Asymmetric iodocyclization catalyzed by Salen-Cr-III Cl: Its synthetic application to swainsonine

The previously developed enantioselective iodocyclization of gamma-hydroxy-cis-alkenes required 30 mol % of (R,R)-salen-Co-11 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 Co-11 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 (CrCl)-Cl-III (84 % ee), (MnCl)-Cl-11 (52% ee) and Co-11 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-(CrCl)-Cl-III complex activated by 0.7 equivalent of NCS in toluene to induce 74 to 93 % ee.