Transfer hydrogenation
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'''Transfer hydrogenation''' is the addition of [[hydrogen]] (H<sub>2</sub>; dihydrogen in [[inorganic chemistry|inorganic]] and [[organometallic chemistry|organometallic]] chemistry) to a [[molecule]] from a source other than gaseous H<sub>2</sub>. It is applied in industry and in [[organic synthesis]], in part because of the inconvenience and expense of using gaseous H<sub>2</sub>. One large scale application of transfer hydrogenation is [[coal liquifaction]] using "donor solvents" such as [[tetralin]].<ref>Speight, J. G. "The Chemistry and Technology of Coal" Marcel Dekker; New York, 1983; p. 226 ff. ISBN 0-8247-1915-8.</ref> <ref>K. Muniz "Bifunctional Metal-Ligand Catalysis: Hydrogenations and New Reactions within the Metal-(Di)amine Scaffold" Angew Chemie, International Edition, 2005, volume 44, 6622 - 6627.</ref>
In the area of [[organic synthesis]], a useful family of hydrogen-transfer catalysts have been developed based on [[ruthenium]] and [[rhodium]] [[diamine]] and [[phosphine]] complexes.<ref>T. Ikariya, K. Murata, R. Noyori "Bifunctional Transition Metal-Based Molecular Catalysts for Asymmetric Syntheses" Org. Biomol. Chem., 2006, volume 4, 393-406.</ref> These [[catalysts]] are mainly employed for the [[organic reduction]] of [[ketones]] and [[imines]] to [[alcohols]] and [[amines]], respectively. The hydrogen-donor (transfer agent) is typically [[isopropanol]], which coverts to [[acetone]] upon donation of hydrogen. Transfer hydrogenations can proceed with high [[enantioselectivity|enantioselectivities]] when the starting material is [[chiral]]:
:RR'C=O + Me<sub>2</sub>CHOH → RR'C*H-OH + Me<sub>2</sub>C=O
where RR'C*H-OH is a chiral product. A typical catalyst is ([[arene]])Ru(''R,R''-HNCHPhCHPhNTs), where Ts = SO<sub>2</sub>C<sub>6</sub>H<sub>4</sub>Me and ''R,R'' refers to the [[absolute configuration]] of the two chiral carbon centers. This work was recognized with the 2001 Nobel Prize in Chemistry to [[Ryoji Noyori]]. Another family of hydrogen-transfer agents are those based on aluminium alkoxides, such as [[Aluminium isopropoxide]].
==Proton donors==
A historically prominent transfer hydrogenation agent is [[diimide]], which becomes oxidized to N<sub>2</sub>. Half of the hydrogen in the [[hydrazine]] is transferred to the substrate.
[[Image:Transfer1.png|center|300px|Transfer hydrogenation]]
The reaction produces the very stable molecule N<sub>2</sub> molecule. Another similar example of the use of transfer hydrogenation where the product is an [[alkane]] is when the hydrogen supplier is [[cyclohexene]] or [[cyclohexadiene]]. In this case an alkane is formed along with the formation of [[benzene]]. The driving force of the reaction being the gain of aromatic stabilization energy when benzene is formed. Pd can be used as a catalyst and a temperature of 100 °C is employed. One limitation of using transfer hydrogenation for the production of alkane is that it cannot be used to prepare methane as no unsaturated hydrocarbon contain only one carbon. More exotic transfer hydrogenations have been reported, including this intramolecular one:
[[Image:Transfer2.png|center|400px|Transfer hydrogenation]]
Many reactions exist with as proton donor a simple alcohol. Examples are the sodium metal mediated [[Birch reduction]] (arenes) and the [[Bouveault-Blanc reduction]] (esters). [[Magnesium]]-[[methanol]] is another combination and used in alkene reductions for instance in this one en route to [[asenapine]] <ref>''Debottlenecking the Synthesis Route of Asenapine'' Marco van der Linden, Theo Roeters, Ramon Harting, Edwin Stokkingreef, Arjan Sollewijn Gelpke, and Gerjan Kemperman Organic Process Research & Development '''2008''' {{DOI|10.1021/op700240c}} </ref>:
[[Image:AsenapineSynthreductionStep.svg|600px|center|Magnesium methanol reduction in asenapine synthesis]]
==Organocatalytic transfer hydrogenation==
[[Organocatalytic]] transfer hydrogenation has been described by the group of List in 2004 in a system with a [[Hantzsch ester]] as proton donor and an amine catalyst <ref>''A Metal-Free Transfer Hydrogenation: Organocatalytic Conjugate Reduction of
a,b-Unsaturated Aldehydes'' Jung Woon Yang, Maria T. Hechavarria Fonseca, Benjamin List [[Angew. Chem. Int. Ed.]] '''2004''', 43, 6660 –6662 {{DOI|10.1002/anie.200461816}}</ref>:
[[Image:OrganocatalyticTransferHydrogenation.svg|600px|Organocatalytic Transfer Hydrogenation Yang 2004]]
In this particular reaction the substrate is an [[Carbonyl#.CE.B1.2C.CE.B2-Unsaturated_carbonyl_compounds|α,β-unsaturated carbonyl compound]]. The proton donor is oxidized to the [[pyridine]] form and resembles the biochemically relevant coenzyme [[NADH]]. In the [[catalytic cycle]] for this reaction the amine and the aldehyde first form an [[iminium ion]], then proton transfer is followed by hydrolysis of the iminium bond regenerating the catalyst. By adopting a chiral imidazolidinone [[MacMillan organocatalyst]] an [[enantioselectivity]] of 81% [[enantiomeric excess|ee]] was obtained:
:[[Image:AsymmetricOrganocatalyticTransferHydrogenation.svg|600px|Asymmetric Organocatalytic Transfer Hydrogenation Yang 2004]]
The group of MacMillan independently published a very similar [[asymmetric reaction]] in 2005 <ref>''Enantioselective Organocatalytic Hydride Reduction'' Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. [[J. Am. Chem. Soc.]]; (Communication); '''2005'''; 127(1); 32-33. {{DOI|10.1021/ja043834g}} </ref>:
:[[Image:MacMillanAsymmetricOrganocatalyticTransferHydrogenation.svg|600px|MacMillan Asymmetric Organocatalytic Transfer Hydrogenation]]
In an interesting case of [[stereoconvergence]], both the [[E-isomer]] and the [[Z-isomer]] in this reaction yield the (S)-[[enantiomer]].
Extending the scope of this reaction towards [[ketone]]s or rather [[enone]]s requires fine tuning of the catalyst (add a [[benzyl]] group and replace the [[t-butyl]] group by a [[furan]]) and of the Hantzsch ester (add more bulky t-butyl groups) <ref>''Organocatalytic Transfer Hydrogenation of Cyclic Enones'' Jamison B. Tuttle, Stephane G. Ouellet, and David W. C. MacMillan [[J. AM. CHEM. SOC.]] '''2006''', 128, 12662-12663 {{DOI|10.1021/ja0653066}}</ref>:
:[[Image:OrganocatalyticTransferHydrogenationEnones.svg|500px|Organocatalytic Transfer Hydrogenation Enones Tuttle 2006]]
With a different organocatalyst altogether, hydrogenation can also be accomplished for [[imine]]s. In one particular reaction the catalysts is a [[BINOL]] based [[phosphoric acid]], the substrate a [[quinoline]] and the product a chiral [[tetradehydroquinoline]] in a [[1,4-addition]], [[isomerization]] and [[1,2-addition]] [[cascade reaction]] <ref>''A Highly Enantioselective Brønsted Acid Catalyzed Cascade Reaction: Organocatalytic Transfer Hydrogenation of Quinolines and their Application in the Synthesis of Alkaloids'' Magnus Rueping, Andrey P. Antonchick, and Thomas Theissmann [[Angew. Chem. Int. Ed.]] '''2006''', 45, 3683 –3686 {{DOI|10.1002/anie.200600191}}</ref>:
:[[Image:TransferhydrogenationImineReduction.svg|600px|Transfer hydrogenation Imine Reduction Rueping 2006]]
The first step in this reaction is protonation of the quinoline nitrogen atom by the phosphoric acid forming a transient chiral [[iminium ion]]. It is noted that with most traditional metal based catalysts, hydrogenation of [[aromatic]] or [[heteroaromatic]] substrates tend to fail.
==References==
<references/>
== See also ==
* [[Dehydrogenation]]
* [[Hydrogenation]]
* [[Hydrogenolysis]]
[[Category:Organic redox reactions]]
[[Category:Hydrogen]]