Pyridinium salts enolate addition

Indole alkaloids.l The ester enolate 1 undergoes 1,4-addition to the pyridinium salt... 

By incorporating a chiral auxiliary, (+ )-rrans-2-(a-cumyl)cyclohexyl (TCC), into pyridinium salt 688, Comins and co-workers were assured of excellent asymmetric induction in a divergent synthesis of three 5,8-disubstituted amphibian indolizidine alkaloids (Scheme 93) (467,499). Addition of but-3-enylmagnesium bromide to 688 yielded the dlhydropyridone 689 as a single diastereomer in 91% yield after recrystallization. After a series of functional group manipulations, the C-8 methyl group was introduced stereoselectively by enolate alkylation (690 -> 691),... 

Pyridinium salt 72 is generated by the treatment of the amide 71 with triflic anhydride in the presence of pyridine followed by treatment with the lithium enolate. Intermediate 72 was used to synthesize tetraponerine T4 in four steps in 38% overall yield. Comins and co-workers used addition of a zinc enolate to an Al-acylpyridinium salt in the synthesis of (+)-hyperaspine <05OL5227>. Additionally, they have studied cuprate addition to A/ -acyl pyridinium salts of nicotine, where addition occurs selectively at the 4-position <050L5059>. 

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. ... 

Some nucleophiles add to Af-fluoropyridinium salts to give dihydropyridines in which elimination of fluoride occurs in situ to give the 2-substituted pyridine, thus avoiding the need for a dehydrogenation step. The main disadvantages of this method are that the preparation of the pyridinium salts require the use of elemental fluorine and that some carbanions give only modest yields due to competitive reactions such as C-fluorination. However, silyl enol ethers do react efficiently stabilised heteronucleophiles (phenolate, azide) can also be used. Addition to N-fluoropyridinium salts shows a strong preference for attack at an a-position. ... 

A procedure has been established for the synthesis of certain aspidospermine alkaloids, based on the addition of an enolate of methyl 2-indolylacetate to a pyridinium salt (367), followed by acid-catalyzed cyclization of the resulting 1,4-dihydropyridine (368) to the tetracyclic structure (369) (Scheme 124) <84H(21)325,89J0C1166,94T5233>. 

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. 

Pyrylium perchlorate 38 forms colourless crystals which are prone to hydrolysis and decompose explosively at 275°C. It can be obtained from A -acceptor substituted pyridinium ions (see p 272), e.g. by the SO3 complex 35, on treatment with NaOH followed by addition of HCIO4. Initially, the orange-coloured sodium salt of 5-hydroxypenta-2,4-dienal (glutaconic dialdehyde in the enol form) 36 is formed which subsequently cyclizes via the red protonated species 37 [7] ... 

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