Enantioselective iridium and ruthenium-catalyzed carbonyl reductive coupling via hydrogen transfer

Xiang, Ming, Ph. D.
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Carbonyl addition is one of the most frequently utilized methods for C−C bond formation in Process Research and Development. Despite its importance, the majority of methods for carbonyl addition rely on the use of stoichiometric organometallic reagents, which are hazardous and sensitive. To address these limitations, we have developed a series of iridium- and ruthenium-catalyzed carbonyl reductive couplings that exploit abundant π-unsaturated pronucleophiles in combination with the green reductant, 2-propanol. Additionally, we have developed catalytic carbonyl reductive couplings that occur hydrogen auto-transfer processes, wherein alcohols serve dually as reductants and carbonyl proelectrophiles. The work presented in this dissertation includes 1: Enantioselective iridium-catalyzed isoprenylation to form dienyl homoallylic alcohols which are important family of terpenoid natural products; 2: Enantioselective iridium-catalyzed anti-(α-aryl)allylation of aqueous fluoral hydrate and difluoroacetaldehyde ethyl hemiacetal to form chiral CF₃- and CHF₂-bearing secondary alcohols; 3: Enantioselective iridium-catalyzed couplings of primary alcohols with phthalimido allene to form vicinal amino alcohols; 4: Enantioselective ruthenium-catalyzed couplings of primary alcohols with 1-aryl-1-propynes to form chiral sec-phenethyl alcohols; 5: Enantioselective ruthenium-catalyzed couplings of alkoxyallenes with primary alchohols to form chiral syn-sec, tert-diols which ubiquitously as substructures across diverse type I polyketide natural products.