Iridium‐Catalyzed Enantioselective Synthesis of Pyrrole‐Annulated Medium‐Sized‐Ring Compounds

Enantioselective synthesis of pyrrole‐annulated medium‐sized‐ring compounds by an iridium‐catalyzed allylic dearomatization/retro‐Mannich/hydrolysis sequence is presented. Various substituted pyrrole‐annulated seven‐ and eight‐membered‐ring products were obtained under mild reaction conditions with moderate to good yields and excellent enantioselectivity. Additionally, these products contain a scaffold widely distributed in natural products and biologically active compounds. The current method provides a convenient way for accessing such pyrrole‐anuulated medium‐sized‐ring compounds.     

Medium‐Sized‐Ring Analogues of Dibenzodiazepines by a Conformationally Induced Smiles Ring Expansion

Analogues of dibenzodiazepines, in which the seven‐membered nitrogen heterocycle is replaced by a 9–12‐membered ring, were made by an unactivated Smiles rearrangement of five‐ to eight‐membered heterocyclic anthranilamides. The conformational preference of the tertiary amide in the starting material leads to intramolecular migration of a range of aryl rings, even those lacking electron‐withdrawing activating groups, and provides a method for n →n +4 ring expansion. The medium‐ring products adopt a chiral ground state with an intramolecular, transannular hydrogen bond. The rate of interconversion of their enantiomeric conformers depends on solvent polarity. Ring size and adjacent steric hindrance modulate this hidden hydrophilicity, thus making this scaffold a good candidate for drug development.     

Internal Nucleophilic Catalyst Mediated Cyclisation/Ring Expansion Cascades for the Synthesis of Medium‐Sized Lactones and Lactams

A strategy for the synthesis of medium‐sized lactones and lactams from linear precursors is described in which an amine acts as an internal nucleophilic catalyst to facilitate a novel cyclisation/ring expansion cascade sequence. This method obviates the need for the high‐dilution conditions usually associated with medium‐ring cyclisation protocols, as the reactions operate exclusively via kinetically favourable “normal”‐sized cyclic transition states. This same feature also enables biaryl‐containing medium‐sized rings to be prepared with complete atroposelectivity by point‐to‐axial chirality transfer.     

Ring Opening of Bicyclo[3.1.0]hexan‐2‐ones: A Versatile Synthetic Platform for the Construction of Substituted Benzoates

Described is the development of a highly efficient 2π disrotatory ring‐opening aromatization sequence using bicyclo[3.1.0]hexan‐2‐ones. This unprecedented transformation efficiently proceeds under thermal conditions and allows facile construction of uniquely substituted and polyfunctionalized benzoates. In the presence of either amines or alcohols formation of substituted anilines or ethers, respectively, is achieved. Additionally, the utility of this method was demonstrated in a short synthesis of sekikaic acid methyl ester.     

Benzodisilacyclobutadienes: 8π‐Electron Systems with an Antiaromatic Silicon Ring

Benzodisilacyclobutadienes 2 a – c were isolated as blue to green crystalline solids from the reaction of stable disilyne 1 and 1,2‐dibromobenzenes in the presence of potassium graphite. In the solid state, substantial bond alternation was observed within the benzene rings of 2 a – c . In hexane, 2 a – c showed remarkable bathochromic shifts of the π→π* (HOMO→LUMO) absorption bands at 625–670 nm. NMR spectra and theoretical calculations indicated that the diamagnetic ring currents of the benzene rings of 2 a – c are considerably reduced by contributions from the antiaromatic 1,2‐disilacyclobutadienes. In their entirety, the obtained results indicate that 2 a – c represent 8π‐electron systems that contain an antiaromatic 1,2‐disilacyclobutadiene.