Radical alkylations, isoquinoline

Isoquinoline has been alkylated with tertiary halides such as terf-butyl40 or adamantyl halides.41 Isoquinoline is reduced more easily than the halides and the mechanism is believed to involve alkyl radicals formed by homogeneous electron transfer from the heteroaromatic anion-radical A. ... 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

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. ... 

Alkyl Isoquinolines. Coal tar contains small amounts of l-methylisoquinoline [1721-93-3] 3-methylisoquinoline [1125-80-0] and 1,3-dimetliylisoquinoline [1721-94-4J. The 1- and 3-methyl groups are more reactive than others in the isoquinoline nucleus and readily oxidize with selenium dioxide to form the corresponding isoquinoline aldehydes (174). These compounds can also be obtained by the hydrolysis of the dihalomethyl group. The 1- and 3-methyhsoquinolines condense with benzaldehyde in the presence of zinc chloride or acetic anhydride to produce 1- and 3-styryhsoquinolines. Radicals formed by decarboxylation of carboxyUc acids react to produce 1-aIkyhsoquinolines. 

The ethyl radical directly attacks the heteroaromatic base, while the acetaldehyde acts as a source of acetyl radical. Photochemical oxy-alkylation has also been tried with ethers. The reaction has been successfully carried out with pyridines, quinolines, isoquinolines,cinno-lines, and quinoxalines. Particularly good yields were obtained with caffeine (16) (Scheme 14). ... 

Radical reductive alkylation of enamines has also been utilized for the intramolecular cyclization reaction34. Enamine 38 bearing an exo-olefin moiety, on treatment with Bu3SnH in the presence of a radical initiator, generates an aryl radical 39 which undergoes exclusive 1,6-cyclization to give the isoquinoline 40 as the sole product in 51.3% yield (equation 9). 

In principle, the photoreactions of CT s are able to offer a great number of photoinitiator systems for radical polymerization. But, so far, this subject has only received little attention, and the current knowledge relative to the photochemistry of such complexes is poor. In addition to the amine complexes mentioned above, chinoline-bromine [124-127], chinoline-chlorine [128], 2-methylpyridine-chlorine [129], pyridine-bromine [130], IV-vinylpyrrolidone-bromine [131], acridone-bro-mine [132], acridone-chlorine [133], benzophenone-S02 [134], isoquinoline-S02 [135, 136], and 2-methylquinoline-S02 [136] combinations are used for radical polymerization of AN, alkyl methacrylates, acrylic and methacrylic acid, and for... 

Photoamination of a variety of aromatic compounds with ammonia and alkyl-amines under photosensitized electron transfer mediated reaction conditions has been extensively investigated by Yasuda and coworkers (Scheme 70) [320-324]. The photoamination reactions of stilbene derivatives with ammonia have been utilized for the synthesis of a variety of isoquinoline derivatives [324]. The photoamination is initiated by photochemical electron transfer from the arenes to the electron acceptor followed by nucleophilic attack of ammonia or primary amines on the aromatic radical cations (Scheme 70). 

Furthermore, they also developed an intermolecular enantioselective alkyl Heck-type coupling cascade for the formation of functionalized chiral indolines, pyrroHdines, and an isoquinoline from acyclic y- and 5-alkenylsulfonamides via a formal alkene C—H functionalization process. The carbon radical intermediate which is formed in situ under copper system could be oxidized to an alkene leading to the desired products [60] (Scheme 8.24). 

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