Asymmetric Iodocyclization Catalyzed by Salen-CrIIICl: Its Synthetic Application to Swainsonine

• Published in: Chemistry : a European journal 2008-01, Vol.14 (3), p.1023-1028
• Main Authors: Kwon, Hyo Young, Park, Chul Min, Lee, Sung Bae, Youn, Joo-Hack, Kang, Sung Ho
• Format: Article
• Language: English
• Subjects: asymmetric catalysis; Catalysis; Chlorides - chemistry; Chromium - chemistry; Cyclization; enantioselectivity; Ethylenediamines - chemistry; Iodine - chemistry; Molecular Conformation; Organometallic Compounds - chemistry; Stereoisomerism; swainsonine; Swainsonine - chemical synthesis; Swainsonine - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200701199

The previously developed enantioselective iodocyclization of γ‐hydroxy‐cis‐alkenes required 30 mol % of (R,R)‐salen–CoII complex as chiral catalyst and 0.75 equivalent of N‐chlorosuccinimide (NCS) as activator to produce 2‐substituted tetrahydrofurans with 61 to 90 % ee. Due to the considerable loading amount of the CoII complex, another more effective catalyst was pursued by screening (R,R)‐salen–transition metal complexes. When 10 mol % of the catalysts were applied with 0.5 equivalent of NCS, a higher level of stereoselectivity was attained with the corresponding CrIIICl (84 % ee), MnIICl (52 % ee) and CoII complexes (66 % ee). Refinement of the conditions established a novel catalytic enantioselective iodocyclization protocol using iodine in the presence of 7 mol % of (R,R)‐salen–CrIIICl complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93 % ee. Enantioselective iodocyclization: Catalytic enantioselective iodocyclization of γ‐hydroxy‐cis‐alkenes has been established using iodine in the presence of 7 mol % of (R,R)‐salen–CrIIICl complex activated by 0.7 equivalents of N‐chlorosuccinimide to provide 2‐substituted tetrahydrofurans with 74 to 93 % ee (see scheme). Its synthetic application has consummated asymmetric synthesis of an indolizidine alkaloid, swainsonine.