The Heck?hiyama?C-H Activation And Buchwald Reaction Of Pyrimidin-2-yl Tosylates

Inrecent years,transition metal catalyzed cross-coupling reaction has become a powerful and indispensable tool for the construction of C-C,C-N bonds etc in synthetic organic chemistry.Although halides have been successfully used as the most commonly electrophiles due to their relatively high reactivity and excellent selectivity in the traditional coupling reactions,they still suffer from numerous drawbacks such as harsh prepared conditions,the coupling byproducts as well as environmental pollutions.Thus,developing new kinds of electrophile replacing the halides is still in demand.The 3,4-dihydropyrimidinones?DHPMs?display wide biological properties,which are advantage structural units for the design of new drugs.Pyrimidin-2-yl tosylates as novel electrophiles are attractive being readily available from DHPMs,stable against hydrolysis and less contaminating the environment.Transition metal catalyzed Heck cross coupling,Hiyama cross coupling,C-H activation of oxazoles and Buchwald coupling of N-heterocycle compounds using pyrimidin-2-yl tosylates as electrophiles have been explored valuably in this thesis.The main research contents and results were as follows:1.The cross-coupling reactions of tosylates with a variety of nucleophiles were reviewed.2.Pd?PPh₃?₂Cl₂ catalyzed Heck coupling reaction of pyrimidin-2-yl tosylates with vinyl compounds has been explored.This protocol proved to be tolerant of various pyrimidin-2-yl tosylates bearing either electron-donating or electron-withdrawing groups as well as various olefins including styrene derivatives,1-hexene,1-octene,electron-rich butyl vinyl ether,electron-deficient acrylates and vinyl cyanide.38 kinds of novel C2-alkenyl pyrimidine derivatives have been synthesized with high?-regioselectivity.3.PdCl₂ catalyzed Hiyama coupling reaction of pyrimidin-2-yl tosylates with phenyltrimethoxysilane has been explored.It was found that various pyrimidin-2-yl tosylatesandaromatic aminopyrimidin-2-yltosylatescoupled with phenyltrimethoxysilane smoothly,showing excellent reactivity in the reaction.Then18 kinds of C2-aryl pyrimidine derivatives have been synthesized with relatively high yields in the presence of TBAF.4.Pd?OAc?₂ catalyzed C-H activation of oxazoles with pyrimidin-2-yl tosylates has been explored valuably.The catalytic system showed good tolerance for the functional groups of reaction substrates,so various pyrimidin-2-yl tosylates bearing either electron-donating or electron-withdrawing groups as well as a variety of benzoxazoles and aryl substituted oxadiazoles have successfully accomplished the C-H activation,which led to the series connection of bioactive pyrimidine and oxazole ring.Then 14 kinds of novel C2-aryl pyrimidine derivatives have been synthesized with excellent yields.5.Ni?dppp?Cl₂ catalyzed Buchwald coupling reaction of pyrimidin-2-yl tosylates with N-heterocycle compounds has been explored valuably.The results showed that Ni?dppp?Cl₂ exhibited a high catalytic activity in the C-N coupling.This reaction proved to be tolerant of various pyrimidin-2-yl tosylates bearing either electron-donating or electron-withdrawing groups as well as nucleophiles including indole,benzimidazole and 1,2,4-triazole.23 kinds of novel C2-aryl pyrimidine derivatives have been synthesized with good yields.Above-mentioned products were confirmed by ¹H NMR?¹³C NMR and HRMS.