In this thesis the synthesis of vicinal stereocenters is investigated in two distinct contexts, namely the construction of 3,3-disubstituted oxindoles and the synthesis of b-hydroxy-a-amino acids. Both scaffolds are prevalent in a range of natural products and biologically relevant compounds and, therefore, methods for their synthesis are of great import. First, the construction of 3,3-disubstituted oxindoles using palladium-catalyzed domino reactions is described.  This covers two stereospecific methods for the construction of the desired oxindoles based on domino carbopalladation sequences.  The termination events for these domino reactions are carbonylation or cross-coupling.  In the carbopalladation-carbonylation reaction, we studied the possibilty of suppressing b-hydride elimination for substrates possessing pendant b-hydrogens.  In the carbopalladation-cross-coupling sequence, we examined the role of the boron source and substrate scaffold in the outcome of the reaction.  In both of these methods, an intricate balance of rates needs to be attained in order to achieve the desired domino sequences.  Thus, these investigations offer insight into the rates of the competing reactions, and the factors that influence these processes. Secondly, the stereoselective synthesis of b-hydroxy-a-amino acids is explored.  This has lead to two separate methods for the construction of this scaffold.  We first examined a 1,3-dipolar cycloaddition of azomethine ylides to aldehydes for the construction of syn-b-hydroxy-a-amino esters.  It was found that one set of azomethine ylides reacted through a 1,3-dipolar cycloaddition, while the other set reacted via a direct aldol reaction.  Finally, we studied an asymmetric transfer hydrogenation reaction to provide anti-b-hydroxy-a-amido esters from the corresponding a-amido-b-ketoesters.  Two protocols were developed for the reduction of these substrates, one using triethylammonium formate and the other using sodium formate in an emulsion.  The latter method gives high yields, diastereoselectivities and enantioselectivities for a broad range of substrates. / QC 20120605

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses. / February 2006

No description available.

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses.

A new class of oxazolidinone chiral auxiliary has been synthesized from various α-amino acids, incorporating a perfluoroalkyl functional chain as a soluble support. This feature allows the chiral auxiliaries to be employed under standard solution-phase reaction conditions, and rapidly purified from crude mixtures using fluorous solid phase extraction (FSPE). Our investigation of these new materials has been divided into two main sections. To obtain the chiral auxiliaries in multi-gram quantities a synthetic protocol was designed, where efficiency and reproducibility were the primary objectives. Meeting these goals required an extensive study of the reactivity of perfluoroalkyl nucleophiles. This study identified a versatile and scalable protocol for the perfluoroalkylation of the required amino acid starting materials. These results have allowed us to design a general, five-step synthetic pathway to create the fluorous chiral auxiliaries quickly and effectively. The new auxiliaries were then applied in several model reactions, specifically chosen to examine the reactivity and behavior of these compounds. In particular, the auxiliaries were tested for their stereoselectivity, recyclability, and ease of purification, in a series of Aldol reactions, 1,3 dipolar cycloadditions, and radical conjugate additions. This set of model reactions, combined with the facile and efficient synthesis clearly demonstrates that these new chiral auxiliaries are useful alternatives to the non-fluorous oxazolidinone chiral auxiliaries currently employed in stoichiometric asymmetric syntheses.

The ortho metallation of some aromatic ring systems has been investigated in regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration. The metallation step allows derivatisation in several useful ways, offering several routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of the phosphonic diamide directing group. This primary phosphine undergoes an unprecedented facile phenyl group exchange process between its two phosphorus atoms, upon di-lithiation of the primary phosphorus centre. The primary phosphorus centre of (14) has been elaborated in several ways to yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate complex has been investigated in several directions. In another direction, (14) has been chemically elaborated to give a new hybrid chiral ditertiary phosphine ligand, &quotSemiPHOS&quot, containing both a chiral phospholane ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in optically pure forms by a stereoselective synthesis and, independently, by a resolution procedure on its racemate. The molecular design of SemiPHOS was devised such that, when chelated to a metal atom, a subtle steric interaction appears to allow the chirality of the phospholane ring to influence the neighbouring diphenylphosphino group to adopt a complementary chiral conformation. This idea was tested and evaluated by applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino) acrylate substrates to produce the R-amino acid precursors. Aryl species lithiated ortho to phosphorus-centred directing groups were coupled oxidatively by a convenient in situ method, to yield biaryl species that could then be elaborated to give biaryl ditertiary phosphine ligands. This method was used to make several atropisomeric chiral ditertiary phosphines.

The ortho metallation of some aromatic ring systems has been investigated in regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration. The metallation step allows derivatisation in several useful ways, offering several routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of the phosphonic diamide directing group. This primary phosphine undergoes an unprecedented facile phenyl group exchange process between its two phosphorus atoms, upon di-lithiation of the primary phosphorus centre. The primary phosphorus centre of (14) has been elaborated in several ways to yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate complex has been investigated in several directions. In another direction, (14) has been chemically elaborated to give a new hybrid chiral ditertiary phosphine ligand, &quotSemiPHOS&quot, containing both a chiral phospholane ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in optically pure forms by a stereoselective synthesis and, independently, by a resolution procedure on its racemate. The molecular design of SemiPHOS was devised such that, when chelated to a metal atom, a subtle steric interaction appears to allow the chirality of the phospholane ring to influence the neighbouring diphenylphosphino group to adopt a complementary chiral conformation. This idea was tested and evaluated by applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino) acrylate substrates to produce the R-amino acid precursors. Aryl species lithiated ortho to phosphorus-centred directing groups were coupled oxidatively by a convenient in situ method, to yield biaryl species that could then be elaborated to give biaryl ditertiary phosphine ligands. This method was used to make several atropisomeric chiral ditertiary phosphines.

Thesis (Ph. D.)--University of New South Wales, 1999. / Includes bibliographical references. Also available online.

Thesis (Ph.D.)--University of Wollongong, 2005. / Typescript. Includes bibliographical references.

Thesis (M.S.)--Michigan State University. Dept. of Chemistry, 2006. / Title from PDF t.p. (viewed on June 19, 2009) Includes bibliographical references. Also issued in print.