Carbamoylations, isoquinoline

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Reaction of isoquinoline, potassium cyanide, and N,iV-diphenyl-carbamoyl chloride gave 67. A similar compound was also obtained through the use of A,iV-diethylcarbamoyl chloride. Again the infrared... 

Diethyl cyanophosphonate converts quinoline and isoqninoline iV-oxides into the 1- and 2-cyano-heterocycles in high yields in a process which must have 0-phosphorylation as a first step, and in which the elimination of diethylphosphate may proceed via a cyclic transition state trimethylsilyl cyanide and diazabicyclonndecene effect the same transformation. A chloroformate and an alcohol convert the iV-oxides into ethers, as illustrated below for isoquinoline iV-oxide, a chloroformate and a Grignard reagent prodnce 2-snbstitnted quinolines, and a chloroformate then an isonitrile produce 2-carbamoyl-... 

Treatment of isoquinoline with sulphuryl chloride and potassium cyanide gives 4-chloro-l-cyanoisoquinoline and l-carbamoyl-3-cyanoisoquinoline, the relative yields of the two products depending upon the proportion of reagents. The Reissert compound from 4-methylisoquinoline gives the bromohydrin (172), and this, on treatment with aqueous sodium hydroxide, affords the benzoylimino-compound (173). Hydrolysis of the latter with dilute hydrochloric acid yields 4-methylisocoumarin (174) (Scheme 71). ... 

Reactions with Radicals. Isoquinoline does react with radicals to give addition to the 1-position with subsequent loss of hydrogen. The Minisci reaction is a well-known example of this transformation. It is an effective reaction for the addition of hydroxymethyl, alkyl, and acyl radicals. Formyl and carbamoyl groups have also be added using this method. Acidic conditions help to promote the reaction. Alkylation is effective when carried out with alkyl iodides or alkyl xanthates. Hydroxymethyla-tion can also be carried out. Photochemical-induced free radical reactions have also been reported. Alkylation is possible using ethanol or propanoic acid but low yields are often obtained. Addition of a phenyl group can be achieved in 81% yield. ... 

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