Piperidinium acetate catalyst

As discussed in Section 7.1.4, polymer-bound acetoacetates can be used as precursors for the solid-phase synthesis of enones [33], For these Knoevenagel condensations, the crucial step is to initiate enolization of the CH acidic component. In general, enolization can be initiated with a variety of catalysts (for example, piperidine, piperidinium acetate, ethylenediamine diacetate), but for the microwave-assisted procedure piperidinium acetate was found to be the catalyst of choice, provided that the temperature was kept below 130 °C. At higher reaction temperatures, there is significant cleavage of material from the resin. 

As seen in many of the above examples, acetic anhydride and zinc chloride each make effective condensation catalysts for the free bases, presumably by efficient coordination with the ring nitrogen. The quaternary salts condense readily in the presence of piperidine. Potassium hydroxide, methoxide or piperidinium acetate are suitable for condensations with 2- and 4-methylpyridine AAoxides. For example, the Claisen condensation is effective with these Af-oxides using ethoxide catalyst (Scheme 45) but the reaction fails with the parent picolines unless activated by nitro substitution (69JHC775). 

E)-3-Alkenoic acids. The condensation of malonic acid with aldehydes in DMSO using piperidinium acetate as catalyst furnishes mostly the unconjugated acids. 

On the other hand the catalyst is of great importance primary, secondary or tertiary amines or their corresponding ammonium salts are usually used, but many other catalysts such as phase transfer catalysts, Lewis acids or potassium fluoride can also be applied. The most widely employed catalysts are pyridine, with or without added piperidine, and ammonium salts, such as ammonium or piperidinium acetate. Condensations that employ strong bases or preformed metal salts of the methylene component are not covered here since transformations under these conditions are not usually considered to be Knoevenagel reactions. 

Syntheses with malonodinitrile, including Knoevenagel condensations, have been reviewed extensive-jy3.iio.iii Malonodinitrile is one of the most reactive methylene compounds employed in the Knoevenagel condensation and alkylidene and arylidene malonodinitriles are readily available. In many cases the condensation proceeds satisfactorily without any added catalyst, although it is efficiently catalyzed by weak bases like ammonium acetate and piperidinium acetate or amino acids like -alanine. " Sevend... 

Xantphos-Ru complex formed in situ from equimolar amounts of Xantphos and Ru(PPh3)(CO)H2 in refluxing toluene containing piperidinium acetate is a good catalyst for akylating active methylene compounds, e.g. /-butyl cyanoacetate, and hydroxy compounds, e.g. PhCH20H, to provide a-substituted cyanoacetates, e.g. /-butyl 2-cyano-3-phenylpropionate [Slatford, Whittlesey and Williams Tetrahedron Lett 47 6787 2006. ... 

Reagents i, NaH, CgH ii, l-broraopent-2-yne iii, O3, Zn-HOAc iv, piperidinium acetate V, NaCl, moist DMSO, 160°C vi, Lindlar catalyst. 

In 1937, Langenbeck reported the first iminium catalyzed conjugated addition. N-Methylglycine and piperidinium acetate were found to be good catalysts for the conjugate addition of water to crotonaldehyde [6]. 

With the cycloaddition substrate 399 in hand, the vital intramolecular aza-[3+3] cycloaddition proceeded smoothly by heating with 0.5 equiv of piperidinium acetate as the catalyst for vinyliminium formation. After 12h, tetracyclic cycloaddition product materialized in 68% yield as a separable 9 1 mixture of diastereomers (400a and 400b) favoring the desired isomer 400a as shown. Importantiy, this isomer possessed the necessary configuration at CIO of the alkaloid. 

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