Partial Reduction of Pyridinium Salts as a Versatile Route to Dihydropyridones

Abstract

[reaction: see text] The addition of two electrons to a pyridinium salt turns it into a nucleophile. The intermediate generated by the reduction of such salts can be reacted successfully with a range of different electrophiles (acids, alkyl halides, and carbonyl compounds) and the intermediate hydrolyzed in situ to provide a wide range of dihydropyridones. Each position on the dihydropyridone ring is then accessible using standard synthetic manipulations.

Synthesis of Tricyclic Marine Alkaloids, Cylindricines, Lepadiformines, Fasicularin, and Polycitorols: A Recent Update

“…Conjugate addition of hexylcuprate under the modified Donohoe protocol 38 proceeded in a diastereoselective manner from the pseudoequatorial position at C(2), and this was followed by basic hydrolysis to give (±)-cylindricine C [(±)-5] as a 7:1 mixture of diastereomers.…”

“…47 The construction of the azadecalin (AB ring) framework commenced with regioselective addition of the Grignard reagent to electron-deficient pyridinium salt 105. 38,48 The reaction of N-(3,4-dimethoxybenzyl)pyridinium salt 105 with 4-chlorobutylmagnesium bromide proceeded by regioselective addition at the C 10…”

Natural product synthesis as a challenging test of newly developed methodology

“…23 However, it was found that reduction of the pyridinium salts sometimes led to variable results on reaction scale-up. As an alternative, in order to access the same products, the nucleophilic addition to a pyridinium salt was considered to be an attractive alternative.…”

Six‐Membered Heterocycles: Pyridines

“…Alkyl halides, tosylates, triflates, and so on react readily with pyridines by an S N 2 reaction to give alkylpyridinium salts (Scheme 16.47) [150]. Bulky substituents around the nitrogen ring atom, or tertiary halides or related compounds cause an increase in the competing elimination reaction giving rise to the corresponding alkene and tertiary salts.…”