Prins-Friedel-Crafts Cyclization: Synthesis of Diversely Functionalized Six- Membered Oxacycles

Abstract

: Prins cyclization is a well-established synthetic protocol to generate a wide range of important oxygen heterocycles. It is a cyclization reaction performed by an oxocarbenium ion that undergoes an intramolecular pi-bond attack to construct a new carbon-carbon bond. When this cyclization process is conjugated with Friedel-Crafts reaction, it further expands the synthetic potential by fabricating two different carbon-carbon bonds in one single reaction. Different acid catalysts mediated, the coupled Prins-Friedel-Crafts reaction is conducted both in stepwise as well as in tandem fashion. In the stepwise route, three different reacting components were utilized whereas, the tandem methodology required proper modification of the initial substrate molecule. An array of allylic, propargylic, other related alkenols, and carbonyl reactants were employed to carry out the cyclization process. Several oxygenated heterocycles equipped with diverse functionalities were constructed in a stereoselective manner which again reinforced the significance of this cyclization protocol undoubtedly. The present mini-review highlights (on) the utilization of different one-pot stepwise Prins-Friedel-Crafts reactions and the subsequent development of cascade Prins-Friedel-Crafts cyclization process to furnish intricate molecular architectures of vital six-membered oxacycles.

MWW-type zeolite nanostructures for a one-pot three-component Prins–Friedel–Crafts reaction

“…8–11 A one-pot acid-catalyzed Prins–Friedel–Crafts reaction between a carbonyl compound, a homoallylic alcohol and an aromatic hydrocarbon is an efficient method for the synthesis of heterocycles with the 4-aryltetrahydropyran moiety. 12–15 This reaction involves Prins cyclization via interaction of a carbonyl compound and a homoallylic alcohol with the formation of an oxocarbenium ion that undergoes an intramolecular π-bond attack to construct a new carbon–carbon bond with a subsequent Friedel–Crafts alkylation with an arene nucleophile. 12,15 As an alternative route, an acid-catalyzed intramolecular (or tandem) Prins–Friedel–Crafts reaction of a homoallylic alcohol appended to a nucleophile with a carbonyl compound also allows one to obtain 4-aryltetrahydropyrans, 16–19 but this methodology is more complex as it requires additional synthesis steps to modify the substrate molecule.…”

Advances in the synthesis of rearranged homoisoflavonoids

“…This cascade process is a powerful tool for organic chemists, enabling the efficient synthesis of highly complex molecular structures. 83,84…”

“…This cascade process is a powerful tool for organic chemists, enabling the efficient synthesis of highly complex molecular structures. 83,84 In 2020, Huang and colleagues reported the synthesis of (+)-brazilin (8) using this strategy. The pivotal intermediate, (R)-122, was obtained in a six-step route, starting from the commercially available 4-bromo-1,2-dimethoxybenzene (118) (Scheme 18).…”

Unusual Cascade Reactions of 8-Acetoxy-6-hydroxymethyllimonene with Salicylic Aldehydes: Diverse Oxygen Heterocycles from Common Precursors

“…Importantly, this process requires that the electron-donating substituent is on the meta-position of the aromatic aldehyde (Scheme ). ,, The Prins–Friedel–Crafts cascade reaction is an effective cascade approach to synthesize complex polycyclic compounds that can strategically avoid isolation and purification of intermediates. ,− For example, the synthesis of hexahydrofluoreno[9,1- bc ]furans 8 from trans -4-hydroxymethyl-2-carene 5 is highly regio- and stereoselective, forming product 8 as a single isomer. Importantly, this product obtained by the reaction of alcohol 5 with 3-hydroxy-4-methoxybenzaldehyde (Scheme , R 3 = OH, R 4 = OMe, R 5 = H) has high cytotoxic activity (CTD 50 0.9 μM) and induces apoptosis of MT-4 lymphoblastoid cells …”