Mechanistic Investigation of the Asymmetric Addition of Trimethylsilyl Cyanide to Aldehydes Catalysed by Dinuclear Chiral (Salen)titanium Complexes

Abstract

Keywords: Asymmetric catalysis / Cyanohydrins / Titanium / AldehydesTitanium complexes 1 derived from chiral salen ligands are highly active precatalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and ketones. Based on spectroscopic studies and the identification of adducts between complexes 1 and carbonyl compounds or trimethylsilyl

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

“…Extensive mechanistic work27–36 on the use of 3 and 4 a as catalysts for asymmetric cyanohydrin synthesis has resulted in the transition-state model shown in Figure 2,27, 33 which shows that (for complexes derived from the ( R , R )-salen ligand) cyanide addition occurs selectively on the re face of the coordinated aldehyde to lead to the ( S )-cyanohydrin trimethylsilyl ether. In contrast, the results presented in this work show that the same complexes will catalyse the formation of ( S )-nitronitriles, which requires cyanide addition to occur on the si face of the coordinated alkene.…”

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

“…Extensive mechanistic work27–36 on the use of 3 and 4 a as catalysts for asymmetric cyanohydrin synthesis has resulted in the transition-state model shown in Figure 2,27, 33 which shows that (for complexes derived from the ( R , R )-salen ligand) cyanide addition occurs selectively on the re face of the coordinated aldehyde to lead to the ( S )-cyanohydrin trimethylsilyl ether. In contrast, the results presented in this work show that the same complexes will catalyse the formation of ( S )-nitronitriles, which requires cyanide addition to occur on the si face of the coordinated alkene.…”

Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis

“…In previous work,8, 9a, 10b, 12 we have determined the kinetics of the asymmetric addition of trimethylsilyl cyanide to benzaldehyde catalysed by complexes 3 , 4 a , 4 b and 5 and have shown that the reactions obey the rate equations shown in Equations (1)–(4), respectively, , , . …”

“…All of the kinetics measurements throughout this work were obtained by monitoring the UV absorbance at λ =240–315 nm of unreacted aldehyde in samples periodically removed from reactions carried out at 0 °C, as we have previously described 8. 9a, 10b, 12 Every kinetics experiment was carried out in duplicate and the average rate constant used to construct the Hammett plot 23. The aldehydes were chosen to provide as wide a range of substituent constants as possible; though for titanium complex 3 , highly electron‐deficient aldehydes (3,4‐dichloro‐, 3,5‐difluoro‐ and 4‐(trifluoromethyl)benzaldehyde) reacted so quickly (100 % conversion in ≈5 s) that it was not possible to monitor the kinetics and this restricted the range of positive substituent constants that could be studied.…”

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

“…The order with respect to the catalyst (1.2) in Eq. 1 provides information on the relative importance of mononuclear and binuclear species in the catalytic cycle [ 28 , 47 ]. A value greater than one implies that the catalyst exists in solution as a mixture of mononuclear and binuclear species, but that the binuclear species is predominantly responsible for the catalysis.…”

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

“…Extensive mechanistic work27–36 on the use of 3 and 4 a as catalysts for asymmetric cyanohydrin synthesis has resulted in the transition-state model shown in Figure 2,27, 33 which shows that (for complexes derived from the ( R , R )-salen ligand) cyanide addition occurs selectively on the re face of the coordinated aldehyde to lead to the ( S )-cyanohydrin trimethylsilyl ether. In contrast, the results presented in this work show that the same complexes will catalyse the formation of ( S )-nitronitriles, which requires cyanide addition to occur on the si face of the coordinated alkene.…”

Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis

“…In previous work,8, 9a, 10b, 12 we have determined the kinetics of the asymmetric addition of trimethylsilyl cyanide to benzaldehyde catalysed by complexes 3 , 4 a , 4 b and 5 and have shown that the reactions obey the rate equations shown in Equations (1)–(4), respectively, , , . …”

“…All of the kinetics measurements throughout this work were obtained by monitoring the UV absorbance at λ =240–315 nm of unreacted aldehyde in samples periodically removed from reactions carried out at 0 °C, as we have previously described 8. 9a, 10b, 12 Every kinetics experiment was carried out in duplicate and the average rate constant used to construct the Hammett plot 23. The aldehydes were chosen to provide as wide a range of substituent constants as possible; though for titanium complex 3 , highly electron‐deficient aldehydes (3,4‐dichloro‐, 3,5‐difluoro‐ and 4‐(trifluoromethyl)benzaldehyde) reacted so quickly (100 % conversion in ≈5 s) that it was not possible to monitor the kinetics and this restricted the range of positive substituent constants that could be studied.…”

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

“…The order with respect to the catalyst (1.2) in Eq. 1 provides information on the relative importance of mononuclear and binuclear species in the catalytic cycle [ 28 , 47 ]. A value greater than one implies that the catalyst exists in solution as a mixture of mononuclear and binuclear species, but that the binuclear species is predominantly responsible for the catalysis.…”

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

“…Extensive mechanistic work27–36 on the use of 3 and 4 a as catalysts for asymmetric cyanohydrin synthesis has resulted in the transition-state model shown in Figure 2,27, 33 which shows that (for complexes derived from the ( R , R )-salen ligand) cyanide addition occurs selectively on the re face of the coordinated aldehyde to lead to the ( S )-cyanohydrin trimethylsilyl ether. In contrast, the results presented in this work show that the same complexes will catalyse the formation of ( S )-nitronitriles, which requires cyanide addition to occur on the si face of the coordinated alkene.…”

Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis

“…In previous work,8, 9a, 10b, 12 we have determined the kinetics of the asymmetric addition of trimethylsilyl cyanide to benzaldehyde catalysed by complexes 3 , 4 a , 4 b and 5 and have shown that the reactions obey the rate equations shown in Equations (1)–(4), respectively, , , . …”

“…All of the kinetics measurements throughout this work were obtained by monitoring the UV absorbance at λ =240–315 nm of unreacted aldehyde in samples periodically removed from reactions carried out at 0 °C, as we have previously described 8. 9a, 10b, 12 Every kinetics experiment was carried out in duplicate and the average rate constant used to construct the Hammett plot 23. The aldehydes were chosen to provide as wide a range of substituent constants as possible; though for titanium complex 3 , highly electron‐deficient aldehydes (3,4‐dichloro‐, 3,5‐difluoro‐ and 4‐(trifluoromethyl)benzaldehyde) reacted so quickly (100 % conversion in ≈5 s) that it was not possible to monitor the kinetics and this restricted the range of positive substituent constants that could be studied.…”

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

“…The order with respect to the catalyst (1.2) in Eq. 1 provides information on the relative importance of mononuclear and binuclear species in the catalytic cycle [ 28 , 47 ]. A value greater than one implies that the catalyst exists in solution as a mixture of mononuclear and binuclear species, but that the binuclear species is predominantly responsible for the catalysis.…”