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Chemicals >> Reducing Agents

Formic acid and formates

Deprotonated formic acid splits into hydride and CO2, wherefore it works as a reducing agent.

> Formic acid as an oxidizing agent.

Name Reactions

Eschweiler-Clark Reaction


Recent Literature

In a biphasic reaction media for the asymmetric biocatalytic reduction of ketones with in situ cofactor regeneration, both enzymes (ADH and FDH) remain stable. Reductions with poorly water-soluble ketones were carried out at substrate concentrations of > 10 mM, and alcohols were formed with good conversions in high enantioselectivity.
H. Groeger, W. Hummel, S. Buchholz, K. Drauz, T. V. Nguyen, C. Rollmann, H. Huesken, K. Abokitse, Org. Lett., 2003, 5, 173-176.

By careful selection of appropriate enzymes (alcohol dehydrogenases [ADH] and cofactor recycling enzymes), cofactor recycling of NADH can be performed in the presence of NADP+ recycling to achieve overall (R)- or (S)-selective deracemisations of sec-alcohols or stereoinversion representing a possible concept for a “green” equivalent to the chemical-intensive Mitsunobu inversion.
C. V. Voss, C. C. Gruber, K. Faber, T. Knaus, P. Macheroux, W. Kroutil, J. Am. Chem. Soc., 2008, 130, 13969-13972.

An on-water Ir(III)-diamine catalysis represents an efficient, simple and environmentally friendly catalytic system for the transfer hydrogenation of aldehydes. The catalyst tolerates various synthetically useful groups including nitro groups, halogens, ketones, esters and olefins.
X. Wu, J. Liu, X. Li, A. Zanotti-Gerosa, F. Hancock, D. Vinci, J. Ruan, J. Xiao, Angew. Chem. Int. Ed., 2006, 45, 6717-6722.

A combination of a chiral Ru complex and KOtBu catalyzes an asymmetric transfer hydrogenation of various benzaldehyde-1-d derivatives with 2-propanol to yield (R)-benzyl-1-d alcohols in high ee and with high isotopic purity. Reaction of benzaldehydes with a DCO2D-triethylamine mixture and the same Ru catalyst affords the S deuterated alcohols in high ee.
I. Yamada, R. Noyori, Org. Lett., 2000, 2, 3425-3427.

Various N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine ligands have been prepared, characterized, and evaluated in the Rh-catalyzed asymmetric transfer hydrogenation (ATH) of a wide range of (hetero)aryl ketones under mild conditions with the formic acid/triethylamine (5:2) system as the hydrogen source. Ligands bearing electron-donating groups exhibited a higher catalytic activity than those having electron-withdrawing groups.
L.-S. Zheng, Q. Llopis, P.-G. Echeverria, C. Férard, G. Guillamot, P. Phansavath V. Ratovelomanana-Vidal, J. Org. Chem., 2017, 82, 5607-5615.

Asymmetric transfer hydrogenation of various simple aromatic ketones by the Ru-TsDPEN catalyst was shown to be feasible in aqueous HCOONa without calling for any catalyst modification, furnishing ee's of up to 95% and significantly faster rates than in the HCOOH-NEt3 azeotrope.
X. Wu, X. Li, W. Hems, F. King, J. Xiao, Org. Biomol. Chem., 2004, 2, 1818-1821.

An asymmetric transfer hydrogenation of diaryl ketones is promoted by bifunctional Ru complexes with an etherial linkage between 1,2-diphenylethylenediamine (DPEN) and η6-arene ligands. An effective discrimination of substituents on the aryl group enables a smooth reduction in a 5:2 mixture of formic acid and triethylamine with a high level of enantioselectivity.
T. Touge, H. Nara, M. Fujiwhara, Y. Kayaki, T. Ikariya, J. Am. Chem. Soc., 2016, 138, 10084-10087.

A formic acid promoted hydration of readily available alkynes followed by an iridium-catalyzed transfer hydrogenation under mild conditions provides alcohols. This transformation is simple, efficient, and can be performed with a variety of alkynes in good yields and with excellent stereoselectivities.
N. Luo, Y. Zhong, J.-T. Liu, L. Ouyang, R. Luo, Synthesis, 2020, 52, 3439-3445.

The neutral gold(I) complex [(IPr)AuCl] is a highly effective catalyst for the regioselective hydration of terminal alkynes, including aromatic alkynes and aliphatic alkynes providing methyl ketones in high yields. Furthermore, optically active alcohols could be obtained in high yields with very good enatioselectivities via one-pot sequential hydration/asymmetric transfer hydrogenation using Cp*RhCl[(R,R)-TsDPEN] as additional catalyst.
F. Li, N. Wang, L. Lu, G. Zhu, J. Org. Chem., 2015, 80, 3538-3546.

In the presence of sodium formate and ethanol as hydrogen sources, a series of alkynyl ketones were hydrogenated by a chiral spiro iridium catalyst to provide propargylic alcohols with high enantiomeric excess.
Y.-M. Zhang, M.-L. Yuan, W.-P. Liu, J.-H. Xie, Q.-L. Zhou, Org. Lett., 2018, 20, 4486-4489.

A catalytic DKR-ATH process for the enantio- and diastereoselective reduction of α-substituted-β-keto carbonitriles enables the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers in high yields and excellent enantio- and diastereoselectivities.
F. Wang, T. Yang, T. Wu, L.-S. Zheng, C. Yin, Y. Shi, X.-Y. Ye, G.-Q. Chen, X. Zhang, J. Am. Chem. Soc., 2021, 143, 2477-2483.

An iridium-catalyzed, chemoselective, asymmetric transfer hydrogenation of α-substituted acetophenones using formic acid as reductant can be performed in water and open to air.
O. Soltani, M. A. Ariger, H. Vázquez-Villa, E. M. Carreira, Org. Lett., 2010, 12, 2893-2895.

An iridium complex catalyzes an environmentally friendly, efficient, and facile one-pot transfer hydrogenation of C=C bond of enones and reductive amination of C=N bond of imines in the presence of formic acid as hydrogen source in aqueous medium. This reaction provides a wide range of α-alkylated amines in excellent yield.
Y. Xia, L. Ouyang, J. Liao, X. Yang, R. Luo, Synthesis, 2021, 53, 1821-1827.

An iridium complex catalyzes pH-dependent selective N-allylation or N-alkylation of amines with allylic alcohols in outstanding yields with water as the environmental benign solvent.
N. Luo, Y. Zhong, H. Shui, R. Luo, J. Org. Chem., 2021, 86, 15509-15521.

Water-soluble amide iridium complexes catalyze transfer hydrogenation reduction of N-sulfonylimines under environmentally friendly conditions, affording a series of sulfonamide compounds in excellent yields. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of sulfonamide compounds.
H. Wen, N. Luo, Q. Zhu, R. Luo, J. Org. Chem., 2021, 86, 3850-3859.

A visible-light-driven reductive carboarylation of styrenes with CO2 and a broad range of aryl iodides and bromides has been achieved in a regioselective manner.
H. Wang, Y. Gao, C. Zhou, G. Li, J. Am. Chem. Soc., 2020, 142, 8122-8129.

In a one-pot synthesis of optically active β-hydroxy sulfones, intermediate β-keto sulfones obtained via a nucleophilic substitution reaction of α-bromoketones and sodium sulfinates were reduced through Ru-catalyzed asymmetric transfer hydrogenation using HCOONa as a hydrogen source. This mild transformation in an aqueous medium provides chiral β-hydroxy sulfones with high yields and excellent enantioselectivities.
D. Zhang, T. Cheng, Q. Zhao, J. Xu, G. Liu, Org. Lett., 2014, 16, 5764-5767.

A pH-independent asymmetric transfer hydrogenation of β-keto esters in water with formic acid/sodium formate can be conducted open to air and gives access to β-hydroxy esters in excellent yields and selectivities.
M. A. Ariger, E. M. Carreira, Org. Lett., 2012, 14, 4522-4524.

The use dynamic kinetic resolution combined with asymmetric transfer hydrogenation in water provides β-hydroxy-α-(tert-butoxycarbonyl)amino esters in good yields, diastereoselectivities, and enantioselectivities. A surfactant is employed to achieve good yields due to the hydrophobic nature of both the catalyst and substrate.
B. Seashore-Ludlow, F. Seint-Dizier, P. Somfai, Org. Lett., 2012, 14, 6334-6337.

A photochemically mediated defluorinative hydroalkylation of ethyl trifluoroacetate with a diverse suite of alkenes in the presence of sodium formate enables a concise synthetic approach to novel gem-difluoro analogs of FDA-approved pharmaceutical compounds. Furthermore, trifluoroacetamides can also be functionalized via synergistic Lewis acid/photochemical activation.
M. W. Campbell, V. C. Polites, S. Patel, J. E. Lipson, J. Majhi, G. A. Molander, J. Am. Chem. Soc., 2021, 143, 19648-19654.

Cp*Ir complexes bearing a 2-picolinamide moiety effectively catalyze a direct reductive amination of ketones to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source.
K. Tanaka, T. Miki, K. Murata, A. Yamaguchi, Y. Kayaki, S. Kuwata, T. Ikariya, M. Watanabe, J. Org. Chem., 2019, 84, 10962-10977.

A well-defined iron-based catalyst system enables the reduction of nitroarenes to anilines using formic acid as reducing agent. A broad range of substrates including other reducible functional groups were converted to the corresponding anilines in good to excellent yields at mild conditions. Notably, the process constitutes a rare example of base-free transfer hydrogenations.
G. Wienhöfer, I. Sorribes, A. Boddien, F. Westerhaus, K. Junge, H. Junge, R. Llusar, M. Beller, J. Am. Chem. Soc., 2011, 133, 12875-12879.

In the presence of iodide ions, an efficient and selective rhodium-catalyzed transfer hydrogenation of nitroarenes with formic acid as the hydrogen source takes place to give amines or formanilides.
Y. Wei, J. Wu, D. Xue, C. Wang, Z. Liu, Z. Zhang, G. Chen, J. Xiao, Synlett, 2014, 25, 1295-1298.

A direct and efficient palladium-catalyzed reductive coupling of nitroarenes with phenols provides various N-cyclohexylaniline derivatives in good yields using safe and inexpensive sodium formate as the hydrogen donor.
K.-J. Liu, X.-L. Zeng, Y. Zhang, Y. Wang, X.-S. Xiao, H. Yue, M. Wang, Z. Tang, W.-M. He, Synthesis, 2018, 50, 4637-4644.

Aryl azides undergo clean reduction by copper nanoparticles in water in the presence of ammonium formate. The surface hydrogen on copper nanoparticles is considered to be the active reducing species. Various functionalized aryl azides and aryl sulfonyl azides are reduced to the corresponding amines with excellent chemoselectivity in high yields.
S. Ahammed, A. Saha, B. C. Ranu, J. Org. Chem., 2011, 76, 7235-7239.

A ruthenium-catalyzed transfer hydrogenation of olefins utilizing formic acid as a hydrogen donor provides a remarkable and chemoselective synthetic tool for the reduction of functionalized alkenes under mild reaction conditions.  An olefin metathesis/transfer hydrogenation sequence under tandem catalysis conditions enables an attractive C(sp3)-C(sp3) bond formation.
G. K. Zieliński, J. Majtczak, M. Gutowski, K. Grela, J. Org. Chem., 2018, 83, 2542-2553.

A transformation of aldehydes into terminal olefins through reduction of the corresponding enol triflates is effective with both linear and α-branched aldehydes.
S. K. Pandey, A. E. Greene, J.-F. Poisson, J. Org. Chem., 2007, 72, 7769-7770.

The reaction of PdCl2 with K2CO3 and HCO2H in dioxane provides a black precipitate, which is an effective catalyst for the semireduction of alkynes to alkenes in the presence of formic acid as the reductant.
R. Iwasaki, E. Tanaka, T. Ichihashi, Y. Idemoto, K. Endo, J. Org. Chem., 2018, 83, 13574-13579.

An unprecedented reduction of alkynes with formic acid can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the reaction conditions via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brĝnsted acid and Pd(0) complex.
R. Shen, T. Chen, Y. Zhao, R. Qiu, Y. Zhou, S. Yin, X. Wang, M. Goto, L.-B. Han, J. Am. Chem. Soc., 2011, 133, 17037-17044.

The use of unsupported nanoporous gold (AuNPore) as a heterogeneous catalyst enables a facile, highly chemo- and stereoselective transfer semihydrogenation of alkynes to Z-olefins in the presence of formic acid as a hydrogen donor. Various alkynes were reduced to the corresponding alkenes in high chemical yields with good functional-group tolerance. The catalyst is robust enough to be reused without leaching.
Y. S. Wagh, N. Asao, J. Org. Chem., 2015, 80, 847-851.

Ni catalysis enables a transfer hydrogenative alkyne semireduction protocol that can be applied to both internal and terminal alkynes in the presence of formic acid and Zn as the terminal reductants. Both (E)- and (Z)-isomers can be accessed selectively under similar reaction conditions.
E. Richmond, J. Moran, J. Org. Chem., 2015, 80, 6922-6929.

Ni catalysis enables a transfer hydrogenative alkyne semireduction protocol that can be applied to both internal and terminal alkynes in the presence of formic acid and Zn as the terminal reductants. Both (E)- and (Z)-isomers can be accessed selectively under similar reaction conditions.
E. Richmond, J. Moran, J. Org. Chem., 2015, 80, 6922-6929.

An unprecedented reduction of alkynes with formic acid can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the reaction conditions via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brĝnsted acid and Pd(0) complex.
R. Shen, T. Chen, Y. Zhao, R. Qiu, Y. Zhou, S. Yin, X. Wang, M. Goto, L.-B. Han, J. Am. Chem. Soc., 2011, 133, 17037-17044.

Commercial first and second generation Hoveyda-Grubbs catalysts enable a selective transfer semihydrogenation of alkynes to yield alkenes in the presence of formic acid as a hydrogen donor. This catalytic system tolerates many functional groups (halogens, cyano, nitro, sulfide, alkenes).
R. Kusy, K. Grela, Org. Lett., 2016, 18, 6196-6199.

A heterogeneous Au/TiO2 catalyzed stereoselective hydrogenation of ynamides provides Z-enamides in a highly stereoselective manner in the presence of inexpensive ammonium formate as the hydrogen source. The commercially available gold nanoparticle catalyst could be recycled multiple times without a significant loss of activity.
L. Lin, X. Zeng, B. Xu, J. Org. Chem., 2019, 84, 11240-11246.

An unprecedented reduction of alkynes with formic acid can selectively produce cis-, trans-alkenes and alkanes by slightly tuning the reaction conditions via the generation of an alkenylpalladium intermediate and subsequent transformation of this complex in a variety of reactions catalyzed by a combination of Brĝnsted acid and Pd(0) complex.
R. Shen, T. Chen, Y. Zhao, R. Qiu, Y. Zhou, S. Yin, X. Wang, M. Goto, L.-B. Han, J. Am. Chem. Soc., 2011, 133, 17037-17044.

Pd/P(t-Bu)3 is an efficient and mild catalyst for selective reduction of various alkenes under transfer-hydrogenation conditions leading to the corresponding saturated derivatives in good yields.
J. M. Brunel, Synlett, 2007, 330-332.

An air-stable half-sandwich ruthenium complex is a highly active catalyst for the anti-Markovnikov reductive hydration of alkynes, involving the decarboxylation of formic acid, hydration of the alkyne, and hydrogenation of the intermediate aldehyde. A wide array of terminal alkynes are efficiently processed to linear alcohols using as little as 2 mol % of catalyst at ambient temperature.
M. Zeng, L. Li, S. B. Herzon, J. Am. Chem. Soc., 2014, 136, 7058-7067.

Starting from readily available aryl iodides and allenes, with formic acid as the CO source and reductant, good yields of α-branched enones were isolated. The use of a CO source avoids the manipulation of CO gas.
H.-Q. Geng, L.-C. Wang, C.-Y. Hou, X.-F. Wu, Org. Lett., 2020, 22, 1160-1163.

Palladium-catalyzed reductive coupling reactions between N-tosylhydrazones and aryl halides provide a general route for the synthesis of triarylmethanes.
Y. Xia, F. Hu, Z. Liu, P. Qu, R. Ge, C. Ma, Y. Zhang, J. Wang, Org. Lett., 2013, 15, 1784-1787.

A mild catalytic asymmetric transfer hydrogenation of β,β-disubstituted nitroalkenes using formic acid as reductant in combination with an Ir catalyst is conducted in water at low pH and open to air to give products in good yield and selectivity.
O. Soltani, M. A. Ariger, E. M. Carreira, Org. Lett., 2009, 11, 4196-4198.

Various carbon-carbon double bonds in olefins and α,β-unsaturated ketones were effectively reduced to the corresponding alkanes and saturated ketones, using ammonium formate as a hydrogen transfer agent in the presence of Pd/C as catalyst in refluxing methanol.
Z. Paryzek, H. Koenig, B. Tabacka, Synthesis, 2003, 2023-2026.

A microwave-assisted, palladium-catalyzed catalytic transfer hydrogenation of different homo- or heteronuclear organic compounds using formate salts as a hydrogen source was performed in ([bmim][PF6]. Essentially pure products could be isolated in moderate to excellent yields by simple liquid-liquid extraction.
H. Berthold, T. Schotten, H. Hönig, Synthesis, 2002, 1607-1610.

Knoevenagel condensation followed by hydrogenation with triethylamine-formic acid in the presence of a ruthenium-amido complex allowed an α-alkylation of various nitriles with carbonyl compounds in good yields. The reaction tolerated various functional groups, including nitro and chloro groups, and a furan ring.
H. Sun, D. Ye, H. Jiang, K. Chen, H. Liu, Synthesis, 2010, 2577-2582.

Transfer hydrogenation utilizing palladium on carbon and formic acid provides a fast and simple removal of O-benzyl groups from carbohydrate derivatives. However, when formic acid is the hydrogen donor, a large amount of palladium has to be used.
T. Bieg, W. Szeja, Synthesis, 1985, 76-77.

Nanopalladium particles supported on a amphiphilic polystyrene-poly(ethylene glycol) resin catalyzed hydrogenation of olefins and hydrodechlorination of chloroarenes under aqueous conditions.
R. Nakao, H. Rhee, Y. Uozumi, Org. Lett., 2005, 7, 163-165.

An operationally simple, tin-free reductive dehalogenation system allows the reduction of activated C-X bonds in good yields with excellent functional-group tolerance and chemoselectivity over aryl and vinyl C-X bonds in the presence of the well-known visible-light-activated photoredox catalyst Ru(bpy)3Cl2 in combination with iPr2NEt and HCO2H or Hantzsch ester as the hydrogen atom donor.
J. M. R. Narayanam, J. W. Tucker, C. R. J. Stephenson, J. Am. Chem. Soc., 2009, 131, 8756-8757.

Various di- and triarylfurans were prepared in high yields from but-2-ene-1,4-diones and but-2-yne-1,4-diones using formic acid in the presence of a catalytic amount of palladium on carbon in poly(ethylene glycol)-200 as solvent under microwave irradiation.
H. S. P. Rao, S. Jothilingam, J. Org. Chem., 2003, 68, 5392-5394.

Several aryl-substituted pyrrole derivates were prepared conveniently in a microwave-assisted one pot-reaction from but-2-ene-1,4-diones and but-2-yne-1,4-diones via Pd/C-catalyzed hydrogenation of the carbon-carbon double bond/triple bond followed by amination-cyclization.
H. S. P. Rao, S. Jothilingam, H. W. Scheeren, Tetrahedron, 2004, 60, 1625-1630.

The synthesis of 3,5-dimethyl-N-nitro-1-pyrazole-1-carboxamidine (DMNPC) has been optimised. A detailed protocol for the preparation of a range of guanidines via nitroguanidines is described using DMNPC as guanidinylating reagent.
J. A. Castillo-Meléndez, B. T. Golding, Synthesis, 2004, 1655-1663.

Amidines can be prepared by reducing acylated amidoximes with potassium formate. This method has proved to be very simple and effective.
K. Nadrah, M. Sollner Dolenc, Synlett, 2007, 1257-1258.

A tandem sequential one-pot reaction employing both hydroamination and asymmetric transfer hydrogenation reactions enables an efficient and practical enantioselective synthesis of 3-substituted morpholines from aminoalkyne substrates. A wide range of functional groups is tolerated. Hydrogen-bonding interactions between the oxygen and the [(S,S)-Ts-DPEN] ligand of the Ru catalyst are crucial for obtaining high ee's.
Y. Y. Lau, H. Zhai, L. L. Schafer, J. Org. Chem., 2016, 81, 8696-8709.

A new diamine ligand for Ru-catalyzed asymmetric transfer hydrogenation (ATH) enabled a highly enantioselective reduction of 2-acylarylcarboxylates. Subsequent in situ lactonization under aqueous conditions provided efficient access to a various 3-substituted phthalides in enantiomerically pure form.
B. Zhang, M.-H. Xu, G.-Q. Lin, Org. Lett., 2009, 11, 4712-4715.

An efficient annulation of phenolic acetates with acrylates in the presence of [Rh2(OAc)4] as catalyst and formic acid as reducing agent provides high yield of coumarin derivatives via C-H bond activation. The addition of NaOAc as a base increased the yield of the products. The reaction is quite successful for both electron-rich as well as electron-deficient phenolic acetates, affording coumarins with excellent regioselectivity.
S. K. Gadakh, S. Dey, A. Sudalai, J. Org. Chem., 2015, 80, 11544-11550.

Arene/Ru/TsDPEN complexes bearing a heterocyclic group catalyze the asymmetric transfer hydrogenation (ATH) of 1-aryl dihydroisoquinolines (DHIQs) to provide tetrahydroisoquinolines of high enantiomeric excess.
J. Barrios-Rivera, Y. Xu, Martin Wills, Org. Lett., 2020, 22, 6283-6287.

Rh-catalyzed asymmetric transfer hydrogenation enables a straightforward access to enantiomerically enriched cis-3-benzyl-chromanols from (E)-3-benzylidene-chromanones in the presence of HCO2H/DABCO as the hydrogen source.
R. M. Betancourt, P. Phansavath, V. Ratovelomanana-Vidal, Org. Lett., 2021, 23, 1621-1625.

An efficient palladium-catalyzed reaction of N-propargyl oxazolidines provides 4-substituted isoquinolines under microwave irradiation through a sequential palladium-catalyzed reductive cyclization/ring-opening/aromatization cascade via C-O and C-N bond cleavages of the oxazolidine ring.
X. Xu, H. Feng, E. V. Van der Eycken, Org. Lett., 2021, 23, 6578-6582.

Due to the poor nucleophilicity of the nitrogen atom of indoles and the competing alkylation reaction at the C-3 position, the use of more sterically hindered ketones with a lower electrophilicity as N-alkylation reagents has been a great challenge. A dearomatization-rearomatization strategy enables a reductive cross-coupling of indoles with ketones in water in good yield.
Z. Wang, H. Zeng, C.-J. Li, Org. Lett., 2019, 21, 2302-2306.