A Catalyst-Enabled Diastereodivergent Aza-Diels-Alder Reaction: Complementarity of N-Heterocyclic Carbenes and Chiral Amines

• Published in: Chemistry : a European journal Vol. 22; no. 28; pp. 9483 - 9487
• Main Authors: Rong, Zi-Qiang, Wang, Min, Chow, Chi Hao Eugene, Zhao, Yu
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 04.07.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Amines; Carbenes; Catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; chiral amines; diastereodivergence; Diels-Alder cycloaddition; enantioselectivity; N-heterocyclic carbenes; Physical Sciences; Science & Technology; Stereoselectivity; Synthesis; enantioselectivity; HIGHLY ENANTIOSELECTIVE SYNTHESIS; chiral amines; BENZOFURAN DERIVATIVES; ALPHA,BETA-UNSATURATED ALDEHYDES; O-QUINONE METHIDES; ENOLATE EQUIVALENTS; Diels-Alder cycloaddition; MODULARLY DESIGNED ORGANOCATALYSTS; DIVERSITY-ORIENTED SYNTHESIS; diastereodivergence; ALPHA-ALLYLATION; ANNULATION REACTION; N-heterocyclic carbenes; ASYMMETRIC REACTIONS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201601626

Highly efficient and diastereodivergent aza‐Diels–Alder reactions have been developed to access either diastereomeric series of benzofuran‐fused δ‐lactams and dihydropyridines in nearly perfect stereoselectivity (d.r. >20:1, >99 % ee for all examples). The complementarity of N‐heterocyclic carbene and chiral amine as the catalyst was demonstrated for the first time, together with an excellent level of catalytic efficiency (1 mol % loading). The complementarity of a N‐heterocyclic carbene or chiral amine as the catalyst for aza‐Diels–Alder reactions was demonstrated. The highly efficient and diastereodivergent synthesis of benzofuran‐fused δ‐lactams and dihydropyridines was achieved in nearly perfect stereoselectivity (d.r. >20:1, >99 % ee for all examples).