Nickel-catalyzed asymmetric reductive ring opening of oxabicyclic alkenes

grantor: University of TorontoOxabicyclo[2.2.1]heptenes were shown to undergo highly enantioselective reductive ring opening with DIBAL-H in the presence of a catalytic amount of Ni(COD)2 and BINAP. The product cyclohexenols were produced in ee's of 81-97% and yields of 50-96%. Slow addition of DIBAL-H to the reaction was found to be crucial for high ee's. Oxabenzonorbornadienes could also be enantioselectively ring opened if the reaction was conducted in THF. Dihydronaphthalenols were produced in ee's of 73-98% and yields of 50-88%. Oxabicyclo[3.2.1]octenes were shown to undergo a highly enantioselective ring opening when the reaction was conducted at >60°C. Various cycloheptenols, were produced in yields of 83-99% and ee's of 93-99.5%. Lower temperatures were found to give significantly lower ee's and low yields. This methodology has been applied to the total synthesis of the important anti-depressant sertraline. The synthesis was completed in nine steps from dihydronaphthalenol with an overall yield of 38%. The dihydronaphthalene skeleton was also found to undergo several highly selective reactions leading to polyfunctionalized tetrahydronaphthalenes. The mechanism of the asymmetric nickel catalyzed hydroalumination reaction was examined by studying the scope of the reaction and by 31P NMR techniques. A reversible hydronickelation followed by an irreversible ß-elimination from the organonickel has been proposed as the key step.Ph.D