Enantioselective iodocyclization ofγ-Hydroxy-cis-Alkenes using chiral lewis acids

Abstract

Reagent-controlled stereoselective electrophilic addition reactions of C=C bonds were studied. N-Iodo electrophilic reagents 48, 51 and 53 were prepared from L-tartaric acid.Intra- and inter-molecular electrophilic addition reactions using these reagents showed little enantioselectivity.Chiral ether type Lewis bases which can make complexes with $I_2$ were synthesized.The reaction using these chiral Lewis bases gave little enantioselectivity. Next chiral electrophiles were prepared using various transition metal complexes.In the case of NIS as a source of electrophile, (R)-Binol-Ti(IV) complex seemed to form chiral electrophiles.Several reactions using catalytic amount of this complex afforded interesting results that chirality could be transferred to substrates from chiral ligands. In the case of $I_2$ as a source of electrophile, salen-Co(II) 63f or salen-Cr(III)-Cl 63c made chiral electrophiles with the aid of N-chlorosuccinimide(NCS).Using 30 mol % of salen-Co(II) 63f and substrate 88, 90% ee of tetrahydrofuran was obtained.Using 5 mol % of salen-Cr(III)-Cl 63c and substrate 88, 93% ee of tetrahydrofuran was obtained in 85% yield.Therefore, asymmetric reagent-controlled iodocyclization using catalytic amount of chiral Lewis acid was realized with excellent enantioselectivity. Using our developed iodocyclization with salen-Cr(III)-Cl and NCS, synthetic studies on the key intermediate 109 for the synthesis of swainsonine 106 were carried out.Substrate 111 gave tetrahydrofuran with 88% ee in 63% yield. When substrate 113 was tried, 97% de of tetrahydrofuran was obtained in 54% yield.