Consecutive Ring Expansion and Contraction for the Synthesis of 1‐Aryl Tetrahydroisoquinolines and Tetrahydrobenzazepines from Readily Available Heterocyclic Precursors

Abstract

Tetrahydroisoquinolines and tetrahydrobenzazepines were prepared by acid-promoted ring contraction of cyclic ureas, which were themselves formed by ring expansion of indolines and tetrahydroquinolines. The consequent overall one-carbon insertion reaction gives these 6- and 7-membered heterocyclic scaffolds in three steps from readily available precursors. Other ring sizes may be formed by an alternative elimination reaction of bicyclic structures. Scalability of the method was demonstrated by operating it in a flow system.

Enantioselective Organocatalytic Four‐Atom Ring Expansion of Cyclobutanones: Synthesis of Benzazocinones

“…DFT calculations allowed a tentative assignment of the relative configuration in ent‐4 k with a stabilization energy of 7.5 kJ mol −1 for the ( R , S ) diastereomers depicted in Scheme (see the Supporting Information for details). It is remarkable that glutarimides 4 b, 4 e, 4 h, 4 i, and ent‐4 k overall derive from the corresponding activated cyclobutanones 1 by an enantioselective ring expansion– ring contraction approach …”

Innentitelbild: Enantioselective Organocatalytic Four‐Atom Ring Expansion of Cyclobutanones: Synthesis of Benzazocinones (Angew. Chem. 2/2019)

“…It is remarkable that glutarimides 4b,4e, 4h,4i, and ent-4 k overall derive from the corresponding activated cyclobutanones 1 by an enantioselective ring expansion-ring contraction approach. [18] In summary,a ne nantioselective synthesis of benzazocinones has been elaborated based on aMichael addition-fouratom ring expansion cascade from activated cyclobutanones and ortho-amino nitrostyrenes using bifunctional aminocatalysts.This newly developed approach allows astraightforward access to aclass of molecules usually difficult to synthesize in optically active form, from readily available starting materials,a nd under mild conditions.T he benzazocinone products can be further converted into functionalized glutarimide derivatives without loss of the enantiomeric purity by abasecatalyzed ring contraction.…”

Preise der Royal Society of Chemistry 2018

“…Clayden erforscht Synthese und Stereochemie mit Bezug zu Konformationen, wie dynamische Foldamere, Atropisomerie, Organolithiumchemie, konformationsinduzierte Reaktivität und stereochemische Effekte über größere Distanzen. In der Angewandten Chemie beschrieb er Wege zu Tetrahydroisochinolinen und Tetrahydrobenzazepinen über Ringerweiterung und ‐verengung …”