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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