Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Beilstein-Institut
2025-04-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.21.59 |
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| Summary: | 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. |
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| ISSN: | 1860-5397 |