Ferric Chloride-promoted Cyclization Of Alkynes

Five(six)-membered carbocyclic and heterocyclic compounds exist widely in numerous natural products and organic molecules. Thus developing more efficient, regioselective, environment-benign, atom-economic and easy-to-handle procedures for the synthesis of this class of compounds is an important goal of organic chemistry. Cyclization of alkynes catalyzed by metal-catalysts is a useful method for the synthesis of carbocyclic and heterocyclic compounds. Based on our previous achievements on iron-catalyzed cyclization, we want to extend the utility of iron-catalyst in the preparation of cyclic products. Hence this dissertation focuses on the cyclization of alkynes with some readily available starting materials catalyzed by iron chloride for the synthesis of substituted benzenes, naphthalenes and phenanthrenes, indenes and isocoumarins. We also have developed some strategies for tuning the selectivity of these reactions. This dissertation can be divided into four parts.Firstly, we explored for the first time the extraordinary effect of FeCl3 on the catalytic activity of rare-earth catalysts. We succeeded in cyclotrimerization of terminal alkynes which cannot be achieved by either trivalent iron or trivalent lanthanide catalysts. Both aromatic and aliphatic terminal alkynes are compatible with this catalytic system giving satisfactory yields. We proposed reasonable reaction mechanism for this reaction and tried to confirm it. The present work opens the way toward new developments in organic synthesis achieved through synergetic effect of cheap organolanthanide and iron catalysts.Secondly, we investigated FeCl3-promoted annulation reaction of aryl acetaldehydes with alkynes. This method provides a new, versatile and straightforward procedure for the regioselective synthesis of mono-, di-and polysubstituted naphthalenes and phenanthrenes under mild conditions. The present catalytic system shows unprecedented complete Me3SiOH elimination selectivity for silyl alkyne substrates. Stoichiometric amount of FeCl3 is needed to obtain satisfactory yield. This probably due to the loss of catalytic activity of FeCl3 caused by the coordination of H2O generated during the reaction. This reaction can be conducted under catalytic FeCl3 with the addition of catalytic amount anhydrous YCl3 as dehydrating reagent.Thirdly, we discovered FeCl3-6H2O-catalyzed cascade electrophilic addition/cyclization of benzylic alochols with alkynes for the synthesis of substituted indenes. Moreover,6-substituted indenes could be obtained via Friedel-Crafts reaction of indenes with an extra molecule of benzylic alcohols. Thus this reaction is atom-economic and environment-begin because alcohols are readily available and only water is generated during the reaction. Furthermore, we also investigated the reaction of Morita-Baylis-Hillman adducts with alkynes catalyzed by FeCl3·6H2O. Unexpectedly,1,5-dicarbonyl compound was obtained which maybe resulting from the hydrolysis of vinylic carbocation intermediate. This dicarbonyl compound can be transformed to substituted pyridine under NH4OAc/AcOH condition. The structure of the product was further confirmed by X-ray single diffraction analysis.Lastly, we investigated the electrophilic addition/cyclization of benzylic alcohols with o-(Alk-1-ynyl)benzoates for the synthesis of substituted isocoumarins. Byproduct can be generated when the activity of alcohols decreased. Besides benzylic alcohols, allylic alcohol could also be applied as pre-electrophile. The structure of some products was further confirmed by X-ray single diffraction analysis.