyst, or
other additives, and secondary amines form when
environmentally friendly acetic acid is used as a
solvent. Both alkyl and aryl amines give high yields.
The scope is broad with good functional group
tolerance and chemoselectivity. The method is
extremely simple, as no inert atmosphere or exclusion
of water is necessary, with the added benefit of 1
In a 5 dram vial containing 1-hydrosilatrane (2 mmol)
was added ketone (1 mmol), secondary amine (1.2 mmol)
and 0.2 mL solvent. The vial was sealed and heated at
70°C overnight. Resulting residue was dissolved in
dichloromethane and extracted with 1M HCl three times.
Aqueous extract was neutralized with 4M NaOH and
extracted with dichloromethane three times. Organic phase
was dried over anhydrous sodium sulfate and the solvent
was removed under low pressure. Resulting residue was
analyzed with no further purification unless otherwise
stated. See supporting information for characterization
details.
5
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10.1002/adsc.201700079
Advanced Synthesis & Catalysis
General procedure for synthesis of secondary amines
from ketones
[7] a) O. Lee, K. Law, C. Ho, D. Yang, J. Org. Chem.,
2008, 73, 8829–8837; (b) Z. Wang, D. Pie, Y. Zhang, C.
Wang, J. Sun, Molecules, 2012, 17, 5151–5163
To a 5 dram vial containing ketone (1 mmol), primary
amine (1.2 mmol) and acetic acid (1 mL) was added 1-
hydrosilatrane (2 mmol). Reaction mixture was stirred
using a magnetic stir bar for 2 hours upon which the
reaction was neutralized using 1M NaOH and extracted
using dichloromethane three times. Organic phase was
dried over anhydrous sodium sulfate and the solvent was
removed under low pressure. Resulting residue was
analyzed with no further purification unless otherwise
stated. See supporting information for characterization
details.
[8] M. Hayashi, T. Yoshiga, N. Oguni, Synlett, 1991, 479-
480.
[9] M. V. Lyuev, M. L. Khidekel, Russ. Chem. Rev. (Engl.
Transl.) 1980, 49, 14-27.
[10] A. F. Abdel-Magid, K. G. Carson, B. D. Haris, C. A.
Maryanoff, R. D. Shah, J. Org. Chem. 1996, 61, 3849-
3862
[11] a) K. Miura, K. Ootsuka, S. Suda, H. Nishikori, A.
Hosomi, Synlett 2001, 10, 1617-1619 b) C. F. Lane,
Synthesis 1975, 135-147. c) C. Wang, A. Pettman, J.
Basca, J. Xiao, Angew. Chem., Int. Ed. 2010, 49, 7548-
7552.
General procedure for synthesis of isoindoles
To a 5 dram vial containing amino acid methyl ester
hydrochloride (1 mmol) phthalaldehyde (1 mmol) and 1
mL of acetic acid was added 1-hydrosilatrane (2 mmol).
Resulting mixture was stirred at room temperature for 2
hours, and quenched with 1M NaOH. Resulting mixture
was extracted three times with dichloromethane, combined
organic layers were dried over anhydrase sodium sulfate
and concentrated under low pressure. Residue was than
purified using column chromatography with hexane/ethyl
acetate (4/1) to give isoindole derivative. See supporting
information for characterization details.
[12] J. J. Kangasmetsä, T. Johnson, Org. Lett. 2005, 7,
5653-5655
[13] N. J. Lawrence, M. D. Drew, S. M. Bushell, J. Chem.
Soc., Perkin Trans. 1, 1999, 3381–3391.
[14] a) S. Chandrasekhar, C. R. Reddy, M. Ahmed, Synlett
2000, 11, 1655–1657 b) T. Mizuta, S. Sakaguchi, Y.
Ishii, J. Org. Chem. 2005, 70, 2195–2199 c) J. P. Patel,
A. H. Li, H. Dong, V. L. Korlipara, M. J. Mulvihill,
Tetrahedron Lett. 2009, 50, 5975-5977 d) C. A. Smith,
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7
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FULL PAPER
Simple Metal-Free Direct Reductive Amination
Using Hydrosilatrane to Form Secondary and
Tertiary Amines
Adv. Synth. Catal. Year, Volume, Page – Page
Sami E. Varjosaari, Vladislav Skrypai, Paolo
Suating, Joseph J. M. Hurley, Ashley M. De Lio,
Thomas M. Gilbert, Marc J. Adler*
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