Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

Abstract

SummaryPropylene carbonate can be used as a green solvent for the asymmetric synthesis of cyanohydrin trimethylsilyl ethers from aldehydes and trimethylsilyl cyanide catalysed by VO(salen)NCS, though reactions are slower in this solvent than the corresponding reactions carried out in dichloromethane. A mechanistic study has been undertaken, comparing the catalytic activity of VO(salen)NCS in propylene carbonate and dichloromethane. Reactions in both solvents obey overall second-order kinetics, the rate of reaction being dependent on the concentration of both the aldehyde and trimethylsilyl cyanide. The order with respect to VO(salen)NCS was determined and found to decrease from 1.2 in dichloromethane to 1.0 in propylene carbonate, indicating that in propylene carbonate, VO(salen)NCS is present only as a mononuclear species, whereas in dichloromethane dinuclear species are present which have previously been shown to be responsible for most of the catalytic activity. Evidence from 51V NMR spectroscopy suggested that propylene carbonate coordinates to VO(salen)NCS, blocking the free coordination site, thus inhibiting its Lewis acidity and accounting for the reduction in catalytic activity. This explanation was further supported by a Hammett analysis study, which indicated that Lewis base catalysis made a much greater contribution to the overall catalytic activity of VO(salen)NCS in propylene carbonate than in dichloromethane.

Asymmetric Addition of Cyanide to β‐Nitroalkenes Catalysed by Chiral Salen Complexes of Titanium(IV) and Vanadium(V)

“…Catalyst 3 is an active catalyst for this reaction, and 100 % conversion of nitroalkene 5 a into nitronitrile 6 a with 62 % ee could be obtained at room temperature by using just 1 mol % of the catalyst with dichloromethane as the solvent (Table 1, entry 1). Under the same conditions, 4 a was less reactive, but more enantioselective (entry 2); a trend that mirrors that seen in asymmetric cyanohydrin synthesis 28–35. The absolute configuration of 6 a was determined as S if using catalyst 3 or 4 a derived from ( R , R )-salen ligand 1 by comparison of both the sign of its specific rotation and its chiral HPLC peak intensities with those reported in the literature 1.…”

“…Titanium-based catalyst 3 and vanadium(V) catalyst 4 a have been previously found to be the most active catalysts for asymmetric cyanohydrin synthesis,28–35 so they were used for this study. Catalyst 3 is an active catalyst for this reaction, and 100 % conversion of nitroalkene 5 a into nitronitrile 6 a with 62 % ee could be obtained at room temperature by using just 1 mol % of the catalyst with dichloromethane as the solvent (Table 1, entry 1).…”

“…Although dichloromethane had been previously found to be the optimal solvent for asymmetric cyanohydrin synthesis catalysed by 3 and 4 a ,28–35 Wang and co-workers showed that toluene was the optimal solvent for nitronitrile synthesis catalysed by the titanium complex of 1 1. Therefore, the use of 3 and 4 a in toluene was investigated.…”

“…For asymmetric cyanohydrin synthesis catalysed by 4 , the structure of the anion significantly influences the catalytic activity, though not the enantioselectivity. The best results were obtained by using complexes with a nucleophilic counter-ion that was capable of acting as a Lewis base to activate the trimethylsilyl cyanide 30, 32, 33, 35. Therefore, 4 b – f were screened as catalysts for the synthesis of 6 a under the conditions of Table 1, entry 13.…”

“…Mechanistic studies27 showed that the active species in both of these systems was actually the bi-metallic complex 3 and just 0.1 mol % of 3 was able to catalyse the asymmetric addition of trimethylsilyl cyanide to aldehydes in less than one hour at room temperature 28, 29. Based on the mechanistic information obtained with titanium complexes,27, 30 we were able to develop vanadium(V)(salen) complexes 4 as even more enantioselective catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes 29–35. In view of this precedent, we decided to investigate whether structurally well-defined metal(salen) complexes 3 and 4 might form highly active and enantioselective catalysts for the asymmetric addition of trimethylsilyl cyanide to nitroalkenes and in this paper we report the results of this work.…”