1,4-Reduction of α,β-unsaturated compounds

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A Pd/C-catalyzed hydrogenation using diphenylsulfide as a catalyst poison selectively reduces olefin and acetylene functionalities without hydrogenolysis of aromatic carbonyls and halogens, benzyl esters, and N-Cbz protective groups.
A. Mori, Y. Miyakawa, E. Ohashi, T. Haga, T. Maegawa, H. Sajiki, Org. Lett., 2006, 8, 3279-3281.

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.

A new recyclable catalyst composed of palladium nanoparticles dispersed in an organic polymer was synthesized by a simple procedure from readily available reagents. This catalyst is robust, and highly active in many organic transformations including alkene and alkyne hydrogenation, carbon-carbon cross-coupling reactions, and aerobic alcohol oxidation.
C. M. Park, M. S. Kwon, J. Park, Synthesis, 2006, 3790-3794.

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.

A system composed of nickel(II) chloride, lithium metal, a catalytic polymer-supported arene, and ethanol, has been efficiently applied to the conjugate reduction of various α,β-unsaturated carbonyl compounds under very mild reaction conditions.
F. Alonso, I. Osante, M. Yus, Synlett, 2006, 3017-3020.

An organotin hydride-catalyzed, silicon hydride-mediated method for effecting the conjugate reduction of α,β-unsaturated ketones was developed.
D. S. Hays, M. Scholl, G. C.Fu, J. Org. Chem., 1996, 61, 6751-6752.

The use of 1,2-bis(dicyclohexylphosphino)ethane (DCyPE) as ligand enabled an iridium-catalyzed transfer hydrogenation of alkenes using 1,4-dioxane as a hydrogen donor. A polystyrene-cross-linking bisphosphine PS-DPPBz produced a reusable heterogeneous catalyst. The reaction tolerates other potentially reducible functional groups such as carbonyl, nitro, cyano, and imino groups.
D. Zhang, T. Iwai, M. Sawamura, Org. Lett., 2019, 21, 5867-5872.

A selective transfer hydrogenation of α,β-unsaturated carbonyl compounds to saturated ones in very good yields was achieved by the use of 2-propanol as a hydrogen donor under the influence of catalytic amounts of [Ir(cod)Cl]₂, 1,3-bis(diphenylphosphino)propane (dppp), and Cs₂CO₃. The reduction of carbonyl compounds to alcohols can also promoted by the same catalytic system.
S. Sakaguchi, T. Yamaga, Y. Ishii, J. Org. Chem., 2001, 66, 4710-4712.

Organoborane reductants have been rendered catalytic through an isodesmic B-O/B-H transborylation applied in the borane-catalyzed, chemoselective alkene reduction and formal hydrofunctionalization of enones. The reaction proceeds via a 1,4-hydroboration of the enone and B-O/B-H transborylation with HBpin, enabling catalyst turnover.
K. Nicholson, T. Langer, S. P. Thomas, Org. Lett., 2021, 23, 2498-2504.

Air-stable cationic hemiboronic acids catalyze chemoselective reduction of enones. Depending on the silane reducing agent, either the conjugate reduction products or the fully reduced products can be obtained in high selectivity.
J. P. G. Rygus, D. B. Boateng, D. G. Hall, Synlett, 2023, 34, 2215-2219.

An efficient and highly enantioselective conjugate transfer hydrogenation of α,β-unsaturated ketones is catalyzed by a salt made from tert-butyl valinate and a recently introduced powerful chiral phosphoric acid catalyst (TRIP).
N. J. A. Martin, B. List, J. Am. Chem. Soc., 2006, 128, 13368-13369.

The use of a chiral imidazolidinone catalyst has provided a new organocatalytic strategy for the enantioselective reduction of β,β-substituted α,β-unsaturated aldehydes to generate β-stereogenic aldehydes using ethyl Hantzsch ester as the hydrogen source. In addition, an acceleration of E-Z isomerization prior to selective E-olefin reduction allows the use of geometrically impure enals in this operationally simple protocol.
S. G. Ouellet, J. B. Tuttle, D. W. C. MacMillan, J. Am. Chem. Soc., 2005, 7, 32-33.

In an operationally simple protocol, a 8-OIQ cobalt complex catalyzes a chemo- and enantioselective 1,4-hydroboration of enones with HBpin to access a broad range of chiral β,β-disubstituted ketones with very good chemo- and enantioselectivties.
X. Ren, Z. Lu, Org. Lett., 2021, 23, 8370-8374.

Nickel-catalyzed asymmetric hydrogenation of α,β-unsaturated esters, nitriles, and ketones as well as allylic alcohols proceeds in high enantioselectivity, using acetic acid or water as the hydrogen source and indium powder as electron donor. Asymmetric deuteration of α,β-unsaturated esters is achieved with the use of deuterated water.
S. Guo, X. Wang, J. S. Zhou, Org. Lett., 2020, 22, 1204-1207.

A nickel/bisphosphine catalyst enables an asymmetric transfer hydrogenation of α,β-unsaturated esters in the presence of N,N-dimethylformamide (DMF) as the hydride source.
S. Guo, J. Zhou, Org. Lett., 2016, 18, 5344-5347.

The combination of CS₂, t-BuOK and DMSO as solvent mediates a reduction of unsaturated ketone derivatives to provide saturated ketones. The in situ generation of xanthate salts through the reaction of carbon disulfide and potassium tert-butoxide is essential. Deuterium-labeling experiments demonstrated that DMSO can act as a hydrogen donor.
S. Rajai-Daryasarei, M. S. Hosseini, S. Balalaie, J. Org. Chem., 2023, 88, 10828-10835.

A chiral phosphoric acid catalyzes an asymmetric transfer hydrogenation of trans-chalcones in the presence of pinacolborane as hydride source. This methodology provides chiral dihydrochalcone derivatives in high yields and with high enantioselectivities under mild conditions.
F. Na, S. S. Lopez, A. Beauseigneur, L. W. Hernandez, Z. Sun, J. C. Antilla, Org. Lett., 2020, 22, 5953-5957.

A direct enantioselective copper hydride (CuH)-catalyzed synthesis of β-chiral amides from α,β-unsaturated carboxylic acids and secondary amines under mild reaction conditions tolerates a variety of functional groups in the β-position including several heteroarenes. A subsequent iridium-catalyzed reduction to γ-chiral amines can be performed in the same flask.
A. Link, Y. Zhou, S. L. Buchwald, Org. Lett., 2020, 22, 5666-5670.

The bulky ligand di-1-adamantylphosphino(tert-butylmethylphosphino)methane is a crystalline solid and can be readily handled in air. Its rhodium(I) complex exhibits very high enantioselectivities and catalytic activities in the asymmetric hydrogenation of functionalized alkenes.
Y. Sawatsugawa, K. Tamura, N. Sano, T. Imamoto, Org. Lett., 2019, 21, 8874-8878.

Selective conjugate reductions of α,β-unsaturated aldehydes were achieved in the presence of rhodium(bisoxazolinylphenyl) complexes as catalysts and alkoxyhydrosilanes as reducing agents.
Y. Kanazawa, H. Nishiyama, Synlett, 2006, 3343-3345.

A highly chemoselective conjugate reduction of electron-deficient Michael acceptors, including α,β-unsaturated ketones, carboxylic esters, nitriles and nitro compounds with PMHS in the presence of a catalytic amount of B(C₆F₅)₃ is described.
S. Chandrasekhar, G. Chandrasekhar, M. S. Reddy, P. Srihari, Org. Biomol. Chem., 2006, 4, 1650-1652.

A ligand-modified, economical version of Stryker's reagent is based on a bidentate, achiral bis-phosphine. Generated in situ, “(BDP)CuH” smoothly effects conjugate reductions of a variety of unsaturated substrates, including those that are normally unreactive toward Stryker's reagent.
B. A. Baker, Ž. V. Bošković, B. H. Lipshutz, Org. Lett., 2008, 10, 289-292.

A complex of catalytic amounts of CuH with a nonracemic JOSIPHOS or SEGPHOS ligand leads to exceedingly efficient and highly enantioselective 1,4-reductions of α,β-disubstituted enoates and lactones using PMHS as the stoichiometric reducing agent.
B. H. Lipshutz, J. M. Servesko, B. R. Taft, J. Am. Chem. Soc., 2004, 126, 8352-8353.

A copper hydride-catalyzed enantioselective reduction of α,β-unsaturated carboxylic acids provides various saturated β-chiral aldehydes in good yields, with high levels of enantioselectivity and broad functional group tolerance. A reaction pathway involving a ketene intermediate is proposed.
Y. Zhou, J. S. Bandar, R. Y. Liu, S. L. Buchwald, J. Am. Chem. Soc., 2018, 140, 606-609.

Bis-methylamido Hantzsch dihydropyridine is an effective transfer hydrogenation reagent for the reduction of α,β-unsaturated ketones. Unreacted Hantzsch amide and the bis-methylamidopyridine byproduct are effectively removed by extraction in contrast to the commonly used Hantzsch diethyl ester. The reaction is more effective for conjugated aromatic substrates than for aliphatics.
S. A. Van Arman, A. J. Zimmet, I. E. Murray, J. Org. Chem., 2016, 81, 3528-3532.

A chiral bisphosphine dioxide catalyzes an asymmetric conjugate reduction of acyclic β,β-disubstituted α,β-unsaturated ketones with trichlorosilane to provide saturated ketones with high enantioselectivities. Due to concomitant E/Z-isomerizations of enone substrates, reduction products with the same absolute configurations are obtained from either (E)- or (Z)-enones.
M. Sugiura, Y. Ashikari, Y. Takahashi, K. Yamaguchi, S. Kotani, M. Nakajima, J. Org. Chem., 2019, 84, 11458-11473.

Chiral rhodium-bis(oxazolinyl)phenyl complexes catalyze the conjugate hydrosilylation of 3,3-diarylacrylate derivatives to prepare optically active 3,3-diarylpropanoate derivatives in high yields and high enantioselectivities.
K. Itoh, A. Tsuruta, J.-i. Ito, Y. Yamamoto, H. Nishiyama, J. Org. Chem., 2012, 77, 10914-10919.

A B(C₆F₅)₃-catalyzed chemoselective hydrosilylation of α,β- and α,β,γ,δ-unsaturated ketones provides the corresponding non-symmetric ketones in mild reaction conditions. The reaction tolerates a broad range of reducible functional groups such as alkynyl, alkenyl, cyano, and aromatic heterocycles.
X.-Y. Zhang, H. Zhang, Y. Dong, J. Yang, S. He, Z.-C. Shi, L. Tang, J.-Y. Wang, J. Org. Chem., 2020, 85, 6578-6592.

Catalytic amounts of copper hydride ligated by a nonracemic SEGPHOS ligand leads in situ to an extremely reactive species capable of effecting asymmetric hydrosilylations of conjugated cyclic enones with very high enantioselectivity.
B. H. Lipshutz, J. M. Servesko, T. B. Petersen, P. P. Papa, A. A. Lover, Org. Lett., 2004, 6, 1273-1275.

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.

Poly(ethylene glycol) (PEG) (400) has been found to be a superior solvent over ionic liquids by severalfold in promoting the hydrogenation of various functional groups using Adams' catalyst. Both the catalyst and PEG were recycled efficiently over 10 runs without loss of activity, and without substrate cross contamination.
S. Chandrasekhar, S. Y. Prakash, C. L. Rao, J. Org. Chem., 2006, 71, 2196-2199.

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.

In a triphenylphosphine oxide-catalyzed reduction of conjugated polyunsaturated ketones using trichlorosilane as reducing reagent, the α,β-C=C double bond was selectively reduced while all other reducible functional groups remained unchanged. Additionally, a tandem one-pot Wittig/conjugate-reduction reaction sequence provides γ,δ-unsaturated ketones from simple building blocks.
X. Xia, Z. Lao, P. H. Toy, Synlett, 2019, 30, 1100-1104.

Palladium-catalyzed hydrosilylation of α,β-unsaturated ketones and cyclopropyl ketones with hydrosilanes gives (Z)-silyl enolates in good yields.
Y. Sumida, H. Yorimitsu, K. Oshima, J. Org. Chem., 2009, 74, 7986-7989.

Superelectrophilic reactivity of α,β-unsaturated amides towards weak nucleophiles such as arenes and cyclohexane is initiated either with triflic acid or with excess AlCl₃. Condensation with aromatics in the presence of AlCl₃ gives 3-arylpropionamides in excellent yields, while a selective ionic hydrogenation of some amides with cyclohexane gives saturated amides.
K. Y. Koltunov, S. Walspurger, J. Sommer, Eur. J. Org. Chem., 2004, 4039-4047.

γ-Hydroxy-α,β-acetylenic esters are used as precursors for the preparation of γ-hydroxy-α,β-alkenoic esters by means of trans-selective additions of two hydrogen atoms or one hydrogen atom and one iodine atom across the triple bonds. These methods allow the preparation of β-substituted and α,β-disubstituted alkenoic esters in highly stereoselective manners.
C. T. Meta, K. Koide, Org. Lett., 2004, 6, 1785-1787.

A highly efficient iridium-catalyzed hydrogenation of α,β-unsaturated carboxylic acids in the presence of chiral spiro-phosphino-oxazoline ligands affords α-substituted chiral carboxylic acids in exceptionally high enantioselectivities and reactivities.
S. Li, S.-F. Zhu, C.-M. Zhang, S. Song, Q.-L. Zhou, J. Am. Chem. Soc., 2008, 130, 8584-8585.

Ruthenium complexes of rigid diphosphane ligands with large dihedral angles are highly efficient catalysts for the asymmetric hydrogenation of α,β-unsaturated carboxylic acids.
X. Cheng, Q. Zhang, J.-H. Xie, L.-X. Wang, Q.-L. Zhou, Angew. Chem. Int. Ed., 2005, 44, 1118-1121.

H₂Se (or HSe^-) produced in situ from Se/DMF/H₂O is an active reducing species. This reduction system with water as an inexpensive, safe, and environmentally friendly hydrogen donor displayed high selectivity and good activity in the reduction of α,β-unsaturated ketones and alkynes.
C. An, G. Wu, G.-X. Li, X.-B. Huang, W.X. Gao, J.-C. Ding, Y.-B. Zhou, M.-C. Liu, H.-Y. Wu, Org. Lett., 2018, 20, 5573-5577.

The use of a highly rigid chiral ferrocenylphosphine-spiro phosphonamidite ligand enables a highly efficient Rh-catalyzed hydrogenation of a wide range of α-dehydroamino acid esters and α-enamides with excellent enantiocontrol.
Y. Chen, X. Yi, Y. Cheng, A. Huang, Z. Yang, X. Zhao, F. Ling, W. Zhong, J. Org. Chem., 2022, 87, 7864-7874.

Rhodium complexes with chiral bisphospholanes are highly enantioselective catalysts for the asymmetric hydrogenation of functionalized olefins such as dehydroamino acid derivatives, itaconic acid derivatives, and enamides. The use of the hydroxyl phospholane system enables hydrogenation of some substrates in water with >99% ee and 100% conversion (e.g., itaconic acid).
W. Li, Z. Zhang, D. Xiao, X. Zhang, J. Org. Chem., 2000, 65, 3489-3496.

A Rh/Cu co-catalytic system enables an asymmetric reduction of aromatic α-dehydroamino acid esters with water as the hydrogen source to provide chiral α-amino acid esters. The reaction tolerates various functional groups and provides access to chiral deuterated α-amino esters by using D₂O.
Y. Dai, J. Chen, Z. Wang, T. Wang, L. Wang, Y. Yang, X. Qiao, B. Fan, J. Org. Chem., 2021, 86, 7141-7147.

A highly enantioselective reduction of α,β-unsaturated nitriles can be conducted by using a Cu(OAc)₂/josiphos complex as the catalyst under hydrosilylation conditions. The reaction provides access to valuable β-aryl-substituted chiral nitriles in good yields and with excellent enantioselectivities.
D. Lee, D. Kim, S. Yun, Angew. Chem. Int. Ed., 2006, 45, 2785-2787.

A range of 3-aryl-3-pyridylacrylonitriles were reduced with high levels of enantioselectivity under optimal conditions employing a copper/Josiphos complex in the presence of polymethylhydrosiloxane (PMHS).
D. Lee, Y. Yang, J. Yun, Org. Lett., 2007, 9, 2749-2751.

A highly efficient and highly enantioselective Hantzsch ester mediated conjugate transfer hydrogenation of β,β-disubstituted nitroolefins is catalyzed by a Jacobsen-type thiourea catalyst.
N. J. A. Martin, L. Ozores, B. List, J. Am. Chem. Soc., 2007, 129, 8976-8977.

A highly efficient and enantioselective Hantzsch ester mediated conjugate reduction of β-nitroacrylates is catalyzed by a Jacobsen thiourea catalyst. The reaction is a key step in a new route to optically active β²-amino acids.
N. J. A. Martin, X. Chen, B. List, J. Am. Chem. Soc., 2008, 130, 13862-13863.

An organocatalyst delivers nitroalkanes from β,β-disubstituted nitroalkenes with a generality otherwise achievable only by a combination of several organo- and organometallic catalysts. The catalyst improves yield and/or enantioselection of the reduction of some major classes of nitroalkenes.
Z. Deng, M. A. Padalino, J. E. L. Jan, S. Park, M. W. Danneman, J. N. Johnston, J. Am. Chem. Soc., 2024, 146, 1269-1275.

A chiral bisphosphine-thiourea ligand was applied in the highly enantioselective hydrogenation of β,β-disubstituted nitroalkenes. The thiourea group of the ligand takes on an important role in this catalytic system as a H-bond donor.
Q. Zhao, S. Li, K. Huang, R. Wang, X. Zhang, Org. Lett., 2013, 15, 4014-4017.

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.

An inert, rigid chiral-at-metal iridium(III) complex enables a highly efficient catalytic asymmetric transfer hydrogenation of β,β′-disubstituted nitroalkenes. The catalysis does not involve any direct metal coordination but operates exclusively through weak interactions with functional groups properly arranged in the ligand sphere of the iridium complex.
L-A. Chen, W. Xu, B. Huang, J. Ma, L. Wang, J. Xi, K. Harms, L. Gong, E. Meggers, J. Am. Chem. Soc., 2013, 135, 10598-10601.

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.

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.

Cu-catalyzed asymmetric conjugate reduction of β-substituted ketones leads to enantiomerically enriched diphenylsilyl enol ethers, which are utilized in a diastereoselective Pd-catalyzed α-arylation of various aryl bromides to yield disubstituted cycloalkanones with excellent levels of enantiomeric and diastereomeric purity. The procedure can be carried out in one-pot.
J. Chae, J. Yun, S. L. Buchwald, Org. Lett., 2004, 6, 4809-4812.

Conjugate reduction of dihydropyridones have generally been carried out using expensive L or K-Selectrides, as catalytic hydrogenation often leads to over reduction. The use of zinc/acetic acid enables a simple, inexpensive, and mild reduction of N-acyl-2,3-dihydro-4-pyridones to various racemic or enantiopure 4-piperidones or indolizidinones.
D. L. Comins, C. A. Brooks, C. L. Ingalls, J. Org. Chem., 2001, 66, 2181-2182.