Study of alpha-amino organolithiums I~Configurational stabiliites II~Alkylation III~Sigmatropic rearrangements and diastereoselectivities of addition of chiral lithio thiazolidines to aldehydes

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

Robert E. Gawley, Committee Chair


Chapter one. Three nonracemic $\alpha$-amino organolithiums: (S)-N-methyl-2-lithiopiperidine, (R)-N-methyl-2-lithiopyrrolidine and (S)-N-methoxyethyl-2-lithiopyrrolidine have been synthesized and their configurational and chemical stabilities have been studied. For N-methyl-2-lithiopiperidine and N-methyl-2-lithiopyrrolidine, the highest temperature with no racemization is $-40\sp\circ$C in THF in the presence of TMEDA. For N-methoxyethyl-2-lithiopyrrolidine, the highest temperature with no racemization is $-60\sp\circ$C. The results indicate that the intramolecular chelation accelerates the racemization.Chapter two. The reactivities of N-methyl-2-lithiopiperidine and N-methyl-2-lithiopyrrolidine with various electrophiles has been studied. 2-Substituted piperidine and pyrrolidine with different functional groups have been synthesized in moderate to good yields.The stereochemistry of the reaction between nonracemic N-methyl-2-lithiopiperidine, N-methyl-2-lithiopyrrolidine and electrophiles has been investigated. When the electrophiles are CO$\sb2$, dimethyl carbonate, acid chloride, alkyl ketones, aldehydes and tributyltin chloride, the products are obtained with retention of configuration at the lithium-bearing carbon. The reaction of nonracemic N-methyl-2-lithiopiperidine, N-methyl-2-lithiopyrrolidine and unactivated alkyl halides affords products with inversion of configuration, although with some racemization in the latter case.Chapter three. Sigmatropic rearrangements of unactivated N-allyl-$\alpha$-lithioamines have been investigated. Also, the stereochemistry of the rearrangement has been probed for nonracemic N-allyl-2-lithiopyrrolidine. It is established that inversion of configuration is the main course at the lithium-bearing carbon.Sigmatropic rearrangement of N,N-diallyl-2-lithiopyrrolidine ylides proceeds via the 2,3-pathway. The product with 100% inversion at the lithium-bearing carbon is obtained.Chapter four. Three chiral thiazolidines 4-12, 4-26 and 4-27 have been synthesized. The stereochemistry of allcylation at C-2 of these chiral thiazolidines was investigated. The facial selectivities of lithiated chiral thiazolidines with aldehydes were evaluated. A 100% diastereoselectivity was reached when 4-isopropyl thiazolidine 4-12 was quenched with deuterium methanol or trimethylsilyl chloride. Only two diastereomers were produced from the reaction between lithio-4-12 and aldehydes. The absolute configurations of these two isomers were established by X-ray crystallography.An 85% diastereoselectivity was obtained from the reaction between lithiated 5-isopropyl thiazolidine 4-27 and pivaldehyde. The absolute configuration of the major isomer has been established by X-ray crystallography.


Chemistry, Organic

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