Enantioselective conjugate addition reactions to α,β-unsaturated-α,γ-substituted-2,5-cyclohexadienones
Mulligan, Kirk Michael
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Enantioselective conjugate addition (ECA) reactions between organometallic reagents and cyclohexadienone 165 are being investigated. Previous studies have shown that ECAs, of organometallic reagents to á,â-unsaturated cyclohexadienones, are useful in many natural product syntheses. The substrates used in earlier studies were simple 2,5-cyclohexadienones, with a proton at the C-3 position, resulting in the synthesis of a trisubstituted C-3 atom. ECAs that afford all-carbon quaternary stereogenic centers are a much more challenging problem and few examples have been reported. Some natural products contain a ã-hydroxy group, however, no ECA substrates have incorporated this motif. ECAs have been accomplished with substrates having a g-ether substituent. The cyclohexadienone 165 system presents three challenging problems to overcome for an ECA reaction: the tertiary methyl substituents at the 3 and 5 positions, facial selectivity and enantioselectivity. An ECA to 165 using an organoaluminum reagent and an external chiral ligand 26 was successful in producing a product that showed the reaction was moderately stereoselective. A diastereoselective conjugate addition reaction (DCA) to 165 using a chiral auxiliary 68 was also successful in producing a product that showed the reaction was moderately enantioenriched. Lastly, a variable temperature NMR study was performed to establish the presence of dynamic motions of the C=N bond present in sulfinyl imines 229 and 230. As a result, the sulfinyl imines 229 and 230 were found to be interconverting at -78°C.
DegreeMaster of Science (M.Sc.)
SupervisorMajewski, Marek; Abrams, Sue
Copyright DateDecember 2007