通过三碳基(特罗酮)铁制备6-氨基环丙烯-2,4-dien-1-1衍生物
Summary
详细介绍了在三碳基(特罗酮)铁中添加胺核亲子的代表性实验程序以及随后产生的复合物的脱金属化。
Abstract
用两种不同的方法合成三碳基(特罗酮)铁的aza-Michael加法。原发性脂肪胺和循环二次胺在无溶剂条件下与三碳基(特罗酮)铁直接aza-Michael反应。 更少的核亲基性阴氨酸衍生物和更多的阻碍二次胺有效地增加了由三碳基(特罗酮)铁的原型形成的阳离子肌结复合物。虽然利用阳离子复合物的协议在获取 aza-Michael 加法方面的整体效率低于对中性复合物的直接、无溶剂添加,但它允许使用更广泛的胺核亲子素。在保护aza-Michael加法的胺作为三丁基卡巴酸盐后,在用硝酸铵处理后,从铁三碳化物片段中解结出二苯基,以提供6-氨基环丙二体-2,4-dien-1-1。这些产品可以作为含有七成员环的各种化合物的前体。由于脱金属化需要保护胺作为碳水化合物,因此,不能使用此处描述的协议来消除二次胺的 aza-Michael 辅量。
Introduction
含有七成员环的结构复杂的胺是许多生物活性分子的共性。值得注意的例子包括巨猿生物碱1和利科普兰2号、达芬奇勒姆3号和单苯类生物碱4族的几个成员。然而,与仅包含五或六个环的类似复杂性化合物相比,这种化合物通常更难合成。因此,我们试图通过将不同的胺核亲子素附着在肌钙素5上来开发一条新的途径来达到这种化合物。生成的加法包含多个功能手柄,用于随后对各种复杂的七成员环基架进行综合细化,否则难以访问。
虽然以前对tropone 6、7的研究表明,它不适合这种变换,但相关的有机金属复合三碳基(tropone)铁8(1,图1)已被证明是多功能合成构件,已用于合成一些天然产物和复杂分子9,10,11,12,13。此外,三碳基(特罗酮)铁的未复合双键已被证明在反应中与β、β-不饱和酮相似,例如,死神14,15,四乙酰乙烷16,氮氧化物17、安卓卡内8、10、有机铜试剂11。因此,我们设想,三碳基(特罗酮)铁的aza-Michael反应将为合成有价值的亚硝基肌酸衍生物提供有效的输入。
艾森施塔特此前曾报告说,在三碳基(特罗酮)铁的自成原体后,产生的阳离子复合物2(图1)可能通过苯胺或三丁胺进行核嗜血性攻击,以产生致微的衍生物。特罗多铁复合体。18然而,这种方法的综合潜力仍未实现。事实上,没有报告其他胺的添加,艾森施塔特的报告没有探讨这些产品的脱金属化。我们已经修改了这个协议,以演示添加各种各样的胺核嗜血杆菌。
我们还描述了一种直接添加三碳基(tropone)铁的方法(图2),该方法不需要合成阳离子复合物,通常与先前报告的方法相比,产量更高。我们在此还报告一个协议,用于对产生的附着件进行脱金属化。总体而言,该协议提供正式的 aza– Michael 的 tropone 加法,从 tropone (和三步从已知的铁复合体) 四个步骤。
Protocol
1. 三碳基(龙)铁(1)19 在气态手套箱中,将 4.1 克二铁非碳化物称重至烤箱干燥的 20 mL 小瓶中。盖住小瓶并将其从手套箱中取出。注意:长期储存二铁非碳化物会导致一些恶化,使三铁二十二基和细分裂的金属铁20。这种恶化在闪亮的橙色二铁非碳化物中存在黑色固体就证明了这一点。铁杂质是热火的,在暴露于空气中时会点燃。将二铁非碳化物储存在2-8°C的…
Representative Results
本研究的所有新化合物均具有1H和13C NMR光谱和高分辨率质谱的特点。 以前报告的化合物具有1个H NMR光谱特征。本节将介绍代表性化合物的 NMR 数据。 图3显示了三碳基(特罗酮)铁的1HNMR光谱。α 4-diene配体的质子产生6.39 ppm(2 H)、3.19 ppm 和 2.75 ppm 的信号。来自未复杂双键的质子出现在6.58和5.05ppm。 <p class="jove_content…
Discussion
是否采用直接添加三碳基(tropone)铁的无溶剂协议(图2),还是采用相应的阳离子复合物作为电友的间接方法(图1),取决于胺基板使用。一般来说,直接加法更可取,因为它需要较少的步骤来生成从tropone的aza-Michael加法,并且总体产量通常较高。 然而,这种更直接的方法通常限于合理不受阻碍的原发性脂肪胺和循环二次胺(例如,烟碱)。少核基质基质,如月胺?…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
向美国化学学会石油研究基金的捐赠者表示同意,以支持这项研究。我们感谢拉斐特学院化学系和拉斐特学院EXCEL学者项目提供财政支持。
Materials
| 10 g SNAP Ultra silica gel columns | Biotage | for automated column chromatography | |
| Acetic anhydride | Fisher Scientific | A10-500 | |
| Acetone | Fisher Scientific | A-16S-20 | for cooling baths |
| Acetonitrile-D3 | Sigma Aldrich | 366544 | |
| Benzene, anhydrous, 99.8% | Sigma Aldrich | 401765 | |
| Biotage Isolera Prime | Biotage | ISO-PSF | for automated chromatography |
| Celite; 545 Filter Aid | Fisher Scientific | C212-500 | diatomaceous earth |
| Cerium(IV) ammonium nitrate, ACS, 99+% | Alfa Aesar | 33254 | |
| Chloroform-D | Acros | 209561000 | |
| Di-tert-butyl dicarbonate, 99% | Acros | 194670250 | |
| Ethyl acetate | Fisher Scientific | E145-4 | |
| Ethyl alcohol, absolute – 200 proof | Greenfield Global | 111000200PL05 | |
| Ethyl ether anhydrous | Fisher Scientific | E138-1 | |
| Hexanes | Fisher Scientific | H302-4 | |
| iron nonacarbonyl 99% | Strem | 26-2640 | air sensitive, synonymous with diiron nonacarbonyl |
| Magnesium sulfate | Fisher Scientific | M65-500 | |
| Methanol | EMD Millipore | MX0475-1 | |
| Methylene chloride | Fisher Scientific | D37-4 | |
| MP alumina, Act. II-III acc. To Brockmann | MP Biomedicals | 4691 | for column chromatography |
| o-toluidine 98% | Sigma Aldrich | 466190 | |
| Phenethylamine 99% | Sigma Aldrich | 128945 | distill prior to use if not colorless |
| Sodium bicarbonate | Fisher Scientific | S233-500 | |
| Sodium carbonate anhydrous | Fisher Scientific | S263-500 | |
| Sodium chloride | Fisher Scientific | S271-500 | dissolved in deionized water to perpare a saturated aqueous solution |
| Sodium sulfate anhydrous | Fisher Scientific | S415-500 | |
| Sonicator | Branson | model 2510 | |
| Sulfuric acid | Fisher Scientific | A300C-212 | |
| Tetrafluoroboric acid solution, 48 wt.% | Sigma Aldrich | 207934 | aqueous solution |
| TLC Aluminium oxide 60 F254, neutral | EMD Millipore | 1.05581.0001 | for thin layer chromatography |
| Tropone 97% | Alfa Aesar | L004730-06 | Light sensitive |
Riferimenti
- Pollini, G. P., Benetti, S., De Risi, C., Zanirato, V. Synthetic Approaches to Enantiomerically Pure 8-Azabicyclo[3.2.1]octane Derivatives. Chemical Reviews. 106, 2434-2454 (2006).
- Ma, X., Gang, D. R. The Lycopodium alkaloids. Natural Product Reports. 21 (6), 752 (2004).
- Kobayashi, J., Kubota, T. The Daphniphyllum alkaloids. Natural Product Reports. 26 (7), 936-962 (2009).
- Leonard, J. Recent progress in the chemistry of monoterpenoid indole alkaloids derived from secologanin. Natural Product Reports. 16, 319-338 (1999).
- Huang, Z., Phelan, Z. K., Tritt, R. L., Valent, S. D., Griffith, D. R. Formal aza-Michael additions to tropone: Addition of diverse aryl- and alkylamines to tricarbonyl(tropone)iron and [(C7H7O)Fe(CO)3]BF4. Tetrahedron Letters. 59 (37), 3432-3434 (2018).
- Pauson, P. L. Tropones and Tropolones. Chemical Reviews. 55 (1), 9-136 (1955).
- Pietra, F. Seven-Membered Conjugated Carbo-and Heterocyclic Compounds and Their Homoconjugated Analogs and Metal Complexes. Synthesis, Biosynthesis, Structure, and Reactivity. Chemical Reviews. 73 (4), 293-364 (1973).
- Johnson, B. F. G., Lewis, J., Wege, D. Transition metal carbonyl complexes derived from cycloocta-2,4,6-trienone and cyclohepta-2,4,6-trienone. Journal of the Chemical Society, Dalton Transactions. 1976, 1874-1880 (1976).
- Franck-Neumann, M., Brion, F., Martina, D. Friedel-Crafts acylation of tropone-irontricarbonyl. Synthesis of β-thujaplicin and β-dolabrin. Tetrahedron Letters. 19 (50), 5033-5036 (1978).
- Saha, M., Bagby, B., Nicholas, K. M. Cobalt-mediated propargylation/annelation: Total synthesis of (±)-cyclocolorenone. Tetrahedron Letters. 27 (8), 915-918 (1986).
- Yeh, M. -. C. P., Hwu, C. -. C., Ueng, C. -. H., Lue, H. -. L. Michael Addition Reactions of the Highly Functionalized Zinc-Copper Reagents RCu(CN)ZnI to (Tropone)iron Tricarbonyl Promoted by Boron Trifluoride Etherate. Organometallics. 13 (5), 1788-1794 (1994).
- Pearson, A. J., Srinivasan, K. Approaches to the synthesis of heptitol derivatives via iron-mediated stereocontrolled functionalization of cycloheptatrienone. The Journal of Organic Chemistry. 57 (14), 3965-3973 (1992).
- Soulié, J., Betzer, J. -. F., Muller, B., Lallemand, J. -. Y. General access to polyhydroxylated nortropane derivatives through hetero diels -alder cycloaddition. Tetrahedron Letters. 36 (52), 9485-9488 (1995).
- Rigby, J. H., Ogbu, C. O. Tricarbonyl(tropone)iron as a useful functionalized enone equivalent. Tetrahedron Letters. 31 (24), 3385-3388 (1990).
- Franck-Neumann, M., Martina, D. Cycloadditions de la tropone avec le cyclopentadiene synthese d’un intermediaire potentiel par utilisation de complexe metallique. Tetrahedron Letters. 18 (26), 2293-2296 (1977).
- Ban, T., Nagai, K., Miyamoto, Y., Harano, K., Yasuda, M., Kanematsu, K. Periselective cycloaddition of tricarbonyliron complexes of seven-membered unsaturated compounds with 1,2,4,5-tetrazine. Masking and activating effects of tricarbonyliron complexes. The Journal of Organic Chemistry. 47 (1), 110-116 (1982).
- Bonadeo, M., Gandolfi, R., De Micheli, C. Reactions of nitrile oxides and of 2,5-dimethyl-3,4-diphenylcyclopentadienone with tricarbonyltroponeiron and oxidation of the adducts with cerium(IV). Gazzetta Chimica Italiana. 107, 577-578 (1977).
- Eisenstadt, A. The reactivity of cycloheptadienyl-1-one iron tricarbonyl cation towards nucleophilic attack. Journal of Organometallic Chemistry. 113 (2), 147-156 (1976).
- Rosenblum, M., Watkins, J. C. Cyclopentannulation reactions with organoiron reagents. Facile construction of functionalized hydroazulenes. Journal of the American Chemical Society. 112 (17), 6316-6322 (1990).
- Pearson, A. J. . Iron Compounds in Organic Synthesis. , (1994).
- Eisenstadt, A. Fluxional behaviour of protonated substituted troponeiron tricarbonyls. Journal of Organometallic Chemistry. 97 (3), 443-451 (1975).
- Shvo, Y., Hazum, E. A Simple Method for the Disengagement of Organic Ligands from Iron Complexes. Journal of the Chemical Society, Chemical Communications. , 336-337 (1974).
- Thompson, D. J. Reaction of tricarbonylcyclohexadieneiron complexes with cupric chloride. Journal of Organometallic Chemistry. 108 (3), 381-383 (1976).
- Franck-Neumann, M., Heitz, M. P., Martina, D. Une methode simple de liberation des ligands organiques de leurs complexes de fer carbonyle. Tetrahedron Letters. 24 (15), 1615-1616 (1983).
- Birch, A. J., Kelly, L. F., Liepa, A. J. Lateral control of skeletal rearrangement by complexation of thebaine with Fe(CO)3. Tetrahedron Letters. 26 (4), 501-504 (1985).
- Ripoche, I., Gelas, J., Grée, D., Grée, R., Troin, Y. A new stereoselective synthesis of chiral optically pure 4-piperidones. Tetrahedron Letters. 36 (37), 6675-6678 (1995).
- Williams, I., Kariuki, B. M., Reeves, K., Cox, L. R. Stereoselective Synthesis of 2-Dienyl-Substituted Pyrrolidines Using an η4-Dienetricarbonyliron Complex as the Stereodirecting Element: Elaboration to the Pyrrolizidine Skeleton. Organic Letters. 8, 4389-4392 (2006).
- Coquerel, Y., Depres, J. -. P., Greene, A. E., Cividino, P., Court, J. Synthesis of Substituted Cycloheptadienes by Catalytic Hydrogenation of Cycloheptatrieneiron Complexes. Synthetic Communications. 31, 1291-1300 (2001).
Citazione di questo articolo
Huang, Z., Phelan, Z. K., Tritt, R. L., Valent, S. D., Guan, Z., He, Y., Weiss, P. S., Griffith, D. R. Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron. J. Vis. Exp. (150), e60050, doi:10.3791/60050 (2019).