| Furans and pyrans constitute an important group of oxygen heterocycles which are extensively found in natural and synthetic products with many biological properties,such as antiviral,antibacterial,and anti-inflammatory and have many applications in pharmacology,catalysis,and materials science including used as dyes or fluorescent materials.This thesis reviews the development methodologies of furan and pyran scaffold,and then develops a novel and efficient methodology for the construction of functionalized five-/six-membered oxa-heterocycles via cascade 1,4-conjugate addition/intramolecular cyclization of propargylamines with 2-hydroxynaphthalene-1,4-diones or2-aminonaphthalene-1,4-diones.The detailed research described as follows:（1）A sodium salt-controllable cascade 1,4-conjugate addition/intramolecular cyclization of propargylamines with cyclohexane-1,3-diones for regioselective synthesis of9-arylacetyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones and 6,7-dihydrobenzofuran-4（5H）-ones.The procedure is proposed to go through a sequence of 1,4-conjugate addition of cyclohexane-1,3-diones to o-alkynyl quinone methides（o-AQMs）in situ generated from propargylamines,intramolecular nucleophilic addition and 5-exo-dig annulation process,and then sodium salt-controllable regioselective C-O cleavage followed by 1,3-H shift and isomerization to afford the 9-arylacetyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones by using Na2CO3（50 mol%）as base while 6,7-dihydrobenzofuran-4（5H）-ones by using NaHCO3（25 mol%）as base.Furthermore,the propargylamines bearing with various electron-donatingand/orelectron-withdrawinggroupsreactedwith cyclohexane-1,3-diones smoothly,affording benzopyrans in good yields（60-83%）and6,7-dihydrobenzofuran-4（5H）-ones in 67-79%yields.In addition,the late-stage transformation of the obtained 9-arylacetyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones,and various alkyl hydrazones derived from carbonyl group on phenylacetyl group were obtained in good yields.Notably,the gram-scale synthesis,with benefits such as undiminished product yield,illustrated the practicality of this method.A possible mechanism was proposed based on the control experiments and deuterated experiment.（2）Anovelandversatileapproachtoconstruct12-phenacyl-11H-benzo[b]xanthene-6,11（12H）-dione derivatives through Lewis acid-catalyzed cascade reaction of propargylamines with 2-hydroxynaphthalene-1,4-diones has been developed.The procedure is proposed to go through a sequence of 1,4-conjugate addition,intramolecular nucleophilic addition/dehydration,and hydrolysis of alkyne followed by an enol-ketone tautomerization.Under the optimal conditions,various2-hydroxynaphthalene-1,4-diones reacted smoothly with various propargylamines that had either electron-donating or electron-withdrawing groups and gave the corresponding products in good to excellent yields（70-88%）.In addition,propargylamine bearing a bulky tert-butyl group at the ortho-and para-position to the hydroxy group was also tolerated in the reaction to give the corresponding product 3ya in 82%yield.Notably,aklynyl groups bearing an extendedπstructure and heteroaryl moieties afforded the desired products 3za and 3a′a in 73%and 71%yields,respectively.The scalability of this catalysis was also evaluated by conducting a gram-scale reaction（1.15 g scale;3na was obtained in 70%yield）.A possible mechanism was proposed based on the control experiments and deuterated experiment.（3）A simple,general route to the functionalized benzofurans,starting from propargylamines and with 2-aminonaphthalene-1,4-dione and benzo[a]phenazin-5-ol,has been developed.This reaction involved an in situ generated o-alkynyl quinone methides（o-AQMs）intermediate followed by intramolecular 5-exo-dig annulation of hydroxy to alkynyl group to construction of functionalized benzofurans with good functional group tolerance and a range of substrate scope.In addition,propargylamine bearing a bulky tert-butyl group at the ortho-and para-position to the hydroxy group as well as 3-thienyl were also tolerated in the reaction to give the corresponding products in 80%,73%,and51%yield,respectively.Notably,aploycyclic benzo[g]benzofuro[2,3-c]quinoline-8,13-diones were able to be obtained via an intramolecular cyclization of 2-amino-3-（2-benzylbenzofuran-3-yl）naphthalene-1,4-diones in the presence of potassium tert-butoxide under oxygen atmosphere.Meanwhile,the2-（2-benzylbenzo[a]furo[2,3-c]phenazin-1-yl）phenol were also obtained from6-（2-benzylbenzofuran-3-yl）benzo[a]phenazin-5-ols in the similar conditions.Overall,this reaction features easily operation,readily available substrates,good functional group tolerance,and easily transformation,and provides a new strategy for construction functionalized benzofurans. |
