Asymmetric Synthesis of beta-Amino Acids

Moffat, David Festus Charles (1986) Asymmetric Synthesis of beta-Amino Acids. PhD thesis, University of Glasgow.

Abstract

Summary Whereas the asymmetric synthesis of alpha-amino acids has received considerable attention 2 over the past two decades, there have been relatively few published investigations which deal with the asymmetric synthesis of beta-amino acids. 22-27 It was the aim of the work described in this thesis to devise an improved asymmetric synthesis of beta-amino acids involving the construction of heterocyclic intermediates in a diastereoselective manner, particularly by the 1,3-dipolar cycloaddition reactions of chiral nitrones with suitably substituted alkenes. The Introduction reviews the natural occurrence of the more important beta-amino acids, previous asymmetric syntheses, and the 1,3-dipolar cycloaddition chemistry of nitrones, including enantio- and diastereoselective processes. Chapter 1 describes the synthesis of a series of chiral and achiral nitrones and the first systematic investigation of the stereochemistry of aliphatic aldonitrones, involving analysis of N-benzyl nitrones (6-8) by Nuclear Overhauser Difference Spectroscopy (NOEDS). The results of this investigation demonstrate that (6-8) are formed exclusively in the Z configuration. Conversion of nitrone (6) into the isoxazolidines (29) and (30) provides the first evidence for the formation of diastereomeric dimers from a nitrone. beta-leucine (71) and beta-tyrosine methyl ether (80) are described in Chapter 2. They depend upon the reaction of chiral nitrones with vinyl acetate to yield isoxazolidines in which substituents have been placed in a regio-and stereoselective manner on the periphery of the five-membered ring, [Scheme I]. Subsequent hydrolysis of the acetate moiety affords a lactol which can be oxidised to the isoxazolidin-5-one system. Catalytic hydrogenolysis of these isoxazolidinones by N-O fission and deprotection of the nitrogen function leads to the free beta-amino acids. cycloadditions of nitrones with alkyl ketene acetals as a potentially new route to beta-amino acids. The chiral induction observed in the formation of isoxazolidines such as (101) from the chiral phenyl nitrone (21) and The asymmetric syntheses of beta-phenyl-beta-alanine (57), Chapter 3 describes an investigation of the 1,3-dipolar [o-xylyl]ketene acetal (85) is far superior to that observed with vinyl acetate, [Scheme II]. An alternative synthesis of the chiral isoxazolidin-5-ones (56), (70) and (79), is described in Chapter 4, entailing a one-pot reaction of hydroxylamine (15) and unsaturated esters ( 123-125), [Scheme III].

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1986
• Depositing User: Enlighten Team
• Unique ID: glathesis:1986-77409
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 11:53
• Last Modified: 14 Jan 2020 11:53
• URI: https://theses.gla.ac.uk/id/eprint/77409