Title page for ETD etd-03282007-221111

Type of Document Dissertation
Author Zhang, Yiqun
URN etd-03282007-221111
Title Stereochemistry of small molecules: Configurational and conformational control
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Carlier, Paul R. Committee Chair
Etzkorn, Felicia A. Committee Member
Hanson, Brian E. Committee Member
Kingston, David G. I. Committee Member
Tanko, James M. Committee Member
  • conformational control
  • chiral Grignard reagents
  • halogen-metal exchange
  • cyclopropylnitrile
  • configurational stability
  • 3-strain
  • allylic 1
  • syn-pentane interaction
  • nitrile aldol
Date of Defense 2007-03-15
Availability unrestricted
Stereochemistry is important aspect of chemistry that customarily includes the study of the relative spatial arrangement of atoms within molecules (static stereochemistry), and the study of the stereochemical requirements and outcomes of chemical reactions (dynamic stereochemistry). These two branches complement each other in modern stereochemistry.

Chiral organometallics feature prominently in organic synthesis as reactive intermediates. The possibility of exploring their stereochemistry in synthesis is associated with the configurational stability of the metal-bearing stereogenic center. We were interested in the configurational stability of lithiated and magnesiated nitriles. We developed a new series of lithio-cyclopropylnitriles bearing chelating groups for intramolecular coordination, as a possible strategy to impart configurational stability. Although this strategy has not yet been successful, using density functional theory (DFT) method, we addressed the effect of chelating groups on racemization via the “conducted tour” mechanism. We then explored metal-bromine exchange on enantiopure bromonitrile as alternative route to metalated nitriles. In this way, we demonstrated that magnesiated 2,2-diphenyl cyclopropylnitrile is configurationally stable on the macroscopic timescale. No other metallated nitrile has ever demonstrated configurational stability on this timescale. In contrast, bromine-lithium exchange of 1-bromo-2,2-diphenyl-cyclopropylnitrile demonstrated fast racemization under the same conditions.

Another major project focused on conformational control of acyclic molecules. Using X-ray crystallography and NMR spectroscopy, we found that the 2,6-disubstituted aryl group eclipses its geminal hydrogen, and induces an antiperiplanar relationship of the geminal and vicinal hydrogens. Interestingly, anti-nitrile aldols or syn-ketone aldols bearing 2,6-disubstituted aryl groups demonstrate unanticipated remote effects on acyclic conformation: the 2,6-disubstituted aryl group prefers to be in a gauche position to the largest vicinal group. The minimization of allylic 1,3-strain and syn-pentane-like interaction works together in establishing this conformational preference.

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