Studies of dipole-stabilized and unstabilized alpha-aminoorganolithiums

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

Robert E. Gawley, Committee Chair


In chapter one, chiral alpha-hydroxy aldehydes and alpha-hydroxy carboxylic acids were synthesized by the asymmetric addition of dipole-stabilized lithiated S,N-acetal to aldehydes. Modest to low diasteroselectivity was achieved during the asymmetric addition reaction. However, most of the diasteromerically enriched carbinols were purified up to 99% d.e after a single recrystallization. The origin of the face selectivity in this particular reaction, is complex as there may be several factors influencing the stability of the organolithium intermediate. Several factors, such as chelation, dipole stabilization, pyramidal inversion, competitive SET mechanism, solvent and aggregation state, may have an effect. The absolute configurations of the alpha-hydroxy aldehydes and alpha-hydroxy carboxylic acids (R) were determined by optical rotation and compared with commercially available compounds.The objective of this work, in chapter two, is to study the alkylation of the "unstabilized" enantiomerically enriched (S)-(+)- N-allyl-2-lithio-pyrrolidine with several electrophiles, such as alkyl halides, aldehydes, and acid chlorides. Transmetalation of 2-tributylstannyl- N-allyl-pyrrolidine with butyllithium/TMEDA in THF affords an alpha-aminoorganolithium species with high configurational stability. This intermediate reacts with near 100% retention of configuration with carbonyl electrophiles, and with inversion of configuration with most alkyl halides. Some racemization, however, was observed with alkyl halide. The removal of the allyl group in this reaction sequence may find use in applications where direct alkylation of BOC-pyrrolidine is inefficient, or when the opposite enantiomer is desired.In chapter three, an effort to obtain a better understanding of the aza-Wittig rearrangement of unstabilized alpha-aminoorganolithium, as a potentially useful methodology for the stereoselective preparation of alpha-alkylamines, we began an investigation into the anionic rearrangement of N-allyl-2-lithiopyrrolidine, an intermediate that possesses extraordinary configurational and chemical stability. We found the first example of a [2,3]-aza-Wittig rearrangement for an unstabilized alpha-aminoorganolithium. Herein, we have demonstrated that N-allyl-2-lithiopyrrolidine, obtained by tin-lithium exchange of N-allyl-2-tributylstannyl pyrrolidine, undergoes [2,3]-anionic rearrangement with inversion of configuration at the lithium-bearing carbon. This mechanism competes with a non-stereoselective [1,2]-aza-Wittig rearrangement. Isotope labeling experiments indicate that the reaction proceeds via 53% [2,3] anionic rearrangement and 47% [1,2]-pathway. The synthesis of enantiomerically enriched 2-(S)-allyl-pyrrolidine was achieved under the reaction conditions.


Chemistry, Organic

Link to Full Text