{{Short description|Conversion of a carbonyl to an amine}} {{Use dmy dates|date=April 2023}} {{Reactionbox | Name = Reductive amination | Type = Coupling reaction | Section3 = {{Reactionbox Identifiers | RSC_ontology_id = 0000335 }} }} '''Reductive amination''' (also known as '''reductive alkylation''') is a form of amination that converts a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is a common method to make amines and is widely used in green chemistry since it can be done catalytically in one-pot under mild conditions. In biochemistry, dehydrogenase enzymes use reductive amination to produce the amino acid glutamate. Additionally, there is ongoing research on alternative synthesis mechanisms with various metal catalysts which allow the reaction to be less energy taxing, and require milder reaction conditions. Investigation into biocatalysts, such as imine reductases, have allowed for higher selectivity in the reduction of chiral amines which is an important factor in pharmaceutical synthesis.<ref name="Thorpe-2022">{{Cite journal |last1=Thorpe |first1=Thomas W. |last2=Marshall |first2=James R. |last3=Harawa |first3=Vanessa |last4=Ruscoe |first4=Rebecca E. |last5=Cuetos |first5=Anibal |last6=Finnigan |first6=James D. |last7=Angelastro |first7=Antonio |last8=Heath |first8=Rachel S. |last9=Parmeggiani |first9=Fabio |last10=Charnock |first10=Simon J. |last11=Howard |first11=Roger M. |last12=Kumar |first12=Rajesh |last13=Daniels |first13=David S. B. |last14=Grogan |first14=Gideon |last15=Turner |first15=Nicholas J. |date=2022-04-07 |title=Multifunctional biocatalyst for conjugate reduction and reductive amination |url=https://www.nature.com/articles/s41586-022-04458-x |journal=Nature |language=en |volume=604 |issue=7904 |pages=86–91 |doi=10.1038/s41586-022-04458-x |pmid=35388195 |bibcode=2022Natur.604...86T |hdl=11311/1232494 |s2cid=248001189 |issn=0028-0836|hdl-access=free }}</ref> 700px|center|frameless
==Reaction process== Reductive amination occurs between a carbonyl such as an aldehyde or ketone and an amine in the presence of a reducing agent.<ref name="Abdel-Magid-1996">{{Cite journal |last1=Abdel-Magid |first1=Ahmed F. |last2=Carson |first2=Kenneth G. |last3=Harris |first3=Bruce D. |last4=Maryanoff |first4=Cynthia A. |last5=Shah |first5=Rekha D. |date=1996-01-01 |title=Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures 1 |url=https://pubs.acs.org/doi/10.1021/jo960057x |journal=The Journal of Organic Chemistry |language=en |volume=61 |issue=11 |pages=3849–3862 |doi=10.1021/jo960057x |pmid=11667239 |issn=0022-3263|url-access=subscription }}</ref> The reaction conditions are neutral or weakly acidic.<ref name="Abdel-Magid-1996" /> thumb|393x393px|The intermediates of a reductive amination reaction.
=== Reaction steps ===
# The nucleophilic amine reacts at the carbon of the carbonyl group to form a hemiaminal species # reversible loss of one molecule of water from the hemiaminal species by alkylimino-de-oxo-bisubstitution to form the imine intermediate.<ref name="Tripathi-2008">{{Cite journal |last1=Tripathi |first1=Rama P. |last2=Verma |first2=Shyam S. |last3=Pandey |first3=Jyoti |last4=Tiwari |first4=Vinod K. |date=2008 |title=Recent Development on Catalytic Reductive Amination and Applications |url=https://www.eurekaselect.com/article/12528 |journal=Current Organic Chemistry |language=en |volume=12 |issue=13 |pages=1093–1115 |doi=10.2174/138527208785740283|url-access=subscription }}</ref> The equilibrium between aldehyde/ketone and imine is shifted toward imine formation by dehydration.<ref name="Abdel-Magid-1996" /> # The intermediate imine can be isolated or reacted in-situ with a suitable reducing agent (e.g., sodium borohydride) to produce the amine product.<ref name="Abdel-Magid-1996" /> Intramolecular reductive amination can also occur to afford a cyclic amine product if the amine and carbonyl are on the same molecule of starting material.<ref>{{Cite journal |last1=Sawant |first1=Rajiv T. |last2=Waghmode |first2=Suresh B. |date=2010-03-13 |title=Intramolecular reductive amination strategy to the synthesis of (R)-N-Boc-2-hydroxymethylmorpholine, N-(3,4-dichlorobenzyl)(R)-2-hydroxymethylmorpholine, and (R)-2-benzylmorpholine |url=https://www.sciencedirect.com/science/article/pii/S0040402010000797 |journal=Tetrahedron |volume=66 |issue=11 |pages=2010–2014 |doi=10.1016/j.tet.2010.01.047 |issn=0040-4020|url-access=subscription }}</ref>
There are two ways to conduct a reductive amination reaction: direct and indirect.<ref name="Abdel-Magid-1996" />
=== Direct reductive amination === In a direct reaction, the carbonyl and amine starting materials and the reducing agent are combined and the reductions are done sequentially.<ref name="Abdel-Magid-1996" /> These are often one-pot reactions since the imine intermediate is not isolated before the final reduction to the product.<ref name="Abdel-Magid-1996" /> Instead, as the reaction proceeds, the imine becomes favoured for reduction over the carbonyl starting material.<ref name="Abdel-Magid-1996" /> The two most common methods for direct reductive amination are hydrogenation with catalytic platinum, palladium, or nickel catalysts and the use of hydride reducing agents like cyanoborohydride (NaBH<sub>3</sub>CN).<ref name="Abdel-Magid-1996" />
=== Indirect reductive amination === Indirect reductive amination, also called a stepwise reduction, isolates the imine intermediate.<ref name="Abdel-Magid-1996" /> In a separate step, the isolated imine intermediate is reduced to form the amine product.<ref name="Abdel-Magid-1996" />
== Designing a reductive amination reaction == There are many considerations to be made when designing a reductive amination reaction.<ref name="Wang-2013">{{Citation |last1=Wang |first1=Chao |title=Asymmetric Reductive Amination |date=2013 |url=https://link.springer.com/10.1007/128_2013_484 |work=Stereoselective Formation of Amines |volume=343 |pages=261–282 |editor-last=Li |editor-first=Wei |access-date=2023-11-06 |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |language=en |doi=10.1007/128_2013_484 |isbn=978-3-642-53928-2 |last2=Xiao |first2=Jianliang |pmid=24158548 |editor2-last=Zhang |editor2-first=Xumu|url-access=subscription }}</ref>
# Chemoselectivity issues may arise since the carbonyl group can also be reduced. # The reaction between the carbonyl and amine are in equilibrium, favouring the carbonyl unless water is removed from the system. # reduction-sensitive intermediates may form in the reaction which can affect chemoselectivity. # The amine substrate, imine intermediate, or amine product might deactivate the catalyst. # Acyclic imines have E/Z isomers. This makes it difficult to create enantiopure chiral compounds through stereoselective reductions.
To solve the last issue, asymmetric reductive amination reactions can be used to synthesize an enantiopure product of chiral amines.<ref name="Wang-2013" /> In asymmetric reductive amination, a carbonyl that can be converted from achiral to chiral is used.<ref name="Reshi-2021">{{Cite journal |last1=Reshi |first1=Noor U Din |last2=Saptal |first2=Vitthal B. |last3=Beller |first3=Matthias |last4=Bera |first4=Jitendra K. |date=2021-11-19 |title=Recent Progress in Transition-Metal-Catalyzed Asymmetric Reductive Amination |url=https://pubs.acs.org/doi/10.1021/acscatal.1c04208 |journal=ACS Catalysis |language=en |volume=11 |issue=22 |pages=13809–13837 |doi=10.1021/acscatal.1c04208 |s2cid=240250685 |issn=2155-5435|url-access=subscription }}</ref> The carbonyl undergoes condensation with an amine in the presence of H<sub>2</sub> and a chiral catalyst to form the imine intermediate, which is then reduced to form the amine.<ref name="Reshi-2021" /> However, this method is still limiting to synthesize primary amines which are non-selective and prone to overalkylation.<ref name="Reshi-2021" />
== Common reducing agents ==
=== Sodium borohydride === Sodium borohydride (NaBH<sub>4)</sub> reduces both imines and carbonyl groups.<ref name="Tripathi-2008" /> However, it is not very selective and can reduce other reducible functional groups present in the reaction.<ref name="Tripathi-2008" /> To ensure that this does not occur, reagents with weak electrophilic carbonyl groups, poor nucleophilic amines and sterically hindered reactive centres should not be used, as these properties do not favour the reduction of the carbonyl to form an imine and increases the chance that other functional groups will be reduced instead.<ref name="Tripathi-2008" />
=== Sodium cyanoborohydride === Sodium cyanoborohydride (NaBH<sub>3</sub>CN) is soluble in hydroxylic solvents, stable in acidic solutions, and has different selectivities depending on the pH.<ref name="Abdel-Magid-1996" /> At low pH values, it efficiently reduces aldehydes and ketones.<ref name="Borch-1969">{{Cite journal |last1=Borch |first1=Richard F. |last2=Durst |first2=H. Dupont |date=July 1969 |title=Lithium cyanohydridoborate, a versatile new reagent |url=https://pubs.acs.org/doi/abs/10.1021/ja01042a078 |journal=Journal of the American Chemical Society |language=en |volume=91 |issue=14 |pages=3996–3997 |doi=10.1021/ja01042a078 |bibcode=1969JAChS..91.3996B |issn=0002-7863|url-access=subscription }}</ref> As the pH increases, the reduction rate slows and instead, the imine intermediate becomes preferential for reduction.<ref name="Borch-1969" /> For this reason, NaBH<sub>3</sub>CN is an ideal reducing agent for one-pot direct reductive amination reactions that don't isolate the intermediate imine.<ref name="Abdel-Magid-1996" />
When used as a reducing agent, NaBH<sub>3</sub>CN can release toxic by-products like HCN and NaCN during work up.<ref name="Abdel-Magid-1996" />
=== Sodium triacetoxyborohydride === Sodium triacetoxyborohydride (STAB, NaBH(OAc)<sub>3</sub>) is a common reducing agent for reductive aminations. STAB selectively reduces the imine intermediate formed through dehydration of the molecule.<ref>{{Cite journal |last1=Abdel-Magid |first1=Ahmed F. |last2=Carson |first2=Kenneth G. |last3=Harris |first3=Bruce D. |last4=Maryanoff |first4=Cynthia A. |last5=Shah |first5=Rekha D. |date=1996-01-01 |title=Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures1 |url=https://pubs.acs.org/doi/10.1021/jo960057x |journal=The Journal of Organic Chemistry |volume=61 |issue=11 |pages=3849–3862 |doi=10.1021/jo960057x |issn=0022-3263|url-access=subscription }}</ref> STAB is a weaker reductant than NaBH<sub>4</sub>, and can preferentially reduce the imine group in the presence of other reduction-sensitive functional groups. While STAB has also been reported as a selective reducing agent for aldehydes in the presence of keto groups, standard reductive amination reaction conditions greatly favour imine reduction to form an amine.<ref>{{Cite journal |last1=Abdel-Magid |first1=Ahmed F. |last2=Mehrman |first2=Steven J. |date=2006-09-01 |title=A Review on the Use of Sodium Triacetoxyborohydride in the Reductive Amination of Ketones and Aldehydes |url=https://pubs.acs.org/doi/10.1021/op0601013 |journal=Organic Process Research & Development |volume=10 |issue=5 |pages=971–1031 |doi=10.1021/op0601013 |issn=1083-6160|url-access=subscription }}</ref><ref>{{Cite journal |last1=Oliphant |first1=Shannon J. |last2=Morris |first2=Robert H. |date=2022-08-30 |title=Density Functional Theory Study on the Selective Reductive Amination of Aldehydes and Ketones over Their Reductions to Alcohols Using Sodium Triacetoxyborohydride |url=https://pubs.acs.org/doi/10.1021/acsomega.2c04056 |journal=ACS Omega |volume=7 |issue=34 |pages=30554–30564 |doi=10.1021/acsomega.2c04056 |doi-access=free|pmid=36061668 |pmc=9434773 }}</ref>
{| class="wikitable" |+Physical and Chemical Characteristics of Common Reducing Agents<ref>{{Cite journal |last1=Podyacheva |first1=Evgeniya |last2=Afanasyev |first2=Oleg I. |last3=Tsygankov |first3=Alexey A. |last4=Makarova |first4=Maria |last5=Chusov |first5=Denis |date=July 2019 |title=Hitchhiker's Guide to Reductive Amination |url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-0037-1611788 |journal=Synthesis |language=en |volume=51 |issue=13 |pages=2667–2677 |doi=10.1055/s-0037-1611788 |issn=0039-7881|url-access=subscription }}</ref> | |'''H<sub>2</sub>/Pd''' |'''NaBH<sub>4</sub>''' |'''NaBH(OAc) <sub>3</sub>''' |'''NaBH<sub>3</sub>CN''' |'''CO/Rh''' |- |'''Selectivity''' |Low |Low |High |High |High |- |'''Atom economy''' |High |Solid wastes |Solid wastes |Solid wastes |High |- |'''Work up''' |Required |Not required |Not required |Not required |Required |- |'''Flammability''' |High |Low |High |High |High |- |'''Sensitivity to H<sub>2</sub>O, O<sub>2</sub>''' |Low |High |High |High |Low |- |'''Toxicity''' |None |High, Carcinogen |Low |High |High |}
== Variations and related reactions == The reductive amination reaction is related to the Eschweiler–Clarke reaction, in which amines are methylated to tertiary amines, the Leuckart–Wallach reaction,<ref>{{cite book|author1=George, Frederick |author2=Saunders, Bernard |name-list-style=amp |title=Practical Organic Chemistry, 4th Ed.|year=1960|publisher=Longman|location=London|isbn=9780582444072|page=223|url=https://www.scribd.com/doc/46973684/Practical-Organic-Chemistry-Frederick-George-Mann}}</ref> and other amine alkylation methods such as the Mannich reaction and Petasis reaction.
A classic named reaction is the '''Mignonac reaction''' (1921)<ref>{{cite journal |first1=Georges |last1=Mignonac |title=Nouvelle méthode générale de préparation des amines à partir des aldéhydes ou des cétones |language=French |trans-title=New general method for preparation of amines from aldehydes or ketones | journal = Comptes rendus | volume=172 | page=223 | year=1921 |url=https://gallica.bnf.fr/ark:/12148/bpt6k3125x/f37.chemindefer}}</ref> involving reaction of a ketone with ammonia over a nickel catalyst. An example of this reaction is the synthesis of 1-phenylethylamine from acetophenone:<ref>{{OrgSynth | title = α-Phenylethylamine |first1=John C. |last1=Robinson |first2=H. R. |last2=Snyder | collvol = 3 | collvolpages = 717 | year = 1955 | prep = cv3p0717 |doi=10.1002/0471264180.os023.27}}</ref> :center|Reductive amination acetophenone ammonia Additionally, many systems catalyze reductive aminations with hydrogenation catalysts.<ref name="Huang-2023">{{Cite journal |last1=Huang |first1=Hao |last2=Wei |first2=Yuejun |last3=Cheng |first3=Yuran |last4=Xiao |first4=Shuwen |last5=Chen |first5=Mingchih |last6=Wei |first6=Zuojun |date=7 October 2023 |title=The Acquisition of Primary Amines from Alcohols through Reductive Amination over Heterogeneous Catalysts |journal=Catalysts |language=en |volume=13 |issue=10 |pages=1350 |doi=10.3390/catal13101350 |issn=2073-4344 |doi-access=free }}</ref> Generally, catalysis is preferred to stoichiometric reactions as they may improve reaction efficiency and atom economy, and produce less waste.<ref name="Ouyang-2023">{{Cite journal |last1=Ouyang |first1=Lu |last2=Miao |first2=Rui |last3=Yang |first3=Zhanhui |last4=Luo |first4=Renshi |date=2023-02-01 |title=Iridium-catalyzed reductive amination of carboxylic acids |url=https://www.sciencedirect.com/science/article/pii/S0021951723000349 |journal=Journal of Catalysis |volume=418 |pages=283–289 |doi=10.1016/j.jcat.2023.01.030 |issn=0021-9517|url-access=subscription }}</ref> These reactions can utilize homogeneous or heterogeneous catalyst systems.<ref name="Huang-2023" /> These systems provide alternative synthesis routes which are efficient, require fewer volatile reagents and are redox-economical.<ref name="Huang-2023" /><ref>{{Cite journal |last1=Burns |first1=Noah Z. |last2=Baran |first2=Phil S. |last3=Hoffmann |first3=Reinhard W. |date=2009-04-06 |title=Redox Economy in Organic Synthesis |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.200806086 |journal=Angewandte Chemie International Edition |language=en |volume=48 |issue=16 |pages=2854–2867 |doi=10.1002/anie.200806086 |pmid=19294720 |issn=1433-7851|url-access=subscription }}</ref> As well, this method can be used in the reduction of alcohols, along with aldehydes and ketones to form the amine product.<ref name="Huang-2023" /> One example of a heterogeneous catalytic system is the Ni-catalyzed reductive amination of alcohols.<ref name="Huang-2023" /><ref>{{cite journal |last1=Kalbasi |first1=Roozbeh Javad |last2=Mazaheri |first2=Omid |year=2015 |title=Synthesis and characterization of hierarchical ZSM-5 zeolite containing Ni nanoparticles for one-pot reductive amination of aldehydes with nitroarenes |url=https://zenodo.org/record/6616124 |journal=Catalysis Communications |volume=69 |pages=86–91 |doi=10.1016/j.catcom.2015.05.016 |doi-access=free}}</ref> Nickel is commonly used as a catalyst for reductive amination because of its abundance and relatively good catalytic activity.<ref name="Huang-2023" /><ref>{{Cite journal |last1=Chernyshev |first1=Victor M. |last2=Ananikov |first2=Valentine P. |date=2022-01-21 |title=Nickel and Palladium Catalysis: Stronger Demand than Ever |url=https://pubs.acs.org/doi/10.1021/acscatal.1c04705 |journal=ACS Catalysis |language=en |volume=12 |issue=2 |pages=1180–1200 |doi=10.1021/acscatal.1c04705 |issn=2155-5435 |s2cid=245795966|url-access=subscription }}</ref> alt=Figure of a reaction scheme of Ni-catalyzed reductive amination: First, the nickel metal dehydrogenates the alcohol to form a ketone and Ni-H complex. Then, the ketone reacts with ammonia to form an imine. Finally, the imine reacts with Ni-H to regenerate catalyst and form primary amine.|center|frameless|485x485px|First, the nickel metal dehydrogenates the alcohol to form a ketone and Ni-H complex. Then, the ketone reacts with ammonia to form an imine. Finally, the imine reacts with Ni-H to regenerate catalyst and form primary amine. An example of a homogeneous catalytic system is the reductive amination of ketones done with an iridium catalyst.<ref>{{Cite journal |last1=Tanaka |first1=Kouichi |last2=Miki |first2=Takashi |last3=Murata |first3=Kunihiko |last4=Yamaguchi |first4=Ayumi |last5=Kayaki |first5=Yoshihito |last6=Kuwata |first6=Shigeki |last7=Ikariya |first7=Takao |last8=Watanabe |first8=Masahito |date=2019-09-06 |title=Reductive Amination of Ketonic Compounds Catalyzed by Cp*Ir(III) Complexes Bearing a Picolinamidato Ligand |url=https://pubs.acs.org/doi/10.1021/acs.joc.9b01565 |journal=The Journal of Organic Chemistry |language=en |volume=84 |issue=17 |pages=10962–10977 |doi=10.1021/acs.joc.9b01565 |pmid=31362498 |s2cid=199000460 |issn=0022-3263|url-access=subscription }}</ref> Homogenous Iridium (III) catalysts have been shown to be effective in the reductive amination of carboxylic acids, which in the past has been more difficult than aldehydes and ketones.<ref name="Ouyang-2023" /> Homogeneous catalysts are often favored because they are more environmentally and economically friendly compared to most heterogeneous systems.<ref name="Huang-2023" /> center|frameless|520x520px|Ketone reacting with ammonium formate, catalyzed by iridium catalyst, to form primary amine. In industry, tertiary amines such as triethylamine and diisopropylethylamine are formed directly from ketones with a gaseous mixture of ammonia and hydrogen and a suitable catalyst.
== In green chemistry == Reductive amination is commonly used over other methods for introducing amines to alkyl substrates, such as S<small>N</small>2-type reactions with halides, since it can be done in mild conditions and has high selectivity for nitrogen-containing compounds.<ref name="Van Praet-2022">{{Cite journal |last1=Van Praet |first1=Sofie |last2=Preegel |first2=Gert |last3=Rammal |first3=Fatima |last4=Sels |first4=Bert F. |date=2022-05-12 |title=One-Pot Consecutive Reductive Amination Synthesis of Pharmaceuticals: From Biobased Glycolaldehyde to Hydroxychloroquine |url=http://dx.doi.org/10.1021/acssuschemeng.2c00570 |journal=ACS Sustainable Chemistry & Engineering |volume=10 |issue=20 |pages=6503–6508 |doi=10.1021/acssuschemeng.2c00570 |s2cid=248767494 |issn=2168-0485|url-access=subscription }}</ref><ref>{{Cite journal |last1=He |first1=Jian |last2=Chen |first2=Lulu |last3=Liu |first3=Shima |last4=Song |first4=Ke |last5=Yang |first5=Song |last6=Riisager |first6=Anders |date=2020 |title=Sustainable access to renewable ''N''-containing chemicals from reductive amination of biomass-derived platform compounds |url=http://dx.doi.org/10.1039/d0gc01869d |journal=Green Chemistry |volume=22 |issue=20 |pages=6714–6747 |doi=10.1039/d0gc01869d |s2cid=225001665 |issn=1463-9262}}</ref> Reductive amination can occur sequentially in one-pot reactions, which eliminates the need for intermediate purifications and reduces waste.<ref name="Van Praet-2022" /> Some multistep synthetic pathways have been reduced to one step through one-pot reductive amination.<ref name="Van Praet-2022" /> This makes it a highly appealing method to produce amines in green chemistry.
== Biochemistry == In biochemistry, dehydrogenase enzymes can catalyze the reductive amination of α-keto acids and ammonia to yield α-amino acids. Reductive amination is predominantly used for the synthesis of the amino acid glutamate starting from α-ketoglutarate, while biochemistry largely relies on transamination to introduce nitrogen in the other amino acids.<ref>Metzler, D. E. "Biochemistry—The Chemical Reactions of Living Cells, Vol. 2" 2nd Ed. Academic Press: San Diego, 2003.</ref> The use of enzymes as a catalyst is advantageous because the enzyme active sites are often stereospecific and have the ability to selectively synthesize a certain enantiomer.<ref name="Wohlgemuth-2022">{{Cite journal |last1=Wohlgemuth |first1=Roland |last2=Littlechild |first2=Jennifer |date=2022-07-22 |title=Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis |journal=Frontiers in Bioengineering and Biotechnology |volume=10 |doi=10.3389/fbioe.2022.958606 |issn=2296-4185 |doi-access=free |hdl=10871/130495 |hdl-access=free |pmc=9355135 }}</ref> This is useful in the pharmaceutical industry, particularly for drug-development, because enantiomer pairs can have different reactivities in the body.<ref name="Thorpe-2022" /><ref>{{Cite journal |last1=Brooks |first1=W. H. |last2=Guida |first2=W. C. |last3=Daniel |first3=K. G. |title=The Significance of Chirality in Drug Design and Development |url=https://www.eurekaselect.com/article/31944 |journal=Current Topics in Medicinal Chemistry |date=2011 |language=en |volume=11 |issue=7 |pages=760–770 |doi=10.2174/156802611795165098 |pmc=5765859 |pmid=21291399}}</ref> Additionally, enzyme biocatalysts are often quite selective in reactivity so they can be used in the presence of other functional groups, without the use of protecting groups.<ref name="Wohlgemuth-2022" /><ref name="Wu-2022">{{Cite journal |last1=Wu |first1=Kai |last2=Huang |first2=Junhai |last3=Shao |first3=Lei |date=2022-11-22 |title=Imine Reductases: Multifunctional Biocatalysts with Varying Active Sites and Catalytic Mechanisms |url=https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cctc.202200921 |journal=ChemCatChem |language=en |volume=14 |issue=22 |doi=10.1002/cctc.202200921 |s2cid=252271457 |issn=1867-3880|url-access=subscription }}</ref> For instance a class of enzymes called imine reductases, IREDs, can be used to catalyze direct asymmetric reductive amination to form chiral amines.<ref name="Thorpe-2022" /><ref name="Wu-2022" />
==In popular culture== In the critically acclaimed drama ''Breaking Bad'', main character Walter White uses the reductive amination reaction to produce his high purity methamphetamine, relying on phenyl-2-propanone and methylamine.
==See also== * Forster–Decker method * Leuckart reaction
==References== {{Reflist}}
== External links == * [https://www.organic-chemistry.org/synthesis/C1N/amines/reductiveamination.shtm Current methods for reductive amination]
Category:Organic redox reactions