Thesis advisor: Marc L. Snapper / Chapter 1. A Practical Synthesis of 3-Acyl Cyclobutanones by [2 + 2] Annulation. Mechanism and Utility of the Zn(II)-Catalyzed Condensation of alpha-Chloroenamines with Electron-Deficient Alkenes. We have developed a catalytic method for the synthesis of highly functionalized 3-acyl cyclobutanones which are useful building blocks for a variety of natural products. Methods for cyclobutanone synthesis have traditionally been limited to Lewis-acid promoted rearrangement of oxaspiropentanes or cyclizations of ketene and syntheses involving keteneiminium salts have required stoichiometric quantities of a Lewis acid. Furthermore, the mechanism for these types of cyclizations remains unknown. This portion of my research focused on an efficient, catalytic method for the synthesis of 3- acyl cyclobutanones and providing insight into the mechanism for cycloaddition. Chapter 2. Enantioselective Synthesis of Boron-Substituted Quaternary Carbons by NHC-Cu-Catalyzed Boronate Conjugate Additions to Unsaturated Carboxylic Esters, Ketones, or Thioesters. We have developed an enantioselective NHC-Cu-catalyzed conjugate addition of boronate esters to acyclic, trisubstituted alpha, beta-unsaturated carbonyl compounds. Enantioselective conjugate addition of a boronic acid pinacol ester through the use of bis(pinacolato)diboron [B2(pin)2,] to alpha, beta-unsaturated aliphatic and aryl esters promoted by 5 mol % of an NHC-Cu catalyst afforded tertiary beta-boryl carbonyls in high efficiency and enantioselectivity. Trisubstituted alpha, beta-unsaturated esters and thioesters were found to be reactive substrates in the presence of a stoichiometric quantity of methanol. Chapter 3. Metal-Free Catalytic C-Si Bond Formation in an Aqueous Medium and C-B Bond Formation in a Protic Medium. Enantioselective NHC-Catalyzed Silyl and Boryl Conjugate Additions to Cyclic and Acyclic alpha, beta-Unsaturated carbonyls. We have developed a method for enantioselective metal-free silyl conjugate additions through the use of dimethylphenylsilyl) boronic acid pinacol ester [PhMe2SiB(pin)] catalyzed by chiral N-heterocyclic carbenes (NHCs) in basic aqueous thf. Optimization of metal-free conditions demonstrated that the presence of water was required for high efficiency. alpha, beta-Unsaturated cyclic ketones and lactones were examined as substrates, and acyclic ketones, esters and aldehydes were also competent substrates for silyl conjugate addition. beta-Silyl carbonyls were isolated in up to >98% yield and >98:2 er. Chapter 4. Elucidation of Mechanism for Enantioselective NHC-Catalyzed Silyl Conjugate Addition. We propose a catalytic cycle for NHC-catalyzed enantioselective silyl conjugate addition. Mechanistic studies of NHC-catalyzed enantioselective silyl conjugate additions are presented. Optimization of conditions for an inefficient alpha, beta-unsaturated electron-deficient ketone provided insight into the roles for dbu and water. Kinetic data indicate that conjugate addition is first order in PhMe2SiB(pin) and carbene, and DFT calculations support the formation of an NHC-silyl anion as a reactive intermediate in the catalytic cycle. / Thesis (PhD) — Boston College, 2012. / Discipline: Chemistry.