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. 2019 Apr 2;9(18):10201-10210.
doi: 10.1039/c9ra01468c. eCollection 2019 Mar 28.

Mechanistic insight into the catalytic hydrogenation of nonactivated aldehydes with a Hantzsch ester in the presence of a series of organoboranes: NMR and DFT studies

Go Hamasaka  1   2 , Hiroaki Tsuji  1   2 , Masahiro Ehara  1   2 , Yasuhiro Uozumi  1   2   3
Affiliations

Mechanistic insight into the catalytic hydrogenation of nonactivated aldehydes with a Hantzsch ester in the presence of a series of organoboranes: NMR and DFT studies

Go Hamasaka et al. RSC Adv. .

Abstract

Mechanistic studies on the organoborane-catalyzed transfer hydrogenation of nonactivated aldehydes with a Hantzsch ester (diethyl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) as a synthetic NADH analogue were performed by NMR experiments and DFT calculations. In the reaction of benzaldehyde with the Hantzsch ester, the catalytic activity of tris[3,5-bis(trifluoromethyl)phenyl]borane was superior to that of other borane catalysts, such as tris(pentafluorophenyl)borane, trifluoroborane etherate, or triphenylborane. Stoichiometric NMR experiments demonstrated that the hydrogenation process proceeds through activation of the aldehyde by the borane catalyst, followed by hydride transfer from the Hantzsch ester to the resulting activated aldehyde. DFT calculations for the hydrogenation of benzaldehyde with the Hantzsch ester in the presence of borane catalysts supported the reaction pathway and showed why the catalytic activity of tris[3,5-bis(trifluoromethyl)phenyl]borane is higher than that of the other boron catalysts. Association constants and Gibbs free energies in the reaction of boron catalysts with benzaldehyde or benzyl alcohol, which were investigated by 1H NMR analyses, also indicated why tris[3,5-bis(trifluoromethyl)phenyl]borane is a superior catalyst to tris(pentafluorophenyl)borane, trifluoroborane etherate, or triphenylborane in the hydrogenation reaction.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Active site of alcohol dehydrogenase for the reduction of acetaldehyde with NADH.
Scheme 1
Scheme 1. Organoborane-catalyzed hydrogenation of nonactivated aldehydes with a Hantzsch ester (our previous work).
Fig. 2
Fig. 2. Possible reaction pathways. (a) Lewis acid activation pathway, (b) borohydride pathway.
Scheme 2
Scheme 2. Hydrogenation of benzaldehyde (1) with Hantzsch ester 2. Reaction conditions: 1 (0.25 mmol), 2 (0.38 mmol), [B] cat. (0.013 mmol), 1,4-dioxane (1 mL), 25 °C, 12 h.
Scheme 3
Scheme 3. Stoichiometric experiments on (a) the reaction of benzaldehyde (1) with tris[3,5-bis(trifluoromethyl)phenyl]borane (B-a) followed by treatment with Hantzsch ester 2; (b) the reaction of benzaldehyde (1) with Hantzsch ester 2.
Fig. 3
Fig. 3. 1H NMR spectra for (a) tris[3,5-bis(trifluoromethyl)phenyl]borane (B-a), (b) benzaldehyde (1), (c) a mixture of 1 and B-a, and (d) after addition of Hantzsch ester 2 in CD2Cl2.
Fig. 4
Fig. 4. Energy diagram in the organoborane-catalyzed hydrogenation of benzaldehyde (1) with Hantzsch ester (2). Red: tris[3,5-bis(trifluoromethyl)phenyl]borane (B-a), blue: tris(pentafluorophenyl)borane (B-b), green: trifluoroborane etherate (B-c), black: triphenylborane (B-d).
Fig. 5
Fig. 5. Calculated structures of transition states TSa (a), TSb (b), TSc (c), and TSd (d) and selected bond distances (the molecular structures were drawn with CYLview).
Scheme 4
Scheme 4. Possible reactions of boron catalysts in the reaction system.
Fig. 6
Fig. 6. VT 1H NMR spectra of a mixture of 1 and B-a (20 °C to −90 °C).
Fig. 7
Fig. 7. van't Hoff plot for a mixture of 1 and B-a (−40 °C to −90 °C).
Fig. 8
Fig. 8. VT 1H NMR spectra for a mixture of 3 and B-a (20 °C to −90 °C).
Fig. 9
Fig. 9. van't Hoff plot for a mixture of 3 and B-a (−60 °C to −90 °C).
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