Isoindolin-l-one

Isoindolin-l-ones can also be prepared by the palladium-mediated carbonylation of o-bromo(aminoalkyl)benzenes (Scheme 50).86 This amidation... 

Reaction of N-benzoyl isoindolin-l-one with 2-lithio-l-phenylsulfonylindole takes place at both lactam and acyclic carbonyl groups generating a separatable 4 3 mixture of ketone 33 with 2-benzoyl-l-phenylsulfonylindole. When the reaction is allowed to proceed for longer than ca. 15 min, cyclized product 34 is formed as the result of an intramolecular nucleophilic substitution. Compound 34 can be obtained from the isolated ketone 33 in good yield on exposure to NaH in refluxing THE (Scheme 5 (1996TL4283)). 

Activation of the carboxylic acid function of 2-(l//-pyrrol-l-yl)isoindolin-l-one 253 yielded 5,5a-dihydropyrro-lo[l, 2 2,3]pyridazino[6,l- ]isoindole-4,10-dione 254 (Equation 64) <1995H(41)689>. 

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. 

A variety of substituted isoindolin-l-ones (18) have been prepared in good to excellent yields under very mild conditions by the reaction of e>-(alk-l-ynyl)benzamidcs (17) with IC1, I2, and NBS,37 as a result of 5(N)-exo-dig cyclization.38 In a few... 

Phthalimide was also hydrogenated to give isoindolin-l-one with addition of a small amount of iron(II) sulfate, although more slowly than in the presence of trifluoroacetic acid. Hexahydrophthalimide and (V-ethoxycarbonylsuccinimide resisted hydrogenation even in the presence of trifluoroacetic acid. 

Jog PV, Brown RE, Bates DK (2003) A redox-mediated molecular brake dynamic NMR study of 2-[2-(methylthio)phenyl]isoindolin-l-one and S-oxidized counterparts. J Org Chem... 

A three-component palladium-catalyzed cascade process has been employed by Grigg and co-workers for the one step preparation of 3-substituted isoindolin-l-ones 103 [91]. This cascade reaction involves Pd-catalyzed car-bonylation of aryl iodide 102 and subsequent trapping of the acyl palladium species by an amino derivative. The resulting amide undergoes an intramolecular Michael addition leading to the bicyclic systems 103 isolated in moderate to good yields (Scheme 39). 

O-tert-Butylcarbamoylquinine (t-BuCQN) and 2,6-diisopropylphenylcarbamoyl-quinine (DIPPCQN) type CSPs have been evaluated for the enantiomer separation of a set of isoindolin-l-one fluorescent derivatives of a-amino adds obtained by their reaction with the ortho-phthalaldehydc, naphthalene-2,3-dicarboxaldehyde, or anthracene-2,3-dicarboxaldehyde. The latter reagent afforded the derivatives of the... 

All other cross-couplings involving terminal alkynes and halo amides have involved ring closure on nitrogen. Thus, o-halobenzamides react with simple terminal alkynes in the presence of a Pd/Cu catalyst to afford either (Z)-3-aryl(alkyl)idene isoindolin-l-ones or the corresponding 2-(l-alkynyl)benza-mides, which are readily cyclized by NaOEt/EtOH or Pd(OAc)2 catalyst to give isoindolin-l-ones (Eq. 11) [35,36]. When acetylenic aryl carbinols are employed as the alkynes, 3-(acylmethyl)isoindolin-l-ones are obtained instead (Eq.l2) [37]. 

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. 

K. Gyimesi-Forras, A. Leitner, K. Akasaka and W. Lindner, Comparative study on the use of ortho-phthalaldehyde, naphthalene-2,3-dicarboal-dehyde and anthracene-2,3-dicarboaldehyde reagents for a-amino acids followed by the enantiomer separation of the formed isoindolin-l-one derivatives using quinine-type chiral stationary phases,/. Chromatogr., A, 2005, 1083, 80-88. 

Cardo PEEK copolymers with pendant hydroxyl ethyl groups (—CH2CH2OH) can be synthesized from 2-(2-hydroxyethyl)-3,3-bis(4-hydroxyphenyl)isoindolin-l-one, 4,4 -biphenol, and 4,4 -dilluorodiphenylsulfone [85]. The monomers are shown in Figure 6.12. 

Schi-f-f bases are probably intermediately -formed during the deoxigenation reactions o-f aromatic nitro compounds with carbon monoxide <150 atm), at 165-170"C, in the presence o-f ortho-phtalaldehyde and with Rh final products are N-aryl-isoindolin-l-ones hydrogen atom o-f the -free carbonyl -function ... 

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

Scheme 2.34 Palladium-catalyzed carbonylative synthesis towards isoindolin-l-ones...

A sequence involving intermolecular Pd-catalyzed carbonylative amidation followed by intramolecular Michael addition has been employed for the construction of isoindolin-l-ones [97dj. For example, treatment of 147 with 4-methoxyaniline under standard conditions for Pd-catalyzed carbonylative coupling gave isoindolinone... 

Amides, carbamates, and ureas are rapidly alkylated, usually on carbonyl oxygen (see the section on ambident nucleophiles). Alkylation of amides with MeOTSf in CH2CI2 followed by reduction of the salts provides a route for the selective reduction of amides esters, nitriles, acetals, and double bonds are left unaffected by this procedure. Alkylation of isoindolin-l-ones and subsequent deprotonation can provide routes to methoxyisoindoles. ... 

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. ... 

The reductive coupling of phthalimides with ketones and aldehydes in THF by low-valent titanium generated from Zn-TiC gave 3-hydroxy-3-(l-hydroxyaIkyl)-isoindolin-l-ones as two-electron reduced products and alkyhdene-isoindolin-l-ones as four-electron reduced products. These could be obtained selectively by controlling the reaction conditions. The geometric ratios of the alkylideneisoindolin-l-ones obtained from phthalimides and aldehydes could be increased by reflux in PPTS/ toluene (catalyst). In particular, the Z-isomers of A-unsubstituted alkylideneisoindolin-l-ones could be obtained exclusively. 

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