A Highly Regio and Stereoselective Synthesis of (Z)-3-Aryl(alkyl)idene Isoindolin-1-ones via Palladium Catalyzed Annulation of Terminal Alkynes

Efficient Synthesis of a (Z)-3-Methyleneisoindolin-1-one Library Using Cu(OAc)2•H2O/DBU under Microwave Irradiation

“…(Z)-3-Benzylidene-2-p-tolylisoindolin-1-one ( 3{ 9 } ) [ 25 ]. 1 H-NMR (CDCl 3 ): δ 7.94 (d, J = 7.2 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 6.98–6.84 (m, 9H), 6.81 (s, 1H), 2.22 (s, 3H); ESI-MS m/z 312 [M+H] + .…”

Efficient Synthesis of Substituted 3‐Azabicyclo[3.1.0]hexan‐2‐ones from 2‐Iodocyclopropanecarboxamides Using a Copper‐Free Sonogashira Coupling

“…The 5-exo-dig cyclization of amide 2 was initially attempted in the presence of EtONa (3 equiv) in EtOH (heated to reflux), by analogy with conditions reported for the ring closure of 2-(arylethynyl)benzamides into the corresponding 3-benzylideneisoindolones. [35] However, an incomplete conversion of amide 2 into the desired enamide 9 was observed (30 %) even after prolonged heating (5 h), indicating that the cyclization was much more difficult to achieve than for 2-(arylethynyl)benzamides. However, when the reaction was run at a higher temperature under microwave irradiation (sealed vial, 150 8C), the cyclization was complete in 0.5 h and the desired 4-benzylidene-3-azabicyclo-…”

“…Not surprisingly, the phenyl substituent on the alkyne in compound 2 stabilizes the developing adjacent negative charge at the vinylic carbon in the transition state of the 5-exo-dig cyclization. [35,36,52] Optimization of the synthesis of 4-benzylidene-3-azabicyclo-[3.1.0]hexan-2-ones: Since the relatively harsh conditions previously used to achieve the cyclization of 2 into enamide (Z)-9 could be incompatible with substrates bearing substituted aromatic groups, the search for milder alternatives was undertaken. Moreover, to optimize the overall efficiency of the synthesis of 4-benzylidene-3-azabicycloA C H T U N G T R E N N U N G [3.1.0]hexan-2ones E', it was envisioned to combine several steps in a onepot manner and avoid the purification of the intermediates.…”

“…Rather than using the classical approach involving bicyclic imides as precursors, we envisioned that these latter reactive species B' could be generated by protonation of enamides E, which in turn would arise from the cyclization of cis-2-alkynylcyclopropanecarboxamides F under basic conditions. Such a 5-exo-dig ring closure, which is unprecedented in the case of substrates F, [35,36] would constitute an interesting access towards a variety of substituted…”

Approaches to the Formation of Condensed Isoindolones

“…Under basic conditions, the analogous Pd-catalyzed intermolecular coupling and heteroannulation of 15 with other imines (17) led to the 3,3-disubstituted isoindole 18 through carbopalladate addition to the C=N bond (Scheme 5) [24].…”