Density functional theory study of the stereoselectivity in small peptide-catalyzed intermolecular aldol reactions

Density Functional Study of Organocatalytic Cross-Aldol Reactions between Two Aliphatic Aldehydes: Insight into Their Functional Differentiation and Origins of Chemo- and Stereoselectivities

“…It is well established that the organocatalyzed asymmetric aldol reactions involving primary and secondary amine catalysts proceed via enamine intermediates, and the nucleophilic addition of enamine to the electrophilic aldehyde acceptor controls the stereoselectivity of the final products. − Obviously, as the reactant entering into the next stereocontrolling step, the enamine with different structures are crucial for the final products. For the subject cross-aldol reactions involving two aliphatic aldehydes both bearing α-methylene protons, the differentiation between these two reaction partnering to form the enamine intermediate would determine the type of the final aldol product among the two cross-aldol and two homoaldol adducts.…”

“…To investigate the mechanism of the two chiral secondary aminocatalysts-promoted asymmetric aldol reactions between two enolizable aldehydes, we have used eqs –2 as the model reactions. Scheme shows these catalysts and the notation used for the enamine intermediates and transition states, analogous to the studies of the previous enamine-based reactions. − …”

“…Therefore, the above interesting observations such as the successful differentiation of the roles between the reaction parters in the aldol reaction and the opposite diastereoselctivity arising from different chiral secondary amine catalysts call for mechanistic and theoretical investigations. Although great success has been achieved to the general understanding of the mechanism of enamine catalytic reactions, − there are no other theoretical investigations concerning the functional differentiation of the reaction components between aldol donor and acceptor, and there are few reports relating to the theoretical study of the syn -aldol processes involving the type of axially chiral amino sulfonamide catalyst. Hence, to extend our understanding in the mechanism and stereoselectivity of the enamine catalytic reactions, the present theoretical study is performed to address the following questions: the origin of the chemoselectivity in the cross-aldol reaction between two potentially enolizable aldehydes with different electronic character and the opposite diastereoselectivities in the proline and axially chiral amino sulfonamide-catalyzed aldol reactions.…”

Highly Enantioselective Co‐Catalytic Direct Aldol Reactions by Combination of Hydrogen‐Bond Donating and Acyclic Amino Acid Catalysts

“…In this context, hydrogen bonding is very important for the reactivity and enantioselectivity of intermolecular aldol reactions catalyzed by small peptides 11c,15. In 2005, Gellman introduced a co‐catalytic system based on the combination of hydrogen‐bond donation and chiral secondary amine catalysts for achieving highly enantioselective CC bond‐formation 16a,b. Shan and co‐workers employed hydrogen‐bond donors as additives for improving proline‐catalyzed direct asymmetric aldol reactions 16d.…”

α‐N‐Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide

“…Dipeptides are also used as additional supplementation of single important amino acid nutrients like glutamine [22][23][24][25][26][27][28][29], tyrosine [25,30,31], and cysteine [25]. Moreover, they provide one-dimensional nanostructured materials [32][33][34][35], ecofriendly anionic surfactants [36], and catalysts for the direct asymmetric aldol reaction [37][38][39][40].…”