Spectroscopic Study of a Cinchona Alkaloid-Catalyzed Henry Reaction

Abstract

A spectroscopic study of an organocatalytic Henry reaction between nitroalkanes and aldehydes catalyzed by a quinidine-derived Cinchona alkaloid is described. The binding modes of the reaction substrates are investigated using electronic absorption and fluorescence spectroscopy and further corroborated by nuclear magnetic resonance measurements. Aldehydes are shown to associate with both the 6′-OH group and the basic quinuclidine nitrogen of the catalyst, whereas nitroalkanes do not exhibit a clear binding mode. Reaction progress kinetic analysis reveals that the reaction is first-order in both of the substrates and the catalyst. Second, the reaction proceeds approximately five times faster in the excess of the nitroalkanes than in the excess of the aldehydes, suggesting that binding of the aldehydes results in the inhibition of the catalyst. Aldehydes deactivate the basic quinuclidine site, thus suppressing the deprotonation of the nitroalkanes which is the proposed initial step in the reaction cycle.

Unraveling the Origin of Solvent Induced Enantioselectivity in the Henry Reaction with Cinchona Thiourea as Catalyst

“…Cinchona derivatives, Figure , are extensively employed as robust stereoselective catalysts and in addition were subject to many computational and experimental studies. − These are flexible compounds that in solution exist as a mixture of conformers. − Their function is directly related to their structure and their activity may be controlled via their conformational dynamics, this resembles enzymes function. , One way for the solvent to affect the reaction is by formation of a molecular complex with the catalyst, which may “select” one of the possible conformers of the asymmetric catalyst. − If this conformer produces the largest ee, the solvent enhances or even determines the enantioselectivity.…”

Photophysics of perylene monoimide-labelled organocatalysts

“…The parent compound BnCPD is well known as an organocatalyst, 35,68 but the added fluorophore in 1 could in principle interfere with this function. To check the organocatalytic activity of compound 1, we used a Michael addition reaction with the fluorogenic BODIPY-maleimide 3, which consists of a BODIPY fluorescent unit and a maleimide as thiol-reactive quenching group.…”

“…31,32 Later, many mecha-nisms for this kind of reactions were investigated, most of them based on computational methodology. 6,33,34 It would be interesting to use the native fluorescence of the cinchona alkaloids [35][36][37][38] to gain insight into the mechanisms of cinchona organocatalysis, but the short wavelengths of absorption renders them unsuitable for the most powerful single molecule techniques, which require absorption and fluorescence in the visible to near IR range. In the present work we designed two new fluorescent probes: cinchona alkaloid catalysts (BnCPD and dHQD) functionalized with a perylene monoimide (PMI) fluorophore.…”

Synthesis and Catalytic Application of Two Mononuclear Complexes Bearing Diethylenetriamine Derivative Ligand

“…The β-nitroalcohol product can be obtained by the Henry reaction, a very classical and applicable C-C bond formation reaction. The most common method of synthesizing β-nitroalcohols is the nucleophilic addition reaction of nitroalkane with the carbonyl compounds in the presence of catalysts, such as organic small molecules [7,8], ionic liquids [9,10], and metal complexes [11,12]. Hence, an enormous amount of effort has been devoted to the research and development of economic and efficient catalysts for this reaction.…”