Synthesis Of Difluoromethylated Enynes And Selective Borylation Of 2-Trifluoromethyl-1,3-enynes

Difluoromethyl and trifluoromethly groups are important fluorinated moieties in agrochemicals and pharmaceuticals.Difluoromethyl acts as a bioisostere of hydroxy or thiol groups as well as a lipophilic hydrogen donor.The introduction of trifluoromethly and difluoromethyl groups to pharmaceutical molecules can increase lipophilicity and metabolic stability.Both difluoromethyl enynes and fluorine-containing organoboronate esters are useful fluorinated blocks,which can be transformed to a variety of organic molecules.1,3-Enynes are important structural units found in natural products and pharmaceuticals,and often used to transformed to other functional groups in multifunctional moleculars and materials sciences.In this dissertation,we have studied the reaction of ?-(trifluoromethyl)styrenes with terminal alkynes with the assistance of NaOtBu and developed the selective borylation of 2-trifluoromethy 1-1,3-enyne.1 Difluoromethyl group is widely found in pharmaceutical and pesticide molecules.With the assistance of NaOtBu,terminal alkynes reacted with the a-(trifluoromethyl)styrenes to give 3-alkynylated 1,1-difluoro-l-alkenes via SN2'path.The 3-alkynylated 1,1-difluoro-l-alkenes are unstable in this reaction and takes place double bond migration of the olefinic bond via a[1,3]hydrogen shift to give the more stable difluoromethylated 1,3-enynes.In the presence of Lewis acid ZrCl4,isomerization(E?Z)of(E/Z)-difluoromethyl-1,3-enyne was developed.The compounds A3ba and A3da displayed complete inhibition of P.aeruginosa at 1 mg/mL.2 Trifluoromethyl-containing pharmaceutical molecules display good membrane permeability and increased bioavailability than non-trifluoromethyl analogues because of a change in their solubility and lipophilicity.Organoboron derivatives are an important class of compounds in organic synthesis due to their high stability,great synthetic utility and low toxicity.Selective borylation of 2-trifluoromethyl-1,3-enynes with B2pin2 was realized in the presence of Cu(OAc)/Xantphos/NaO/tBu.Through the addition of B2pin2 to double bond,the borylated compounds bearing trifluoromethyl and alkynyl groups was obtained.N-methyl-iminodiacetic acid(MIDA)boronates are air-stable and fully compatible with gel chromatography,therefore we used compound B3a as an example to convert Bpin group to BMIDA.