Grignard with pyridinium salts

The regioselectivity of Grignard addition to (V-alkoxycarbon y I pyridinium salts can often be controlled by changing the conditions. For example, C(4) addition can be enhanced by the presence of catalytic amounts of copper salts reaction of salt 288 (R = Me) with lithium dimethylcuprate gives also almost exclusively the 1,4-dihydro product 290 (R = Me, R Me). 

Silylation at nitrogen with t-butyldimethylsilyl triflate, generates pyridinium salts which, because of the size of the A -substitutent, react with Grignard reagents exclusively at C-4 montmorillonite-catalysed addition of silyl enol ethers to pyridines has a comparable effect in producing l-trimethylsilyl-l,4-dihydropyridines carrying an acylalkyl substituent at C-4. ... 

This reaction was first reported by Breckpot in 1923. It is the synthesis of )0-lactam via the cyclization of esters of /3-amino acids with Grignard reagent and is known as the Breckpot -lactam synthesis. This reaction has been modified to form )0-lactam by the treatment of )0-amino acid with Mukaiyama s reagent, or the /3-amino ester with /V-methyl pyridinium salt." ... 

The synthesis of pentazocine is comparatively short. The Grignard reaction with a pyridinium salt is followed by partial hydrogenation. Cleavage of the methyl ether is accompanied by acid-catalysed alkylation, which leads to the buildup of the quaternary centre. Finally, the amino-function is demethylated with cyanogen bromide and alkylated with isopentenyl bromide. 

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