To prepare the fully functionalized B ring, 49, of Gambierol, we have attempted several synthetic routes. First, cyclization reaction was conducted through methylcuprate addition to 70 and the ensuing hetero-Michael addition. However, the method for cyclization was changed from hetero-Michael addition to iodocyclization because of the failure of addition reaction of the acetylide anion to aldehyde 68. Iodocyclization of δ-hydroxy alkene 71 yielded the 5-membered tetrahydrofuran 94. Therefore, we devised other method, ring opening reaction of epoxide 89, 96 under acidic condition. In the case of the epoxide 89, the precursor of selective reduction was not formed. Next, to secure the tetrahydropyran 97, the epoxy alcohol 89 was exposed to various acids. But the product was 5-membered ring instead of the desired tetrahydropyran 105.
We have studied the asymmetric iodocyclization of r-hydroxy-cis-alkenes, because it is synthetically useful and chiral iodonium reagents are rare until now. First, chiral iodo-reagent 130 modeled on N-iodosuccinimide (NIS) was synthesized but failed to promote the iodoetherification. Second, a variety of chiral Lewis bases were synthesized to attain the cyclization at low temperature. 1 : 1 Complexes of I2 and chiral Lewis bases 135 and 138-141 were generated in situ, and then additives and substrate 136 were added to give 20~30\% ee. Among several Lewis bases, bisoxazoline 141 showed the best stereoselectivity of 34\% ee. Application of the best conditions to other substrates 142-146 resulted in 31~41\% ee.
