Isoquinolinium salts, Grignard addition

A review of the literature prior to 1953 on reactions of pyridinium, quinolinium, and isoquinolinium salts is available (31). The reactions will be described here only briefly. The initial observation was that of Freund et al. (32-37), who found that treatment of various derivatives of hydra-stinine (15) with Grignard reagents yielded addition products, such as 16. 

The addition (150-157) of Grignard reagents, alkoxides, hydroxide, sulfides, cyanide, and enolate anions to pyridinium and isoquinolinium salts again provides a variety of cyclic enamines of potential synthetic use. 

The Zincke salt (A -(2,4-dmitrophenyl) salt) of isoquinoline is easily transformed into chiral isoquinolinium salts on reaction with chiral amines - an ANRORC sequence in which the ninogen of the chiral amine ends up as the nitrogen of the isoquinolinium product - nucleophilic addition of Grignard reagents to these salts shows good stereoselectivity. ... 

The Zincke salt of isoquinoline is easily transformed into chiral isoquinolinium salts on reaction with chiral amines.Nucleophilic addition of Grignard reagents to these salts shows good stereoselectivity. " ... 

Isoquinolinium 369 and [2,7]naphthyridin-2-ium 371 salts have also been used for the preparation of 2,3,8,8a-tetrahydro-57/-oxazolo[3,2-tf]pyridine derivatives (Scheme 98) addition of Grignard reagents to 369 is followed by a spontaneous cyclization to 370 <1998JOC1767> while an asymmetric version of the Bradsher cycloaddition between 371 and chiral enol ether 372 gives 373 in good yield and selectivities <1996TL7019>. 

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