Organocatalytic Strategy for the Enantioselective Cycloaddition to Trisubstituted Nitroolefins to Create Spirocyclohexene-Oxetane Scaffolds

• Published in: Angewandte Chemie 2016-02, Vol.128 (7), p.2524-2528
• Main Authors: Monleón, Alicia, Glaus, Florian, Vergura, Stefania, Jørgensen, Karl Anker
• Format: Article
• Language: eng ; ger
• Subjects: Carbon; Catalysis; Chemistry; Cycloaddition; Cycloadditionen; Enantiomers; Oxetane; Scaffolds; Selectivity; Spirocyclen; Strategy; Synthesis; Transformations; Trienamin-Katalyse; Trisubstituierte Nitroolefine
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201510731

The first catalytic enantioselective cycloaddition reaction to α,β,β‐trisubstituted nitroolefins is reported. For this purpose, nitroolefin oxetanes were employed in the reaction with 2,4‐dienals promoted by trienamine catalysis. This methodology provides a facile and efficient strategy for the synthesis of highly functionalized chiral spirocyclohexene‐oxetanes with two adjacent tetrasubstituted carbon atoms in high yields and excellent selectivities. This strategy also enabled access to chiral spirocyclohexene‐cyclobutanes and ‐azetidines. Additionally, the obtained scaffolds can undergo diverse transformations leading to complex structures with up to four stereocenters, and we demonstrate that the nitro group, under nucleophilic conditions, can be applied for ring‐opening of the oxetane. Baukastenprinzip: Die enantioselektive Cycloaddition von α,β,β‐trisubstituierten Nitroolefinen mit 2,4‐Dienalen in Gegenwart eines Trienamin‐Katalysators liefert hoch funktionalisierte Spirocyclohexenoxetane mit zwei tetrasubstituierten Kohlenstoffatomen in hohen Ausbeuten (bis 86 %) und Enantioselektivitäten (bis 98 % ee).