3 -Isoquinolinones, synthesis

Similar 1 1 and/or 1 2 coupling reactions of benzamides with alkynes were reported by Guimond s, Rovis s, and Li s groups [35]. Later, ruthenium- [36], palladium- [37], and nickel-catalyzed [38] versions for isoquinolinone synthesis were disclosed. Shi et al. reported similar lactam formation through dehydrogenative annu-lation of an indolecarboxamide 91 with 2c under palladium catalysis (Scheme 25.45) [39],... 

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

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. 

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... 

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>. 

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>. 

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

The synthesis of isoquinolinones by amidoalkylation may also be achieved from other starting materials. N-Substituted derivatives were synthesized by the reaction of arylacetyl chlorides and azomethines in the presence of A1C13 to obtain a number of new compounds, such as 48 (Scheme 13) [75MI1 78ACH(98)315 81MI1 82S216]. 

The synthesis of 3-substituted isoquinolinones and fused isoquinolinones can be performed by the photoinduced SRN1 reactions in DMSO of o-iodobenzamide with the enolates of acyclic aromatic and aliphatic ketones and cyclic ketones, respectively. These reactions proceed from moderate to good yields (Schemes 10.47 and 10.48) [65],... 

A synthesis of substituted phenanthrenes has been reported using the bicyclooctadienes (61) as starting material. The process makes use of the nucleofugal group on C-8 and follows the path outlined in Scheme 3. This involves a di-rr-methane bridging process followed by the collapse of the intermediate biradical (62). Normal di-Ti-methane behaviour is reported in the acetophenone-sensitized irradiation of the isoquinolinone derivative (63a). This yields the two products (64) and (65) as a 3 1 mixture in a total yield of 75%. An N-oxide derivative gave a brown polymer with little evidence for the formation of di-n-methane products. The influence of ring substituents was also studied for the derivatives (63b, d) and the results of this are shown in Scheme 4. The authors conclude that the cyclization process is under LUMO control. Irradiation of the dihydropyridine (66) affords the oxidised pyridine (67) as the major product. A minor product (68) is also formed by a di-ir- methane process. ... 

Interestingly, the methoxy group of 138 and 141 can immediately be used as a leaving group as exemplified by the synthesis of regioisomeric pyridazino[4,5-c]isoquinolinones 144 and 145. The mechanism of the ring closure reaction probably involves imine formation followed by an electrocyclic reaction and subsequent aromatization via elimination of methanol [68]. 

The intramolecular Friedel-Crafts cyclisation of N-2-naphthylalkylalanines proceeds with retention of configuration and subsequent reduction of the resulting isoquinolinone provides a stereospecific synthesis of the diastereoisomeric 1,2,3,4-tetrahydrobenzo[f]isoquinolin-1-ols (93 and 94) (E. Gellert, N. Kumar and D. Tober,... 

Kitamura et al. have described a remarkable high-yield photochemical synthesis of isoquinolinones (26) from the vinyl bromides (27) in the presence of water, dichloromethane, potassium isocyanate and a phase transfer agent. Binkley and Hehemann have described a novel high-yield procedure for the removal of protecting benzyl groups in carbohydrate derivatives. 

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