Tripeptides as Efficient Asymmetric Catalysts for 1,4‐Addition Reactions of Aldehydes to Nitroolefins–A Rational Approach

Abstract

Bridging the gap: Conformational analysis of a peptidic catalyst for aldol reactions led to the development of H‐D‐Pro‐Pro‐Asp‐NH2 as a highly efficient catalyst for conjugate addition reactions between aldehydes and nitroolefins (see scheme). Only 1 mol % of catalyst suffices to obtain γ‐nitroaldehydes in excellent yields and stereoselectivities.

6. Experimental procedures for conducting organic reactions in continuous flow

“…Whereas small rigid organocatalysts offer only a limited number of sites for structural and functional diversity, peptides have a modular nature, which allows the creation of optimized catalysts. large number of peptidic catalysts have been designed [37], and it has been shown that N-terminal prolyl-peptides efficiently catalyze reactions proceeding via enamine intermediates [38]. Earlier, we reported the first continuous-flow approach for the selective asymmetric synthesis of -nitroaldehydes, utilizing solid supported peptidic catalysts readily synthesized and immobilized in a single step [39].…”

Folded biomimetic oligomers for enantioselective catalysis

“…A variety of strategies have been explored for de novo construction of modular catalysts that enable chemical selectivity, regioselectivity, or enantioselectivity as a consequence of their structural organization. For example, synthetic peptides equipped with catalytic artificial amino acid groups or transition metal sites have been demonstrated to be effective enantioselective catalysts due to the proximity of the catalytic sites to the asymmetric environment created by their backbone (2)(3)(4). Similarly, it has been reported that nucleic acids can be used as chiral scaffolds for asymmetric synthesis and catalysis (5,6).…”

Exploiting the benefits of continuous-flow processing for the development of novel sustainable catalytic procedures

“…Initially, the peptide H-D-Pro-Pro-Asp-NHresin was employed, immobilized on PS-MBHA resin with a loading of 0.64 mmol g -1 (catalyst 58). 131 For the CF reactions, 150 mg of the heterogeneous catalyst was incorporated into a stainless steel cartridge with internal dimensions of 70×4 mm. To provide accessibility of the immobilized catalyst molecules, the matrix of the supporting polymer should be swollen.…”

“…The supported peptidic catalyst was obtained in a TFA salt form after the SPPS, and the effect of a basic additive was next examined to promote the liberation of the N-terminal secondary amine and maybe facilitate catalysis. 129 On the basis of literature data, Nmethylmorpholine (NMM) was chosen as base, 131 and the effects of different amounts of NMM were then investigated under the previously optimized CF reaction conditions. It emerged that the diastereoselectivity decreased dramatically upon addition of the base, whereas the yield and enantioselectivity remained intact (Table 9).…”

“…The structures of the utilized catalysts are shown in Figure 17. 131 However, the batch reaction required a reaction time of 24 h, whereas the flow process proved much more rapid with a short residence time on the catalyst bed, and the ease of product isolation further enhanced sustainability of the CF method.…”