Executive Summary : | ?-Oxycarbonyls have been widely used for the preparation of structurally diverse building blocks for the synthesis of natural products, pharmaceuticals and bioactive molecules. The majority of transformation of ?-Oxycarbonyls involve C-O cleavage/oxirane ring opening leading to ?-hydroxy carbonyl derivatives. Many of these methods suffer from disadvantages associated with the use of toxic reagents (SmI2, Al-Hg, Zn, Cr2+, Bu3SnH/AIBN, etc.) harsh reaction conditions, and poor yields and selectivity. Nevertheless, mainly epoxy ketone, carboxylic acid, ester, and amide derivatives participate in these C-O bond cleavage reactions under strongly reducing conditions. On the other hand, C-O cleavage of more sensitive epoxyaldehyde was primarily accomplished via N-heterocyclic carbine (NHC) catalyzed reactions. However, the reductive C-O cleavage of epoxy aldehyde is accompanied by the unwanted oxidative modification of aldehyde to the corresponding ester, acid, or amide functionality which eliminates the possibility of applying uninterrupted synthetic elaborations of aldehyde functionality of the desired ?-hydroxyaldehyde. 1,3-Aminoalcohol moiety is found as a key structural unit of many natural products, bioactive molecules and pharmaceutical drugs, in particular, antidepressant drugs. The synthesis of enantioenriched amino alcohols is tedious, involving multiple steps. Moreover, many methods necessitate the use harsh reductive C-O bond cleavage step, which puts a limit on the use of sensitive substrates such as epoxyaldehyde. To address these difficulties, a proposal for the development of an unprecedented method of aminative C-O cleavage of ?-oxyketone and ?-oxyaldehyde is presented. This method will work under metal-free mild conditions and thus can be applied to a sensitive substrate such as ?-oxyaldehyde. The reaction will have the versatility to provide ?-hydroxy ketone/aldehyde and 1,3-aminoalcohols via hydrolysis and reduction of imino diene, respectively. The developed methodology will be applied for the facile and efficient asymmetric synthesis of aminoalcohol-based antidepressant drugs duloxetine and atomoxetine. |