CN116675606A - Novel allene, preparation method and application thereof - Google Patents

Novel allene, preparation method and application thereof Download PDF

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CN116675606A
CN116675606A CN202310511431.3A CN202310511431A CN116675606A CN 116675606 A CN116675606 A CN 116675606A CN 202310511431 A CN202310511431 A CN 202310511431A CN 116675606 A CN116675606 A CN 116675606A
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phosphine
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黄有
赖镜雄
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Nankai University
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Nankai University
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    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
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Abstract

The invention relates to a novel allene compound, a preparation method and application thereof in construction of a medium-ring compound. The compounds contain high-activity alkenyl and electron-deficient alkenyl and can pass through [6+1] under the catalysis of trivalent phosphine]The cycloaddition reaction mode is effective in constructing a medium ring compound including a seven-membered nitrogen ring and a seven-membered carbon ring. Is the first phosphine catalyzed intermolecular [6+1] reported at present]The highest yield of cycloaddition reaction can reach 99 percent. The preparation method of the diene compound has the advantages of simple operation, easily available raw materials and reagents, and the like. The novel allene compound of the present invention has the following structure.

Description

Novel allene, preparation method and application thereof
Technical Field
The invention relates to a novel alkylene compound, a preparation method and application thereof in construction of a medium-ring compound. The compounds contain high-activity alkenyl and alkenyl, and can efficiently construct the intermediate ring compound comprising nitrogen ring and carbocycle through the reaction mode of [6+1] cycloaddition under the catalysis of trivalent phosphine. Is the first phosphine catalyzed intermolecular [6+1] cycloaddition reaction reported at present.
Background
Over the last two decades, allenes have evolved greatly in the construction of cyclic compounds under the catalysis of organophosphines. Lu in 1995 reported for the first time [3+2 ] of unsubstituted dienoic acid esters]Cyclization (Zhang, C.; lu, X.J.Org.chem.1995, 60, 2906.) opened the hot spot of research into the cyclization of dienoic acid esters under the catalysis of organophosphines. Up to now, various dienoic acid esters including unsubstituted, α -substituted, γ -substituted and the like have been developed, and various cyclization reactions for synthesizing five-and six-membered ring compounds under phosphine catalysis have been developed. In the aspect of unsubstituted diene, the cyclization mode of the synthesized five-membered ring compound which is reported at present is mainly [3+2 ]](Cowen, B.J., miller, S.J.J., am.chem.Soc.129, 10988-10989; meng, X.; huang, Y.; chen, R.org.Lett.2009, 11, 137-140; han, X.; methong, F.; wang, Y.; lu, Y.Angew.Chem., int.Ed.2012, 51, 767-770.;), while in the construction of six-membered rings, [4+2 ]]The reaction pattern of (Zhu, x. -f.; schaffner, a. -p.; li, r.c.; kwon, o.org. lett.2005,7, 2977.) was also developed. For alpha-substituted dienoic acid esters, [3+2 ] can likewise occur under phosphine catalysis](Henry，C.E.；Xu，Q.；Fan，Y.C.；Martin，T.J.；Belding，L.；Dudding，T.；Kwon，O.J.Am.Chem.Soc.2014，136，11890-11893；Liao，J.-Y.；Shao，P.-L.；Zhao，Y.J.Am.Chem.Soc.2015，137，628-631；Ni，C.；Wang，M.；Tong，X.Org.Lett.2016，18，2240-2243；Zielke，K.；Waser，M.Org.Lett.2018，20，768-771.)、[4+1](Zhang，Q.；Yang，L.；Tong，X.J.Am.Chem.Soc.2010，132，2550-2551；Ziegler，D.T.；Riesgo，L.；Ikeda，T.；Fujiwara，Y.；Fu，G.C.Angew.Chem.，Int.Ed.2014，53，13183-13187；Han，X.；Yao，W.；Wang，T.；Tan，Y.R.；Yan，Z.；Kwiatkowski，J.；Lu，Y.Angew.Chem.，Int.Ed.2014，53，5643；Kramer，S.；Fu，G.C.J.Am.Chem.Soc.2015，137，3803；Cao，Z.-H.；Wang，Y.-H.；Kalita，S.J.；Schneider，U.；Huang，Y.-Y.Angew.Chem.，Int.Ed.2020，59，1884-1890.)、[4+2](Tran，Y.S.；Kwon，O.J.Am.Chem.Soc.2007，129，12632-12633；Zhong，F.；Han，X.；Wang，Y.；Lu，Y.Chem.Sci.2012，3，1231；Chen，X.Y.；Ye，S.Eur.J.Org.Chem.2012，2012，5723；Wang，C.；Gao，Z.-Z.；Zhou，L.-J.；Yuan，C.-H.；Sun，Z.-H.；Xiao，Y.-M.；Guo，H.-C.Org.Lett.2016，18，3418-3421.)、[3+3](Guo, H.; xu, Q.; kwon, O.J.am.chem.Soc.2009, 131, 6318-6319; hu, J.; dong, W.; wu, X.; Y.; tong, X.org.Lett.2012, 14, 5530; ni, C.J.; tong, X.F.J.am.chem.Soc.2016, 138, 7872-7875; wang, Y.; zhao, Z.; kalita, S.J.; huang, Y.; Y.org.Lett.2021, 23, 8147.) and the like. Similarly, for gamma-substituted dienoic acid esters, it is possible not only to pass through the conventional [3+2 ]](Xu，S.；Zhou，L.；Ma，R.；Song，H.；He，Z.Chem.-Eur.J.2009，15，8698-8702；Szeto，J.；Sriramurthy，V.；Kwon，O.Org.Lett.2011，13，5420-5423；Dakas，P.-Y.；Parga，J.A.；S.；/>H.R.；Sterneckert，J.；Kumar，K.；Waldmann，H.Angew.Chem.，Int.Ed.2013，52，9576-9581.)、[4+2](Li, E.; huang, Y.; liang, L.; xie, P.org.Lett.2013, 15, 3138-3141; gicqul, M.; gomez, C.; retailleau, P.; voituriliez, A.; marinetti, A.org.Lett.2013, 15, 4002-4005.) cyclization process creates five-and six-membered ring compounds that can be further created by a continuous cyclization process (Li, N.; jia, P.H.; huang, Y.chem. Commun.2019, 55, 10976-10979; feng, J.X.; huang, Y.chem. Commun.2019, 55, 14011-14014; feng, J.X.; chen, Y.Y.Qin. W.433, Y.433, and so forth). But howeverThroughout the development of phosphane-catalyzed allene chemistry, only a few pass through [4+3 ]](Kumar，K.；Kapoor，R.；Kapur，A.；Ishar，M.P.S.Org.Lett.2000，2，2023；Na，R.；Jing，C.；Xu，Q.；Jiang，H.；Wu，X.；Shi，J.；Zhong，J.；Wang，M.；Benitez，D.；Tkatchouk，E.；Goddard，W.A.；Guo，H.；Kwon，O.J.Am.Chem.Soc.2011，133，13337-13348；Li，Z.；Yu，H.；Feng，Y.；Hou，Z.；Zhang，L.；Yang，W.；Wu，Y.；Xiao，Y.；Guo，H.RSC Adv.2015，5，34481.)、[4+4](Ni, H.; tang, X.; zheng, W.; yao, W.; ullah, N.; lu, Y.Angew.Chem., int.Ed.2017, 56, 14222-14226.) the cyclization process yields a mesocompound, which is in particular a compound containing a seven-membered ring structure that is found in a wide variety of natural products, and therefore, development of a new cyclization reaction mode under phosphine catalysis is imperative.
In recent years, a group of problems have developed a plurality of new gamma-substituted dienoic acid esters under phosphine catalysis, but the synthesis based on the dienoic acid esters on the intermediate ring compound under phosphine catalysis has not been realized due to the unfavorable entropy effect of the intermediate ring compound on synthesis and the need to overcome the trans-ring interaction during the cyclization process. Based on the urgent realization of the synthesis of the intermediate ring compound, we creatively introduce allyl containing electron withdrawing group activation at alpha position of the allenate, so that the allene becomes a 1, 6-amphiphilic compound, explores a new reaction mode of the allene as a six-membered synthon, and obtains compounds comprising seven-, eight-, nine-, ten-membered rings and the like under phosphine catalysis. And the design of the method is preliminarily verified by synthesizing seven-membered carbocycle and nitrogen ring through [6+1] cyclization reaction of the first phosphine catalyzed dienoic acid ester.
Disclosure of Invention
The invention aims to provide a novel allene compound.
The invention also provides a preparation method of the novel alkylene oxide compound.
It is another object of the present invention to provide the use of the above-described allene compound in phosphine-catalyzed intermolecular [6+1] cycloaddition reactions.
The novel alkylene oxide compound of the present invention has a compound structural formula shown below:
wherein R is 1 Is H, alkyl, aryl, heteroaryl. R is R 2 Is H, alkyl, aryl, heteroaryl. R is R 3 Is H, alkyl, aryl, heteroaryl. R is R 4 、R 5 The electron withdrawing group is one of a sulfoxide group, a cyano group, a carboxyl group, an ester group or a ketocarbonyl group.
The multifunctional phosphine compounds of this invention can be obtained from known phosphine ylides by two-step reactions with allyl compounds.
Specifically, phosphine ylide reacts with halogenated, boc substituted and AcO substituted allyl compounds for 12-24 hours in an organic solvent at a certain reaction temperature to generate the high allyl quaternary phosphonium salt. Then removing the organic solvent under reduced pressure, dissolving the quaternary phosphonium salt with dichloromethane, dropwise adding organic base into the solution, reacting for 2-24 hours, then dropwise adding acyl chloride under a certain temperature condition, reacting until a large amount of products are generated, removing the organic solvent under reduced pressure, and performing column chromatography to obtain the target allene.
The novel alkylene oxide compound can be used for phosphine-catalyzed intermolecular [6+1] cycloaddition reaction, and the specific reaction equation is as follows:
description of the embodiments
The following implementations are helpful in understanding the present invention, but are not limited to the context of the present invention.
Example 1: diethyl2-methyl-4-vinylidenenetanedioate
3.8g (20 mmol) of ylide is dissolved in 50mL of organic solvent, 7.0g (20 mmol) of allyl bromide is added at a certain temperature, the reaction is carried out for 12-24h at a certain temperature, the reaction is monitored by TLC, after the reaction is finished, quaternary phosphonium salt is obtained by rotary evaporation, the quaternary phosphonium salt is dissolved in 50mL of organic solvent, 6.2mL of organic base is dropwise added and reacted for 2-24h, 2mL of acetyl chloride is dropwise added to the system at a certain temperature, the reaction is carried out for 2-24h, most of the solvent is removed by rotary evaporation under reduced pressure, and 2.17g is obtained by adopting silica gel column chromatography for purification, and the yield is 48%.
The product structure data are characterized as follows: an oily liquid; 1 H NMR(400MHz，CDCl 3 )δ6.20(s，1H)，5.57(s，1H)，5.09(t，J＝2.8Hz，2H)，4.17(m，4H)，3.24(s，2H)，1.25(m，6H)； 13 C NMR(101MHz，CDCl 3 )δ214.14，166.47，166.43，144.87，122.97，97.45，79.97，61.42，60.40，31.29，14.34，14.32；HRMS(ESI)：m/z calcd for C 12 H 17 O 4 ([M+H] + )：225.1121；found：225.1120。
example 2: dimethyl 2-methyl-4-vinylidenenetanedioate
The synthesis was carried out in 58% yield as in example 1.
The product structure data are characterized as follows: an oily liquid; 1 H NMR(400MHz，CDCl 3 )δ6.19(s，1H)，5.59(s，1H)，5.10(t，J＝2.7Hz，2H)，3.70(s，6H)，3.22(s，2H)； 13 C NMR(101MHz，CDCl 3 )δ214.21，166.91，137.15，126.81，97.93，79.50，52.24，51.83，30.94；HRMS(ESI)：m/z calcd for C 10 H 13 O 4 ([M+H] + )：197.0809；found：197.0809。
example 3:1-butyl 5-ethyl 2-methyl-4-vinylidenenededitate
The synthesis was carried out in the same manner as in example 1 and with a yield of 56%.
The product structure data are characterized as follows: an oily liquid; 1 H NMR(400MHz，CDCl 3 )δ6.19(s，1H)，5.56(s，1H)，5.08(d，J＝1.2Hz，2H)，4.08-4.18(m，4H)，3.22(s，2H)，1.66-1.54(m，2H)，1.41-1.29(m，2H)，1.27-1.19(m，3H)，0.93-0.85(m，3H)； 13 C NMR(101MHz，CDCl 3 )δ214.07，166.54，166.47，137.61，126.39，98.35，79.42，64.54，61.05，30.92，30.59，19.11，14.15，13.63；HRMS(ESI)：m/z calcd for C 14 H 21 O 4 ([M+H] + )：253.1434；found：253.1433。
example 4:1- (tert-butyl) 5-methyl 2-methyl-4-vinylidenenetantedate
The synthesis was carried out in the same manner as in example 1 and the yield was 37%.
The product structure data are characterized as follows: an oily liquid; 1 H NMR(400MHz，CDCl 3 )δ6.08(s，1H)，5.48(d，J＝1.3Hz，1H)，5.07(t，J＝2.9Hz，2H)，3.69(s，3H)，3.18(s，2H)，1.42(s，9H)； 13 C NMR(101MHz，CDCl 3 )δ214.08，166.96，165.58，138.84，125.58，98.32，80.52，79.54，52.17，30.99，27.91；HRMS(ESI)：m/z calcd for C 13 H 18 O 4 Na([M+Na] + )：261.1097；found：261.1094。
example 5: phosphine-catalyzed [6+1] cyclization studies of novel dienes
Dissolving a double nucleophilic reagent and a phosphinous catalyst in an organic solvent, adding diene, reacting at a certain temperature under the protection of argon, monitoring the reaction by TLC, and directly performing column chromatography separation after the reaction is finished to obtain a target product. The results are shown in tables 1 and 2.
Table 1: phosphine catalyzed intermolecular [6+1] cycloaddition reaction research
Table 2: the invention relates to phosphine-catalyzed intermolecular [6+1] cycloaddition reaction research.

Claims (4)

1. A novel alkylene oxide compound is characterized by having the following structural formula:
wherein R is 1 Is H, alkyl, aryl, heteroaryl, acyl. R is R 2 Is H, alkyl, aryl, heteroaryl. R is R 3 Is H, alkyl, aryl, heteroaryl. R is R 4 、R 5 The electron withdrawing group is one of a sulfoxide group, a cyano group, a carboxyl group, an ester group or a ketocarbonyl group.
2. The process for preparing a novel diene compound according to claim 1, wherein phosphine ylide is reacted with a halogenated, boc-substituted or AcO-substituted allyl compound in an organic solvent at a reaction temperature for 6 to 24 hours to produce a homoallylic quaternary phosphonium salt. Then removing the organic solvent under reduced pressure, dissolving the quaternary phosphonium salt with dichloromethane, dropwise adding organic base into the solution, reacting for 1-5h, then dropwise adding acyl chloride at the temperature of 0 ℃ until a large amount of products are generated, removing the organic solvent under reduced pressure, and performing column chromatography to obtain the target allene.
3. The use of a novel alkylene oxide compound according to claim 1, wherein the compound is used for phosphine-catalyzed intermolecular [6+1] cycloaddition to build a mesocycle.
4. The use of a novel alkylene oxide compound according to claim 3 for the preparation of a nitrogen-ring, carbocycle-intermediate compound of the formula:
wherein: the EWG is an electron withdrawing group, and is one of a sulfoxide group, a cyano group, a carboxyl group, an ester group or a ketocarbonyl group. R is R 1 Is an alkyl group including methyl, ethyl, isopropyl, benzyl, and the like. R is R 2 Is an alkyl group including methyl, ethyl, isopropyl, benzyl, and the like.
CN202310511431.3A 2023-05-09 2023-05-09 Novel allene, preparation method and application thereof Pending CN116675606A (en)

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