Studies On The Cyclization Reactions Of N-(Buta-2,3-dienyl)Amides

Functionalized allenes bearing a nucleophilic group may be cyclized upon treatment with a wide variety of transition metal catalysts and electrophilic reagents. Now this methology has been regarded as an efficient way to form various heterocycles and carbocycles. Previously, Dr. Chen in our group reported the palladium-catalyzed coupling-cyclization reaction of N-(buta-2,3-dienyl)amides in the presence of organic halides furnishing oxazoline derivatives facilely. On this basis, this thesis has been focused on1,2-induction of the coupling-cyclizaiton reaction of N-(buta-2,3-dienyl)amides and developed a new synthetic method to oxazoline derivatives via the electrophilic cyclization of N-(buta-2,3-dienyl)amides.Firstly, the electrophilic cyclization of N-(buta-2,3-dienyl)amides was studied. Treatment of N-(buta-2,3-dienyl)amides with N-bromosuccinimide afforded a series of a-halovinyl oxazolines in moderate to good yields. The reaction was also extended to the synthesis of the bisoxazoline via bromocyclization of N1, N3-bis(buta-2,3-dienyl)isophthalamide with2.4equivalents of NBS. In addition, the obtained2,5-disubstituted oxazolines could be conveniently converted into synthetically useful building blocks such as ethynyl oxazolines, which could be achieved when the products were treated with TBAF·3H2O for the elimination of HBr. And the copper-catalyzed C-N coupling reaction of oxazolines with indole furnished structurally complex hererocycles.Secondly,1,2-induction of the Pd-catalyzed coupling-cyclizaiton reaction of N-(buta-2,3-dienyl)amides was studied. Different substituents were introduced to the a-position of N-(buta-2,3-dienyl)amides for the coupling-cyclization reaction with organic iodides catalyzed by palladium and high trans-diastereoselectivity was observed. As usual, the diastereoselectivity increased with the increase of subsituent size. Optically active (S)-N-(buta-2,3-dienyl)amides were also prepared and applied to the coupling-cyclization reaction, providing a convenient access to optically active oxazoline derivatives with excellent1,2-induction and complete retention of enantiopurity.