Henry Reaction To Construct Fluorinated Quaternary Carbon Center

The Henry reaction (or nitroaldol reaction) is a fundamental carbon-carbon bond-forming reaction in organic synthesis. The resulting product of this reaction is aβ-nitroalcohol, which is a versatile intermediate in synthetic organic chemistry. On the other side, because of the specific properties of fluorine atom(s), including their small steric size, high electronegativity and high lipophilicity, the introduction of fluorine atom(s) into organic compounds especially biologically active molecules has attracted considerable attention. Among them those compounds with a fluorinated quaternary carbon center is one of interesting topics for chemist.PartⅠ:Firstly, we prepared a series of nitro compounds started from halogenated alkanes, then a-fluorinated nitro compounds was synthesized by direct fluorinations with an electrophilic fluorinating agent. Then our work was mainly focused on the Henry reaction between a-fluorinated nitro compounds and various aldehydes, owing to only one a-proton exsited within the starting nitro compounds, a quaternary carbon center was built in the final products. To determine the relative configuration of the newly generated stereogenic center, X-ray single crystal analysis of one major isomer of compound 48bf was carried out. It was found that F atom was anti to -OH group in 48bf.PartⅡ:Several C2-symmetric chiral Cu-bis(oxazoline) compounds was used to catalyze the Henry reaction in order to get optically activeβ-fluoro-β-nitro-a-hydroxy compounds. It is regrettable that the yield is relatively low, and a good yield and moderate enantiomeric excess (51% ee) was obtained when large excess (about 10equiv) of fluorinated nitro compounds was used, but in this case the atom economy is less satisfactory.