Categories: N-H Bond Formation >
Reduction of imines
A nickel-catalyzed enantioselective transfer hydrogenation of N-sulfonyl imines offers excellent α-selectivity. The use of inexpensive 2-propanol-d8 as a deuterium source enables a deuteration with high deuterium content. In addition, no deuteration of β-C-H and the remote C-H of N-sulfonyl amines occurred, which is hard to achieve using other imines or by hydrogen isotope exchange with D2O.
P. Yang, L. Zhang, K. Fu, Y. Sun, X. Wang, J. Yue, Y. Ma, B. Tang, Org. Lett., 2020, 22, 8278-8284.
Asymmetric reduction of ketimines with trichlorosilane can be catalyzed by N-methylvaline-derived Lewis-basic formamides with high enantioselectivity and low catalyst loading at room temperature in toluene. Appending a fluorous tag to the catalyst simplifies the isolation procedure and allows the catalyst to be recycled.
A. V. Malkov, M. Figlus, S. Stončius, P. Kočovský, J. Org. Chem., 2007, 72, 1315-1325.
Chiral Ru-catalysts in combination with formic acid/triethylamine as the hydrogen donor enable a highly efficient ATH of N-diphenylphosphinyl acyclic imines. Substrates include various aryl alkyl and heteroaryl alkyl substituted imines, and the corresponding reduced amines were obtained with excellent enantiomeric excess and yields.
D. He, C. Xu, X. Xing, Org. Lett., 2022, 24, 8354-8358.
A cationic [IrH(THF)(P,N)(imine)][BArF] catalyst containing a P-stereogenic MaxPHOX ligand enables a direct asymmetric hydrogenation of N-methyl and N-alkyl imines with high enantioselectivity. The labile tetrahydrofuran ligand allows for effective activation and reactivity, even at low temperatures.
E. Salomó, A. Gallen, G. Sciortino, G. Ujaque, A. Grbulosa, A. Lledós, A. Riera, X. Verdaguer, J. Am. Chem. Soc., 2018, 140, 16360-16367.
L-Piperazine-2-carboxylic acid derived N-formamides are highly enantioselective Lewis basic catalysts for the hydrosilylation of imines with trichlorosilane. High isolated yields and enantioselectivities were obtained for a broad range of substrates, including aromatic and aliphatic ketimines.
Z. Wang, M. Cheng, P. Wu, S. Wei, J. Sun, Org. Lett., 2006, 8, 3045-3048.
L-Pipecolinic acid derived formamides are highly efficient and enantioselective Lewis basic organocatalysts for the mild reduction of various N-aryl imines with trichlorosilane.
Z. Wang, X. Ye, S. Wei, P. Wu, A. Zhang, J. Sun, Org. Lett., 2006, 8, 999-1001.
The combination of molecular iodine and a hydrosilane enables a practical reduction of N-sulfonyl aldimines to the corresponding N-alkylsulfonamides.
J. Jiang, L. Xiao, Y.-L. Li, J. An, Synlett, 2021, 32, 291-294.
A benzenedithiolate Rh(III) complex [TpMe2Rh(o-S2C6H4)(MeCN)], which can heterolytically activate H2, catalyzes hydrogenation of imines under ambient temperature and pressure with high chemoselectivity.
Y. Misumi, H. Seino, Y. Mizobe, J. Am. Chem. Soc., 2009, 131, 14636-14637.
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.
Various benzaldimines and ketimines can be hydrosilated efficiently with PhMe2SiH employing B(C6F5)3 as a catalyst. Spectral evidence supports the intermediacy of a silyliminium cation with a hydridoborate counterion formed via abstraction of a hydride from PhMe2SiH by B(C6F5)3 in the presence of imines.
J. M. Blackwell, E. R. Sonmor, T. Scoccitti, W. E. Piers, Org. Lett., 2000, 2, 3921-3923.
A simple and convenient procedure allows the reductive amination of aldehydes and ketones using sodium borohydride as reducing agent and boric acid, p-toluenesulfonic acid monohydrate or benzoic acid as activator under solvent-free conditions.
B. T. Cho, S. K. Kang, Tetrahedron, 2005, 61, 5725-5734.
1,2,4,3-triazaphospholenes halides catalyze the 1,2 hydroboration of imines and α,β unsaturated aldehydes with pinacolborane, including examples that did not undergo hydroboration by previously reported diazaphospholene systems. DFT calculations support a mechanism where a triazaphospholene cation interacts with the substrate.
C.-H. Tien, M. R. Adams, M. J. Ferguson, E. R. Johnson, A. W. H. Speed, Org. Lett., 2017, 19, 5565-5568.
A simple [Ru(p-cymene)Cl2]2 complex is used as a catalyst precursor in a catalyzed hydroboration of nitriles and imines using pinacolborane with unprecedented catalytic efficiency.
A. Kaithal, B. Chatterjee, C. Gunanathan, J. Org. Chem., 2016, 81, 11153-11161.
Photoredox catalysis mediates an umpolung reactivity of imines exemplified by proton abstraction from water as a key step in the reduction of benzophenone ketimines to amines in very good yields. Deuterium is introduced into amines efficiently using D2O as an inexpensive deuterium source.
R. Wang, M. Ma, X. Gong, G. B. Panetti, X. Fan, P. J. Walsh, Org. Lett., 2018, 20, 2403-2406.
A visible-light photocalytic method for the chemoselective transfer hydrogenation of diarylketimines in batch and continuous flow utilizes Et3N as both hydrogen source and single-electron donor. The reaction tolerates other reducible functional including nitriles, halides, esters, and ketones. Continuous-flow processing facilitates straightforward scale-up of the reaction.
D. J. van As, T. U. Connell, M. Brzozowski, A. D. Scully, A. Polyzos, Org. Lett., 2018, 20, 905-908.
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.
Transfer hydrogenation of chiral α,β-unsaturated N-(tert-butylsulfinyl)ketimines followed by removal of the sulfinyl group provides primary allylic amines with enantiomeric excesses from 97 to >99%.
E. Selva, Y. Sempere, D. Ruiz-Martínez, O. Pablo, D. Guijarro, J. Org. Chem., 2017, 82, 13693-13699.
A triazole-based N-heterocyclic carbene borane (NHC-borane) enables an efficient and highly diastereoselective reduction of various of tert-butanesulfinyl ketimines. The reagent was more efficient than or comparable to commonly used reductive reagents such as NaBH4, NaBH3CN, l-selectride, a Ru catalyst, or BH3-THF.
T. Liu, L-y. Chen, Z. Sun, J. Org. Chem., 2015, 80, 11441-11446.
The combination of HMPA and SmBr2 in THF is a powerful reductant that is capable of reducing ketimines and alkyl chlorides at room temperature.
B. W. Knettle, R. A. Flowers, II, Org. Lett., 2001, 3, 2321-2324.
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.
A novel process for the efficient, enantioselective hydrosilylation of ketimines based on catalytic amounts of copper hydride, (R)-DTBM-SEGPHOS, and an inexpensive silane (tetramethyldisiloxane, TMDS) has been developed. The resulting products are converted to their free-base form upon mild hydrolysis.
B. H. Lipshutz, H. Shimizu, Angew. Chem. Int. Ed., 2004, 43, 2228-2230.
An aryloxotitanium complex is a highly chemo- and regioselective catalyst for intermolecular hydroamination of terminal alkynes. Branched imines are obtained in good yield with various primary aromatic and aliphatic amines.
V. Khedkar, A. Tillak, M. Beller, Org. Lett., 2003, 5, 4767-4770.
An efficient Pd(OAc)2-catalyzed asymmetric hydrogenation of α-iminoesters at 1 atm hydrogen pressure and room temperature provides chiral α-arylglycine fragments, which are widely found in many chiral products and bioactive molecules.
J. Chen, F. Li, F. Wang, Y. Hu, Z. Zhang, M. Zhao, W. Zhang, Org. Lett., 2019, 21, 9060-9065.
α-Imino esters derived from aryl and alkyl keto esters could be reduced to the corresponding α-amino esters in excellent yields and in high enantiomeric excesses using 5 mol-% of a chiral phosphoric acid as catalyst, Hantzsch ester as hydride donor, and toluene as solvent.
G. Li, Y. Liang, J. C. Antilla, J. Am. Chem. Soc., 2007, 129, 5830-5831.
Brønsted acid catalysis enables highly efficient, regioselective, and enantioselective transfer hydrogenation of α-keto ketimines and reductive amination of diketones. A series of chiral α-amino ketones is prepared in high yields, excellent regioselectivities, and enantioselectivities.
W. Wen, Y. Zeng, L.-Y. Peng, L.-N. Fu, Q.-X. Guo, Org. Lett., 2015, 17, 3922-3925.
A BINOL-derived boro-phosphate catalyzes an enantioselective reduction of α-trifluoromethylated imines to provide chiral α-trifluoromethylated amines in high yields and with excellent enantioselectivities in the presence of catecholborane as hydride source under mild conditions.
H. He, X. Tang, Y. Cao, J. C. Antilla, J. Org. Chem., 2021, 86, 4336-4345.