Chapter 1 – The gold(I)-catalyzed, stereoselective hydrofluorination of electron-deficient alkynes with triethylamine trihydrogen fluoride (Et3N·3HF) is described. Fluorinated α,β-unsaturated aldehydes, amides, esters, ketones, and nitriles were isolated in moderate to good yields as single diastereomers. In all but four cases, the (Z)-vinyl fluorides were initially formed in ≥97% diastereoselectivity. This work constitutes the first catalytic example of the diastereoselective preparation of a variety of β-alkyl, β-fluoro Michael acceptors from alkynes. Additionally, the described work expands access to β-aryl, β-fluoro Michael acceptors to the synthesis of β-fluoro- α,β-unsaturated amides and nitriles. The monofluoroalkenes formed through this strategy were readily transformed into other fluorine-containing compounds, and the developed method was applied to the synthesis of a fluorinated analogue of Exoderil, a topical antimycotic.

Chapter 2 – The copper-catalyzed silylation of propargylic difluorides to generate axially chiral, tetrasubstituted, monofluoroallenes in both good yields (24 examples >80%) and enantioselectivities (82–98% ee). Compared to previously reported synthetic routes to axially chiral allenes (ACAs) from prochiral substrates, a mechanistically distinct reaction has been developed: the enantiodiscrimination between enantiotopic fluorides to set an axial stereocenter. DFT calculations and vibrational circular dichroism (VCD) suggest that β-fluoride elimination from an alkenyl copper intermediate likely proceeds through a syn-β-fluoride elimination pathway rather than an anti- elimination pathway. The effects of the C1-symmetric Josiphos-derived ligand on reactivity and enantioselectivity were investigated. Not only does this report showcase that alkenyl copper species—like their alkyl counterparts— can undergo β-fluoride elimination, but that this elimination can be achieved in an enantioselective fashion. The resulting monofluoroallenes were shown to undergo a copper-catalyzed desilylative acylation. A kinetic resolution was developed, generating propargyl fluorine-containing quaternary stereocenters. Current efforts are underway to better understand the system that aim to achieve dynamic kinetic resolution.