Preparation of Macrocyclic Z‑Enoates and (E,Z)- or (Z,E)‑Dienoates through Catalytic Stereoselective Ring-Closing Metathesis

• Published in: Journal of the American Chemical Society Vol. 136; no. 47; pp. 16493 - 16496
• Main Authors: Zhang, Hanmo, Yu, Elsie C, Torker, Sebastian, Schrock, Richard R, Hoveyda, Amir H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.11.2014; Amer Chemical Soc
• Subjects: Catalysis; Chemistry; Chemistry, Multidisciplinary; Communication; Cyclization; Ketones - chemical synthesis; Ketones - chemistry; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - chemistry; Molecular Structure; Physical Sciences; Science & Technology; Stereoisomerism; MO; NATURAL-PRODUCT SYNTHESIS; PHORBOXAZOLE-B; COMPLEXES; MACROLIDE; (+)-ASPICILIN; ENANTIOSELECTIVE TOTAL-SYNTHESIS; EFFICIENT; (-)-DICTYOSTATIN; SELECTIVE CROSS-METATHESIS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja510768c

The first examples of c​atalyst-controlled stereo­selective macrocyclic ring-closing metathesis reactions that generate Z-enoates as well as (E,Z)- or (Z,E)-dienoates are disclosed. Reactions promoted by 3.0–10 mol % of a Mo-based mono­aryl­oxide pyrrolide complex proceed to completion within 2–6 h at room temperature. The desired macrocycles are formed in 79:21 to >98:2 Z/E selectivity; stereo­isomerically pure products can be obtained in 43–75% yield after chromatography. Utility is demonstrated by application to a concise formal synthesis of the natural product (+)-aspicilin.