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Reduction of carbonyl compounds
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.
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.
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 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.
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 acive 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.
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.
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.
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.
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.
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.
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.
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.
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.