Maximizing Step‐Normalized Increases in Molecular Complexity: Formal [4+2+2+2] Photoinduced Cyclization Cascade to Access Polyheterocycles Possessing Privileged Substructures

Abstract

A new complexity building photoinduced cascade which amounts to an unprecedented formal [4+2+2+2] cycloaddition topology is developed to access complex nitrogen polyheterocycles. This photocascade is initiated by the excited state intramolecular proton transfer (ESIPT) in aromatic amino ketones with tethered dual unsaturated pendants, i.e. pyrrole and alkenic moieties, resulting in the formation of four σ‐bonds and setting six new stereogenic centers in a single experimentally simple photochemical step with up to 220 mcbit complexity increases.

Spacial Score – A Comprehensive Topological Indicator for Small Molecule Complexity

“…[14] It has generated significant interest, resulting in a rapid increase in its popularity since its introduction, notably by the organic synthesis community. [23][24][25][26][27][28][29] Considering the general interest in this scoring system and apparent improvement over the alternative complexity measures, we explored whether the Böttcher complexity score may also serve as a descriptor that could correlate compound complexity with biological activity and selectivity. In this case it might be employed to rationalize trends observed in the biological analysis of our in-house compound libraries.…”

Spacial Score─A Comprehensive Topological Indicator for Small-Molecule Complexity

“…The Böttcher score C m is inspired by the Shannon entropy and defines molecular complexity in an additive manner by the consideration of atomic connectivity, the number of valence electrons for atoms, heteroatom diversity, stereogenicity, and molecular symmetry. It has generated significant interest, resulting in a rapid increase in its popularity since its introduction, notably by the organic synthesis community. − Considering the general interest in this scoring system and apparent improvement over the alternative complexity measures, we explored whether the Böttcher complexity score may also serve as a descriptor that could correlate compound complexity with biological activity and selectivity. In this case, it might be employed to rationalize trends observed in the biological analysis of our in-house compound libraries.…”

Three-Component Chemo-Selective Synthesis of N-(o-Alkenylaryl) Pyrazoles by Pyrazole Annulation and Rh-Catalyzed Chemo-Selective Aryl C–H Addition Cascade

“…Improving the step economy is of strategic importance for modern organic synthesis. Achieving a target product with minimum synthetic operation saves not only working time but also the bulky consumption of chemicals resulting from intermediate purification. − Meanwhile, controlling the selectivity of a reaction constitutes the longstanding goal of chemical synthesis. − Although recent years have witnessed drastic advances in both step economical and selectivity tunable organic synthesis, developing more reactions by one-step construction of molecular complexity and disclosing the unconventional reaction selectivity associated with the designation of step economical reaction fashion is yet an issue of challenge. For example, as well-recognized powerful tools, the Rh-catalyzed C–H activation reactions have been proven to be highly reliable protocols in the synthesis of numerous organic compounds by the Rh insertion into inert C–H bond under the assistance of a coordinative directing group (DG); − the general requirement of a substrate containing such coordination structure, however, requires additional operation, which undermines the step efficiency of these Rh-catalyzed C–H activation reactions.…”