麦克尔/环化串联反应高效合成多官能团的3,4-二氢-2H-硫吡喃[2,3-b]喹啉
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摘要
为了高效合成具有喹啉并硫吡喃骨架的化合物,以新型底物2-异硫氰酸酯肉桂醛为起始原料,经过一个分子内森田-贝利斯-希尔曼反应,高收率地得到了2-巯基-3-喹啉甲醛,2-巯基-3-喹啉甲醛能与缺电子烯烃发生麦克尔/环化串联反应.结果表明,森田-贝利斯-希尔曼反应能高收率且高选择性地合成喹啉并硫吡喃衍生物.该方法具有条件温和、收率高、非对映选择性好等特点.
In order to efficiently synthesize a compound having a quinoline thiopyran structure, the novel substrate 2-isothiocyanate cinnamaldehyde was used as the starting material, and a 2-indolyl-3-quinolinaldehyde was obtained in a high yield after a molecular Morita-Bellis-Hilman reaction. 2-mercapto-3-quinolinecarboxaldehyde underwent a Michael/cyclization series reaction with an electron-deficient olefin, and a series of quinoline thiopyran derivatives was obtained with high yield and high selectivity. The method had the characteristics of mild conditions, high yield and good diastereoselectivity.
In order to efficiently synthesize a compound having a quinoline thiopyran structure, the novel substrate 2-isothiocyanate cinnamaldehyde was used as the starting material, and a 2-indolyl-3-quinolinaldehyde was obtained in a high yield after a molecular Morita-Bellis-Hilman reaction. 2-mercapto-3-quinolinecarboxaldehyde underwent a Michael/cyclization series reaction with an electron-deficient olefin, and a series of quinoline thiopyran derivatives was obtained with high yield and high selectivity. The method had the characteristics of mild conditions, high yield and good diastereoselectivity.
引文
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[2]YEBOAH E M O,YEBOAH S O,SINGH G S.Recent applications of cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis[J].Tetrahedron,2011,67(10):1725-1762.
[3]MULCHIN B J,NEWTON C G,BATY J W,et al.The anti-cancer,anti-inflammatory and tuberculostatic activities of a series of 6,7-substituted-5,8-quinolinequinones[J].Bioorg Med Chem,2010,18(9):3238-3251.
[4]KIDWAI M,BHUSHAN K R,SAPRA P,et al.Alumina-supported synthesis of antibacterial quinolines using microwaves[J].Bioorg Med Chem,2000,8(1):69-72.
[5]QUAGLIA W,PIGINI M,PIERGENTILI A,et al.Structure-activity relationships in 1,4-benzodioxan-related compounds.7.Selectivity of 4-phenylchroman analogues for α1-adrenoreceptor subtypes[J].J Med Chem,2002,45(8):1633-1643.
[6]VANVLIET L A,RODENHUIS N,DIJKSTRA D,et al.Synthesis and pharmacological evaluation of thiopyran analogues of the dopamine D3 receptor-selective agonist(4aR,10bR)-(+)-trans-3,4,4a,10b-tetrahydro-4-n-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol(PD 128907)[J].J Med Chem,2000,43(15):2871-2882.
[7]WU L,WANG Y,SONG H,et al.Synthesis of optically active 2H-thiopyrano[2,3-b]quinolines with three contiguous stereocenters via an organocatalytic asymmetric tandem Michael-Henry reaction[J].Adv Synth Catal,2013,355(6):1053-1057.
[8]ARAI T,YAMAMOTO Y.Diversity-oriented asymmetric catalysis(DOAC):Stereochemically divergent synthesis of thiochromanes using an imidazoline-aminophenol-nickel-catalyzed michael/henry reaction[J].Org Lett,2014,16(6):1700-1703.
[9]DODDA R,GOLDMAN J J,MANDAL T,et al.Synthesis of 2,3,4-trisubstituted thiochromanes using an organocatalytic enantioselective tandem michael-henry reaction[J].Adv Synth Catal,2008,350(4):537-541.
[10]PING X N,WEI P S,XIE J W,et al.Catalyst-controlled cwitch in diastereoselectivities:Enantioselective construction of functionalized 3,4-dihydro-2H-thiopyrano[2,3-b]quinolines with three contiguous stereocenters[J].J Org Chem,2017,82(4):2205-2210.
[11]谢建武,余超波,徐美兰.手性伯胺催化麦克尔/烷基化串联反应:螺靛红环丙烷衍生物的高效合成[J].浙江师范大学学报(自然科学版),2017,40(1):51-57.
[12]ZENG X M,XIE J W.Enantioselective synthesis of ring-fused spiroannulated 1,2,3-thiadiazole derivatives[J].J Org Chem,2016,81(9):3553-3559.
[13]ZHU X Q,WU J S,XIE J W.Stereoselective construction of bi-spirooxindole frameworks via a Michael addition/cyclization and an unexpected redox/oxidative coupling/cyclization[J].Tetrahedron,2016,72(50):8327-8334.
[14]WU J S,ZHANG X,XIE J W,et al.Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives[J].Org Biomol Chem,2015,13(17):4967-4975.
[15]WEI P S,WANG M X,XIE J W,et al.Synthesis of 2,3-dihydrothieno(2,3-b)quinolines and thieno(2,3-b)-quinolines via an unexpected domino aza-MBH/alkylation/aldol reaction[J].J Org Chem,2016,81(3):1216-1222.
[16]NANDESHWARAPPA B P,KUMAR D B A,NAIK H S B,et al.A fast and large-scale synthesis of 3-formyl-2-mercaptoquinolines[J].Phosphorus Sulfur Silicon Relat Elem,2006,181(9):1997-2003.