膦催化的吡咯烷-螺吲哚酮类化合物的合成
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摘要
小分子膦催化环化反应是构建五/六元碳(杂)环的重要有机合成方法之一。醛亚胺由于其较高的反应活性,在膦催化的有机反应中得到了广泛的关注,然而酮亚胺在反应中的应用却鲜有报道,因此研究了三苯基膦催化联烯酸酯与酮亚胺的[3+2]环化反应。试验通过对反应催化剂、溶剂、温度及催化剂用量的考察,对反应条件进行了优化。结果表明,以四氢呋喃为反应溶剂,三苯基膦为催化剂,在室温条件下反应0.5 h,可获得较高的化学收率。该方法可用于一系列吲哚骨架的吡咯烷-螺吲哚酮类化合物的合成制备。
The phoshpine catalyzed organic synthesis has become one of the most efficient and direct methods for the synthesis of five and six member ring systems. The aldimine has been widely adopted in the phosphine catalysis because of the highly reactive activity. However, the application of ketimine is still rarely reported. This paper studied the triphenylphosphine(PPh_3) catalyzed [3+2] cyclization between allenoate and ketimine. The best reaction conditions were achieved through a series of optimization of reaction catalysts, solvents, temperatures as well as the catalyst loadings. The high chemical yield was obtained with 0.1 eq PPh_3 as catalyst and THF as solvent when the reaction was performed at room temperature for 0.5 h. The developed methodology can be applicable to the synthesis and preparation of a series of 3,2'-pyrrolidinyl spirooxindoles.
The phoshpine catalyzed organic synthesis has become one of the most efficient and direct methods for the synthesis of five and six member ring systems. The aldimine has been widely adopted in the phosphine catalysis because of the highly reactive activity. However, the application of ketimine is still rarely reported. This paper studied the triphenylphosphine(PPh_3) catalyzed [3+2] cyclization between allenoate and ketimine. The best reaction conditions were achieved through a series of optimization of reaction catalysts, solvents, temperatures as well as the catalyst loadings. The high chemical yield was obtained with 0.1 eq PPh_3 as catalyst and THF as solvent when the reaction was performed at room temperature for 0.5 h. The developed methodology can be applicable to the synthesis and preparation of a series of 3,2'-pyrrolidinyl spirooxindoles.
引文
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[2] GUO H,FAN Y C,SUN Z,et al.Phosphine organocatalysis[J].Chemical Reviews,2018,118(20):10049.
[3] NI H Z,CHAN W L,LU Y X.Phosphine-catalyzed asymmetric oganic reactions[J].Chemical Reviews,2018,118(18):9344.
[4] ZHAO Q Y,HAN X Y,YIN W,et al.Asymmetric [3+2] annulation of allenes with maleimides catalyzed by dipeptide-derived phosphines:facile creation of functionalized bicyclic cyclopentenes containing two tertiary stereogenic centers[J].Chemical Communication,2012,48(7):970.
[5] MA S S,YU A M,MENG X T.Phosphine-catalyzed [4+2] annulation of γ-benzyl allenoates:facile synthesis of benzothieno[3,2-b]pyran derivatives[J].Organic and Biomolecular Chemistry,2018,16(16):2885.
[6] MAO B M,SHI W Y,LIAO J N,et al.Phosphine-catalyzed [4+2] annulation of allenoate with sulfamate-derived cyclic imines:a reaction mode involving γ'-carbon of α-substituted allenoate[J].Organic Letters,2017,19(23):6340.
[7] QIN Z F,LIU W,WANG D Y,et al.Phosphine-catalyzed [4+1] annulation of o-hydroxyphenyl and o-aminophenyl ketones with allylic carbonates:syntheses and transformations of 3-hydroxy-2,3-disubstituted dihydrobenzofurans and indolines[J].The Journal of Organic Chemistry,2016,81(11):4690.
[8] HAN X Y,YAO W J,WANG T L,et al.Asymmetric synthesis of spiropyrazolones through phosphine-catalyzed [4+1] annulation[J].Angewandte Chemie (International ed.in English),2014,53(22):5643.
[9] GHOSH A K,ChAPSAL B D,MITSUYA H.Design of HIV protease inhibitors targeting protein backbone:an effective strategy for combating drug resistance[J].Accounts of Chemical Research,2008,41(1):78.
[10] SHINTANI R,HAYASHI S Y,MURAKAMI M,et al.Stereoselective synthesis of spirooxindoles by palladium-catalyzed decarboxylative cyclization of γ-methy-lidene-δ-valerolactones with Isatins[J].Organic Letters,2009,11(16):3754.
[11] YU B,LIU H.Spirooxindoles:prominsing scaffoleds for anticancer agnets[J].European Journal of Medicinal Chemistry,2015,97(32):673.
[12] CUI C B,KAKEYA H,OSADA H.Novel mammalian cell cycle inhibitors,spirotryprostatins A and B,produced by Aspergillus fumigatus,which inhibit mammalian cell cycle at G2/M phase[J].Tetrahedron,1996,52(39):12651.
[13] MATHUSALINI S,ARASAKUMAR T,LAKSHMI K,et al.Synthesis and biological evaluation of new spirooxindoles with embedded pharmacophores[J].New Journal of Chemsitry,2016,40(6):5164.
[14] MA Y,FAN C,JIA B,et al.Total synthesis and biological evaluation of spirotryprostatin A analogs[J].Chirality,2017,29(11):737.
[15] YAN W J,WANG D,FENG J C,et al.Synthesis of N-alkoxycarbonyl ketimines derived from isatins and their application in enantioselective synthesis of 3-aminooxindoles[J].Organic Letters,2012,14(10):2512.
[16] LANG R W,HANSEN H.α-Allenic esters from α-phosphoranylidene esters and acid chlorides:ethyl 2,3-pentadienoate[J].Organic Synthesis,1984,62:202.