Application of carefully designed Cinchona alkaloid based squaramides resulted in the formation of three contiguous stereocenters in enantio‐ and diastereoselective Sulfa‐Michael/intramolecular aldol reactions cascade. Increase of the temperature to 333 K in reaction of mercaptoacetic aldehyde and various en‐ynones allowed the rise of the reaction rate while not affecting the enantioselectivity nor diastereoselectivity. Stereoselectivity was dependent on the structure of the hydrogen‐bonding unit, thus revealing the importance of weak interactions in the formation of the multifunctional tetrahydrothiophenes. Kohn‐Sham Density Functional Theory results suggest that a perfect fit of the electrophile and squaramide via tailored (+)N−H hydrogen bonding and π–π stacking interactions were the main factors of the chirality transfer.

By varying the steric and electronic surroundings of the hydrogen-bonding motif, the novel chiral Cinchona-alkaloid based selenoureas were developed. Acting as bifunctional catalysts, they were applied in the Michael reactions of dithiomalonate and nitrostyrene providing chiral adducts with up to 96% ee. The asymmetric Michael–-hemiacetalization reaction of benzylidene pyruvate and dimedone, performed with the assistance of 5 mol% of selenoureas, furnished the product with up to 93% ee and excellent yields. The effectiveness of the new hydrogen-bond donors was also proved in solvent-free reactions under ball mill conditions, supporting the sustainability of the devised catalytic protocol.

The Cover Feature shows that Cinchona hits the bull's‐eye! In their Full Paper, Ż. A. Mała et al. describe step‐by‐step how chiral Cinchona alkaloid squaramide plays a key role in the decomposition of dithiane diol to generate reactive mercaptoaldehyde. This reactive species adds to various en‐ynones in stereoselective fashion under the control of a bifunctional hydrogen‐bonding system. The Kohn‐Sham Density Functional Theory calculations indicate the key role of the weak π‐stacking interactions in achieving the favorable orientation of the reagents. As a result, chiral tetrahydrothiophenes with a triple bond close to the sulfur atom and the three contiguous stereocenters are formed. More information can be found in the Full Paper by Ż. A. Mała et al.