Date of Award
Master of Science (MS)
Chemistry and Biochemistry
A common structural motif in complicated natural product molecules is an alkyl group at an alpha position to a carbonyl and an alcohol at the beta position anti to each other. This arrangement occurs in bioactive molecules that are important for medical research such as spongistatin A at the C15-C16 position and in (-)-baconipyrone C at C12-C13. Bioactive molecules such as these generally occur in such a low concentration in the organism in which they originate that deriving them from the natural source for research is not practical so efficient syntheses are sought. Reactions that produce 1,2 syn aldol products have been perfected under most circumstances, but methods to produce 1,2 anti aldol products without bulky alkyl groups on the enolizable compound still need to be perfected. In the case of 3-pentanone under conditions of E-enolization the yield is only approximately 70:30 E: Z. Anti aldol reactions generally result from E-enolates but in the case of the enolate of 3-pentanone without large alkyl groups to enforce a particular geometry in the pericyclic transition state between the enolate and carbonyl compound the yield of 70:30 E:Z goes down to 64:36 anti:syn. Quoting Erick M. Carrera "additions that produce anti substituted aldol adducts remain elusive and intractable". Since the best yields of E-enolates and anti-aldol reactions rely on the short Lewis Acid-oxygen bond length to maximize steric interactions in the transition states perhaps different Lewis Acids can be developed that have shorter LA-oxygen bond lengths.
Anderson, Matthew Grant, "Aldol Reactions: E-Enolates and Anti-Selectivity" (2005). All Graduate Plan B and other Reports, Spring 1920 to Spring 2023. 1312.
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