Tortora C, Fischer C, Kohlbauer S, Zamfir A, Ballmann G, Pahl J, Harder S, Tsogoeva S (2025)
Publication Type: Journal article
Publication year: 2025
Book Volume: 21
Pages Range: 755-765
DOI: 10.3762/bjoc.21.59
Asymmetric hydrocyanation of hydrazones, catalyzed by a calcium–BINOL phosphate complex, has been studied for the first time both experimentally and computationally with DFT methods. A full catalytic cycle for the enantioselective synthesis of α-hydrazinonitriles is proposed based on insights gained from DFT calculations. Trimethylsilyl cyanide (TMSCN) has been used as a sacrificial cyanide source. We found that isocyanide (rather than cyanide) is a preferred coordination to calcium during the catalytic cycle, while the active catalyst prefers a side-on coordination of cyanide. The configuration-determining step is a hydrocyanation via a calcium isocyanide complex, whereas the rate-limiting step is that which recovers the calcium catalyst and replaces the TMS-bound product from the catalyst. While our experimental data demonstrate enantioselectivity values as high as 89% under certain conditions, the overall enantioselectivity achieved with the calcium catalyst remains modest, mainly due to competing pathways for the Z- and E-hydrazone isomers leading to opposite enantiomers. The experimental results confirm these computational proposals.
APA:
Tortora, C., Fischer, C., Kohlbauer, S., Zamfir, A., Ballmann, G., Pahl, J.,... Tsogoeva, S. (2025). Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones. Beilstein Journal of Organic Chemistry, 21, 755-765. https://doi.org/10.3762/bjoc.21.59
MLA:
Tortora, Carola, et al. "Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones." Beilstein Journal of Organic Chemistry 21 (2025): 755-765.
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