Synthesis of Isoindolin-l-ones

The latter process must play a key role in the recently reported Pd-catalyzed alternative copolymerization of ethene and CO in water. It is also involved as a mechanistic step in a new synthesis of isoindolin-l-ones 40 by Pd-catalyzed intermolecular coupling and heteroannelation between 2-iodobenzoyl chloride (37) and imines 38 (Scheme 11). In this case, however, a /3-hydride elimination in the intermediate 39 would not be possible at all. 

Scheme 1.20 (a-d) Palladium-catalyzed carbonylative synthesis of isoindolin-l-ones. 

Cho, C.S., Shim, S.C., Choi, H.-J., Kim, T.-J., Shim, S.C. and Kim, M.C. (2000) Synthesis of isoindolin-l-ones via palladium-catalyzed intermolecular coupling and heteroannulation between 2-iodobenzoyl chloride and imines. Tetrahedron Letters, 41, 3891-3893. 

Phthalimidines (isoindolin-l-ones) can be valuable intermediates for the synthesis of isoindoles and some natural products, and there has been recent interest in the development of simple methods for the direct conversion of o-phthalaldehyde into /V-substituted phthalimidines. Condensation of o-phthalaldehyde with primary aliphatic amines using acetonitrile as solvent gives disappointing yields with a-methylbenzylamine, for example, the yield of the phthalimidine 1 is only 21%. By contrast, treatment of o-phthalaldehyde with a-amino acids in hot acetonitrile gives generally excellent yields of the corresponding phthalimidines. With L-valine, for example, 2 is formed in 87% yield. 

Parham cyclizations have been employed extensively to construct isoindolin-l-ones, which are embodied in a large number of natural products, and 3-alkylidenephthalimidines. An example of the latter is 53- 54. Imides unsubstituted on nitrogen were initially treated with sodium hydride prior to exposure with -butyllithium. The synthesis of chromeno[4,3,2-cti]isoindolin-2-one 56 was achieved via a Parham ring closure, as were the related chromeno[4,3,2-tfe]isoquinolin-3-ones. ... 

Kundu et al. have reported a highly regio- and stereoselective synthesis of (Z)-arylidene isoindolin-l-ones via a palladium-catalyzed [4 + 1] cycloaddition process using alkynes as acceptor molecules (eq 74). 

Collard, S. and Keep, A. (2003) Synthesis of 3-substituted isoindolin-l-ones via a palladium-catalysed 3-component carbonylation/amination/Michael addition process. Tetrahedron Letters, 44, 7441-7443. 

The ehiral phosphoiie aeid (i )-(231) has been shown as an efficient Bronsted aeid eatalyst in asymmetrie synthesis of various acyclic and endo exocyclic p-hydroxyenones (230) through a regiospecific aldol condensation between a,p- unsaturated ketones (228) and ethyl glyoxalate (229) (Seheme 60). Enantioseleetive synthesis of 3-indolyl-substituted isoindolin-l-ones (234) through the ehiral phosphoric add (235) catalysed asymmetric Friedel-Crafts alkylation of indoles (232) with 3-hydroxyisoindolin-l-ones (233) in excellent ehemieal yields (up to 99%) and with moderate to good enantioselectivities (up to 99% ee), has been described by Zhou et al. (Scheme 61). ... 

---