Tandem Deoxygenative Geminal Fluorosulfonimidation of 1,2-Diketones via Formal N–F Insertion Enabled by Dealkylation-Resistant Phosphoramidite

Abstract

Our group has recently developed α-fluoroamine synthesis using dioxaphospholenes derived from various 1,2-diketones and the dealkylation-resistant phosphoramidite as carbene surrogates that enabled the formal insertion into the N–F bond of (PhSO2)2NF. This full account presents the scope and limitation in terms of the reactivity and the site-selectivity, which were rationalized through the computational analysis. In addition, the efforts to broaden the synthetic utility of the current process by incorporating other nitrogen nucleophiles and halogen electrophiles are described.

Fluorine-Assisted Rearrangement of Geminal Azidofluorides to Imidoyl Fluorides

“…Alternatively, double acyl substitution of bis-Weinreb amide or benzoin condensation/oxidation sequence could be employed. The detailed procedures have been described in our earlier works. ,, …”

Access to Multifunctionalized Tetrasubstituted Carbon Centers Bearing up to Three Different Heteroatoms via Tandem Geminal Chlorofluorination of 1,2-Dicarbonyl Compounds

“…Only MeCN provided a product yield comparable with the standard conditions, albeit with decreased selectivity (entry 6). The combined use of PhCF 3 and CH 2 Cl 2 , which was found to be optimal in our previous work on fluorosulfonimidation, did not lead to any meaningful improvement (entry 7). With CH 2 Cl 2 , a few other halogenating reagents were examined (entries 8 and 9).…”

“…With CH 2 Cl 2 , a few other halogenating reagents were examined (entries 8 and 9). Unfortunately, the reactivity of Selectfluor was poor, and insoluble LiCl could not supply the necessary chloride anion, which led to the participation of sulfonimide anion, instead, to give a large amount of nitrogenated side products . Finally, when P­(NMe 2 ) 3 was employed to prevent potential Arbuzov-type dealkylation of the phosphorus moiety, the corresponding dioxaphospholene decomposed rapidly before the halogen sources were added (entry 10).…”

“…To rationalize the origin of the different site-selectivities among the evaluated 1,2-dicarbonyl substrates, computational analysis was carried out (Figure A). On the basis of the previous mechanistic study with a related transformation, the initial electrophilic fluorination step was presumed irreversible and, thus, selectivity-determining. Therefore, the partial charge distribution of each dioxaphospholene was calculated with the natural bond orbital (NBO) analysis at the M06-2X/6-31++G­(d,p)/SMD­(CH 2 Cl 2 ) level of theory.…”