A detailed investigation of the aza-Prins reaction

Abstract

The development of a Lewis acid-promoted aza-Prins reaction to form piperidines and pyrrolidines is described. Indium trichloride has been found to be a highly successful and mild Lewis acid for promoting this reaction. A thorough mechanistic investigation is described, including the factors that influence the formation of the 5- or 6-membered ring product(s).

Aminomethylation of Aryl Halides Using α-Silylamines Enabled by Ni/Photoredox Dual Catalysis

“…2 Equally as common are approaches that rely on an electrophilic α-carbon, wherein the C–C bond linking the aminomethyl group to the target of interest is formed via alkylation of iminum ions by carbon nucleophiles (e.g., Mannich, Strecker, or aza-Prins type reactions). 3 The umpolung strategy, wherein the α-carbon serves as the nucleophile, is much less common, owing to difficulties in generating such species. To accomplish this, surrogates, such as nitroalkanes, are employed, and further functional group manipulation is required to obtain the desired aminomethylated products (i.e., reduction in the case of nitroalkanes).…”

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

“…We have had a long standing interest in the Lewis acid-promoted Prins reaction 1,2 and have, along with others, more recently reported on the nitrogen equivalent of this reaction, the aza-Prins reaction, [3][4][5][6][7][8][9][10][11][12] together with its silicon modified counterpart the aza-silyl-Prins reaction. 2,[13][14][15][16] Both reactions involve the intermolecular reaction of a carbonyl or related compound (aldehyde, ketone or epoxide) with a secondary homoallylic amine in order to form an iminium ion, which then undergoes intramolecular Prins cyclisation to give either piperidines or tetrahydropyridines, depending on the absence or presence of the silicon moiety on the alkene (Scheme 1).…”

“…17,[33][34][35] This also adds a further layer of complexity to the cascade process, making it now three sequential steps: following cyclisation/iminium ion formation and aza-Prins cyclisation, the transformation may be terminated with Friedel-Crafts or Ritter reaction. In general, the trapping of an external nucleophile occurs most readily when employing a Lewis acid poor in providing an anion for capture.…”

Bioinspired Total Synthesis of Sespenine

“…[2,8] Scheme 1 illustrates such a reaction from 3 to 1. Oxidation at the indole C3-position may give the hydroxyindolenine 5, [9] which, upon the activation of the imine by an acid, could undergo an aza-Prins cyclization [10] to form the cationic species 6. It is noteworthy that a similar aza-Prins reaction was observed during our synthesis of indotertine A.…”