biostudies-literatureUnknown11(1)Barton KThe Wagner-Jauregg reaction produces up to four new carbon-carbon bonds and eight new stereocenters, but limitations, such as high requisite temperatures, a restricted substrate scope, and significant undesired polymer formation, have resulted in this reaction receiving minimal attention. While generally considered a subtype of the Diels-Alder reaction, in which a styrenyl diene is employed in a tandem double-Diels-Alder reaction, a second, structurally distinct, stereochemically complex product can also be produced by the Wagner-Jauregg reaction, resulting from a Diels-Alder-ene cascade. Very few attempts to improve reaction conditions, expand substrate scope, or optimize product selectivity have been published. Through reaction optimization, supplemented by density functional theory calcACS omega1360-1368https://www.ebi.ac.uk/biostudies/studies/S-EPMC12809351biostudies-literatureEnhanced Reactivity for the Wagner-Jauregg Reaction Under Aqueous Conditions.PMC12809351Tartakoff SSBarton KTartakoff SAStasio JHill ADSmith CRothe EDickhens LfalseEnhanced Reactivity for the Wagner-Jauregg Reaction Under Aqueous Conditions.The Wagner-Jauregg reaction produces up to four new carbon-carbon bonds and eight new stereocenters, but limitations, such as high requisite temperatures, a restricted substrate scope, and significant undesired polymer formation, have resulted in this reaction receiving minimal attention. While generally considered a subtype of the Diels-Alder reaction, in which a styrenyl diene is employed in a tandem double-Diels-Alder reaction, a second, structurally distinct, stereochemically complex product can also be produced by the Wagner-Jauregg reaction, resulting from a Diels-Alder-ene cascade. Very few attempts to improve reaction conditions, expand substrate scope, or optimize product selectivity have been published. Through reaction optimization, supplemented by density functional theory calc2026-01-01T00:00:00Z2026 Jan2026-06-12T04:51:56.772Z2026-06-12T03:08:20.536ZS-EPMC128093514155247210.1021/acsomega.5c07465