Oxetanes and Oxetenes: Monocyclic

Synthesis of functionalized spirocyclic oxetanes through Paternò–Büchi reactions of cyclic ketones and maleic acid derivatives

“…Oxetanes (four-membered cyclic ethers) enjoy considerable interest as motifs within drug molecules and as valued synthetic intermediates. 1,2 For example, oxetanes have been used as “replacement groups” for metabolically vulnerable groups such as gem -dimethyl and carbonyl groups, 3 and spirocyclic oxetanes are valuable in studying hitherto inaccessible areas of chemical space. 4 As a result, the expedient synthesis of diverse oxetanes bearing varied substitution patterns is of broad interest.…”

“…Of the main synthetic approaches to oxetanes, 2 the Paternò–Büchi reaction 5 ([2+2] photocycloaddition of an aldehyde or a ketone with an alkene) is arguably the most attractive, as the oxetane ring is constructed in a single step. However, despite recent advances, 6 the substrate scope of the Paternò–Büchi reaction remains limited; typically, aromatic aldehydes/ketones and electron-rich alkenes are required, as exemplified by the original Paternò–Büchi reaction involving benzaldehyde and 2-methyl-2-butene (Fig.…”

Oxetan-3-ols as 1,2-bis-Electrophiles in a Brønsted-Acid-Catalyzed Synthesis of 1,4-Dioxanes

“…3,3-Disubstituted oxetanes display high stability toward external nucleophiles, which has led to this substitution pattern in particular being adopted in medicinal chemistry. 10 , 11 However, they can remain susceptible to ring opening by internal nucleophiles (i.e., intramolecular processes), especially under acidic conditions. 11 , 12 This intramolecular cyclization strategy has been successfully employed for the synthesis of heterocycles from prefunctionalized oxetane intermediates.…”

“… 10 , 11 However, they can remain susceptible to ring opening by internal nucleophiles (i.e., intramolecular processes), especially under acidic conditions. 11 , 12 This intramolecular cyclization strategy has been successfully employed for the synthesis of heterocycles from prefunctionalized oxetane intermediates. 13 , 14 In particular, Sun has exploited this in the enantioselective syntheses of heterocycle derivatives employing a chiral phosphoric acid catalyst.…”

“…112 kJ mol –1 for epoxides and 25 kJ mol –1 for THFs), which can be modulated by substituents. 3,3-Disubstituted oxetanes display high stability toward external nucleophiles, which has led to this substitution pattern in particular being adopted in medicinal chemistry. , However, they can remain susceptible to ring opening by internal nucleophiles (i.e., intramolecular processes), especially under acidic conditions. , This intramolecular cyclization strategy has been successfully employed for the synthesis of heterocycles from prefunctionalized oxetane intermediates. , In particular, Sun has exploited this in the enantioselective syntheses of heterocycle derivatives employing a chiral phosphoric acid catalyst. This has included the enantioselective synthesis of 1,4-dioxanes from preformed hydroxy-ether-containing oxetanes (Figure C) .…”