60th Annual Report on Research 2015

Reaction of bifunctional reagent, alk-3-yn-1-one (propargyl ketone) with unsymmetrically substituted o-phenylenediamines was investigated. At a room temperature the reaction leads to enaminones (3-amino-2-alkenones) with high yields, however, formation of two isomers was observed. Thus, so far the reaction did not proceed with regioselectivity expected. However, conditions for successful isolation of a single regioisomer were elaborated. Following, the reaction of single isomer enaminone (3-amino-2-alkenone) containing the unit of unsymmetrical o-phenylenediamine at elevated temperature, in microwave-accelerated conditions, proceeded in ethanol, in the presence of acetic acid, to yield corresponding 1,5-benzodiazepines with good yields. Depends on the character of a substituent in phenylenediamine (electron-withdrawing or electron-donating), one of the amino group reacted faster, and accordingly the position of the substituent was reflected in the product. This combination of non-catalyzed amination reaction with subsequent condensation reaction provides effective access with high atom economy to diverse 2,4-disubstituted 1,5-benzodiazepines. The methodology allows for the introduction of benzyl-type substituents at the C-2 position of benzodiazepine that is not easily carried out by current methods. With a high degree of rearrangement, this reaction provides a convenient and temperature-controlled synthetic method for the synthesis of benzodiazepines with the regioselective positioning of o-phenylenediamine with no need to protect one of the amino functions.

In separate efforts, we were attracted to the synthesis of 3,4,5-substituted triaryl phosphines oxides containing groups that offer a starting point for further synthetic transformations. Our attention focused on the 4-hydroxyphenyl substituent, which can be converted into various ligands including perfluoroalkyl (fluorous) chains. The 3,5-diiodomotif has also been synthetically followed for applications such as the construction of organometallic units. Combining, the synthesis of diversely trisubstituted phosphine oxides containing thyroxine-related 4-hydroxy-3,5-diiodophenyl fragments has been approached. Accordingly (4-hydroxy-3,5-diiodophenyl)diphenylphosphine oxide, bis(4-hydroxy-3,5-diiodophenyl)(phenyl)phosphine oxide, and tris(4-hydroxy-3,5-diiodophenyl)phosphine oxide were obtained via iodination reactions of corresponding mono-, bis-, and tris(4-hydroxyphenyl)phosphine oxides. Single-crystal X-ray diffraction studies showed each homologue forms O-H•••O=P and pi-stacking interactions with neighboring molecules to give inversion related dimeric motifs.

This year three undergraduate students were involved in this project and two enjoyed a summer research opportunity (the third went to Germany for another summer program). All students are remaining in the PI's laboratory, while pursuing their B.S. in Chemistry (ACS accredited).