Browsing by Author "Wood, John, committee member"
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Item Open Access N-heterocyclic carbene catalyzed α-redox reaction: catalytic synthesis of amides and carboxylic acids(Colorado State University. Libraries, 2011) Vora, Harit, author; Rovis, Tomislav, advisor; Williams, Robert, committee member; Wood, John, committee member; Chen, Eugene, committee member; McNeil, Michael, committee memberN-heterocyclic carbene catalyzed α-redox reaction has been utilized towards the catalytic synthesis of amides utilizing amines and substoichiometric quantities of an acyl transfer reagent in a waste reduced acylation process. The reaction is amenable to a plethora of amines and amine hydrochloride salts as nucleophiles. The reaction is applicable towards a variety α-reducible aldehydes as α,α-dichloro aldehydes, enals, epoxy and aziridnyl aldehydes all provide the respective amides in moderate to excellent yields with the latter in high diastereoselectivity. The asymmetric amidation reaction provides chiral amides in moderate enantioselectivity. Additionally, the N-heterocyclic carbene catalyzed α-redox reaction was also utilized for the synthesis of enantioenriched α-chloro and α-fluoro carboxylic acids. The reaction also provide for a mild installation of a deuterium from D2O furnishing enantioenriched isotopically labeled compounds. Investigations in to the mechanism have revealed that the carbene displays behavior of a phase transfer reagent by shuttling hydroxide from the aqueous phase to the organic phase. Additionally, it has been found that the turnover limiting step in this acylation process in the hydrolysis of the acyl azolium.Item Open Access Progress towards proposed biosynthetic intermediates of stephacidin A(Colorado State University. Libraries, 2009) Geiser, Andrea, author; Williams, Robert M., advisor; Wood, John, committee member; Slayden, Richard, committee memberProgress towards three potential biosynthetic intermediates of stephacidin A are presented. The first precursor has a 7-prenylated indole ring system, the second precursor has a 7-prenyl 6-hydroxy indole ring system, and the third precursor has a 6- hydroxy indole ring system. The synthesis of the 7-prenyl indole precursor proved challenging. However, once addition of the reverse prenyl group had been achieved the synthesis proceeded without any further challenges. The remaining three steps of the synthesis should follow Williams group chemistry. Once an efficient route to the starting material of the 7-prenyl-6-hydroxy and the 6-hydroxy precursors had been achieved, the synthesis progressed nicely. However, protecting group issues at the end of the 6-hydroxy precursor synthesis prevented the final product from being obtained. This also affected the efforts towards the 7-prenyl-6-hydroxy precursor indole. Once an adequate protecting group can be found, the synthesis of the 6-hydroxy precursor should follow group chemistry to completion.Item Open Access Progress towards the enhanced synthesis of FK228 and analogs; and the total synthesis of Largazole-Azumamide hybrid(Colorado State University. Libraries, 2009) Troutman, Ann E., author; Williams, Robert M., advisor; Wood, John, committee member; Thamm, Douglas, committee memberProgress towards an improved synthesis of HDAC inhibitor FK228 and work towards the completion of FK228 and Largazole Azumamide hybrids are presented. Through investigation of previous syntheses of FK228, a synthesis aimed at improving the overall yield and efficiency was planned out. After overcoming initial synthetic hurtles, a synthesis was attempted with moderate success. Further optimization would be needed for completion. Interest in creating Class specific HDAC inhibitors has gained popularity due to results of recent studies. The potent biological activity of FK228 and Largazole made them ideal candidates for modification. We were interested in developing these analogs by attaching side chains of other known HDAC inhibitors onto each macrocyle core, and in doing so we hoped to increase the reactivity of each molecule. Synthesis of the FK228-Azumamide hybrid began well, but hit several synthetic obstacles that have yet to be overcome. In contrast, the synthesis of Largazole- Azumamide hybrid proceeded smoothly, and was completed in thirteen steps and 11% yield. We are currently waiting for results of the biological activity studies.Item Open Access Utilizing silicon for the synthesis of tri- and tetrasubstituted olefins(Colorado State University. Libraries, 2013) Rooke, Douglas Alexander, author; Ferreira, Eric, advisor; Wood, John, committee member; Fisk, John D., committee member; Shores, Matthew, committee member; Peersen, Olve, committee memberFunctionalized organosilanes serve an important role as reactive precursors for a number of synthetic transformations. Consequently there is still great use for the development of new methods that allow for facile and efficient generation of organosilicon compounds. Herein, a number of such methods are described. The stereoselective syntheses of α-silylenones using catalytic PtCl2 are reported. Via alkyne activation, α-hydroxypropargylsilanes are converted to (Z)-silylenones through a highly selective silicon migration. A trans halosilylation of alkynes is also reported. Both the PtCl2 catalyzed silyl migration the halosilylation reaction proceed through a 1,2-silicon shift onto the activated alkyne intermediate in an anti fashion relative to the activating agent. Both reactions afford excellent yields and selectivity for the product tri- and tetrasubstituted alkenes. The high yielding Pt catalyzed hydrosilylation reactions of internal alkynes are described with a focus on understanding the factors that govern the regioselectivity of the process. Electronic, steric, and functional group properties all influence the selectivity, an understanding of which allows the selective formation of trisubstituted vinylsilanes, which are synthetically useful compounds for accessing stereodefined alkenes. Finally, efforts to show the synthetic utility of tri- and tetrasubstituted vinylsilanes for the formation of C-C bonds using Hiyama coupling and halodesilylation reactions are reported. Hiyama couplings of tetraorganosilanes with and without the use of fluoride activators are thoroughly evaluated. Coupling reactions with vinylsiloxanes are also shown. Finally, stereoretentive halodesilylation reactions are explored with the product vinylhalides subsequently subjected to Suzuki cross coupling conditions affording high yields of highly substituted all-carbon alkenes with good retention of alkene geometry.