Selective reductions, isoquinoline

A variety of new methods for the selective reduction of pyridine Ar-oxides to the corresponding pyridine have been developed. A procedure that is limited to the reduction of relatively electron-rich pyridine Ar-oxides utilizes hexamethyldisilane in the presence of methyllithium in THF/HMPA <1999JOC2211>. This reduction can also be performed on quinoline and isoquinoline Ar-oxides. Tris(2-carboxyethyl)phosphine (TCEP) can be used to... 

Heteroaromatic cations undergo reduction when treated with 1,4-dihydronicotinamide. An early study showed that the 10-methylacridinium ion (87) was rapidly reduced in a redox reaction to the 9,10-dihydro adduct by 1,4-dihydronicotinamides (M Scheme 18). A variety of systems including py-ridines, isoquinolines, quinolines and phenanthridines have been studied using this and related procedures. The selective reduction of pyridinium and quinolinium salts with 1-benzyl-1,2-dihydro-isonicotinamide (89) has been achieved. The selective conversion to the thermodynamically more stable 1,4-dihydro species (90 Scheme 18) is rationalized by the reversibility in the formation of the kinetic products (i.e. the 1,2-adducts) in the presence of pyridinium ions. In the pyridinium case 1,6-di-hydro adducts were also observed in some cases. Reactivity in such systems is sometimes hindered due to hydration of the dihydropyridine system. This is particularly so in aqueous systems designed to replicate biological activity. Dihydroazines derived from isoquinolines and 3,5-disubstituted pyridines have been reported to overcome some of these difficulties. ... 

Both platinum and palladium catalysts can be used for the hydrogenation of heteroaryl derivatives, although platinum is more common. Selective reduction of the heterocyclic ring in 8-methyl-7-hydroxy isoquinoline (440) gave 441 in 67% yield, in Woodward and von E. Doering s synthesis of quinine. 33... 

Reduction of isoquinoline is carried out by catalytic hydrogenation, by hydride reagents or by metals. Catalytic hydrogenation is controlled by the acidity of the reaction medium selective reduction of the pyridine ring to the 1,2,3,4-tetrahydro compound 26 occurs in CH3CO2H, whereas in coned HCl, the benzene moiety is selectively reduced to afford the 5,6,7,8-tetrahydro compound 25. Further hydrogenation leads to the decahydroisoquinoline 27 (cis/trans mixture) ... 

Selective reduction of either the pyridine or the benzene rings in quinolines and isoquinoline can be achieved the heterocyclic ring is reduced to the tetrahydro level by sodium cyanoborohydride in acid solution,by sodium borohydride in the presence of nickel(II) chloride, by zinc borohydride," or, traditionally, by room temperature and room pressure catalytic hydrogenation in methanol. However, in strong acid solution it is the benzene ring which is selectively saturated " longer reaction times can then lead to decahydro-derivatives. 

Selective reduction of either the pyridine or the benzene rings in quinolines and isoquinoline can be achieved the heterocyclic ring is reduced by sodium... 

Isoquinoline can be reduced quantitatively over platinum in acidic media to a mixture of i j -decahydroisoquinoline [2744-08-3] and /n j -decahydroisoquinoline [2744-09-4] (32). Hydrogenation with platinum oxide in strong acid, but under mild conditions, selectively reduces the benzene ring and leads to a 90% yield of 5,6,7,8-tetrahydroisoquinoline [36556-06-6] (32,33). Sodium hydride, in dipolar aprotic solvents like hexamethylphosphoric triamide, reduces isoquinoline in quantitative yield to the sodium adduct [81045-34-3] (25) (152). The adduct reacts with acid chlorides or anhydrides to give N-acyl derivatives which are converted to 4-substituted 1,2-dihydroisoquinolines. Sodium borohydride and carboxylic acids combine to provide a one-step reduction—alkylation (35). Sodium cyanoborohydride reduces isoquinoline under similar conditions without N-alkylation to give... 

The reaction of the fused 5,7-dihalopyrimidine (19) to form the 7-methoxy derivative (20) also shows that the more readily displaced chlorine is next to the azole ring (67T675). Hydrazinolysis of the isoquinoline analogue (21) is stepwise with initial 4-substitution (22). The difference in reactivity at C-4 and C-6 in (22) is sufficient for selective acid hydrolysis of the hydrazino group in (22). Reductive cleavage of the hydrazino C—N bond is achieved in the usual manner by the reaction of its tosyl derivative with alkali (75JCS(Pi)2l90). 

The reduction of the isoquinoline nucleus of compound 7 proceeded with high stereocontrol. What factors could be responsible for the selectivity ... 

Selective hydrogenation of quinolines and isoquinolines. Catalytic hydrogenation of quinolines and isoquinolines usually occurs preferentially in the pyridine ring. However, if the hydrogenation is conducted in trifluoroacetic acid, the reverse situation obtains and the benzene ring is reduced more rapidly. The same result can be obtained with mineral acids, but such hydrogenations are much slower. Both 2- and 4-phenylpyiidine can also be reduced preferentially in the benzene ring. Platinum oxide or palladium or rhodium catalysts can be used. Further reduction of 5,6,7,8-tetrahydroquinolines with sodium and ethanol provides a convenient route to rrans-decahydroquinolines. 

Isoquinolines halogenated in the 1-position are particularly reactive towards S Ar replacement. For instance, 1,3-dichloroisoquinoline is selectively substituted in the 1-position by methoxide to form the 1-methoxy compound 8. Reductive dehalogenation also removes the 1-halogen substituent and produces 3-chloroisoquinoline 9 which, by a SnAt reaction with methoxide, yields 10 ... 

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