Łukasz Albrecht

Hydrogen-bonding in aminocatalysis: from proline and beyond.

This Concept article summarizes recent progress in the field of hydrogen-bonding aminocatalysis using proline-derived systems. The aminocatalysts available in the literature are categorized by the incorporated hydrogen-bonding scaffold and its mode of recognition. Both mono- and double-hydrogen-bonding motifs are discussed and examples of their application in asymmetric synthesis are given.

Chiral Iminophosphoranes—An Emerging Class of Superbase Organocatalysts

Chiral Brønsted base catalysis is a fascinating and highly explored field of research. For many years catalysts based on chincona alkaloid chiral scaffolds have constituted privileged systems widely employed in numerous base-promoted organic transformations. Recently, a novel group of chiral base catalysts has been successfully introduced. The application of organosuperbases, namely cyclopropenimines, guanidines, and iminophosphoranes, as chiral catalysts is receiving increasing attention. The aim of this Concept article is to summarize recent progress in the field of chiral iminophosphorane superbase organocatalysis. Catalysts design, different approaches to their synthesis, and applications in asymmetric synthesis are outlined and discussed in detail.

Aryl, hetaryl, and ferrocenyl thioketones as versatile building blocks for exploration in the organic chemistry of sulfur

GRAPHICAL ABSTRACT ABSTRACT Methods for the synthesis of hetaryl and ferrocenyl thioketones as well as applications of this class of organic sulfur compounds in the synthesis of both sulfur-containing and sulfur-free organic products are summarized. The most important applications relate to [2+2]-, [3+2]-, and [4+2]-cycloadditions. Aromatic thioketones react with diazomethane at −70°C, and the formed 1,3,4-thiadiazolines can be used as convenient precursors of reactive thiocarbonyl S-methanides. In contrast, the hetaryl thioketones do not form this type of cycloadducts. Reactions of hetaryl thioketones with thiocarbonyl S-methanides are proposed to occur via a stepwise diradical mechanism. Aryl and hetaryl thioketones react as prone heterodienophiles with cyclic and acyclic dienes. The first asymmetric synthesis of dihydrothiopyranes from aryl and hetaryl thioketones was performed using a l-proline-derived organocatalyst. Hetaryl thiochalcones are useful heterodienes for the preparation of hetaryl-substituted dihydrothiopyrans.

Assessing the correlation between the degree of disc degeneration on the Pfirrmann scale and the metabolites identified in HR-MAS NMR spectroscopy

OBJECTIVE The objective of this study is to assess the correlation between the degree of degeneration of lumbar discs according to the Pfirrmann classification system and the concentrations of metabolites determined by means of 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR) spectroscopy. MATERIALS AND METHODS Twenty-six human intervertebral lumbar discs that were operated on due to degenerative disease were analyzed. Routine preoperative 1.5T, T2-weighed magnetic resonance (MR) images were used to classify the cases according to the Pfirrmann classification system. In all the cases, during microdiscectomy, the fragments of the annulus fibrosus and nucleus pulposus were harvested and their metabolic profile was examined by means of 1H HR MAS. The grades of disc degeneration on the Pfirrmann scale were correlated with the metabolite concentrations. RESULTS Spectral analyses of the intervertebral discs with Pfirrmann grades IV and V demonstrated significantly higher concentrations of creatine, glycine, hydroxyproline, alanine, leucine, valine, acetate, isoleucine, α,β-glucose, and myo-inositol, and a lower intensity of the N-acetyl peak of chondroitin sulfate, compared to the spectra with Pfirrmann grade III. CONCLUSION Our results demonstrate correlations between metabolite concentrations and the degree of lumbar disc degeneration assessed using the Pfirrmann grading system and provide another step toward the potential use of in vivo MR spectroscopy for investigation of biomarkers in lumbar disc degeneration.

The Application of 2-Benzyl-1,4-naphthoquinones as Pronucleophiles in Aminocatalytic Synthesis of Tricyclic Derivatives

This study demonstrates an unprecedented reactivity of 2-substituted-1,4-naphthoquinones. By applying the principle of vinylogy, they have been employed as vinylogous pronucleophiles in the organocatalytic cascade reaction for the first time. This novel catalytic activation of 1,4-naphthoquinones enables access to carboannulated naphthalen-1(4 H)-one derivatives of biological importance. The site-selectivity and stereoselectivity of a process proved possible to control by the proper choice of reaction conditions.

Synthesis of γ,γ‐Disubstituted Butenolides through a Doubly Vinylogous Organocatalytic Cycloaddition

A novel organocatalytic approach to γ,γ-disubstituted butenolides is described. It is based on a fully site-selective functionalization of 5-alkylidenefuran-2(5H)-ones via trienamine-mediated [4+2]-cycloaddition with α,β,γ,δ-diunsaturated aldehydes. The developed methodology proceeds with excellent stereocontrol and constitutes a unique example of trienamine chemistry with vinylogous dienophiles. Importantly, the reaction has very broad scope and allows for the introduction of substituents also in the α- or the β-position of the butenolide ring. Usefulness of the products obtained has been confirmed in the intramolecular Stetter reaction leading to polycyclic product.

Breaking aromaticity with aminocatalysis ‐ novel 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.