Efficient Recovery and Reuse of an Immobilized Peptidic Organocatalyst

Abstract

Readily reusable immobilized organocatalysts are important from a practical, economic, and environmental viewpoint. However, their successful development has proven challenging and only limited reaction and recovery cycles have been achieved. We report an extraordinarily robust resinbound tripeptidic organocatalyst that can be readily reused for at least 30 reaction and recovery cycles without loss in catalytic activity or stereoselectivity. The immobilized catalyst can be directly reused for conjugate addition reactions between aldehydes and nitroolefins after a simple filtration from the reaction products. The catalytic efficiency and chemoselectivity of the immobilized peptidic catalysts is so high that a broad range of g-nitroaldehydes were isolated easily after filtration and removal of all volatiles in quantitative yields, excellent diastereoselectivities and enantioselectivities and, most remarkably, perfect analytical purities. The ease of handling allows for a facile scale-up of reactions catalyzed by the immobilized peptidic catalyst. In addition, the results provide a guide for the further development of immobilized organocatalysts.

Adapting to Substrate Challenges: Peptides as Catalysts for Conjugate Addition Reactions of Aldehydes to α,β‐Disubstituted Nitroolefins

“…[2] Consequently, manifold chiral-amine-based catalysts have been explored that promote the conjugate addition reaction of aldehydes to b-substituted nitroolefins. [3][4][5][6][7] However, examples of addition reactions of carbonyl compounds to nitroolefins, which bear not only a substituent in the b-but also in the a-position, are rare. [8][9][10][11][12] The development of conjugate addition reactions of aldehydes to such a,b-disubstituted nitroolefins is highly desirable, as the resulting g-nitroaldehydes bear three consecutive stereogenic centers and are therefore valuable intermediates for the synthesis of, for example, chiral pyrrolidines and fully substituted g-amino acids or g-butyrolactams (Scheme 1).…”

“…[11] Our group has recently introduced peptides of the general type Pro-Pro-Xaa, where the turn inducing Pro-Pro-motive is combined with a C-terminal acidic amino acid (Xaa), as effective catalysts for enamine catalysis. [5][6][7]13] For example, the peptide H-d-Pro-Pro-Glu-NH 2 (1 a) is an excellent catalyst for conjugate addition reactions of aldehydes to b-monosubstituted nitroolefins. [5][6][7] In the presence of as little as 1 mol % of 1 a a broad variety of aldehydes react readily with both aliphatic and aromatic nitroolefins to provide the corresponding g-nitroaldehydes in very good yields and steAbstract: Conjugate addition reactions of aldehydes to a,b-disubstituted nitroolefins are important because they provide synthetically useful g-nitroaldehydes bearing three consecutive stereogenic centers.…”

“…[5][6][7]13] For example, the peptide H-d-Pro-Pro-Glu-NH 2 (1 a) is an excellent catalyst for conjugate addition reactions of aldehydes to b-monosubstituted nitroolefins. [5][6][7] In the presence of as little as 1 mol % of 1 a a broad variety of aldehydes react readily with both aliphatic and aromatic nitroolefins to provide the corresponding g-nitroaldehydes in very good yields and steAbstract: Conjugate addition reactions of aldehydes to a,b-disubstituted nitroolefins are important because they provide synthetically useful g-nitroaldehydes bearing three consecutive stereogenic centers. Such reactions are challenging due to the drastically lower reactivity of a,b-diA C H T U N G T R E N N U N G substituted nitroolefins compared to, for example, b-monosubstituted nitroolefins.…”

Asymmetric catalysis with short-chain peptides

“…More recently, the group showed that the peptidic catalysts are so robust that an immobilized variant of 9, H-DPro-Pro-Glu-NH-TentaGel (9-TG), can be reused after a simple filtration for at least 30 times without loss in activity and stereoselectivity [34]. Reactions catalyzed by 9-TG are so clean and high yielding that simple removal of all volatiles under reduced pressure suffices to provide the desired products in excellent yields, stereoselectivities and purities that do not require column chromatographic purification [34].…”

“…Reactions catalyzed by 9-TG are so clean and high yielding that simple removal of all volatiles under reduced pressure suffices to provide the desired products in excellent yields, stereoselectivities and purities that do not require column chromatographic purification [34]. The immobilized catalyst can even be used in a flow system: 0.8 mmol of 9-PS allowed for the continuous synthesis of more than 100 g (>450 mmol) of conjugate addition products with very high to excellent stereoselectivities (Figure 3c) [35 ].…”