螺[3.4]辛-6-酮的合成研究
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摘要
在二聚醋酸铑的催化作用下,5-环丁基-2-重氮-3-氧代戊酸甲酯经C-H插入反应得到6-氧代螺[3.4]辛烷-5-羧酸甲酯,再在酸性条件下经脱羧反应得到目标化合物螺[3.4]辛-6-酮;通过~1HNMR和ESI-MS对中间体及目标化合物的结构进行了确证,并对合成工艺进行了考察。确定C-H插入反应的最佳条件如下:二聚醋酸铑与5-环丁基-2-重氮-3-氧代戊酸甲酯物质的量比为0.05∶1、反应溶剂为二氯甲烷、反应温度为25℃、反应时间为2 h;脱羧反应的最佳条件如下:反应温度为70℃、反应时间为8 h。在上述条件下,反应总收率达到60.6%。该方法操作简单、收率高,为螺[3.4]辛-6-酮衍生物的合成提供了一种简便有效的途径。
Using dirhodium tetraacetate as a catalyst,we synthesized spiro[3.4]octan-6-one by a two-step reaction,which involves the C-H insertion reaction from methyl 5-cyclobutyl-2-diazo-3-oxopentanoate to obtain methyl 6-oxospiro[3.4]octane-5-carboxylate and the decarboxylic reaction of methyl 6-oxospiro[3.4]octane-5-carboxylate in the acid condition.Moreover,we characterized the structure of the intermediates and target compound by ~1HNMR and ESI-MS,and investigated the synthesis process.The results show that the optimal C-H insertion reaction conditions are determined as follows:the molar ratio of dirhodium tetraacetate to methyl 5-cyclobutyl-2-diazo-3-oxopentanoate is 0.05∶1,the solvent is dichloromethane,the reaction temperature is 25 ℃,and the reaction time is 2 h;the decarboxylic reaction conditions are determined as follows:the reaction temperature is 70 ℃,and the reaction time is 8 h.Under above conditions,the total yield of spiro[3.4]octan-6-one reaches 60.6%.The method has the advantages of simple operation and high yield,which provides a simple and effective way for the synthesis of spiro[3.4]octan-6-one derivative.
Using dirhodium tetraacetate as a catalyst,we synthesized spiro[3.4]octan-6-one by a two-step reaction,which involves the C-H insertion reaction from methyl 5-cyclobutyl-2-diazo-3-oxopentanoate to obtain methyl 6-oxospiro[3.4]octane-5-carboxylate and the decarboxylic reaction of methyl 6-oxospiro[3.4]octane-5-carboxylate in the acid condition.Moreover,we characterized the structure of the intermediates and target compound by ~1HNMR and ESI-MS,and investigated the synthesis process.The results show that the optimal C-H insertion reaction conditions are determined as follows:the molar ratio of dirhodium tetraacetate to methyl 5-cyclobutyl-2-diazo-3-oxopentanoate is 0.05∶1,the solvent is dichloromethane,the reaction temperature is 25 ℃,and the reaction time is 2 h;the decarboxylic reaction conditions are determined as follows:the reaction temperature is 70 ℃,and the reaction time is 8 h.Under above conditions,the total yield of spiro[3.4]octan-6-one reaches 60.6%.The method has the advantages of simple operation and high yield,which provides a simple and effective way for the synthesis of spiro[3.4]octan-6-one derivative.
引文
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[11] 刘斌,张方成,高苗苗,等.5-环丁基-2-重氮-3-氧代戊酸甲酯的合成[J].广东药科大学学报,2018,34(6):47-51.LIU B,ZHANG F C,GAO M M,et al.Synthesis of methyl 5-cyclobutyl-2-diazo-3-oxopentanoate[J].Journal of Guangdong Pharmaceutical University,2018,34(6):47-51.
[2] AHMAD K,CHANG C R,LI J.Mechanistic investigations of Co(Ⅱ)-catalyzed C-N coupling reactions[J].Journal of Organometallic Chemistry,2018,868:144-153.
[3] 廖进喜,刘慧,孙建松.过渡金属催化的偶联反应在合成C-糖苷中的应用[J].有机化学,2017,37(6):1382-1391.LIAO J X,LIU H,SUN J S.Applications of transition metal catalyzed coupling reactions in the synthesis of C-glycosides[J].Chinese Journal of Organic Chemistry,2017,37(6):1382-1391.
[4] 张珍辉.铑(Ⅲ)-催化吲哚导向卡宾体插入芳基C-H键/环化反应研究[D].广州:华南理工大学,2017.ZHANG Z H.Rhouidm(Ⅲ)-catalyzed indole-directed carbenoid aryl C-H insertion/cyclization:access to 1,2-benzocarbazoles[D].Guangzhou:South China University of Technology,2017.
[5] ADLY F G,GARDINER M G,GHANEM A.Design and synthesis of novel chiral dirhodium(Ⅱ) carboxylate complexes for asymmetric cyclopropanation reactions[J].Chemistry,2016,22(10):3447-3461.
[6] ZHU D X,CHEN W W,XU M H.Rhodium-catalyzed asymmetric intramolecular addition of arylboronic acids to ketones:catalytic enantioselective access to 3-hydroxy-2,3-dihydrobenzofurans bearing a tetrasubstituted carbon stereocenter[J].Tetrahedron,2016,72(21):2637-2642.
[7] ROBERTO P,BENEDETTO N,BAHMAN M S,et al.The reaction of α-diazo-β-hydroxy esters with boron trifluoride etherate:generation and rearrangement of destabilized vinyl cations.a detailed experimental and theoretical study[J].Journal of the American Chemical Society,2009,118(1):1-12.
[8] TABER D F,JOSHI P V.Cyclopentane construction by Rh-catalyzed intramolecular C-H insertion:relative reactivity of a range of catalysts[J].Journal of Organic Chemistry,2004,69(12):4276-4278.
[9] GIANOTTI M,ANDREOTTI D,CASOTTO D,et al.Asymmetric route to spirotetracyclic(1S)-5′,11′-dihydro-3H-spiro[cyclopentane-1,10′-dibenzo[a,d]cyclohepten]-3-one derivatives[J].Tetrahedron Letters,2011,52(2):329-331.
[10] 方芙容,李雪枫,陈小宇,等.5,5-二甲基-2-氧代环戊烷羧酸甲酯的合成[J].精细与专用化学品,2018,26(10):15-18.FANG F R,LI X F,CHEN X Y,et al.Synthesis of methyl 5,5-dimethyl-2-oxocyclopentanecarboxylate[J].Fine and Specialty Chemicals,2018,26(10):15-18.
[11] 刘斌,张方成,高苗苗,等.5-环丁基-2-重氮-3-氧代戊酸甲酯的合成[J].广东药科大学学报,2018,34(6):47-51.LIU B,ZHANG F C,GAO M M,et al.Synthesis of methyl 5-cyclobutyl-2-diazo-3-oxopentanoate[J].Journal of Guangdong Pharmaceutical University,2018,34(6):47-51.