Synthesis of functionalized pyridinium salts bearing a free amino group

Abstract

Tetrasubstituted N-methylpyridinium salts bearing a free tertiary amino group have been synthesized by a straightforward procedure starting from inexpensive starting materials. The key feature of the synthesis is the use of a proton as a simple effective protecting group to achieve selective N-methylation of the pyridine ring without attacking the amino group.

Total Synthesis of the Tetracyclic Pyridinium Alkaloid epi‐Tetradehydrohalicyclamine B

“… [25] Therefore it seemed advisable to carry the quarternization out as late as possible; to this end, we planned to resort to intramolecular N‐alkylation as a way of crafting the strained 13‐membered ring in the final stages of the synthesis (Scheme 2 ). In this case, however, the reaction has to take place in the presence of the more nucleophilic tertiary amine of the adjacent piperidine, which renders the maneuver delicate; [26] at the same time, all transformations leading to the required precursor H must be compatible with one or both of these basic entities. Under this proviso, we opted for ring closing alkyne metathesis (RCAM) followed by semi‐reduction of the triple bond for the formation of the other macrocycle,[ 27 , 28 , 29 ] since molybdenum alkylidynes endowed with silanolate ligands are remarkably tolerant towards many different donor sites,[ 13 , 30 , 31 , 32 ] most notably complexes with a tripodal silanolate ligand framework (“canopy catalysts”).…”

Total Synthesis of the Tetracyclic Pyridinium Alkaloid epi‐Tetradehydrohalicyclamine B

“…Therefore it seemed advisable to carry the quarternization out as late as possible; to this end, we planned to resort to intramolecular N‐alkylation as a way of crafting the strained 13‐membered ring in the final stages of the synthesis (Scheme 2). In this case, however, the reaction has to take place in the presence of the more nucleophilic tertiary amine of the adjacent piperidine, which renders the maneuver delicate; [26] at the same time, all transformations leading to the required precursor H must be compatible with one or both of these basic entities. Under this proviso, we opted for ring closing alkyne metathesis (RCAM) followed by semi‐reduction of the triple bond for the formation of the other macrocycle, [27–29] since molybdenum alkylidynes endowed with silanolate ligands are remarkably tolerant towards many different donor sites, [13, 30–32] most notably complexes with a tripodal silanolate ligand framework (“canopy catalysts”) [33–36] .…”