University of Louisville
Selective Ring Opening Reactions Using HF-DMPU
Institution
University of Louisville
Faculty Advisor/ Mentor
Gerald Hammond
Abstract
The utility of fluorine in medicinal and manufacturing chemistry is undisputed. Despite its usefulness, the incorporation of fluorine in organic molecules is not without challenges. Regardless of their electrophilic or nucleophilic nature, most, if not all, fluorinating reagents derive from HF. Nucleophilic reagents are less expensive compared with their counterparts, and many are not commercially available. The popular Olah’s reagent (pyridine-HF complex) and triethylamine-HF have been explored extensively as nucleophilic sources of fluorine in many reactions. Laurence and co-workers recently published a comprehensive library of hydrogen bond basicity for various organic and inorganic compounds. This library guided our path towards improving the reactivity of HF as well as to tame its corrosiveness and led to our initial finding that DMPU, a relatively common solvent, formed a stable complex with HF. We showcased the usefulness of the HF-DMPU complex in the fluorination of alkynes. Our success on the investigation of HF-DMPU on the hydrofluorination of alkynes, which was cited on the American Chemical Society’s Chemical & Engineering News, inspired and motivated us to investigate further the synthetic utility of HF-DMPU reagent. In this poster we will show some recent studies on the selective fluorinations of aziridine, epoxides and thiiranes.In our preliminary findings, we observed that the opening of aziridines by HF-DMPU gave high yields of 60-90% and also gave high regioselectivity of > 30:1 of the corresponding β-fluoroamines. More importantly, the reactions were well tolerated by different N-substituents on the aziridine, especially the acid sensitive N-Boc group. Tuning the reaction condition slightly, we observed that HF-DMPU was effective in the ring opening of epoxides, giving good yields of 56-92% and good to moderate regioselectivity of the corresponding fluorohydrins.
Selective Ring Opening Reactions Using HF-DMPU
The utility of fluorine in medicinal and manufacturing chemistry is undisputed. Despite its usefulness, the incorporation of fluorine in organic molecules is not without challenges. Regardless of their electrophilic or nucleophilic nature, most, if not all, fluorinating reagents derive from HF. Nucleophilic reagents are less expensive compared with their counterparts, and many are not commercially available. The popular Olah’s reagent (pyridine-HF complex) and triethylamine-HF have been explored extensively as nucleophilic sources of fluorine in many reactions. Laurence and co-workers recently published a comprehensive library of hydrogen bond basicity for various organic and inorganic compounds. This library guided our path towards improving the reactivity of HF as well as to tame its corrosiveness and led to our initial finding that DMPU, a relatively common solvent, formed a stable complex with HF. We showcased the usefulness of the HF-DMPU complex in the fluorination of alkynes. Our success on the investigation of HF-DMPU on the hydrofluorination of alkynes, which was cited on the American Chemical Society’s Chemical & Engineering News, inspired and motivated us to investigate further the synthetic utility of HF-DMPU reagent. In this poster we will show some recent studies on the selective fluorinations of aziridine, epoxides and thiiranes.In our preliminary findings, we observed that the opening of aziridines by HF-DMPU gave high yields of 60-90% and also gave high regioselectivity of > 30:1 of the corresponding β-fluoroamines. More importantly, the reactions were well tolerated by different N-substituents on the aziridine, especially the acid sensitive N-Boc group. Tuning the reaction condition slightly, we observed that HF-DMPU was effective in the ring opening of epoxides, giving good yields of 56-92% and good to moderate regioselectivity of the corresponding fluorohydrins.