62nd Annual Report on Research 2017

Br∅nsted acids are among the most commonly employed catalysts and are used to promote a wide variety of chemical transformations. They provide an excellent alternative to transition metal containing catalysts in that they tend to be tolerant of air and water, are generally thought to be less toxic, and maybe more sustainable. Substrate activation commonly takes place by hydrogen bonding or proton transfer, both of which lower the lowest unoccupied molecular orbital (LUMO) energy thereby facilitating nucleophilic attack. Different types of Br∅nsted acid organocatalysts have been developed with a wide range of acidities including thioureas, a,a,a,a-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs), 1,1'-bi-2-naphthol (BINOL) and phosphoric acid derivatives, and their utility has been extensively demonstrated. Of these compounds, phosphoric acids are inherently the most acidic. Given that acidity commonly correlates with reactivity, these species are of particular interest. Charge containing phosphoric acids 1 and 2 were synthesized and their ability to catalyze organic transformations such as Friedel-Crafts alkylations (eq. 1) and Diels-Alder cycloadditions (eq. 2) were investigated. Reaction rates for these processes were measured and compared to diphenyl phosphate [(PhO)2P(O)OH] catalyzed processes; a non-charged analog. Rate accelerations of more than three orders of magnitude were observed for the pyridinium ion containing species. As a result, chiral phosphoric acids with charged substituents are of interest and were explored. A series of six BINOL derived phosphoric acids containing n-octyl-pyridinium or triarylphosphonium ions at the 3 and 3'-positions along with tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (BArF4-) counterions were prepared (3 and 4). Their ability to catalyze a series of Friedel-Crafts reactions were optimized and high yields of up to 99% and enantioselectivies of up to 90% ee were obtained.