Carbocation Organocatalysis in Interrupted Povarov Reactions to cis‐Fused Pyrano‐ and Furanobenzodihydropyrans

Abstract

Tritylium cation‐catalyzed interrupted Povarov reactions afforded cis‐4‐aminobenzodihydropyrans in excellent yields (90 %) within 10 min by low catalyst loadings (1 mol‐%). A mechanism involving Lewis acidic catalysis by a carbocation was proposed and validated. Changing a one‐pot batch version of the reaction into a two‐stage convergent continuous flow procedure led to a 10‐fold time reduction (to 1 min) with 88 % yield.

Carbocation Lewis Acid TrBF4-Catalyzed 1,2-Hydride Migration: Approaches to (Z)-α,β-Unsaturated Esters and α-Branched β-Ketocarbonyls

“…Since the discovery of the first trityl cation in 1901, stable carbocations as non-metal Lewis acid catalysts have been widely applied in organic synthesis. − However, carbonyl compounds have mainly been used as substrates in carbocation Lewis acid catalysis (Scheme B). Recently, we developed latent carbocation catalysis with chiral phosphate as a counteranion of the trityl cation, which efficiently promoted the asymmetric Friedel–Crafts reaction, HDA reaction, and carbonyl-ene reaction .…”

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

“…Experimental findings involving the trapping of III by a nucleophilic solvent (for instance, ethanol) provide evidences for the non-concertedness character of the PR. [42][43][44] Because of its synthetic utility, this methodology has been referred as interrupted PRs, [2,20,34,45] and has been employed in the enantioselective synthesis of cis-4aminofuranobenzopyrans. [46] However, it is important to highlight that the failure in trapping the cationic intermediate does not represent an irrefutable proof that the mechanism is concerted, since the intramolecular reaction (which can also be viewed as a trapping step) is a relevant competitive pathway.…”

Recent advances in continuous-flow organocatalysis for process intensification

“…Triphenylmethylium (tritylium) cation has shown effectiveness in catalyzing the diastereoselective synthesis of benzodihydropyran derivatives from salicylaldimines and electron-rich alkenes via interrupted Povarov reactions (Scheme 2). 18,19 Very positive results have been reported for batch transformations using 2,3-dihydrofuran (DHF), ethyl vinyl ether and 1-vinylpyrrolidin-2-one as alkene substrates in the presence of tritylium tetrafluoroborate (TrBF4, 1 mol%) in THF solvent at room temperature, which produced the target products in excellent yield (up to 92%) and stereoselectivity (up to 95:5 cis/trans ratio) (Scheme 2A). As depicted in Scheme 2B for the reaction between DHF and salicylaldimine, it was proposed that the latter is initially activated by tritylium ion to form intermediate 3 which is then intercepted by the nucleophilic alkene.…”