The Synthesis of Stable,Complex Organocesium Tetramic Acids through the Ugi Reaction and Cesium‐Carbonate‐Promoted Cascades

Two structurally unique organocesium carbanionic tetramic acids have been synthesized through expeditious and novel cascade reactions of strategically functionalized Ugi skeletons delivering products with two points of potential diversification. This is the first report of the use of multicomponent reactions and subsequent cascades to access complex, unprecedented organocesium architectures. Moreover, this article also highlights the first use of mild cesium carbonate as a cesium source for the construction of cesium organometallic scaffolds. Relativistic DFT calculations provide an insight into the electronic structure of the reported compounds.     

Highly Stereoselective Synthesis of Natural‐Product‐Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence

In an endeavor to provide an efficient route to natural product hybrids, described herein is an efficient, highly stereoselective, one‐pot process comprising an organocatalytic conjugate addition of 1,3‐dicarbonyls to α,β‐unsaturated aldehydes followed by an intramolecular isocyanide‐based multicomponent reaction. This approach enables the rapid assembly of complex natural product hybrids including up to four different molecular fragments, such as hydroquinolinone, chromene, piperidine, peptide, lipid, and glycoside moieties. The strategy combines the stereocontrol of organocatalysis with the diversity‐generating character of multicomponent reactions, thus leading to structurally unique peptidomimetics integrating heterocyclic, lipidic, and sugar moieties.     

Split‐Ugi Reaction with Chiral Compounds: Synthesis of Piperazine‐ and Bispidine‐Based Peptidomimetics

A simple, one‐step, stereoconservative synthesis of diamine‐based peptidomimetics is described, by split‐Ugi multicomponent reaction, involving chiral N‐protected amino acids and α‐substituted isocyanoacetate. In particular, piperazine and bispidine (3,7‐diazabicyclo[3.3.1]nonane) are exploited as diamine components, bispidine being the first example of a sterically demanding bicyclic system employed in a split‐Ugi reaction.     

Base‐Dependent Stereodivergent Intramolecular Aza‐Michael Reaction: Asymmetric Synthesis of 1,3‐Disubstituted Isoindolines

The nucleophilic addition (A_N) / intramolecular aza‐Michael reaction (IMAMR) process on Ellman’s tert‐butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3‐disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza‐Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C₂‐symmetric bisacetate‐substituted isoindolines. In addition, bisacetate isoindolines bearing two well‐differentiated ester moieties are also noteworthy because they may allow for the orthogonal synthesis of β,β′‐dipeptides using a single nitrogen atom as a linchpin.     

Ruthenium(II)/Chiral Brønsted Acid Co‐Catalyzed Enantioselective Four‐Component Reaction/Cascade Aza‐Michael Addition for Efficient Construction of 1,3,4‐Tetrasubstituted Tetrahydroisoquinolines

An elegant synergistic catalytic system comprising a ruthenium complex with a chiral Brønsted acid was developed for a four‐component Mannich/cascade aza‐Michael reaction. The ruthenium‐associated ammonium ylides successfully trapped with in situ generated imines indicates a stepwise process of proton transfer in the ruthenium‐catalyzed carbenoid N?H insertion reaction. The different decomposition abilities of various ruthenium complexes towards diazo compounds were well explained by the calculated thermodynamic data. The transformation features a mild, rapid, and efficient method for the synthesis of enantiomerically pure 1,3,4‐tetrasubstituted tetrahydroquinolines bearing a quaternary stereogenic carbon center from simple starting precursors in moderate yields with high diastereo‐ and enantioselectivity.