The Construction And Application Of C-X(X= P, C, N) Bond With H-Phosphonate Participation

It is well known that H-phosphonates play a major role in the research and application of the organic phosphorus chemistry. As an important intermediate, it has been widely used in the synthesis of a large variety of biologically active phosphorus-containing compounds. Such as: amino phosphonic acid, amino phosphonate, bisphosphonates, alkynylphosphonates, α-hydroxylphosphonates, epoxy alkyl phosphonates, phosphoramides, nucleoside phosphonates etc. Compared to POCl3, PCl3 and other phosphorus reagents, H-phosphonates have advantages of being cheap, easy to preserve and stable structure. In the past few years, a lot of work have been focused on the H-phosphonate related research.C-H bond is one of the most abundant chemical bond in nature. Building C-X(X = N, S, O, C, P) bond via the activation of C-H bond has become much more popular and attracted more and more attention in recent years due to its outstanding atom-economic advantages. C-H bond is generally a very stable covalent bond. So, it is often challenging to directly functionalize the C-H bond. Therefore, direct functionalization of C-H bond is known as "the Holy Grail for Chemistry". However, what needs to be mentioned here is that almost all the C-H bond activation reactions published previously were realized through metal-involved reactions. It is also worth noticing here that some metals empolyed for this purpose are noble, or even toxic metals. Therefore, the development of metal free or inexpensive metal involved reaction has already become the theme of current organic synthesis in the aspect of reducing energy consumption and pollutant emissions.It is especially worth mentioning here that lots of synthetic methods concerning the construction of C-P bond via metal involved C-H bond activation have been developed in very recent years. By contrast, the H-phosphonates mediated construction of the C-C, C-N bonds, especially H-phosphonates mediated metal free or cheap metal involved direct construction of the C-C, C-N bonds via C-H bond activation has rarely been reported. This paper focuses on H-phosphonates mediated metal free or inexpensive metal involved reactions, and efficiently developed several green synthetic ways to construct C-X(X = P, C, N) bonds. All these newly developed methods have shown a great potential of H-phosphonates in aspect of construction of the C-C, C-N and C-P bond by using cheap metals or under metal free reaction conditions. These methods, completed by one pot one step, are of green process with remarkable atom economy. Meanwhile, the H-phosphonates mediated reaction mechanisms were studied by the use of phosphorus spectrum tracking techniques and theoretical calculation technology. The newly developed methods lay the preliminary theoretical basis of these reaction systems, widen the application scope of H-phosphonates mediated syntheses.The research contents are as follows:(I) H-phosphonates mediated C-P bond construction to synthesize β-carbonyl phosphonate ester derivative:By the use of cheap and readily available Ag NO3/Cu SO4·5H2O as catalyst, K2S2O8 as the oxidant, a series of β-carbonyl phosphonate derivatives were efficiently synthesized from the raw material, terminal alkynes and H-phosphonates at room temperature. And the reaction conditions, such as catalyst, oxidation agent and solvent, were optimized. 27 compounds were synthesized and their structures were identified by 1H NMR、13C NMR and HRMS. The reaction mechanism was explored and discussed. This method provides a new way to construct C-P bond to synthesize β-carbonyl phosphonate derivatives.(II) H-phosphonates mediated C-C bond construction via C-H bond activation to synthesize 1,3-conjugated enyne derivatives:With inexpensive Cu SO4·5H2O and diethanyl H-phosphonates as catalyst system and relatively mild reaction conditions, the dimerization of terminal alkyne, C-C bond construction, was realized in a head-to-head form through the activation of C-H bond, and series high stereo and regional selection 1,3- conjugated enyne compounds were synthesized. Through screening the catalyst, solvent, temperature and organic phosphorus reagent conditions, the best reaction conditions were obtained. 20 1,3-conjugated enyne compounds were synthesized and their structures were identified by 1H NMR, 13 C NMR. The mechanism of reaction to synthesize 1,3-conjugated enynes was verified through series of experiments, which gave the in-depth study and exploration of the reaction and provided a good method for the synthesis of 1,3-conjugated enynes compounds.(III) H-phosphonates mediated aryl C-N bond construction via C-H bond activation to synthesize 2-aminoquinoline/pyridine derivatives:With quinoline and pyridine N-oxide derivatives as substrate, organic amine(secondary or tertiary amine) as nucleophiles, under mild and metal-free conditions C-N bond was formed via 2 position C-H bond activation of quinoline N-oxide, and a series of 2-aminoquinoline/pyridine derivatives were efficiently synthesized. Through optimizing the reaction solvent, temperature, and the amount of phosphorus reagents, the optimum reaction condition was obtained. 24 2-aminoquinoline/pyridine derivatives were synthesized and their structures were identified by 1H NMR、13C NMR and HRMS. The reaction mechanism was explored by phosphorus spectrum tracking technology and a new method for the synthesis of 2-amino quinoline/pyridine compounds was provided.(IV) Peroxide as switch of Dialkyl H?phosphonate: Two Mild and Metal-Free Methods for Preparation of 2?Acylbenzothiazoles and Dialkyl Benzothiazol-2-ylphosphonates:By using the two reaction centers of H-phosphonates: phosphorus atom and α-carbon atom of alkoxy, with different radical initiator, under mild and metal-free conditions, C-C bond and C-P bond were built directly and two kinds of new 2-acylbenzothiazole and 2-benzothiazolyl phosphonate derivatives were efficiently synthesized. By studying the reaction temperature, solvent, reaction time, dosage of H-phosphonates, the optimum reaction conditions are determined. 26 2-acylbenzothiazole derivatives and 21 2-benzothiazolyl phosphoric ester derivatives were synthesized and their structures were identified by 1H NMR、13C NMR and HRMS. Through series of verification experiments, 31 P NMR spectra tracking technique and calculation of density functional theory, the reaction mechanism was provided. This research revealed the new characteristics of H-phosphonates, namely the "flexibility", which expanded the applicable scope of H-phosphonates.