Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

Abstract

A catalytic protocol for the enantio-and diastereoselective reduction of α-substituted-β-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-β-keto carbonitriles were obtained in high yields (94%−98%) and excellent enantio-and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.

Photocatalytic Chemoselective Transfer Hydrogenation of Quinolines to Tetrahydroquinolines on Hierarchical NiO/In2O3–CdS Microspheres

“…(2) After that, the absorbed benzyl alcohol is oxidized to benzaldehyde by h + but the active hydrogen species are left on the surface of NiO. , (3) Subsequently, a quinoline molecule is absorbed by the hydrogen bond interaction between N in quinoline and reactive hydrogen species on the NiO surface . (4) Finally, tetrahydroquinoline is produced by the active hydrogen species . Moreover, the excess active hydrogen species is converted into H 2 by the e– accumulated on the NiO surface.…”

“…3 (4) Finally, tetrahydroquinoline is produced by the active hydrogen species. 13 Moreover, the excess active hydrogen species is converted into H 2 by the e− accumulated on the NiO surface. The partial NiO can be photoreduced to metallic Ni during the TH process and then the produced metallic Ni during this process can be recovered to NiO through an in situ oxidation process by molecular O 2 and the produced active • O 2 − and • OH in air atmosphere under visible light irradiation.…”

“…Alternatively, the easily transported liquids with high-hydrogen content, such as alcohol and formic acid, serving as safe hydrogen donors, have emerged as potential candidates to address the issue of molecular hydrogen. Therefore, the hydrogen transfer reaction has been attracting more and more attention in organic synthesis processes. − …”

Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-Diphenylethylene-1,2-Diamine Complexes: Efficient Catalysts for Asymmetric Transfer Hydrogenation

“…10 The ATH of -keto--acetal enamides 15 has been studied with complex (R,R)-B and the HCO 2 H/Et 3 N (5:2) azeotropic mixture delivering a wide range of enantioenriched -hydroxy--acetal enamides 16 with a high chemoselectivity observed toward the reduction of the carbonyl group over the C=C bond, yields up to quantitative and enantioselectivities up to 99% (Table 1, F). 11 The same catalytic system was used to access 1,2,3,4tetrahydroquinolin-4-ols 18 conveniently through ATH of 4-quinolone derivatives 17 with excellent enantioselectivi-(F) ATH of -keto--acetal enamides 11 -Access to -hydroxy--acetal enamides -Mild conditions -Low catalyst loading -Excellent chemo-and enantioselectivities (G) ATH of Quinolone Derivatives 12 -Efficient and practical access to 1,2,3,4-tetrahydroquinolin-4-ols -Catalytic ATH cascade reaction -Mild conditions -Excellent enantiofacial discrimination (H) ATH/DKR of 3-Benzylidene Chromanones 13 -One-pot ATH cascade protocol to access cis-benzyl-chromanols -Low catalyst loading -2 stereogenic centers controlled in a single step -Excellent diastereo-and enantioselectivities (I) ATH/KR of 2-Aryl-2,3-dihydroquinolin-4(1H)-ones 14 -Synthesis of 2-aryl-2,3-dihydroquinolin-4(1H)-ones and 2-aryl tetrahydro-4quinolols -Efficient kinetic resolution -Excellent enantioselectivities (J) ATH of -Aminoalkyl ′-Chloromethyl Ketones 15 -Access to both diastereomers of 3-amino-1-chloro-2-hydroxy-4-phenylbutanes -Low catalyst loading -Excellent yields and high diastereoselectivities -Key building blocks for pharmaceutical intermediates -Broad scope (K) ATH/DKR of -Substituted -Keto Carbonitriles 16 -Efficient access to -substituted -hydroxy carbonitriles -Building blocks for biologically active pharmaceuticals -Excellent yields -High diastereoselectivities and excellent enantioselectivities -Rationalization of the diastereoselectivity by DFT calculations -Wide substrate scope…”

“…15 -Substituted -keto carbonitriles 27 and 28 were efficiently reduced with (R,R)-B and HCO 2 H/Et 3 N (5:2) to the corresponding -substituted -hydroxy carbonitriles 29 and 30 in excellent enantio-and diastereoselectivities (up to >99% ee, up to >99:1 dr) through a DKR process offering rapid access to key intermediates of biologically active pharmaceuticals (Table 1, K). 16 Rh-tethered complexes (R,R)-B-(R,R)-E have been developed and used in the ATH of a wide range of functionalized ketones exhibiting excellent activities and selectivities. Among them, complex (R,R)-B was particularly efficient to produce a series of enantioenriched alcohols including oxygen-and nitrogen-containing heterocycles such as cis 3-hydroxymethyl chroman-4-ols, cis-3-benzyl-chromanols, 1,2,3,4-tetrahydroquinolin-4-ols, and 2-aryl tetrahydro-4quinolol derivatives as well as carbocycles such as -substituted -hydroxy carbonitriles.…”