Catalytic enamines from dialkylamide-dialkylacetals

The Knoevenagel reaction: a review of the unfinished treasure map to forming carbon–carbon bonds

“…This DBU catalyzed reaction yielded an E-factor of 12.8 and the triethylamine an E-factor of 14.9, both with low conversions. Other reported use of triethylamine produced E-factors of 2.1 (1) and 6.7 (63). In 1898, Knoevenagel himself used benzylidene-aniline for a condensation reaction.…”

Mechanistic considerations and characterization of ammonia-based catalytic active intermediates of the green Knoevenagel reaction of various benzaldehydes

“…He isolated catalytic intermediates and as a result of this laid the fundamentals of "organocatalysis" (6,7). Unfortunately, the impact of his research has not yet been valued by everyone (8)(9)(10)(11). Organocatalysis is the catalysis of reactions with small organic molecules and generally seen as a more environmentally friendly form of catalysis opposed to for example (toxic) transition metal catalysts (12,13).…”

Synthesis, Biological Evaluation, and Molecular Modeling of New 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-Dimethylmorpholino)-2-oxoethyl) Oxime (GEBR-7b) Related Phosphodiesterase 4D (PDE4D) Inhibitors

“…To prepare compounds 11a−c, the intermediate (E)-3-(3-(cyclopentyloxy)-4-methoxyphenyl)acrylic acid 18 was obtained in high yield by condensing the 3-(cyclopentyloxy)-4methoxybenzaldehyde 14 with malonic acid in the presence of N,N-dimethylformamide dimethylacetal (DMF−DMA) and triethylamine, following a recently reported method for carbonyl olefination in mild conditions. 21 The reaction mechanism involves the formation of an enamine intermediate starting from malonic acid and DMF−DMA; the latter reacts with the carbonyl group of compound 14, giving an iminium intermediate which evolves in the final trans-cinnamic acid. The subsequent reaction with the suitable cycloamine in the presence of diphenylphosphorylazide (DPPA) gave the desired 11a−c as reported in Scheme 2.…”

“…1 (6). To a suspension of 3-(cyclopentyloxy)-4-methoxybenzaldehyde oxime 16 (0.63 g, 2.68 mmol) and anhydrous K 2 CO 3 (0.69 g, 5 mmol) in anhydrous DMF (2 mL), 1-(chloroacetyl)piperidin-4-ol (21) (1.1 g, 6 mmol) was added. The reaction mixture was stirred at 50−60 °C for 18 h. After cooling to room temperature, the mixture was poured into water (20 mL), the aqueous phase was extracted with diethyl ether (2 × 20 mL), the organic phases were washed with water (2 × 10 mL) and brine (2 × 10 mL), dried (Na 2 SO 4 ), and evaporated under reduced pressure.…”

“…1-(Chloroacetyl)piperidin-4-ol (21). Piperidin-1-ol (1 g, 10 mmol) was solved in a mixture of saturated Na 2 CO 3 solution (75 mL) and ethyl acetate (150 mL), and chloroacetyl chloride (1.2 mL, 15 mmol) was added.…”