Browsing by Subject "Asymmetric"
- Results Per Page
- Sort Options
Item Open Access Part I: The Development of the Organocatalytic Asymmetric Mannich and Sulfenylation Reactions Part II: Progress Towards the Synthesis of Lagunamide A(2012) Kohler, Mark ChristopherThis dissertation deals with the development of asymmetric carbon-carbon and carbon-heteroatom bond-forming reactions and the synthesis of Lagunamide A. Asymmetric C-C and C-X bond formations are critical transformations in synthetic chemistry. While a variety of approaches are available to effect such reactions, organocatalytic methods have attracted considerable recent attention. Common themes have emerged from these studies with regard to both the mode of asymmetric catalysis and the nature of the substrates they are applied to. We have been investigating alternatives to these themes for both carbon-carbon and carbon-heteroatom bond formation. We will describe some of our efforts to expand the parameters of asymmetric organocatalysis, which include the development a novel biomimetic proximity-assisted soft enolization approach to the asymmetric Mannich reaction, as well as the use of nitrosoalkenes for the asymmetric a-sulfenylation of ketones and aldehydes. Lagunamide A was recently isolated from Palau Hantu Besar, Singapore and has shown strong antimalarial activity and cytotoxicity against leukemia. The work presented describes the progress towards the first asymmetric total synthesis of this natural product.
Item Open Access Regioselective Asymmetric a,a-Bisalkylation of Ketones via N-Amino Cyclic Carbamate Chiral Auxiliaries: Methodology Development and Application to the Total Synthesis of both (+)- and (-)-Stigmolone and Apratoxin D(2012) Wengryniuk, Sarah ElizabethThe α-alkylation of ketones is a transformation of central importance to organic synthesis. Our lab recently introduced the N-amino cyclic carbamate (ACC) chiral auxiliaries for asymmetric ketone α-alkylation. ACCs provide significant advantages over existing asymmetric ketone alkylation methods as they are easy to introduce, both deprotonation and alkylation can be run at relatively mild temperatures, stereoselectivity of alkylation is excellent and auxiliary removal is facile. A unique feature of ACCs is their ability to control the regioselectivity of deprotonation through what we have termed Complex Induced Syn-Deprotonation. In what follows, we describe several projects relating to the development and synthetic application of ACCs.
An optimized synthesis of our most successful ACC auxiliary was developed, including an improved method for the formation of the key N-N hydrazide bond.
A detailed mechanistic investigation of four ACC auxiliaries was conducted, examining the regio- and stereoselectivity of the alkylations at the level of the ACC hydrazone. This work culminated in a theoretical study of ACC auxiliaries, conducted through a collaboration with the Houk Group at UCLA.
We also describe the use of ACCs in the development of the first method for the regiocontrolled asymmetric α,α-bisalkylation of ketones. The method proceeds in excellent yield and with >99:1 diastereoselectivity. This method was also extended to the asymmetric α,α,α',α'-tetraalkylation of ketones, enabled by the development of a mild, epimerization-free LDA-mediated isomerization of the α,α-bisalkylated ACC hydrazones.
Additionally, we discuss three synthetic applications of the ACC α,α-bisalkylation methodology. We report an asymmetric formal synthesis of (+)- and (-)-stigmolone, as well as two approaches to the polyketide fragment of the novel cyclic depsipeptide apratoxin D, which have led to the completion of the first asymmetric total synthesis of apratoxin D.