biostudies-literatureUnknown21Tortora CAsymmetric 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 catalysBeilstein journal of organic chemistry755-765https://www.ebi.ac.uk/biostudies/studies/S-EPMC12018919biostudies-literatureDevelopment and mechanistic studies of calcium-BINOL phosphate-catalyzed hydrocyanation of hydrazones.PMC12018919Harder STsogoeva SBKohlbauer STortora CPahl JBallmann GMFischer CAZamfir AfalseDevelopment 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 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 catalys2025-01-01T00:00:00Z20252025-07-01T03:05:48.323Z2025-07-01T03:05:48.323ZS-EPMC120189194027627910.3762/bjoc.21.59