A Sonogashira Cross-Coupling/5-exo-dig Cyclization/Ionic Hydrogenation Sequence: Synthesis of 4-Substituted 3-Azabicyclo[3.1.0]hexan-2-ones from 2-Iodocyclopropanecarboxamides

Abstract

A variety of 4-substituted 3-azabicyclo[3.1.0]hexan-2-ones have been prepared from 2-iodocyclopropanecarboxamides by a three-step sequence involving a copper-free Sonogashira coupling with terminal aryl- or heteroarylalkynes, followed by a 5-exo-dig cyclization and an ionic hydrogenation.

H-bonding vs Protonation of Alkynes in Regioselective Hydroamination Reactions: A Glimpse into the Reactivity of Arylogous Ynolethers and Ynamines

“…In addition, it is difficult to protonate alkynes into vinylic cationic species. Therefore, harsh reaction conditions are required for the acidic cyclization of alkynylphenyl amines into pyrrolidines . While the electronic density of the alkyne is expected to be a key contributor for establishing H-bonding, we were curious to examine the impact on the activation of the electronic delocalization of the aromatic substituents within the alkyne: the arylogous reactivity.…”

Formal [4+1] Annulation Reactions in the Synthesis of Carbocyclic and Heterocyclic Systems

“…hexan-2-ones 390 , with generally high yields. The enamide moieties in the products 390 can undergo a further Pictet–Spengler cyclization and ionic hydrogenation to provide structurally complex polycyclic and bicyclic systems . Subsequently, Nájera and Alonso’s group noted a similar Pd-catalyzed copper-free tandem Sonogashira coupling/hydroalkoxylation between 2-bromo- or chlorobenzylic alcohols and terminal alkynes in microwave irradiation, which provide efficient access to dihydroisobenzofurans …”

Advances toward the Synthesis of Functionalized γ-Lactams

“…The diastereo control was attributed to the hydride transfer, occurring at the less sterically hindered face of the N-acyliminium (compound 8). 11 All attempts to reduce compound 8 using heterogeneous catalysts opened the cyclopropane ring and resulted in various side products. A few examples are shown to highlight functional group compatibility (9a-9c, Scheme 1).…”