Sequential Photochemical and Prins Reactions for the Diastereoselective Synthesis of Tricyclic Scaffolds

Abstract

Cyclobutene alcohols undergo Prins cyclizations to generate single diastereomers of novel tricyclic heterocycles with five contiguous stereocenters. Reaction times are significantly shorter (~15 mins) than with traditional alkene substrates. Stereoselective aza-Prins cyclizations of cyclobutene amine derivatives give fused aza-heterocyclic scaffolds. Computational studies provide insight into the observed stereocontrol. The modular approach is flexible enabling the introduction of a variety of functionality (including amides, nitriles, alkynes and arenes) to the sp 3-rich heterocyclic scaffolds with scope.

Hexafluoroisopropanol‐Promoted or Brønsted Acid‐Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides

“…The utility of the cyclobutenyl products was further proven by their utility as starting materials in a variety of transformations (Scheme 3). First, we demonstrated the synthesis of different polycyclic products, such as compounds 39 and 40 , in excellent yields (Scheme 3A) [9e] . Furthermore, the double bond of 24 was oxidized utilizing m ‐CPBA, leading to tricyclic epoxide 41 in 74 % yield (Scheme 3B).…”

Six-membered ring systems: with O and/or S atoms

“…Diastereoselective synthesis of tricyclic cyclobutaneefused tetrahydropyrans bearing an amide moiety can be achieved through PrinseRitter cyclization reactions of (2-hydroxyethyl)cyclobutene-type compounds with various aldehydes promoted by trifluoromethanesulfonic (triflic) acid (TfOH) in acetonitrile at room temperature. Using a series of acetals catalyzed by HBF 4 in dichloromethane produces similar tricyclic compounds with a tertiary fluoride (Scheme 15) (19AGE9095). Palladium(0)-catalyzed decarboxylative heterocyclization reaction of [60]fullerene with 2-alkylidenetrimethylene carbonates in 1,2-dichlorobenzene produces [60] fullerene-fused 3-methylenetetrahydrofurans (19CC14498).…”

Recent Applications of Ritter Reactions in Organic Syntheses

“…In 2019, Milburn and co-workers reported a sequential photochemical reaction through the combination Prins and Ritter reactions of acetonitrile 47 with various aldehydes 37 and 6-(2-hydroxyethyl)-3-azabicyclo [3.2.0] hepta-6-ene-2,4-diones 48 in the presence of triflic acid as catalyst to produce different acetamids 49 (Scheme 14). [30] Scheme 11. The synthesis of 4-amido-substituted tetrahydropyrans 39.…”