Efficient consecutive alkylation-Knoevenagel functionalisations in formyl aza-heterocycles using supported organic bases

Synlett

Volumn , Issue 19, 2006, Pages 3324-3328

  Coelho, Alberto ^a   El Maatougui, Abdelaziz ^b   Raviña, Enrique ^b   Cavaleiro, José A S ^a   Silva, Artur M S ^a  

^a UNIVERSITY OF AVEIRO   (Portugal)

^b UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

Author keywords

Catalysis; Consecutive functionalisations; Knoevenagel condensation; Michael addition; Supported bases

Indexed keywords

1,5,7 TRIAZABICYCLO[4.4.0]DEC 5 ENE; 2 TERT BUTYLIMINO 2 DIETHYLAMINO 1,3 DIMETHYLPERHYDRO 1,3,2 DIAZAPHOSPHORINE; 3 FORMYL 4 QUINOLONE; 3 FORMYL INDOLE; BICYCLO COMPOUND; GUANIDINE DERIVATIVE; INDOLE DERIVATIVE; MALONIC ACID DERIVATIVE; ORGANOPHOSPHORUS COMPOUND; PYRIDAZINONE DERIVATIVE; QUINOLONE DERIVATIVE;

ALKYLATION; ARTICLE; CHEMICAL STRUCTURE; KNOEVENAGEL CONDENSATION; MICHAEL ADDITION; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 33845635624     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-951559     Document Type: Article

References (49)

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49. Representative Procedure for the Alkylation-Knoevenagel (Method A) or Aza-Michael-Knoevenagel (Method B) Sequences: In a coated Kimble vial was charged a mixture of the scaffold A1-A3 (0.60 mmol) in the appropriate solvent [THF (3 mL) for A1 or A3, toluene for A2]. The supported organic base (1.5 mmol of PS-TBD 2 for method A, 0.12 mmol for method B) and the alkyl halide (0.66 mmol; method A) or the Michael acceptor (0.72 mmol; method B) were added at the appropriate temperature (40 °C for A1 and A3, r.t. for A2 in method A, 60 °C for all scaffolds in method B). The sample was vortexed for 30 min to give the corresponding N-blocked adduct. Addition of the appropriate malonic acid derivative (1.1 equiv, stirring for 4-14 h; see Figure 4) to the adduct at the appropriate temperature (40 °C for A1, 60 °C for A2, r.t. for A3 in method A; 50 °C, 60 °C and r.t. for A1, A2 and A3, respectively in method B) in the corresponding solvent, led to the Knoevenagel product after simple filtration of the supported reagents by a fritted syringe. Evaporation of the solvent and purification by a parallel short chromatographic filtration (on silica gel) employing a vacuum manifold (Visiprep®) to remove the small excess of malonic acid derivative afforded pure samples that were characterised by spectroscopic and analytical data.