Nucleophilic Halogenations of Diazo Compounds, a Complementary Principle for the Synthesis of Halodiazo Compounds: Experimental and Theoretical Studies

Three
new protocols for the nucleophilic halogenations of diazoesters,
diazophosphonates, and diazopiperidinylamides as complementary methods
to our previously reported electrophilic halogenations are presented
for the first time. On the basis of hypervalent α-aryliodonio
diazo triflate salts 1A, 2A, and 3A, the corresponding halodiazo compounds are generated via nucleophilic
halogenations with tetrabutylammonium halides or potassium halides.
The products from subsequent catalytic intermolecular cyclopropanations
of the halodiazoesters and halodiazophosphonates and thermal intramolecular
C–H insertion of the brominated diazopiperidinylamide are obtained
in moderate to good yields after two steps. DFT calculations are presented
for the diazoesters to give insight into the mechanism and transition
states of the nucleophilic substitutions with the neutral nucleophiles
dimethyl sulfide and triethylamine and the bromination with Br–.

本研究首次报道了三种适用于重氮酯（diazoesters）、重氮膦酸酯（diazophosphonates）与重氮哌啶酰胺（diazopiperidinylamides）的亲核卤化新方案，作为此前已报道的亲电卤化（electrophilic halogenations）反应的补充方法。研究以高价α-芳基碘鎓重氮三氟甲磺酸盐（hypervalent α-aryliodonio diazo triflate salts）1A、2A与3A为起始底物，通过与四丁基卤化铵（tetrabutylammonium halides）或卤化钾（potassium halides）发生亲核卤化反应，即可得到对应的卤代重氮化合物。经两步反应后，卤代重氮酯与卤代重氮膦酸酯经后续催化分子间环丙烷化（catalytic intermolecular cyclopropanations）反应、溴代重氮哌啶酰胺经热分子内C-H插入（thermal intramolecular C–H insertion）反应所得到的产物，均可获得中等至良好的收率。本研究还针对重氮酯开展了密度泛函理论（DFT）计算，以阐明其与中性亲核试剂二甲基硫醚（dimethyl sulfide）、三乙胺（triethylamine）的亲核取代反应，以及与Br⁻的溴代反应的反应机制与过渡态（transition states）。