Total Synthesis of Eupomatilones 1, 2, and 5 by Enantioselective [2,3]-Wittig Rearrangement

• Published in: European journal of organic chemistry Vol. 2013; no. 4; pp. 721 - 727
• Main Authors: Hirokawa, Yoshimi, Kitamura, Maria, Mizubayashi, Makoto, Nakatsuka, Rie, Kobori, Yuya, Kato, Chiharu, Kurata, Yuki, Maezaki, Naoyoshi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.02.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Asymmetric synthesis; Chemistry; Chemistry, Organic; Enantioselectivity; Lignans; Natural products; Physical Sciences; Rearrangement; Science & Technology; Total synthesis; PUTATIVE STRUCTURE; Enantioselectivity; Lignans; MODEL; ABSOLUTE-CONFIGURATIONS; Total synthesis; TUMOR INHIBITORS; NMR; Asymmetric synthesis; Natural products; ALLYL BENZYL ETHERS; ASSIGNMENT; LIGAND; 2,3 SIGMATROPIC REARRANGEMENT; Rearrangement
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201201247

In this study, the asymmetric total synthesis of eupomatilones 1, 2, and 5 has been accomplished. These compounds are lignan congeners containing a biaryl system bearing an α‐methylene γ‐lactone. They were isolated from the Australian shrub Eupomatia bennettii. Two chiral centers were constructed enantioselectively by the asymmetric [2,3]‐Wittig rearrangement of highly oxygenated biaryl compounds, using a bis(oxazoline) chiral ligand. Optimization of the key reaction using nBuLi as the base and ether as the co‐solvent increased the enantioselectivity to 88–91 % ee. An asymmetric total synthesis of eupomatilones 1, 2, and 5 was carried out. The asymmetric [2,3]‐Wittig rearrangement of biarylmethyl ethers was used for the construction of the chiral centers, using a bis(oxazoline) chiral ligand. Optimization of the reaction conditions enabled the synthesis of eupomatilones 1, 2, and 5 with high enantioselectivities (88–91 % ee).