Organic Chemistry Portal
Reactions > Organic Synthesis Search

Categories: C-N Bond Formation > Amines > Secondary and tertiary amines, Aryl amines >

Reductive Amination

Related
Reduction of imines


Name Reactions


Eschweiler-Clarke Reaction


Recent Literature


By optimizing the metal hydride/ammonia mediated reductive amination of aldehydes and hemiacetals, primary amines were selectively prepared with no or minimal formation of the usual secondary and tertiary amine byproduct. The methodology was performed on a range of functionalized aldehyde substrates, including in situ formed aldehydes from a Vasella reaction.
E. M. Dangerfield, C. H. Plunkett, A. L. Win-Mason, B. L. Stocker, M. S. M. Timmer, J. Org. Chem., 2010, 75, 5470-5477.


A simple and convenient procedure enables the reductive alkylation of primary and secondary amines and N,N-dimethylation of amino acids using sodium borohydride as reducing agent in 2,2,2- trifluoroethanol without use of a catalyst or any other additive. The solvent can be revovered and reused.
M. Taibakhsh, R. Hosseinzadeh, H. Alinezhad, S. Ghahari, A. Heydari, S. Khaksar, Synthesis, 2011, 490-496.


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.


Reductive amination of aldehydes and ketones with the InCl3/Et3SiH/MeOH system is highly chemoselective and can be applied to various cyclic, acyclic, aromatic, and aliphatic amines. Functionalities including ester, hydroxyl, carboxylic acid, and olefin are tolerated.
O.-Y. Lee, K.-L. Law, C.-Y. Ho, D. Yang, J. Org. Chem., 2008, 73, 8829-8837.


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.


Nickel nanoparticles catalyse the reductive amination of aldehydes by transfer hydrogenation with isopropanol at 76░C.
F. Alonso, P. Riente, M. Yus, Synlett, 2008, 1289-1292.


N-heterocyclic carbene boranes (NHC-boranes) are among the most nucleophilic classes of neutral hydride donors. Reductions of highly electron-poor C=N and C=C bonds provide hydrogenation products along with new, stable borylated products. The results suggest that NHC-boranes have considerable untapped potential as neutral organic reductants.
M. Horn, H. Mayr, E. Lac˘te, E. Merling, J. Deaner, S. Well, T. McFadden, D. P. Curran, Org. Lett., 2012, 14, 82-85.


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.


Cooperative catalysis of an Ir(III)-diamine complex and a chiral phosphoric acid or its conjugate base enables a direct reductive amination of a wide range of ketones.
C. Li, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc., 2009, 131, 6967-6969.


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 direct reductive amination of ketones using the Hantzsch ester in the presence of S-benzyl isothiouronium chloride as a recoverable organocatalyst converts a wide range of ketones as well as aryl amines to the expected products in good yields.
Q. P. B. Nguyen, T. H. Kim, Synthesis, 2012, 44, 1977-1982.


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.


An experimentally simple Microwave-assisted reductive alkylation of methyl carbamate with a range of aldehydes provides, after basic work-up, structurally diverse primary amines. This method is particularly amenable to high-throughput synthesis.
F. Lehmann, M. Scobie, Synthesis, 2008, 1679-1681.


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 Br°nsted 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.