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Reduction of carbonyl compounds
[Cp*Ir(2,2′-bpyO)(H2O)] is a highly efficient and general catalyst for transfer hydrogenation of carbonyl compounds and chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol under neutral conditions. The reaction tolerates deducible groups such as nitro, cyano, ester, and halide.
R. Wang, Y. Tang, M. Xu, C. Meng, F. Li, J. Org. Chem., 2018, 83, 2274-2281.
An anionic iridium complex [Cp*Ir(2,2'-bpyO)(OH)][Na] is a general and highly efficient catalyst for transfer hydrogenation of ketones and imines with methanol as hydrogen source under base-free conditions. Nitro, cyano, and ester groups were tolerated under the reaction conditions.
R. Wang, X. Han, J. Xu, P. Liu, F. Li, J. Org. Chem., 2020, 85, 2242-2249.
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.
PhanePhos-ruthenium-diamine complexes efficiently catalyze an asymmetric hydrogenation of a wide range of aromatic, heteroaromatic, and α,β-unsaturated ketones with excellent enantioselectivity.
M. J. Burk, W. Hems, D. Herzberg, C. Malan, A. Zanotti-Gerosa, Org. Lett., 2000, 2, 4173-4176.
An air stable iridium complex of ferrocene-based phosphine-oxazoline ligand exhibits excellent performance for the asymmetric hydrogenation of simple ketones. Exo-α,β-unsaturated cyclic ketones could also be regiospecifically hydrogenated to give chiral allylic alcohols with good results.
Y. Wang, G. Yang, F. Xie, W. Zhang, Org. Lett., 2018, 20, 6135-6139.
Aryl ketones were reduced to the corresponding alcohols with excellent enantioselectivity by trichlorosilane in the presence of a catalytic amount of N-formyl-α'-(2,4,6-triethylphenyl)-L-proline as an activator.
Y. Matsumura, K. Ogura, Y. Kouchi, F. Iwasaki, O. Onomura, Org. Lett., 2006, 8, 3789-3792.
The catalytic asymmetric borane reduction of both electron-deficient and electron-rich ketones was achieved with high enantioselectivity with a C3-symmetric chiral tris(β-hydroxy phosphoramide) ligand .
D.-M. Du, T. Fang, J. Xu, S.-W. Zhang, Org. Lett., 2006, 8, 1327-1330.
A family of chiral iminophenyl oxazolinylphenylamines (IPOPA) ligands enables an efficient cobalt-catalyzed asymmetric hydrosilylation of simple ketones with a low catalyst loading of CoCl2 to afford chiral alcohols in good yields with high enantioselectivities.
X. Chen, Z. Lu, Org. Lett., 2016, 18, 4658-4661.
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.
A complex of CuH and Takasago's nonracemic ligand, DTBM-SEGPHOS, is an especially reactive reagent for asymmetric hydrosilylation of heteroaromatic ketones under very mild conditions. PMHS serves as an inexpensive source of hydride for the in situ generation of CuH.
B. H. Lipshutz, A. Lower, K. Noson, Org. Lett., 2002, 4, 4045-4048.
The combination of lipase and a ruthenium complex catalyzes the asymmetric transformation of enol acetates or ketones to chiral acetates in high yields with high optical purities in the presence of 2,6-dimethylheptan-4-ol as a hydrogen donor and 4-chlorophenyl acetate as an acyl donor.
H. M. Jung, J. H. Koh, M.-J. Kim, J. Park, Org. Lett., 2000, 2, 397-399.
Ketones were transformed to chiral acetates by a one-pot process using a lipase and an achiral ruthenium complex under 1 atm of hydrogen gas in ethyl acetate. The same catalyst system was also effective for an asymmetric transformation of enol acetates to acetates under hydrogen without additional acyl donors.
H. M. Jung, J. H. Koh, M.-J. Kim, J. Park, Org. Lett., 2000, 2, 2487-2490.
An efficient reduction of various prochiral ketones such as acetopehones, α-azido aryl ketones, β-ketoesters, and aliphatic acyclic and cyclic ketones to the corresponding optically active secondary alcohols with good chemical yield was achieved by using Daucus carota, root plant cells under extremely mild and environmentally benign conditions in aqueous medium.
J. S. Yadav, S. Nanda, P. T. Reddy, A. Bhaskar, Rao, J. Org. Chem., 2002, 67, 3900-3903.
A chiral oxazaborolidinium ion (COBI) catalyst enables a highly enantioselective hydrosilylation of ketones for the synthesis of various chiral secondary alcohols in good yields and excellent enantioselectivities.
B. C. Kang, S. H. Shin, J. Yun, D. H. Ryu, Org. Lett., 2017, 19, 6316-6319.
A chemoselective reduction of the carbonyl functionality via hydrosilylation using low loadings of a copper(I) catalyst bearing an abnormal NHC takes place at ambient temperature in excellent yield within a very short reaction time. The hydrosilylation reaction of α,β-unsaturated carbonyl compounds gives allyl alcohols in good yields. The catalyst can also be used for azide-alkyne cycloadditions.
S. R. Roy, S. C. Sau, S. K. Mandal, J. Org. Chem., 2014, 79, 9150-9160.
Small amounts of n-BuLi catalyze a highly efficient and selective hydroboration of aldehydes and ketones with HBpin. The reaction proceeds rapidly under mild conditions with exceptional functional group compatibility, ample substrate scope, and high selectivity for aldehydes over ketones.
Z. Zhu, X. Wu, X. Xu, Z. Wu, M. Xue, Y. Yao, Q. Shen, X. Bao, J. Org. Chem., 2018, 83, 10677-10683.
A nonanuclear copper(II) complex obtained by a facile one-pot self-assembly catalyzes the hydroboration of ketones and aldehydes with the absence of an activator under mild, solvent-free conditions. The air- and moisture-stable catalyst displays high efficiency and chemoselectivity on aldehydes over ketones and ketones over imines.
H. Zeng, J. Wu, S. Li, C. Hui, A. Ta, S.-Y. Cheng, S. Zheng, G. Zhang, Org. Lett., 2019, 21, 401-406.
A recyclable cobalt(II)-terpyridine coordination polymer (CP) is a highly effective hydroboration precatalyst for reductions of ketones, aldehydes, and imines with pinacolborane (HBpin). A wide range of substrates containing polar C=O or C=N bonds have been hydroborated selectively in excellent yields under ambient conditions.
J. Wu, H. Zeng, J. Cheng, S. Zheng, J. A. Golen, D. R. Manke, G. Zhang, J. Org. Chem., 2018, 83, 9442-9448.
Homoleptic cyclopentadienyl lanthanide complexes are excellent catalysts for the hydroboration of various aldehydes and ketones with pinacolborane. These robust lanthanide catalysts exhibited high reactivity with low catalyst loadings under mild conditions, good functional group tolerability, and unique carbonyl-selectivity.
S. Chen, D. Yan, M. Xue, Y. Hong, Y. Yao, Q. Shen, Org. Lett., 2017, 19, 3382-3385.
The reduction of ketones with pinacolborane is catalyzed by NaOt-Bu at ambient temperature. The reaction is high yielding and general, providing complete conversion of aryl and dialkyl ketones. The active hydride source is the trialkoxyborohydride, which is believed to be present in low concentration under the reaction conditions.
I. P. Query, P. A. Squier, E. M. Larson, N. A. Isley, T. B. Clark, J. Org. Chem., 2011, 76, 6452-6456.
An operationally convenient hydroboration of aldehydes and ketones employing Fe(acac)3 as precatalyst proceeded efficiently at room temperature to yield, after work up, 1° and 2° alcohols. A σ-bond metathesis mechanism with an Fe-H intermediate as key reactive species is postulated.
S. R. Tamang, M. Findlater, J. Org. Chem., 2017, 82, 12857-12862.
NHC-boranes such as 1,3-dimethylimidazol-2-ylidine trihydridoborane serve as practical hydride donors for the reduction of aldehydes and ketones in the presence of silica gel to give alcohols in good yields under ambient conditions. Aldehydes are selectively reduced in the presence of ketones. The process is attractive because all the components are stable and easy to handle and because the isolation procedure is convenient.
T. Taniguchi, D. P. Curran, Org. Lett., 2012, 14, 4540-4543.
Activation of diphenylsilane in the presence of a catalytic amount of an N-heterocyclic carbene (NHC) enables hydrosilylation of carbonyl derivatives under mild conditions. Presumably, a hypervalent silicon intermediate featuring strong Lewis acid character allows dual activation of both the carbonyl moiety and the hydride at the silicon center. Some interesting selectivities have been encountered.
Q. Zhao, D. P. Curran, M. Malacria, L. Fensterbank, J.-P. Goddard, E. Lacôte, Synlett, 2012, 23, 433-437.
Decaborane was found to be an effective agent for the chemoselective reduction of ketones to alcohols in the presence of pyrrolidine and cerium(III) chloride heptahydrate in methanol.
J. W. Bae, S. H. Lee, Y. J. Jung, C.-O. Maing, C. M. Yoon, Tetrahedron Lett., 2001, 42, 2137-2139.
A highly efficient silver-catalyzed chemoselective method enables the reduction of aldehydes to their corresponding alcohols in water by using hydrosilanes as reducing agents. Ketones remained essentially inert under the same reaction conditions.
Z. Jia, M. Liu, X. Li, A. S. C. Chan, C.-J. Li, Synlett, 2013, 24, 2049-2056.
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.
An iron complex containing electronically coupled acidic and hydridic hydrogens catalyzes the hydrogenation of ketones under mild conditions and shows high chemoselectivity for aldehydes, ketones, and imines. Isolated carbon double and triple bonds, aryl halides, nitrates, epoxides, and ester functions are unaffected by the hydrogenation conditions.
C. P. Casey, H. Guan, J. Am. Chem. Soc., 2007, 129, 5816-5817.
A chiral imidazole iminopyridine as a ligand enables a highly enantioselective cobalt-catalyzed hydroboration of diaryl ketones with pinacolborane to provide chiral benzhydrols in very good yields and ee. This protocol could be carried out in a gram scale under mild reaction conditions with good functional group tolerance.
W. Liu, J. Guo, S. Xing, Z. Lu, Org. Lett., 2020, 22, 2532-2536.
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.
The use of (R)-(−)-(DTBM-SEGPHOS)CuH effects a highly enantioselective 1,2-hydrosilylation of prochiral diaryl ketones to yield nonracemic diarylmethanols in excellent yields.
C.-T. Lee, B. H. Lipshutz, Org. Lett., 2008, 10, 4187-4190.
For highly stereoselective reductions of a large number of five- and six-membered cyclic ketones to the most thermodynamically stable alcohols, ketones are treated with lithium dispersion and either FeCl2ˇ4H2O or CuCl2ˇ2H2O in THF at room temperature. This protocol is more convenient and efficient than those commonly reported for similar reductions.
N. Kennedy, T. Cohen, J. Org. Chem., 2015, 80, 8134-8141.
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.
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.
Pincer-aryl ruthenium(II) complexes form active catalysts in the reduction of ketones by hydrogen transfer in i PrOH using KOH as promoter. At a KOH/Ru molar ratio of 20/1 only trace amounts of aldol products are formed. Under these conditions, the σ Ru-C bond is stable and the [Ru(PCP)PPh3] fragment is preserved.
P. Dani, T. Karlen, R. A. Gossage, S. Gladiali, G. van Koten, Angew. Chem., 2000, 112, 759-761.
The reduction of ketones and aldehydes with lanthanide metals (La, Ce, Sm, Yb) and a catalytic amount of iodine (5 mol %) in iPrOH proceeded smoothly to produce the corresponding alcohols as the major products in good yield, while in THF, methanol, and ethanol the pinacols were mainly produced. The yields of alcohols were improved most effectively by the use of Sm metal.
S.-I. Fukuzawa, N. Nakano, T. Saitoh, Eur. J. Org. Chem., 2004, 2863-2867.
The organic reductant 1-acetyl-2,3-dimethylimidazolidine is able to directly reduce a series of aromatic, aliphatic and α,β-unsaturated aldehydes as well as imines in high yields.
D. Li, Y. Zhang, G. Zhou, W. Guo, Synlett, 2008, 225-228.
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.
The use of diethylaluminum benzenethiolate enables an efficient discrimination between aldehydes and other carbonyl functions and allows a chemoselective in situ reduction of ketones and methyl esters in the presence of aldehydes without using traditional protecting group methodologies.
G. Bastug, S. Dierick, F. Lebreux, I. E. Markó, Org. Lett., 2012, 14, 1306-1309.
Optically pure C2-symmetrical cyclic amines were efficiently synthesized from the corresponding diols obtained from an enantioselective borohydride reduction of diketones in the presence of a chiral β-ketoiminato cobalt(II) catalyst.
M. Sato, Y. Gunji, T. Ikeno, T. Yamada, Synthesis, 2004, 1434-1438.
Reduction of β-hydroxyketones by SmI2/H2O/Et3N provided 1,3-diols in quantitative yields with no byproduct formation.
T. A. Davis, P. R. Chopade, G. Hilmersson, R. A. Flowers, Org. Lett., 2005, 7, 119-122.
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.
A mild, enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters using axially chiral BINAM N-heterocyclic carbene (NHC)-Rh(III) complexes as catalysts gave 3-hydroxy-3-arylpropionic acid methyl or ethyl esters in good yields with good to excellent enantioselectivities under mild conditions.
Q. Xu, X. Gu, S. Liu, Q. Duo, M. Shi, J. Org. Chem., 2007, 72, 2240-2242.
A combination of tricyclohexylphosphine and chiral alkenylborane derived in situ from a diyne as a frustrated Lewis pair catalyst enables a highly enantioselective hydrosilylation of 1,2-dicarbonyl compounds. Various optically active α-hydroxy ketones and esters were obtained in good yields with high ee’s.
X. Ren, H. Du, J. Am. Chem. Soc., 2016, 138, 810-813.
Red-Al is an efficient chelation-controlled reducing reagent for acyclic acetal-protected R-hydroxy ketones. Typically, high diastereomeric ratios and yields can be achieved for the synthesis of 1,2-anti-diols.
N. Bajwa, M. P. Jennings, J. Org. Chem., 2008, 73, 3638-3641.
α-Keto esters can be prepared via Mannich addition of ethyl diazoacetate to imines followed by oxidation of the diazo group with Oxone. Implementation of a recently developed dynamic kinetic resolution of β-substituted-α-keto esters via Ru(II)-catalyzed asymmetric transfer hydrogenation provides enantioenriched anti-α-hydroxy-β-amino acid derivatives in high diastereo- and enantioselectivity.
C. G. Goodman, D. T. Do, J. S. Johnson, Org. Lett., 2013, 15, 2446-2449.
An asymmetric α-alkylative reduction of prochiral ketones with primary alcohols has been disclosed. The reaction is catalyzed by both iridium and ruthenium complexes and gave optically active alcohols with elongation of the carbon skeleton with high enantioselectivity.
G. Onodera, Y. Nishibayashi, S. Uemura, Angew. Chem. Int. Ed., 2006, 45, 3819-3822.
Carrots (Daucus carota) were used as cheap, eco-compatible, and efficient reducing reagent for the conversion of cyclic amino-ketones into amino-alcohols in high yields and enantiomeric excesses. The procedure allows an easy access to precursors of biologically active products.
R. Lacheretz, D. G. Pardo, J. Cossy, Org. Lett., 2009, 11, 1245-1248.
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.
(R)-β-Hydroxy nitriles were obtained via a reduction catalyzed by a recombinant carbonyl reductase with excellent optical purity and were further converted to (R)-β-hydroxy carboxylic acids via a nitrilase-catalyzed hydrolysis. The present study allows ready access to both chiral β-hydroxy nitriles and β-hydroxy carboxylic acids of pharmaceutical importance.
D. Zhu, H. Ankati, C. Mukherjee, Y. Yang, E. R. Biehl, L. Hua, Org. Lett., 2007, 9, 2561-2563.
Various enantiomerically pure α-hydroxy esters were synthesized by a Ru-Cn-Tunephos-catalyzed asymmetric hydrogenation of α-keto esters. High enantiomeric excess has been achieved for both α-aryl and α-alkyl substituted α-keto esters.
C.-J. Wang, X. Sun, X. Zhang, Synlett, 2006, 1169-1172.
An iridium-catalyzed hydrogenation of α-fluoro ketones provides β-fluoro alcohols with good enantiomeric and diastereomeric selectivities using a strategy of dynamic kinetic resolution. A C-FˇˇˇNa charge-dipole interaction in the transition state of hydride transfer is responsible for the diastereomeric control.
X. Tan, W. Zeng, J. Wen, X. Zhang, Org. Lett., 2020, 22, 7230-7233.
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 C2-symmetric copper-bound N-heterocyclic carbene (NHC) exhibits excellent reactivity and enantioselectivity in the hydrosilylation of a variety of structurally diverse ketones including challenging substrates as 2-butanone and 3-hexanone. Even at low catalyst loading (2.0 mol %), the reactions occur in under an hour at room temperature and often do not require purification beyond catalyst and solvent removal.
A. Albright, R. E. Gawley, J. Am. Chem. Soc., 2011, 133, 19680-19683.
The rhenium-catalyzed hydrosilation of aldehydes and ketones under ambient temperature and atmosphere gave protected alcohol as silyl ether in good yields. The mechanism is discussed.
E. A. Ison, E. R. Trivedi, R. A. Corbin, M. M. Abu-Omar, J. Am. Chem. Soc., 2005, 127, 15374-15375.
Optimizations to generate CuH in situ have led to an efficient and inexpensive hydrosilylation method for dialkyl ketones.
B. H. Lipshutz, C. C. Caires, P. Kuipers, W. Chrisman, Org. Lett., 2003, 5, 3085-3088.
Aliphatic carboxyl derivatives (acids, acyl chlorides, esters) and aldehydes were efficiently reduced to the methyl group by HSiEt3 in the presence of catalytic amounts of B(C6F5)3. Aromatic carboxylic acids, as well as other carbonyl functional equivalents, underwent smooth partial reduction to the corresponding TES-protected benzylic alcohols in competition with a Friedel-Crafts-like alkylation decreasing the overall selectivity of the reduction process.
V. Gevorgyan, M. Rubin, J.-X. Liu, Y. Yamamoto, J. Org. Chem, 2000, 66, 1672-1675.
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.