Titanium tetrachloride Knoevenagel reaction

Titanium tetrachloride and a tertiary amine are a useful catalyst for Knoevenagel condensation [149] as shown in Eq. (45) [150]. Because the reaction can be performed under mild conditions, acid-sensitive functional groups survive the reaction conditions and the optically active center at the enolizable position did not racemize (Eq. 45). More examples of the titanium-catalyzed Knoevenagel condensation are shown in Table 5. Alkylation of an (unsaturated) (iV,0)-acetal with active methylene compounds was performed analogously in the presence of TiCU and NEts (Eq. 46) [154]. Depending on the structure of the active methylene compounds, carbon-carbon bond... 

As a new generally applicable catalyst for the Knoevenagel condensation, a mixture of titanium tetrachloride and a tertiary organic base in solvents like tetrahydrofuran or dioxane was introduced by Lehnert. " The procedure is often superior to standard methods in reactions of sensitive compounds because it can be performed at low temperature. As an example, the reaction of the aldehyde (4) with malonate or cyanoacetate in the presence of titanium tetrachloride and pyridine gives the desired products (5) in high yield, whereas the classical method using piperidine acetate fails (Scheme 3). ... 

In 1970, Willy Lehnert showed that in the presence of titanium tetrachloride and a tertiary amine such as pyridine or triethylamine, the Knoevenagel condensation of both aldehydes and ketones with diethylmalonate proceeded under mild conditions (0 °C to room temperature) to provide the condensation products in good yield (e.g., 47—>48). The scope of the reaction was therefore increased as hindered ketones could be coupled with malonate esters in reasonable yield. ... 

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