β,γ-trans-selective γ-butyrolactone formation via homoenolate cross-annulation of enals and aldehydes catalyzed by sterically hindered N-heterocyclic carbene

• Published in: Tetrahedron Vol. 91; pp. 132191 - 132199
• Main Authors: Kyan, Ryuji, Kitagawa, Yuya, Ide, Ryuji, Sato, Kohei, Mase, Nobuyuki, Narumi, Tetsuo
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 02.07.2021; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Diastereoselective synthesis; Homoenolate annulation; N-Heterocyclic carbene; Organocatalysis; Physical Sciences; Science & Technology; γ-Butyrolactone; Diastereoselective synthesis; γ-Butyrolactone; Homoenolate annulation; Organocatalysis; N-Heterocyclic carbene; MELDRUMS ACID; NATURAL-PRODUCTS; CHAIN; COOPERATIVE CATALYSIS; CONJUGATE UMPOLUNG; LIGNANS; gamma-Butyrolactone; STEREOSELECTIVE-SYNTHESIS; ADDITIONS; IMIDAZOLIUM SALTS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2021.132191

Highly sterically hindered N-heterocyclic carbenes (NHCs), can be readily prepared from the corresponding anilines, and serve as organocatalysts in NHC-catalyzed homoenolate cross-annulation of α,β-enals and aryl aldehydes. This catalysis enables the convergent construction of β,γ-trans-disubstituted γ-butyrolactones that are an important class of molecules in synthetic and medicinal chemistry. The steric features of N-aryl substituents contribute to the selectivity and electronic ones affected the efficiency of this reaction, which proceeds with high diastereoselectivity and affords a variety of β,γ-diaryl-γ-butyrolactones in up to 91% yield with up to 1:99 dr. [Display omitted]