Many known synthetic methods enable the hydrolysis of alkynes with Markovnikov regioselectivity. In contrast, the synthetic chemist’s toolbox lacks broadly effective processes for the hydrolysis of alkynes with anti-Markovnikov regioselectivity. This thesis describes the development of new synthetic method that will help address this deficiency. This document begins with a review of the concepts of Markovnikov and anti-Markovnikov regioselectivity and an explanation of the broad extension of this terminology that is applied throughout the remainder of this thesis to encompass all alkyne substrates. Next, a review of the published methods of alkyne hydrolysis is presented, with emphasis on the internal alkyne substrates. The remainder, and bulk, of this thesis details the development of a new synthetic methodology that leverages regioselective radical thiolation chemistry to achieve anti-Markovnikov hydrolysis of alkynes. Internal alkynes are first converted to oxathiolanes or vinyl sulfides with anti-Markovnikov regioselectivity followed by hydrolysis of these moieties to the corresponding anti-Markovnikov ketones. In the case of aryl-alkyl alkyne substrates, complete anti-Markovnikov selectivity is demonstrated with a broad range of examples. Aryl-aryl alkyne substrates offer a mixture of regioisomers favoring anti-Markovnikov products. Finally, the utility of this methodology is demonstrated with its application to the successful first total synthesis of the bioactive natural product isomeranzin. / Thesis / Master of Science (MSc)