Combinatorial Knoevenagel Reactions

Abstract

Chlorotrimethylsilane (TMSCl) has been utilized as an efficient promoter and water scavenger in the Knoevenagel condensations of aromatic aldehydes with various methylene active compounds. High yields and a simple workup of target compounds enables the facile generation of combinatorial libraries comprising 11,000 compounds of high structural and functional diversity.

Application of chlorotrimethylsilane in Pictet–Spengler reaction

“…Indeed, halosilanes are known to be condensing agents in Mannich-type reactions [14,15] Spengler reaction [16] as a particular case), and, as we found previously, Me 3 SiCl is also effective in some other condensations of carbonyl compounds [17], e.g., the Knoevenagel [18], Biginelli [19], and Friedlaender [20] reactions. Moreover, silylation of free functionalities (often used to protect them from undesired reactions) should be especially advantageous, since it enables the Pictet-Spengler reaction to be performed with polyfunctional substrates.…”

2.14 Other Condensation Reactions (Knoevenagel, Perkin, Darzens)

“…66 For example, the three-component reaction of bifunctional electrophilic aldehyde (74) with dimenone (75) in the presence of thiophenol (76) gave the adduct (77) (Scheme 23). Deblocking the Knoevenagel product (77) to release a new aldehyde functional group was to be followed immediately by deprotonation and intramolecular aldol cyclization to afford spirocycles (79).…”

New spiro (thio) barbiturates based on cyclohexanone and bicyclo [3.1.1]heptan-6-one by nonconcerted [1+5] cycloaddition reaction and their conformational structures

“…Crossed-aldol condensation can be operated with the aid of strong acids or bases [2,13]. Several catalytic methods have been achieved for crossed-aldol condensation [4,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31].…”

“…), 168.7 (C 1 or C 5 ), 170.0 (C 1 or C 5 ), 177.8 (C 3 ), 206.8 (C 9 ). [5.5]undecane -1,5,9-trione (7ca'd'') [46] (50), 69 (100, base peak), 41 (27). [5.5] [5.5] 3 or C 5' ), 114.1 (C-ar.…”