Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

Methods for rapid preparation of densely functionalized and stereochemically complex N-heterocyclic scaffolds are in demand for exploring potential new bioactive chemical space. This work describes experimental and computational studies to better understand the features of aziridinium ylides as intermediates for the synthesis of highly substituted dehydromorpholines. The development of this chemistry has enabled the extension of aziridinium ylide chemistry to the concomitant formation of both a C–N and a C–O bond in a manner that preserves the stereochemical information embedded in the substrate. The chemistry is tolerant of a wide range of functionalities that can be employed for DNA-encoded library (DEL) synthesis to prepare diverse libraries of heterocycles with potential bioactivity. In addition, we have uncovered several key insights that describe the importance of steric effects, rotational barriers around the C–N bond of the aziridinium ylide, and non-covalent interactions (NCIs) on the ultimate reaction outcome. These critical insights will assist in the further development of this chemistry to generate novel and complex N-heterocycles that will further expand complex amine chemical space.

Atropisomerism in Styrene: Synthesis, Stability, and Applications

Atropisomeric styrenes are a class of optically active compounds, the chirality of which results from restricted rotation of the C(vinyl)–C(aryl) single bond. In comparison with biaryl atropisomers, the less rigid skeleton of styrenes usually leads them to have lower rotational barriers. Although it has been overlooked for a long time, scientists have paid attention to this class of unique molecules in recent years and have developed many methods for the preparation of optically active atropisomeric styrenes. In this article, we review the development of the concept of atropisomeric styrenes, along with their isolation, asymmetric synthesis, and synthetic applications.1 Introduction2 The Concept of Styrene Atropisomerism3 Early Research: Separation of Optically Active Styrenes4 Synthesis of Optically Active Styrenes5 Stability of the Chirality of Atropisomeric Styrenes6 Outlook

The Nature of S-N Bonding in Sulfonamides and Related Compounds: Insights into π-Bonding Contributions from Sulfur K-Edge XAS

Molecules containing sulfur-nitrogen bonds, like sulfonamides, have long been of interest due to their many uses and chemical properties. Understanding the factors that cause sulfonamide reactivity is important, yet their continues to be controversy regarding the relevance of S-N π bonding in describing these species. In this paper, we use sulfur K-edge x-ray absorption spectroscopy (XAS) in conjunction with density functional theory (DFT) to explore the role of S_3p contributions to π-bonding in sulfonamides, sulfinamides and sulfenamides. We explore the nature of electron distribution of the sulfur atom and its nearest neighbors and extend the scope to explore the effects on rotational barriers along the sulfur-nitrogen axis. The experimental XAS data together with TD-DFT calculations confirm that sulfonamides, and the other sulfinated amides in this series, have essentially no S-N π bonding involving S_3p contributions and that electron repulsion and is the dominant force that affect rotational barriers.

The Nature of S-N Bonding in Sulfonamides and Related Compounds: Insights into π-Bonding Contributions from Sulfur K-Edge XAS

Molecules containing sulfur-nitrogen bonds, like sulfonamides, have long been of interest due to their many uses and chemical properties. Understanding the factors that cause sulfonamide reactivity is important, yet their continues to be controversy regarding the relevance of S-N π bonding in describing these species. In this paper, we use sulfur K-edge x-ray absorption spectroscopy (XAS) in conjunction with density functional theory (DFT) to explore the role of S_3p contributions to π-bonding in sulfonamides, sulfinamides and sulfenamides. We explore the nature of electron distribution of the sulfur atom and its nearest neighbors and extend the scope to explore the effects on rotational barriers along the sulfur-nitrogen axis. The experimental XAS data together with TD-DFT calculations confirm that sulfonamides, and the other sulfinated amides in this series, have essentially no S-N π bonding involving S_3p contributions and that electron repulsion and is the dominant force that affect rotational barriers.

Catalyst-Control over Sixfold Stereogenicity

Governing higher-order stereogenicity is a long-standing goal in stereoselective catalysis, because it allows to achieve selectivity for more than a twofold number of stereoisomers per stereogenic unit. Current methods warrant control over the power of two stereoisomers and the configurations are routinely assigned using the descriptors ( R ) and ( S ), or related binary codes. In contrast, conformational analysis ranges beyond this dualistic treatment of stereoisomerism, which constitutes an unmet challenge for catalyst stereocontrolled processes. Herein, we now report that sixfold stereogenicity can be governed by stereoselective catalysis. By controlling a configurationally stable stereogenic axis with six large rotational barriers, a catalytic [2+2+2]-cyclotrimerization selectively governs the formation of one out of six stereoisomers with up to 0:0:2:98:0:0 stereocontrol. The underpinnings of conformational analysis and stereoselective catalysis are thereby conceptually reunited. Novel molecular architectures featuring distinct chemical topologies and unexplored chemical designs are anticipated from catalystcontrol over higher-order stereogenicities

Catalyst-Control over Sixfold Stereogenicity

Governing higher-order stereogenicity is a long-standing goal in stereoselective catalysis, because it allows to achieve selectivity for more than a twofold number of stereoisomers per stereogenic unit. Current methods warrant control over the power of two stereoisomers and the configurations are routinely assigned using the descriptors ( R ) and ( S ), or related binary codes. In contrast, conformational analysis ranges beyond this dualistic treatment of stereoisomerism, which constitutes an unmet challenge for catalyst stereocontrolled processes. Herein, we now report that sixfold stereogenicity can be governed by stereoselective catalysis. By controlling a configurationally stable stereogenic axis with six large rotational barriers, a catalytic [2+2+2]-cyclotrimerization selectively governs the formation of one out of six stereoisomers with up to 0:0:2:98:0:0 stereocontrol. The underpinnings of conformational analysis and stereoselective catalysis are thereby conceptually reunited. Novel molecular architectures featuring distinct chemical topologies and unexplored chemical designs are anticipated from catalystcontrol over higher-order stereogenicities

Hindered rotational barriers in conjugated donor–acceptor substituted systems: calculations vs. experiments

Calculation of a barrier to rotation within push–pull derivatives requires considering at least three states: ground, donor and acceptor rotational transition states.