Transfer Hydrogenation with Hantzsch Ester

Overall Score4.5

Generality
Reagent Availability
Experimental User Friendliness
Criteria #4
Criteria #5

General Characteristics

Dihydropyridine (Diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) synthesized from formaldehyde and ethyl acetoacetate is commonly called the Hantzsch ester.

The Hantzsch ester is used as a hydride donor reagent in reduction reactions, often with organocatalysts or photo-redox catalysts. It can be regarded as the chemical analogue of NADH (the biological reductant), since they share the dihydropyridine active structure.

General References

Norcross, B. E., Klinedinst, Jr., P. E., Westheimer, F. H. J. Am. Chem. Soc. 1962, 84, 797. DOI: 10.1021/ja00864a024
Singh, S.; Sharma, V. K.; Gill, S.; Sahota, R. I. K. J. Chem. Soc. Perkin Trans. 1. 1985, 437. DOI: 10.1039/P19850000437

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Torchy, S.; Cordonnier, G.; Barbry, D.; Eynde, J. J. V. Molecules 2002, 7, 528. doi:10.3390/70700528
Connon, S. J. Org. Biomol. Chem. 2007, 5, 3407. DOI: 10.1039/B711499K
de Vries, J. G.; Mrsic, N. Catal. Sci. Technol. 2011, 1, 727. DOI: 10.1039/C1CY00050K
Rueping, M.; Dufour, J.; Schoepke, F. R. Green Chem. 2011, 13, 1084. DOI: 10.1039/C1GC15027H
Zheng, C.; You, S.-L. Chem. Soc. Rev. 2012, 41, 2498. DOI: 10.1039/C1CS15268H
McSkimming, A.; Colbran, S. B. Chem. Soc. Rev. 2013, 42, 5439. DOI: 10.1039/C3CS35466K
Wang, D.; Astruc, D. Chem. Rev. 2015, 115, 6621. DOI: 10.1021/acs.chemrev.5b00203

Reaction Mechanism
Examples

Asymmetric conjugate reduction of α,β-unsaturated aldehydes with Hantzsh ester catalyzed by MacMillan’s imidazolidinone catalyst.^[1]

Metal-free and chemoselective reduction of amide.^[2]

Asymmetric reduction of quinolines catalyzed by the Terada-Akiyama phosphoric acid catalyst.^[3]

Experimental Procedure
Experimental Tips
References

Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 128, 32. DOI: 10.1021/ja043834g
(a) Barbe, G.; Charette, A. B. J. Am. Chem. Soc. 2008, 130, 18. DOI: 10.1021/ja077463q (b) Improvement with Et3SiH: Pelletier, G.; Bechara, W. S.; Charette, A. B. J. Am. Chem. Soc. 2010, 132, 12817. DOI: 10.1021/ja105194s
Rueping, M.; Theissmann, T. Chem. Sci. 2010, 1, 473. DOI: 10.1039/C0SC00206B