3 -Isoquinolinones

Thus, while the 3-hydroxyisoquinoline-3-isoquinolinone equilibrium (80 81) and that... 

Isoquinol-4(l H)-one, 2,3-dihydro-synthesis, 2, 73 Isoquinolinones from isocoumarins, 3, 691 magnetic circular dichroism, 2, 129 synthesis,... 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

Heating 3//-2,3-benzodiazepin-4(5//)-ones 1 in acidic media gives the isomeric isoquinolinones... 

CN ( )-4-[3-[(l,l-Dimethylethyl)amino]-2-hydroxypropoxy]-2-methyl-l(2//)-isoquinolinone hydrochloride ( )-base... 

The importance of proper immobilization of enzymes can be shown in the kinetic resolution of racemic a-acetoxyamides. This group of compounds is an important class of chemicals since they can be readily transformed into a-amino acids [17], N-methylated amino acids, and tripeptide mimetics [18], amino alcohols [19], 1,2-diols [20], 1,2-diamines [21], and enantiopure l,4-dihydro-4-phenyl isoquinolinones [22]. 

A chelation-assisted Pd-catalyzed Cope rearrangement was proposed in the reaction of phenanthroline to generate isoquinolinone derivatives (Eq. 12.78).177 The use of aqueous media and ligands enables a double-Heck reaction on a substrate favoring alkene insertion over (J>-hydride elimination. 

A combination of 2,3 sigmatropic rearrangement (Pummerer-type reaction) followed by an electrophilic aromatic substitution of the intermediate sulfenium ion, the formation of an iminium ion and, finally, a second electrophilic aromatic substitution, was used by Daich and coworkers for the synthesis of iso-indolo-isoquinolinones as 4-314 (Scheme 4.68) [106]. Thus, reaction of the two diastereo-meric sulfoxides 4-313, easily obtainable from 4-312 by a Grignard reaction and oxidation, led to 4-314 as a single product after crystallization in 42% yield. 

Several bacterial strains utilizing isoquinoline have been isolated, which metabolized isoquinoline via l(2H)isoquinolinone, such as Brevundimonas diminuta strain 7. 

D. 4a(S),8a(R)-2-Benzoyloctahydro-6(2H)-isoquinolinone (4). Palladium (Pd), 10% on carbon, 4.0 g, (Note 21) is placed in a 500-mL Parr bottle under N2 and carefully wetted with 50 mL of cold denatured ethanol (EtOH). A slurry of 34.7 g of enone 3 (0.14 mol) in denatured EtOH (250 mL) is added and the Parr shaker apparatus assembled. After the system is purged with nitrogen-hydrogen (N2/H2), the reaction is shaken at 50 psi H2 and 50°C until H2 uptake is complete (1 hr, Note 22). The catalyst is filtered over a Celite pad (Note 23) and rinsed with warm chloroform (CHCI3) (4 x 75 mL). The filtrate is concentrated under reduced pressure, dissolved in 90 mL of CH2CI2 and crystallized with 200 mL of hexanes. The crystalline solid is filtered, rinsed with hexanes and dried to afford 34.3 g (98%, Note 24) of the ketone 4, representing a 51% yield over four steps. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Darrell R. Hutchison, Vien V. Khau, Michael J. Martinelli, Naresh K. Nayyar, Barry C. Peterson, and Keven A. Sullivan 223 SYNTHESIS OF cis-4a(S),8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES FROM QUININE 4a(S), 8a(R)-2-BENZOYLOCTAHYDRO-6(2H)-ISOQUINOLINONE... 

SYNTHESIS OF cis-4a(S),8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES FROM QUININE 4a(S), 8a(R)-2-BENZOYLOCTAHYDRO-6(2H)-ISOQUINOLINONE... 

C. 4a(S),8a(R)-2-Benzoyl-1,3,4,4a,5,8a-hexahydro-6(2H)-isoquinolinone (3). A 1-L, three-necked, round-bottomed flask is equipped with a mechanical stirrer, Teflon-coated thermocouple, 500-mL addition funnel and a N2 inlet. Concentrated sulfuric... 

Six- and seven-membered rings (dihydroisoquinolines 178, isoquinolinones 179, 180 and benzazepines 181) were obtained starting from orf/io-halobenzaldehydes or orf/to-halobenzoic acids [144, 145]. In all the cases, the exo-trig cyclization mode was strongly favoured. However, for 178 and 180, isomerization of the double bond from exocyclic to endocyclic occurred spontaneously under the Heck conditions. 

To explain these results, Lee and colleagues " showed that in the absence of Lewis acids the rotational barrier of the C=N double bond is fairly high, but in the presence of catalysts the rotational barrier is lowered. The complex formation of tosylate and AICI3 makes the double bond rotation possible and the product distribution is determined by the relative stability of the oxime E-Z isomers (equation 89). A cychc transition state affords the corresponding quinolinone 281 and the isoquinolinone 282. 

Xie, C. et al., Flavonoid glycosides and isoquinolinone alkaloids from Corydalis bungeana, Phytochemistry, 65, 3041, 2004. 

The direct anionic cyclization of 2-alkynylbenzonitriles 45 was applied to the synthesis of isoquinolinones <99T13193> and phenanthridines <990L767>. A bw-alkylation process of an amine with a hii-mesylate afforded the tetrahydroisoquinoline ring system <99SC645>. 

Thus, while the 3-hydroxyisoquinoline-3-isoquinolinone equilibrium (80 81) and that of the cinnoline derivatives (82 83) favour the keto forms (81, 83), the proportion of hydroxy tautomers is considerably greater than in the corresponding unfused systems. The benzo-fusion in 2- and 4-quinolinone and in 1-isoquinolinone has the effect of reducing the aromaticity of the heterocyclic ring, and consequently of lowering the proportion of the hydroxy tautomers. 

Since isoquinolinones are known to be very potent inhibitors of poly(ADP-ribose)polymerase (PARP), thieno[3,4-( ]pyridin-4-ones have been studied for their potential as PARP inhibitors <1999BMC297>. Early studies indicate that the sulfur analogues also act as potent PARP inhibitors. Thienopyridine diazonium salts can be converted into heterocyclic dyes that are useful as disperse dyes for polyester fabrics <2005DP(64)223, 2006DP(70)60>. 

Solid-phase syntheses have become increasingly popular during the period of this review, with examples including the synthesis of 5,6,7,8-tetrahydro[l,6]naphthyridines from Meldrum s acids derived from /3-amino alcohols via Hantzsch condensation and cyclization with cyclative cleavage from the resin (using 70% trifluoroacetic acid (TFA)/dichloromethane (DCM) followed by 5% triethylamine/DCM) <1999S1951> and also of isoquinolinones and 5-oxo-5,6-dihydro-[l,6]naphthyridines <1995JOC5748>. 

In the final example of the Heck reaction on solid support, a Chiron group54 55 used a palladium-catalyzed cyclization step to prepare heterocycles. An example of their work, the production of l-(2H)-isoquinolinones, is shown in Scheme 22. 

Goff, D. A. Zuckermann, R. N. Solid-Phase Synthesis of Highly Substituted Peptoid 1 (2H)-Isoquinolinones, J. Org. Chem. 1995, 60, 5748-5749. 

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