Versatile and Enantioselective Total Synthesis of Naturally Active Gnetulin

• Published in: Advanced synthesis & catalysis Vol. 361; no. 16; pp. 3768 - 3776
• Main Authors: Shang, Changhui, Kang, Yulong, Yang, Qingyun, Zhu, Qibin, Yao, Chunsuo
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 21.08.2019; Wiley Subscription Services, Inc
• Subjects: Antipodes; Aromatic compounds; asymmetric synthesis; Chemistry; Chemistry, Applied; Chemistry, Organic; Dimers; Enantiomers; enantioselectivity; gnetulin; natural products; Physical Sciences; Science & Technology; Synthesis; total synthesis; enantioselectivity; BIOMIMETIC SYNTHESIS; RESVERATROL; ASYMMETRIC-SYNTHESIS; EXCITON CHIRALITY METHOD; STILBENE DIMERS; gnetulin; OLIGOMERS; LIANAS; natural products; asymmetric synthesis; ABSOLUTE-CONFIGURATION; REDUCTION; total synthesis; DERIVATIVES
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201900336

A versatile and efficient enantioselective total synthesis of natural isorhapontigenin dimers (−)‐gnetulin, (+)‐gnetulin, and (±)‐gentulin was proposed. By using this method, we were able to synthesize the dimers from commercial available achiral materials in 13 steps, and achieve a 7%–9% overall yield with >98% enantiomeric excess. The key features of the method include the stereocontrolled enantioselective conjugate reduction of 3‐arylindenone catalyzed by methyloxazaborolidine (Me‐CBS) and the α‐arylation of 3‐aryl‐1‐indanones. Benzylic sulfide was accessed in excellent yield through the InCl3‐catalyzed thio‐etherification reaction between 2,3‐diarylindanol and bezylic thiol. The method is practical and might thus be useful in the enantioselective synthesis of the optical antipodes of natural indane derivatives with or without methoxy groups at aromatic rings.