Chiral oxazolines as auxiliaries for stereoselective alkylations of 1,2,3,4-tetrahydroisoquinolines

Date of Award




Degree Name

Doctor of Arts (D.A.)



First Committee Member

Robert E. Gawley - Committee Chair


Alkaloids containing the tetrahydroisoquinoline skeleton have a wide and varied distribution within nature. The members of this alkaloidal class demonstrate a broad range of pharmacological activity and have generated substantial synthetic interest. It is the purpose of this treatise to show how an L-valine derived chiral oxazoline was used as an auxiliary for the stereoselective alkylation of the number one position of 1,2,3,4-tetrahydroisoquinolines. The synthesis of the chiral oxazoline from L-valine, involved three relatively simple high yield steps. Condensation of the oxazoline with a variety of substituted tetrahydroisoquinolines yielded the corresponding chiral aminooxazolines in high yields. Alkylation of all the chiral aminooxazolines synthesized with alkyl halides, yielded products with diastereomeric excesses of 67 percent or greater. The degree of asymmetric induction was found to be dependent on the identity of the benzyl halide (ArCH$\sb2$Cl showing more degree of asymmetric induction than ArCH$\sb2$Br). The degree of asymmetric induction was found not to be a function of the temperature of deprotonation, the identity of the alkyllithium base (n-BuLi, s-BuLi, or t-BuLi), or the alkyl halide (RBr and RI give equal selectivity, while RCl was found to be rather unreactive under the normal experimental conditions). Removal of the chiral oxazoline to unmask the corresponding chiral tetrahydroisoquinolines involved one very high yield step. Use of the chiral Pirkle column during High Pressure Liquid Chromatographic analyses of the corresponding naphthamides showed that the absolute configuration of the major stereoisomer was R.


Chemistry, Organic

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