Direct Hydrogenation of Amides to Alcohols and Amines under Mild Conditions

Balaraman, Ekambaram; Gnanaprakasam, Boopathy; Shimon, Linda J. W.; Milstein, David

doi:10.1021/ja1080019

Cited by 410 publications

(285 citation statements)

References 28 publications

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“…17,18 Although catalytic hydrogenations are appealing on the basis of their atom economy, most amide deoxygenations via hydrogenation require forcing conditions, including high pressure and elevated temperature (>150°C). In addition, hydrodeoxygenation of primary and secondary amines often yields mixtures resulting from alkyl group disproportionation.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In addition, hydrodeoxygenation of primary and secondary amines often yields mixtures resulting from alkyl group disproportionation. 3,13,17,18 Although a range of late metal complexes have been reported to efficiently reduce amides through hydrosilylation, 8,9,19 new catalytic processes are still needed to address the challenges facing amide deoxygenations (Scheme 1). Few catalytic systems are able to effectively reduce primary, secondary, and tertiary amides, 11 and few catalysts are based on metal complexes other than nonoxophilic late metals.…”

Section: ■ Introductionmentioning

confidence: 99%

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Magnesium-Catalyzed Mild Reduction of Tertiary and Secondary Amides to Amines

et al. 2015

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The first example of a catalytic hydroboration of amides for their deoxygenation to amines is reported. This transformation employs an earth-abundant magnesium-based catalyst. Tertiary and secondary amides are reduced to amines at room temperature in the presence of pinacolborane (HBpin) and catalytic amounts of ToMMgMe (ToM = tris(4,4-dimethyl-2-oxazolinyl)phenylborate). Catalyst initiation and speciation is complex in this system, as revealed by the effects of concentration and order of addition of the substrate and HBpin in the catalytic experiments. ToMMgH2Bpin, formed from ToMMgMe and HBpin, is ruled out as a possible catalytically relevant species by its reaction with N,N-dimethylbenzamide, which gives Me2NBpin and PhBpin through C-N and C-C bond cleavage pathways, respectively. In that reaction, the catalytic product benzyldimethylamine is formed in only low yield. Alternatively, the reaction of ToMMgMe and N,Ndimethylbenzamide slowly gives decomposition of ToMMgMe over 24 h, and this interaction is also ruled out as a catalytically relevant step. Together, these data suggest that catalytic activation of ToMMgMe requires both HBpin and amide, and ToMMgH2Bpin is not a catalytic intermediate. With information on catalyst activation in hand, tertiary amides are selectively reduced to amines in good yield when catalytic amounts of ToMMgMe are added to a mixture of amide and excess HBpin. In addition, secondary amides are reduced in the presence of 10 mol % ToMMgMe and 4 equiv of HBpin. Functional groups such as cyano, nitro, and azo remain intact under the mild reaction conditions. In addition, kinetic experiments and competition experiments indicate that B-H addition to amide C═O is fast, even faster than addition to ester C═O, and requires participation of the catalyst, whereas the turnover-limiting step of the catalyst is deoxygenation. ABSTRACT:The first example of a catalytic hydroboration of amides for their deoxygenation to amines is reported. This transformation employs an earth-abundant magnesium-based catalyst. Tertiary and secondary amides are reduced to amines at room temperature in the presence of pinacolborane (HBpin) and catalytic amounts of To M MgMe (To M = tris(4,4-dimethyl-2-oxazolinyl)phenylborate). Catalyst initiation and speciation is complex in this system, as revealed by the effects of concentration and order of addition of the substrate and HBpin in the catalytic experiments. To M MgH 2 Bpin, formed from To M MgMe and HBpin, is ruled out as a possible catalytically relevant species by its reaction with N,N-dimethylbenzamide, which gives Me 2 NBpin and PhBpin through C−N and C−C bond cleavage pathways, respectively. In that reaction, the catalytic product benzyldimethylamine is formed in only low yield. Alternatively, the reaction of To M MgMe and N,N-dimethylbenzamide slowly gives decomposition of To M

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Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Magnesium-Catalyzed Mild Reduction of Tertiary and Secondary Amides to Amines

et al. 2015

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“…Treatment of the Milstein PNN ligand bearing phosphinotert-butyl groups [15] with FeCl 2 in THF afforded iron pincer complex 7 in 72 % yield [Eq. (1)].…”

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confidence: 99%

Iron‐Catalyzed, Atom‐Economical, Chemo‐ and Regioselective Alkene Hydroboration with Pinacolborane

et al. 2013

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“…Formic acid joins other challenging substrates for which the homogeneous hydrogenation has been recently reported, including carboxylic acids, [20] esters [9] and amides. [21] The formic acid reaction employs a catalyst bearing simple ligands, avoids the use of organic solvents and H 2 gas, and features very low catalyst loadings. Future efforts will focus on improving the overall methanol yield by increasing catalyst selectivity and/or recycling the H 2 and CO 2 byproducts.…”

Section: Angewandte Zuschriftenmentioning

confidence: 99%