Asymmetric Iodocyclization Using (R,R)-Salen-Cr(III)Cl Complex and Its Synthetic Application to (-)-Swainsonine and 1-Deoxycastanospermine

Abstract

Electrophile-mediated cyclization is appraised as one of the reliable ways to form heterocycles. While its stereochemistry issue has mainly focused on diastereoselectivity utilizing preexisting stereogenic centers in substrates, its enantioselective version has seldom been investigated. The previously developed enantioselective iodocyclization of \gamma-hydroxy-cis-alkenes required 30 mol% of (R,R)-salen-Co(II) 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(II) 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 Cr(III)Cl (84% ee), Mn(II)Cl (52% ee) and Co(II) 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-Cr(III)Cl complex activated by 0.7 equivalent of NCS in toluene to provide 2-substituted tetrahydrofurans with 71 to 93% ee. The synthetic value of the developed iodocylcization has been demonstrated in the synthesis of the indolizidine alkaloids, (\mdash)-swainsonine and 1-deoxycastanospermine. The two indolizidine alkaloids were envisioned to be elaborated from the pyrrolidinone 178 and piperidinone 194, respectively, which would be conceivably derived from the common intermediate 162. Our synthetic strategy for the target molecules would culminate in preparation of 162 using our asymmetric iodocyclization, and the unprecedented chemoselective oxidation of 162 to the corresponding lactam or lactone depending on the protecting group. For the synthesis of neooxazolomycin, 2-substituted serinol 237 was used to generate the amino alcohol derivatives which have the chiral quaternary carb...