Green Strategies For Construction Of Heterocyclic Frameworks From Alkynes

The most suitable type of organic reaction for connecting scientific studies to industrial manufacture should be in line with four principles:(i)starting with simple,inexpensive and easy-to-get molecules;(ii)proceeding under mild,safe and expandable conditions;(iii)having atom-economy and step-economy;and(iv)obtaining valuable products.These type of organic reactions are also the ultimate aim of synthetic chemists.As we know,alkynyl group is a special and important carbon-carbon bond,which can be found in a large number of natural products and bioactive molecules.The coupling reaction of alkynes can easily introduce unsaturated bonds and other functional groups into the target molecules,therefore,they have become basic raw materials of many organic synthesis routes.On the other hand,heterocyclic scaffolds are widely existed in many synthetic drug or material molecules such as pharmaceuticals,pesticides,dyes,plastics,paints,cosmetics and organic light-emitting diodes.Based on the two points above,it is valuable to develop the construction of heterocyclic compounds by using alkynes as synthesis.The two keys of this study are: i)to hunt for simple and easy-to-obtain alkynes and ii)to develop high-efficiency and green transformation paths.In this context,we focused our work on new green synthetic strategies.We have mainly utilized internal alkynes,ene-yne-ketones and calcium carbides as substrates to synthesize pyrones,pyridones,furans and pyrazoles via C-C,C-O,C-N and C-P bonds formation.A series of new results will be presented in the following five chapters:In chapter two,we have researched palladium-catalyzed oxidative annulations of internal alkynes and acrylic acid or amide that afford ?-pyrones and pyridones in good to excellent yields with high regioselectivity.The usage of O2(1 atm)as a stoichiometric oxidant with H2 O as the only byproduct under mild conditions makes this process more attractive and practical.In chapter three,we have reported an efficient and highly regioselective strategy for the synthesis of various phosphorylated furans via Cu-catalyzed Csp3-P or base promoted Csp2-P bond construction between ene-yne-ketones and H-phosphonates.A copper carbene generation or a Michael addition is proposed as the key step in these two processes,which is supported by carbine capture reactions and interval 31 P NMR experiments.Furthermore,no use of oxidant,high atom economy,and good regioselectivity of products via catalyst-controlled make this method a new valuable approach for the formation of precious C-P bonds.In chapter four,we have developed a Michael-addition/cyclization procedure between ene-yne-ketones and TMSCN under metal-free conditions.A wide range of cyanofurans were delivered in high yields,which could be further transformed to a series of furo-furanimines,furo-pyridazines or carboxamido-furans.In addition,deuteriumlabeling experiments have been conducted to clarify the reaction pathway.In chapter five,we have reported an efficient and highly regioselective strategy for the synthesis of 3-substituted or 3,4-disubstituted pyrazoles via transition-metal-free [3+2] cycloaddition/[1,5]-sigmatropic rearrangements.In this process,calcium carbide was used as the acetylide source to perform with N-tosylhydrazones derived from aldehydes or ketones.In addition,the available starting material(Ca C2),the superbasic catalytic conditions(Cs2CO3/DMSO),and the valuable reaction products make this protocol attractive for both academia and industry.In chapter six,we present a convenient one-pot/two-step procedure for transition metal-free coupling between calcium carbide and N-tosylhydrazones generated in situ from cyclic ketones,affording saturated spirocyclic pyrazoles via [3+2] cycloadditions.In certain cases,the spirocyclic pyrazoles could undergo a ring expansion to give the fused analogues,in which process calcium carbide was used as a one-carbon unit.In addition,deuterium-labeling experiments have been conducted to clarify the reaction pathway that multiple [1,5]-sigmatropic rearrangements were involved in the transformation.