Categories: C-N Bond Formation > Amines > Secondary and tertiary amines, Aryl amines >
Reductive Amination
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 Reduction of imines |
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Recent Literature
Sodium triacetoxyborohydride is a general, mild, and selective reducing agent
for the reductive amination of various aldehydes and ketones. 1,2-Dichloroethane
(DCE) is the preferred reaction solvent, but reactions can also be carried out
in tetrahydrofuran and occasionally in acetonitrile. Acetic acid may be used as
catalyst with ketone reactions. Acid sensitive functional groups
such as acetals and ketals, and reducible functional groups such as C-C multiple
bonds and cyano and nitro groups are tolerated.
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C.
A. Maryanoff, R. D. Shah, J. Org. Chem., 1996, 61,
3849-3862.
In the reductive amination of some aldehydes with primary amines where dialkylation is a problem, a stepwise procedure involving imine formation in MeOH followed by reduction with
NaBH4 was developed.
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C.
A. Maryanoff, R. D. Shah, J. Org. Chem., 1996, 61,
3849-3862.
Aldehydes and ketones were easily converted to the corresponding amines by
the reaction of amines in methanol using decaborane (B10H14)
at room temperature under nitrogen. The reaction is simple and efficient.
J. W. Bae, S. H. Lee, Y. J. Cho, C. M. Yoon, J. Chem. Soc., Perkin Trans. 1, 2000, 145-146.
A simple and convenient procedure allows the reductive amination of aldehydes
and ketones using sodium borohydride as reducing agent and boric acid, p-toluenesulfonic
acid monohydrate or benzoic acid as activator under solvent-free conditions.
B. T. Cho, S. K. Kang, Tetrahedron, 2005,
61, 5725-5734.
An effective reductive alkylation of electron-deficient o-chloroarylamines
was developed. The derived N-alkylated o-chloroarylamines were
elaborated to N-alkylazaindoles and N-alkylindoles via a novel
one-pot process comprising copper-free Sonogashira alkynylation and a
base-mediated indolization reaction.
M. McLaughlin, M. Palucki, I. W. Davies, Org. Lett.,
2006,
8, 3307-3310.
An efficient methodology for the reductive alkylation of secondary amines with
aldehydes and Et3SiH using an iridium complex as a catalyst has been developed. In addition, a cheaper, easy-to-handle, and
environmentally friendly reducing reagent such as polymethylhydrosiloxane (PMHS)
in place of Et3SiH was also useful.
T. Mizuta, S. Sakaguchi, Y. Ishii, J. Org. Chem., 2005,
70, 2195-2199.
α-Imino esters derived from aryl and alkyl keto esters could be reduced
to the corresponding α-amino esters in excellent yields and in high enantiomeric
excesses using 5 mol-% of a chiral phosphoric acid as catalyst, Hantzsch ester
as hydride donor, and toluene as solvent.
G. Li, Y. Liang, J. C. Antilla, J. Am. Chem. Soc., 2007,
129, 5830-5831.
A biomimetic direct reductive amination of ketones relies on selective imine
activation by hydrogen bond formation with thiourea as hydrogen bond donor
and utilizes the Hantzsch ester for transfer hydrogenation. The method
allows the efficient synthesis of structurally diverse amines.
D. Menche, J. Hassfeld, J. Li, G. Menche, A. Ritter, S. Rudolph, Org. Lett.,
2006,
8, 741-744.
A hydrogen-bond-catalyzed, acid- and metal-free direct reductive amination of aldehydes uses thiourea as organocatalyst and the
Hantzsch ester for transfer-hydrogenation. This methods allows for the high-yielding
synthesis of diverse amines.
D. Menche, F. Arikan, Synlett,
2006, 841-844.
A selective and direct access to secondary amines by reductive
mono-N-alkylation of primary amines with carbonyl compounds in the presence
of Ti(i-PrO)4 and NaBH4 gave exclusively
secondary amines.
H. J. Kumpaty, S. Bhattacharyya, E. W. Rehr, A. M. Gonzalez, Synthesis,
2003, 2206-2210.
Treatment of ketones with
ammonia in ethanol and titanium(IV) isopropoxide, followed by in situ reduction
with sodium borohydride allows a highly chemoselective reductive
mono-alkylation of ammonia. A simple workup afforded primary amines in good to
excellent yields. Reductive alkylation of ammonia with aldehydes afforded the corresponding symmetrical secondary amines selectively.
B. Miriyala, S.
Bhattacharyya, J. S. Williamson, Tetrahedron, 2004, 60,
1463-1471.
A mild and efficient one-pot
reductive amination of aldehydes and ketones with amines using α-picoline-borane
as a reducing agent in the presence of small amounts of AcOH is described.
The reaction has been carried out in MeOH, in H2O, and in neat
conditions. This is the first successful reductive amination in water and
in neat conditions.
S. Sato, T. Sakamoto, E. Miyazawa, Y. Kikugawa, Tetrahedron,
2004, 60, 7899-7906.
N-Alkylaminobenzenes
were prepared in a simple and efficient one-pot synthesis by reduction of
nitrobenzenes followed by reductive amination with decaborane (B10H14)
in the presence of 10% Pd/C.
J. W. Bae, Y. J. Cho,
S. H. Lee, C.-O. M. Yoon, C. M. Yoon, Chem. Commun., 2000,
1857-1858.
J. W. Bae, Y. J. Cho,
S. H. Lee, C.-O. M. Yoon, C. M. Yoon, Chem. Commun., 2000,
1857-1858.
An efficient, directed reductive amination of β-hydroxy-ketones allows the
stereoselective preparation of 1,3-syn-amino alcohols using Ti(iOPr)4
for coordination of the intermediate imino alcohol and PMHS as the reducing
agent.
D. Menche, F. Arikan, J. Li, S. Rudolph, Org. Lett., 2007,
9, 267-270.
An achiral amine in combination with a catalytic amount of a chiral Brønsted
acid can accomplish an aldol addition-dehydration-conjugate reduction-reductive
amination with 2,6-diketones to provide cyclohexylamines as potential
intermediates of pharmaceutically active compounds in good yields and excellent
enantioselectivities.
J. Zhou, B. List, J. Am. Chem. Soc., 2007,
129, 7498-7499.
A one-pot, tandem reductive amination-transamidation-cyclization reaction
produces substituted piperazin-2-ones in good yields.
D. C. Beshore, C. J. Dinsmore, Org. Lett., 2002, 4,
1201-1204.
