Quinolines aluminum hydrides

Reduction of quinoline with lithium aluminum hydride gives 1,2-dihydroquinoline. Neutral pyridines bearing electron-withdrawing substituents are also reduced by sodium borohydride (Scheme 32). 

Different hydrogenolytic reactivity of trifluoromethyl groups with respect to their position on the quinoline ring is observed. All C-F bonds in 2-, 4- and 6-(trifluoromethyl)quinoline are hydrogenolyzed by lithium aluminum hydride (Table 4), but the 3-trifluoromethyl isomer gave 3-(difluoromethyl)-l,2-dihydroquinoline (10) under the same experimental conditions in contrast to these results, sodium borohydride surprisingly reduces 3-(trifluoromethyl)quinoline to the corresponding 3-methylquinoline (Table 4).149... 

Numerous reducing agents were tried at this point unsuccessfully. For example, lithium aluminum hydride destroyed the substrate, whereas DIBAH or lithium borohydnde in THF and sodium borohydride in ethanol led to reduction of the quinoline system. On the other hand, both potassium borohydride (either with or without 18-crown-6) and zinc borohydride (with or without ethanol) produced no reaction at all. Lithium triethylborohydride resulted in de-methoxylation, and sodium borohydride in refluxing THF gave a 45% yield of diol 16 together with overreduced product. 

The reduction of isoquinolinium ions has been extensively investigated with borohydride and aluminum hydride ions. The use of boro-hydride ion in a protonic solvent normally leads to the formation of 1,2,3,4-tetrahydroisoquinolines, whereas the reduction with aluminum hydride ion in an aprotic medium generally gives a 1,2-dihydroiso-quinoline. This 1,2-dihydroisoquinoline contains an enamine system and may undergo further reaction on treatment with acid. The 1,2-and 3,4-dihydroisoquinolines as well as isoquinolinium ions are reduced by the borohydride ion in a protonic medium to the 1,2,3,4-tetrahydroisoquinolines. 

The reduction of quinolinium salts or quinolines with lithium aluminum hydride gives predominantly the 1,2-dihydroquino-lines.78,92, 95- 97-103 The yield of product appears to depend upon the... 

Quinolines generally produce 1,2-dihydroqulnolines with aluminum hydrides. Diisobutylaluminum hydride and Red-Al have been used to reduce quinolines and quinoline-A -boranes (42 Scheme 9). The reactions are believed to proceed via aminoalanes or boranes and the dihydroquinolines produced are quenched and trapped as the carbamates by the addition of chloroformate esters. Minor amounts of 1,4-dihydro- and 1,2,3,4-tetrahydro-quinolines are also formed. The possession of a 2-substituent hinders reaction. At low temperatures the kinetic product, i.e. (43), is favored, but at higher temperatures reduction at the 4-position predominates which subsequently produces the tetrahydro derivative (44). A similar approach has been employed with isoquinoline, generating 1,2-disubstituted tetrahydroisoquinolines (45 Scheme 9). ... 

Generally, quinolines are reduced to their 1,2-dihydro derivatives with LAH. Use of diisobutylaluminum hydride and sodium bis(2-methoxyeth-oxy)aluminum hydride with quinoline (133) has shown that 1,2-dihydro-quinolines (160) can be conveniently and cleanly generated at low tempera-... 

In contrast to the quinoline and isoquinoline series, thienopyridines are apparently resistant to reduction by tin-hydrochloric acid, since the parent systems can be obtained by reductive dehalogenation or chloro-derivatives. Quaternary salts are reduced to the JV-alkyl-4,5,6,7-tetra-hydrothienopyridine by sodium borohydride,45,48,89-91 and the azo-methine bond in dihydro derivatives (e.g. 69) is reduced by lithium aluminum hydride.47... 

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