Oxazolines as mediators in the asymmetric alkylation and hydroxyalkylation of tetrahydroisoquinolines and oxazolidinones as mediators for acyclic stereoselection in the synthesis of primary amines

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

R. E. Gawley, Committee Chair


Chapter one. The stereoselective alkylation of chiral (tetrahydroisoquinolyl)-oxazolines has proven to be a useful technique for the synthesis of optically active isoquinoline alkaloids. We report here the details of a systematic study of the factors affecting the selectivity of this key reaction. These studies include the structure of the oxazoline substituent, a comparison of monodentate vs. bidentate coordination of the organolithium, and an evaluation of the effect of the solvent and chelating solvent additives. We have also established that our mechanistic model in which lithium is coordinated by the nitrogen of the oxazoline is correct.Chapter two. The addition of carbonyls to chiral 1-metalloisoquinolyloxazolines may yield as many as four stereoisomers. We have determined that when the metal is magnesium, two erythro isomers are produced in a 2:1 ratio. To our surprise, the major isomer results from attack upon the opposite face of the isoquinoline when compared to the alkylation. When the metal is lithium, a 1.5:1 mixture of threo and erythro isomers (both of which consist of a 1:1 mixture of isomers) are produced. We provide evidence to suggest that the enhanced selectivity when the metal is magnesium is due to a change in mechanism from single electron transfer (for lithium) to a polar process (for magnesium). We have used this reaction as the key step in the synthesis of the phthalideisoquinoline alkaloid bicuculline and the first syntheses of the phthalideisoquinoline hemiacetal alkaloids egenine and corytensine. We have also established that the alkaloids decumbensine and epi-$\alpha$-decumbensine are indeed egenine and corytensine.Chapter three. The asymmetric alkylation of N-benzyl oxazolidinones has been employed as the key step in the synthesis of primary amines by asymmetric alkylation $\alpha$ to nitrogen. Primary benzylic amines have been prepared in selectivities ranging from 70 to 100% ee. This represents the first example of the use of dipole stabilized anions for acyclic stereoselection.


Chemistry, Organic

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