The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

Abstract

International audienceThe classical Prins cyclization reaction has been one of the most studied reactions during the last two decades and it has found many applications in key steps of natural product syntheses, especially for products containing pyran units and related structures in their core skeletons. The nitrogen-based version of the Prins reaction, aza-Prins cyclization, has found its own relevance in organic synthesis owing to the fact that it gives direct access to piperidines, which are even more widespread in natural products and in drugs. Even though the potential scope of the reaction is vast, and despite it having afforded significant progress in the synthesis of various azaheterocycles, its applications in the field of natural product synthesis is massively underdeveloped in comparison with the classical Prins reaction. A compilation of the applications of azaPrins cyclization in the preparation of natural products and selected analogues, especially compounds of potential biological interest, is presented, with emphasis placed on the key roles of this reaction in the total synthesis of these products

Total Synthesis of Talatisamine

“…The last task in our total synthesis was oxidative aza‐Prins cyclization of the remaining F‐ring according to Wiesner's report . Reproducing the transformation in Scheme was problematic, however, because the detailed protocol was not available in the literature.…”

“…Thelast task in our total synthesis was oxidative aza-Prins cyclization [38] of the remaining F-ring according to Wiesners report. [8,13] Reproducing the transformation in Scheme 1w as problematic,however, because the detailed protocol was not available in the literature.O ur extensive investigation disclosed that both oxidants and solvents significantly affected the oxidation sites and reaction outcomes (Table 1).…”

The Pivotal Role of N‐O bonds in the Synthesis of Natural Products: A mini‐review

“…This strategy has been extensively used for the synthesis of piperidine alkaloids (figure 5). [14] In this strategy, cleavage of the N-O bond occurs immediately after cycloaddition, which excludes the introduction of additional substituents. We have designed an alternative strategy based on a nitroso Diels-Alder cycloaddition, in which several synthetic transformations are undertaken after cycloaddition and before N-O bond cleavage.…”

Synthesis of 1‐Aminoindenes through Aza‐Prins‐Type Cyclization

“…[1] On the other hand, the aza-Prins-type exo cyclization of an imine bearinga n alkene moiety on the imine carbon is relatively rare, while useful cyclic compounds having ap rotected amino group can be obtained (Scheme 1b). In most cases, an iminium carbon reacts with an alkene moiety on the iminium nitrogen to give the nitrogen heterocycles, whicha re frequently used in alkaloid synthesis (Scheme 1a).…”