Dearomative, aminocatalytic formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines.

In the manuscript the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines is described. The developed approach utilizes aminocatalytic activation of 2-alkyl-3-furfurals that proceeds via formation of the dearomatized dienamine intermediate. Initially obtained cycloadducts have been subjected to subsequent transformations providing access to tetrahydrofuropyridines or functionalized cinnamates. The mechanism of the process has been confirmed by DFT calculations.

Hydroxyl-group-activated azomethine ylides in organocatalytic H-bond-assisted 1,3-dipolar cycloadditions and beyond.

1,3-Dipolar cycloaddition constitutes a powerful means for the synthesis of five-membered heterocycles. Recently, the potential of this field of chemistry has been expanded by the employment of organocatalytic activation strategies. One group of substrates, namely imines derived from salicylaldehydes, is particularly useful. Additional activation via intramolecular H-bonding interactions offered by the presence of an ortho-hydroxyl phenolic group in their structure results in increased reactivity of these reactants. Furthermore, it can be utilized in subsequent reactions creating chemical and stereochemical diversity. This minireview provides a summary of the recent progress in this field of organocatalysis and indicates other important applications of hydroxyl-group-activated azomethine ylides in asymmetric organocatalysis.

Doubly vinylogous and doubly rearomative functionalization of 2-alkyl-3-furfurals.

The manuscript describes a straightforward functionalization of 2-alkyl-3-furfurals via simple aminocatalytic conjugate addition. The reaction proceeds through the formation of dearomatized dienamine-like intermediate that undergoes 1,6-addition to 4-alkylidene-2,6-dialkylcyclohexa-2,5-dienones. This process can be described as doubly rearomative as it proceeds with the re-formation of both furan and phenyl aromatic moieties. Target products have been obtained in a highly stereoselective manner, providing an interesting example of 2-alkyl-3-furfural functionalization via doubly vinylogous Michael addition. The mechanism of the reaction has been studied by means of computational methods.

On the origins of stereoselectivity in the aminocatalytic remote alkylation of 5-alkylfurfurals.

In the manuscript, computational studies on the remote alkylation of 5-alkylfurfurals proceeding via formation of the corresponding trienamine intermediate are presented. By the means of density functional theory (DFT) calculations and the symmetry-adapted perturbation theory (SAPT) method, interesting insights into the mechanism of the reaction have been provided explaining the influence and contribution of different molecular interactions on the observed reactivity as well as on the enantio- and diastereoselectivity of the process. The studies have been extended to the thiophene analogue of the starting furfural derivative and the results obtained verified experimentally.

Breaking Aromaticity with Aminocatalysis: A Convenient Strategy for Asymmetric Synthesis.

Since the turn of the millennium, catalytic reactions promoted by primary or secondary amines have emerged as a highly useful method for organic chemistry. Very recently, the potential of such synthetic strategies has been vastly expanded by incorporating the principle of aromaticity breaking. Novel reaction pathways can now be accessed through the intermediacy of polyenamine intermediates derived from (hetero)aromatic systems. The proper design of carbonyl starting materials, combined with the high stereochemical efficiency provided by well-established aminocatalysts, has enabled the synthesis of products with (hetero)aromatic frameworks in highly enantio- and diastereomerically enriched form. In this Minireview, we provide an overview of recent advances in this field of research and familiarize the reader with new synthetic opportunities offered by these interesting methodologies.

Brønsted-base-catalyzed remote cascade reactivity of 2,4-dienones - asymmetric synthesis of tetrahydrothiophenes.

This study demonstrates that the remote cascade functionalization of 2,4-dienones can be realized by employing Brønsted base catalysis. The developed cascade involving 1,6-addition followed by the intramolecular aldol reaction provides a straightforward access to polysubstituted tetrahydrothiophene derivatives of biological and synthetic importance. Target products, bearing three contiguous stereocenters including one quaternary, have been obtained with excellent yields (up to 98%) and with good to high stereocontrol (>20 : 1 dr, up to 97 : 3 er) with the reaction cascade being promoted by a simple and readily available cinchona alkaloid cinchonine.

Organocatalytic Nonclassical Trienamine Activation in the Remote Alkylation of Furan Derivatives.

A new approach for the stereoselective remote alkylation of furan derivatives is reported. The reaction of 5-alkylfurfurals with nitroolefins as electrophilic counterparts occurs at their exocyclic ε-position and proceeds through the intermediacy of a nonclassical catalytic trienamine intermediate. The aminocatalyst bearing a H-bonding unit is used to control the stereochemical reaction outcome confirming the usefulness of such catalytic systems for the remote functionalizations of carbonyl compounds. Target products with two adjacent stereogenic centers are obtained in excellent yields and with good to moderate stereoselectivities.