Isoquinolinium salts, 3,4-dihydro

Lithium aluminum hydride reduction of pyridinium salts is very similar to sodium horohydride reduction and gives similar products, but the ratio of 1,2- and 1,4-dihydro- or tetrahydropyridines differs considerably (5). Isoquinolinium salts are reduced hy sodium borohydride or lithium aluminum hydride in a manner identical to pyridinium salts (5). Quino-linium salts are reduced by sodium borohydride to give primarily tetra-hydroquinolines (72) as shown by the conversion of 33 to 34 and 35. When lithium aluminum hydride is used, the product is usually the dihydroquinoline (73) as shown in the conversion of 36 to 37 and 38. 

The disproportionation reaction of isoquinolinium salts to 1,2-dihydro-isoquinolines and isocarbostyril derivatives (Scheme 16) was used by Brown and Dyke for the synthesis of berberine and 8-oxoberberine derivatives (277-279). 

Sodium borohydride is the reagent of choice for the reduction of the pyridine ring in isoquinolinium salts. It reacts so rapidly that even the carbonyl group of a 1-aroyl substituent can survive (equation 154) (63JCS2487). A 1,2-dihydro intermediate has been isolated during the cyclization of (253) to 2,3-dimethoxyberbine by sodium borohydride, which suggests that a similar mechanism to that described above is operative here (equation 155) (60JOC90). 

Cyclization of 1-isoquinolyl derivatives (201) in a cold solution of perchloric acid or in cone, sulfuric acid at room temperature afforded 4-hydroxy-3,4-dihydro-2//-[l,3]thiazino[2,3-a]isoquinolinium perchlorates (202) and 2H-[l,3]thiazino[2,3-a]isoquinolinium salts (203), respectively (74IJC1242). Heating l-[(3-phenyl-3-hydroxypropyl)thio]isoquinoline in PPA yielded the l-phenyl-3,4-dihydro-2//-[l,3]thiazino[2,3-a]isoquin-olinium salt (74IJC1242). 6,7-Dihydro derivatives of 2//-[l,3]thiazino-[2,3-a]isoquinolinium perchlorate (203, R = Me) and 4-methyl-2,3,4,6,7, llh-hexahydro-[l,3]thiazino[2,3-a]isoquinoline were obtained by cyclization of the 3,4-dihydro derivative of 201 (R = Me) and 4-[(l,2,3,4-tetrahydroisoquinolin-l-yl)thio]-2-butanol, respectively, in cone, sulfuric acid or in PPA [81IJC(B)372],... 

The reduction of 2-substituted-isoquinolinium salts has been reported by Torossian65 with potassium borohydride in water, by Mirza,68 and by Durmand et al.,87,68 using sodium borohydride in aqueous methanol to yield 1,2,3,4-tetrahydroisoquinolines. The reduction of the second double bond appears to arise from a mechanism similar to that leading to tetrahydropyridines from pyridinium ions (see Section I). Mirza66 (see also Bose60) found that the reduction of berberine (60) with sodium borohydride could be stopped at the 1,2-dihydro-intermediate (61), and Karrer and Brook70 showed that the 1,2-dihydroisoquinoline formed by the lithium aluminum hydride reduction of l-phenyl-2-methylisoquinolinium iodide (62) could be further reduced to the 1,2,3,4-tetrahydroisoquinoline (63) with sodium borohydride in methanol. Awe et al.71,72 and Huffman73... 

Methods of synthesis of bisbenzylisoquinoline alkaloids have been reviewed83 and the use of electrochemical methods for the reduction of the dihydro-isoquinolinium salts that result from Bischler-Napieralsky ring-closures in the synthesis of, for example, espinidine has been studied.84... 

Wenkert et al.100 hydrogenated the isoquinolinium salt 30 to the dihydro derivative 31, which also had a stable vinylogous amide moiety (Scheme 12.14) (see also eq. 12.39). 

Scheme 12.14 Partial hydrogenation of isoquinolinium salt with 3-methoxycarbonyl group to the dihydro derivative.

Qulnolinium salts (68 Scheme 15) can undergo attack at either the 2- or 4-position. The former normally predominates and the latter leads to 1,2,3,4-tetrahydroquinolines (69). 3-Substituents generally produce mixtures of the 1,2- and 1,4-dihydro adducts. Isoquinolinium salts (70 Scheme 15) produce both 1,2-dihydrolsoqulnolines (71) and 1,2,3,4-tetrahydroisoquinolines (72). Reduction in protlc solvents normally produces the tetrahydro adducts, in anhydrous pyridine or dimethylformamide the reduction generally stops at the 1,2-dihydroisoquinoline. Reaction of the enamine system of 1,2-dihydroisoqui-nollnes with electrophiles has been used as a method for generation of 4-substituted isoquinolines. 

With some 4-substltuents reduction with borohydride does not proceed past the dihydro adduct even in protic solvents. Certain l-(2-nitrophenylmethyl)isoquinolinium salts, e.g. (73), have been found to undergo substituent cleavage on reduction with borohydride. ... 

Quinolinium and isoquinolinium salts form predominantly 1,2-dihydro products with LAH reductions in aprotic solvents. With the latter the enamine system revealed is amenable to functionalization... 

Isoquinolinium saV., 3,4-dihydro-2-methyl-1-substituted reduction, 2, 44 i Isoquinolinium salts, 2-methyl-reactions... 

However, l-benzyl-3-cyanoquinolinium bromide (168) gives a 75% yield of the 1,4-dihydro adduct 169 when reduced with NBH and allowed to equilibrate in the presence of the parent quinolinium salt. 1,4-Dimethyl-2-methylaminoquinolinium iodide (170) undergoes hydride attack at the 2 position with borohydride to give the product 171 as an unstable yellow oil. Alstonilin or benz[ ]indolo[2,3-fl]chinolizidine-type alkaloids (173) have been successfully prepared in high yields from the isoquinolinium salt 172 via hydride reduction. ... 

Similar 1,3-dipolar additions have been observed recently in the reaction of carbon disulfide with N-benzyl isoquinolinium salts (CXLVIII) in basic medium (228). The dipolarophile carbon disulfide also adds readily to these azomethinylides (CXLIXa, b) and, via the 3-(R)-2J-dihydro-l i H-thiazolo[2,3-aJisoquinoline-2-thiones (CL), the meso-ionic compound (CLI) is formed by a redox-reaction. 

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