Thesis advisor: Amir H. Hoveyda / Chapter 1. We have developed a single-vessel catalytic protocol for double protoboryl additions to terminal alkynes with B2(pin)2 promoted by Cu complex derived from chiral N-heterocyclic carbene (NHC), to achieve enantiomerically enriched versatile vicinal diborons. Since an alkenyl(pinacolato)boron, which was in situ generated by the first protoboration of a terminal alkyne, can serve as an effective substrate for the second protoboration (alkenylboron can allow delocalization of π electrons of olefin to a partially vacant p orbital on boron), single-vessel catalytic process with 2 equiv. of B2(pin)2 in the presence of sulfonate-bearing chiral NHC–Cu complex, affords enantiomerically enriched 1,2-diborons in up to 93% yield and 97.5:2.5 enantiomeric ratio (e.r.). Site-selective Pd-catalyzed cross-coupling with alkenyl bromide shows the versatility of the resulting diboron compounds, which delivers the coupling product efficiently. Interestingly, only the less hindered, primary C–B bond on vicinal diboron compound participates in the cross coupling. Chapter 2. Cu-catalyzed protocol for selective formation of α-alkenylborons has been demonstrated. With achiral NHC–Cu complex, readily prepared from commercially available imidazolinium salt, various terminal alkynes are converted to internal alkenylborons in up to 93% yield with high to exclusive α selectivity. Propargyl ethers, amides and aryl alkynes are proved to be suitable substrates. Utility of α-alkenylborons is demonstrated by conversion to methyl ketone and synthesis of cyclic alkenylboron compound. In addition, when Cu complex bearing a stronger electron-donating NHC is used, the site selectivity of protoboration reaction becomes reversed, which delivers the alternative isomer, β-alkenylboron efficiently. By altering the steric and electronic nature of NHC, site selectivity is dramatically changed. Mechanistic basis for site selectivity is presented. Chapter 3. Efficient and selective protocol for synthesis of enantiomerically enriched silylborons is described. In the presence of achiral NHC–Cu complex, site- and stereoselective protosilyl additions to terminal alkynes afford a wide range of alkyl- and aryl-substituted (E)-β-alkenylsilanes. Chiral monodentate NHC−Cu complex promotes enantioselective protoboration of alkyl- or alkenyl-bearing alkenylsilanes, delivering vicinal borosilanes with up to 96.5:3.5 e.r. When an alkene bearing both silyl and aryl groups is utilized, on the other hand, geminal silylboron is obtained with high enantio- (93:7–98.5:1.5 e.r.) and site selectivity (up to >98% geminal). In this case, we have reasoned that the electronic attribute of aryl unit is more dominant than the silyl group to control site selectivity. To demonstrate the utility of the Cu-catalyzed transformation, we have illustrated the formal synthesis of bruguierol A, natural product active against Gram-positive and also Gram-negative bacteria. The key intermediate geminal borosilane is provided by sequential NHC–Cu-catalyzed protosilylation and protoboration of terminal alkyne in 77% overall yield with 97.5:2.5 e.r. and 97% site selectivity. Additionally, stereochemical models to account for levels and trends in site- and enantioselectivity are proposed. Chapter 4. New methods for enantioselective protonation of 2-B(pin)-bearing allylcopper, which is in situ generated by site-selective Cu–B addition to 1,1-disubstituted allene, are presented. Transformations are promoted by a chiral NHC–Cu complex, affording an alkenylboron containing α-carbon stereogenic center. Enantiomerically enriched aryl-, heteroaryl- and silyl-bearing alkenylborons are generated in high yield (up to 98%) and selectivities (up to >98% site selectivity and 96.5:3.5 e.r.). To explore the utility of enantiomerically enriched alkenylborons, we have developed Cu-catalyzed enantioselective allylic alkenyl addition to allylic phosphate. A chiral NHC–Cu complex promotes the allylic substitution of enantiomerically enriched alkenylboronic acid with ally phosphate to deliver 1,4-diene in 62% yield with 96:4 d.r. (>98% stereoselectivity). Chapter 5. We have developed a single-vessel, multicomponent process to synthesize N-bearing quaternary carbon stereogenic centers with exceptional diastereo- (>98:2 d.r. for all cases) and high enantioselectivity (88:12 to >99:1 e.r. except one case). Especially, protecting group-free ketoimine (“N–H” ketoimine), which can be prepared by alkylation of a readily available nitrile, has been utilized for the study. The transformation of “N–H” ketoimine is very useful because the obtained amine has no protecting group, which allows us to avoid the deprotection step as well as to be able to choose appropriate protecting group for subsequent chemical reactions. By oxidation of α-tertiary carbamine with NaBO3, β-amino ketones (Mannich reaction product) are obtained in up to 83% yield. A stereochemical model to account for the level of diastereo- and enantioselectivity are presented using DFT calculations. To show the utility of the present method, we have synthesized a medicinally active compound, which was studied for Alzheimer’s disease. The Cu-catalyzed protocol delivers the core structure of the target molecule with exclusive diastereo- and enantioselectivity (>98:2 d.r. and 99.5:0.5 e.r.). / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.