Organocatalyzed Asymmetric Conjugate Addition of Heteroaryl and Aryl Trifluoroborates: a Synthetic Strategy for Discoipyrrole D

• Published in: Angewandte Chemie International Edition Vol. 54; no. 34; pp. 9931 - 9935
• Main Authors: Shih, Jiun-Le, Nguyen, Thien S., May, Jeremy A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.08.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Aromatic compounds; Biphenyl Compounds - chemistry; bis-aryl stereocenters; Catalysis; Chemistry; Chemistry, Multidisciplinary; Conjugates; Enantiomers; enantioselective catalysis; Fluorides; heterocycles; Heterocyclic Compounds, 3-Ring - chemical synthesis; Heterocyclic Compounds, 3-Ring - chemistry; Molecular Structure; Naphthalenes - chemistry; Nucleophiles; organocatalysis; Physical Sciences; Pyrrolidinones - chemical synthesis; Pyrrolidinones - chemistry; Salts; Science & Technology; Stereoisomerism; trifluoroborate salts; ENANTIOSELECTIVE SYNTHESIS; bis-aryl stereocenters; trifluoroborate salts; FRIEDEL-CRAFTS ALKYLATIONS; BORONIC ESTERS; SALTS; organocatalysis; ALKENYLBORONIC ACIDS; KETONES; CROSS-COUPLING REACTIONS; heterocycles; ENONES; STEREOGENIC CENTERS; INHIBITORS; enantioselective catalysis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201503528

Bis‐heteroaryl or bis‐aryl stereocenters were formed by an organocatalytic enantioselective conjugate addition using the respective trifluoroborate salts as nucleophiles. Control studies suggested that fluoride dissociation is necessary in the anhydrous conditions. This strategy is applicable to the synthesis of discoipyrrole D, an inhibitor of BR5 fibroblast migration. Fluoride has to go: Bis‐heteroaryl or bis‐aryl stereocenters are formed through an organocatalytic enantioselective conjugate addition using heteroaryl or aryl trifluoroborate salts, respectively, as nucleophiles. Control experiments suggest that fluoride dissociation in the anhydrous conditions is necessary. The reaction was applied toward the synthesis of discoipyrrole D, an inhibitor of DDR2‐dependent migration of BR5 fibroblasts.