Synthesis Of Trifluoromethyl-substituted Conjugated Enyne

Enyne compounds are not only important in organic synthesis of raw materials and intermediates, but also are important building blocks for anti-cancer drugs, antibiotics and natural products. Enyne-containing natural compounds are one of the strongest antibacterial active compounds of known anti-cancer compounds. Conjugated enyne is the major structural units of many natural products and drugs with the physiological activity, such as the anticancer and antibiotics Calicheamycin and the natural drug Terbinafine. Due to the reactivity diversity of double and triple bonds, conjugated enyne is very useful in organic synthesis of compounds and plays an important role in organic synthesis. Thus, conjugated compounds have been an important part in finding new synthetic method in synthetic organic chemistry. Fluorine is a special element. Fluorine-containing especially trifluoromethyl-containing compounds play an important role in pesticides and other agricultural chemicals which makes it one of the hottest researching field in fluorine-containing compounds. In this thesis, the reaction of tributyl (3,3,3-trifluoropropynyl) stannane with different terminal alkynes and aryl iodides catalyzed by palladium and copper were investigated for construction of trifluoromethyl-substituted conjugated enyne at mild condition. Also their application in organic synthesis was studied in detail.This thesis contains the following aspects:(1) The dimerization reaction of the terminal alkynes to conjugated enyne was reviewed based on the difference of the catalysts. Several types of cross-coupling reaction and their respective research were reviewed, especially for Stille cross-coupling reaction with a more detailed explanation, and the speciality of fluorine chemistry was introduced briefly.(2) Seven different trifluoromethyl substituted conjugated enynes were synthesized via carbstanylation reaction of tributyl (3,3,3trifluoropropynyl) stannane and the terminal alkyne. All the structures were analyzed by1H NMR,19F NMR,13C NMR,119Sn NMR, MS, IR and elemental analysis.(3) The cross-coupling of tributyl (3,3,3-trifluoropropynyl) stannane and aromatic iodides and carbstanylation reaction catalyzed by palladium and tritertialtutylphosphine gives trifluoromethyl-containing vinylstannanes via an one-pot two steps reactions. All the structures were analyzed by’H NMR,19F NMR,13C NMR,119Sn NMR, MS, IR and elemental analysis. We also studied the one-pot two steps reaction in detail from reaction conditions and its mechanism step by step separately. First, we tried the reaction of2eq of tributyl (3,3,3-trifluoropropynyl) stannane and1eq of aromatic iodides catalyzed by Pd2(dba)3without the phosphine, and it resulted the stille cross-coupling product exclusively. Without separation of the stille cross-coupling product, tritertialtutylphosphine was added further, after the corresponding reaction time, it resulted the carbstanylation product of trifluoromethyl-containing vinylstannane.At last, the one-pot two-steps reaction mechanism is also studied in detail.