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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Beilstein-Institut
2025-04-01
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| Series: | Beilstein Journal of Organic Chemistry |
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| Online Access: | https://doi.org/10.3762/bjoc.21.59 |
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| author | Carola Tortora Christian A. Fischer Sascha Kohlbauer Alexandru Zamfir Gerd M. Ballmann Jürgen Pahl Sjoerd Harder Svetlana B. Tsogoeva |
| author_facet | Carola Tortora Christian A. Fischer Sascha Kohlbauer Alexandru Zamfir Gerd M. Ballmann Jürgen Pahl Sjoerd Harder Svetlana B. Tsogoeva |
| author_sort | Carola Tortora |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1b5d0e542b7848f3a0e6a48ffb0d4a95 |
| institution | OA Journals |
| issn | 1860-5397 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Beilstein-Institut |
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| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj-art-1b5d0e542b7848f3a0e6a48ffb0d4a952025-08-20T02:11:12ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972025-04-0121175576510.3762/bjoc.21.591860-5397-21-59Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazonesCarola Tortora0Christian A. Fischer1Sascha Kohlbauer2Alexandru Zamfir3Gerd M. Ballmann4Jürgen Pahl5Sjoerd Harder6Svetlana B. Tsogoeva7Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger Strasse 10, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Chair of Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger Strasse 10, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger Strasse 10, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Chair of Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Chair of Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Chair of Inorganic and Organometallic Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany Department of Chemistry and Pharmacy, Organic Chemistry Chair I and Interdisciplinary Center for Molecular Materials (ICMM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger Strasse 10, 91058 Erlangen, Germany 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.https://doi.org/10.3762/bjoc.21.59asymmetric synthesiscalcium–binol phosphate catalysishydrocyanationhydrazonesisocyanides |
| spellingShingle | Carola Tortora Christian A. Fischer Sascha Kohlbauer Alexandru Zamfir Gerd M. Ballmann Jürgen Pahl Sjoerd Harder Svetlana B. Tsogoeva Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones Beilstein Journal of Organic Chemistry asymmetric synthesis calcium–binol phosphate catalysis hydrocyanation hydrazones isocyanides |
| title | Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones |
| title_full | Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones |
| title_fullStr | Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones |
| title_full_unstemmed | Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones |
| title_short | Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones |
| title_sort | development and mechanistic studies of calcium binol phosphate catalyzed hydrocyanation of hydrazones |
| topic | asymmetric synthesis calcium–binol phosphate catalysis hydrocyanation hydrazones isocyanides |
| url | https://doi.org/10.3762/bjoc.21.59 |
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