Asymmetric Cascade Cyclization Reactions Triggered By Gold-Catalyzed Functionalization Of Alkynes

Heterocyclic structural skeletons are prevalent in biologically active natural products, Pharmaceuticals, organic materials and numerous functional molecules. Therefore, the development of new synthetic methods to directly access heterocycles is of greatly synthetic importance. Cascade or domino reactions, because they are able to build up structurally complex molecules from relatively simpler substrates, have received increasing attention. In recent years, the gold catalysis has allowed a variety of cascade reactions, some of which were capable of efficiently accessing structurally complex heterocycles. Most importantly, the gold complexes, as strong π-Lewis acids, are able to catalyze the addition of nucleophiles to carbon-carbon triple bond very efficiently and have drawn more attention.The1,3-butadiene derivatives, generated from the cycloisomerization of enyne alcohols catalyzed by an appropriate gold complex, was able to participate in either the Diels-Alder reaction as dienes or the inverse-electron-demand hetero-Diels-Alder reaction as dieneophiles. The oxa-bridged [2,2,2] multiply cyclic compounds, which would be difficult to be accessed by a traditional transformation, have been obtained by the cascade cycloisomerization-Diels-Alder reaction in one-pot. In addition, the dihydropyrano-y-lactone derivatives could be accessed by the cycloisomerization-hetero-Diels-Alder reaction. Besides, the asymmetric synthesis of dihydropyrano-y-lactone derivatives was achieved with high enantioselectivity by using copper complex in combination with the gold complex.We have established a chiral gold (I) complex-catalyzed enantioselective cycloisomerization-amination csacde of2-(alkynyl)phenyl boronic acids with diazenes, leading to a family of unprecedented chiral molecules, heteroaryl atropisomers involving B-O bond. The atropisomers were obtained in up to89%yield and up to91%ee by using (R)-BINAP(AuNTf2)2as catalyst generated in situ from (R)-BINAP(AuCl)2and AgNTf2. The protocol tolerated a wide scope of substrates bearing various functional groups and the chirality of such atropisomers is relatively stable at room temperature.The structure was determined by X-ray diffraction and the configuration of the novel chiral C-N axis was tentatively assigned by vibrational circular dichroism (VCD) calculation.