Name: efficient synthesis of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc bromides
Uploaded: 2019-05-26T15:00:00
Description: Watch this Scientific Journal Video about Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides at JoVE.com

作者感谢美国化学学会 (ACS) 石油研究基金本科生新研究员方案 (第558488-uni1 号奖)、ACS 和 Pfizer (对 t. j. f. 的 Surf 支持)、Bucknell 大学 (向 t. j. f. 研究金) 和该部化学 (对 k. m. t. 的研究金), 为这项工作提供慷慨的支持。Peter M. Findeis 博士和 Brian Breczinski 因实验和仪器辅助而获得认可。

注意: 在使用本程序中的化学品之前, 请参考材料安全数据表 (MSDS)。使用适当的个人防护设备 (PPE), 包括安全眼镜、实验室涂层和丁腈或丁基手套, 因为许多试剂和溶剂具有腐蚀性、毒性或易燃性。在通风罩中进行所有反应。有必要使用火焰干燥玻璃器皿, 并使用惰性气氛 (氮气或氩) 为该协议。在协议的前两个步骤中使用的液体是注射器转移。
1. 功能化单有机溴化物的形成<sup cl...

<ol>
	<li>Hawner, C., Alexakis, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metal-Catalyzed+Asymmetric+Conjugate+Addition+Reaction:+Formation+of+Quaternary+Stereocenters.">Metal-Catalyzed Asymmetric Conjugate Addition Reaction: Formation of Quaternary Stereocenters.</a> Chemical Communications. 46 (39), 7295-7306 (2010).</li><li>Quasdorf, K. W., Overman, L. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Catalytic+Enantioselective+Synthesis+of+Quaternary+Carbon+Stereocentres.">Catalytic Enantioselective Synthesis of Quaternary Carbon Stereocentres.</a> Nature. 516 (7530), 181-191 (2014).</li><li>Knochel, P., Leuser, H., Cong, L. -. Z., Perrone, S., Kneisel, F. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polyfunctional+Zinc+Organometallics+for+Organic+Synthesis.">Polyfunctional Zinc Organometallics for Organic Synthesis.</a> Handbook of Functionalized Organometallics. , 251-346 (2005).</li><li>Dagousset, G., Fran&#231;ois, C., Le&#243;n, T., Blanc, R., Sansiaume-Dagousset, E., Knochel, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+of+Functionalized+Lithium,+Magnesium,+Aluminum,+Zinc,+Manganese,+and+Indium+Organometallics+From+Functionalized+Organic+Halides.">Preparation of Functionalized Lithium, Magnesium, Aluminum, Zinc, Manganese, and Indium Organometallics From Functionalized Organic Halides.</a> Synthesis. 46 (23), 3133-3171 (2014).</li><li>Kim, J. H., Ko, Y. O., Bouffard, J., Lee, S. -. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+Tandem+Reactions+with+Organozinc+Reagents.">Advances in Tandem Reactions with Organozinc Reagents.</a> Chemical Society Reviews. 44 (8), 2489-2507 (2015).</li><li>Benischke, A. D., Ellwart, M., Becker, M. R., Knochel, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polyfunctional+Zinc+and+Magnesium+Organometallics+for+Organic+Synthesis:+Some+Perspectives.">Polyfunctional Zinc and Magnesium Organometallics for Organic Synthesis: Some Perspectives.</a> Synthesis. 48 (8), 1101-1107 (2016).</li><li>Hird, A. W., Hoveyda, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Catalytic+Enantioselective+Alkylations+of+Tetrasubstituted+Olefins.+Synthesis+of+All-Carbon+Quaternary+Stereogenic+Centers+Through+Cu-Catalyzed+Asymmetric+Conjugate+Additions+of+Alkylzinc+Reagents+to+Enones.">Catalytic Enantioselective Alkylations of Tetrasubstituted Olefins. Synthesis of All-Carbon Quaternary Stereogenic Centers Through Cu-Catalyzed Asymmetric Conjugate Additions of Alkylzinc Reagents to Enones.</a> Journal of the American Chemical Society. 127 (43), 14988-14989 (2005).</li><li>Lee, K. -. S., Brown, M. K., Hird, A. W., Hoveyda, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Practical+Method+for+Enantioselective+Synthesis+of+All-Carbon+Quaternary+Stereogenic+Centers+Through+NHC-Cu-Catalyzed+Conjugate+Additions+of+Alkyl-+and+Arylzinc+Reagents+to+&#946;-Substituted+Cyclic+Enones.">A Practical Method for Enantioselective Synthesis of All-Carbon Quaternary Stereogenic Centers Through NHC-Cu-Catalyzed Conjugate Additions of Alkyl- and Arylzinc Reagents to &#946;-Substituted Cyclic Enones.</a> Journal of the American Chemical Society. 128 (22), 7182-7184 (2006).</li><li>Brown, M. K., May, T. L., Baxter, C. A., Hoveyda, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=All-Carbon+Quaternary+Stereogenic+Centers+by+Enantioselective+Cu-Catalyzed+Conjugate+Additions+Promoted+by+a+Chiral+N-Heterocyclic+Carbene.">All-Carbon Quaternary Stereogenic Centers by Enantioselective Cu-Catalyzed Conjugate Additions Promoted by a Chiral N-Heterocyclic Carbene.</a> Angewandte Chemie International Edition. 46 (7), 1097-1100 (2007).</li><li>Knochel, P., Yeh, M. C. P., Berk, S. C., Talbert, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+Reactivity+Toward+Acyl+Chlorides+and+Enones+of+the+New+Highly+Functionalized+Copper+Reagents+RCu(CN)ZnI.">Synthesis and Reactivity Toward Acyl Chlorides and Enones of the New Highly Functionalized Copper Reagents RCu(CN)ZnI.</a> The Journal of Organic Chemistry. 53 (10), 2390-2392 (1998).</li><li>Yeh, M. C. P., Knochel, P., Butler, W. M., Berk, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=1,4-Additions+of+the+Highly+Functionalized+Copper+Reagents+RCu(CN)-ZnI&#8226;2+BF3+to+Trisubstituted+Enones.+A+New+BF3+Promoted+Cyclization+Reaction.">1,4-Additions of the Highly Functionalized Copper Reagents RCu(CN)-ZnI&#8226;2 BF3 to Trisubstituted Enones. A New BF3 Promoted Cyclization Reaction.</a> Tetrahedron Letters. 29 (51), 6693-6696 (1988).</li><li>Knochel, P., Chou, T. S., Chen, H. G., Yeh, M. C. P., Rozema, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nucleophilic+Reactivity+of+Zinc+and+Copper+Carbenoids.+Part+II.">Nucleophilic Reactivity of Zinc and Copper Carbenoids. Part II.</a> The Journal of Organic Chemistry. 54 (22), 5202-5204 (1989).</li><li>Tamaru, Y., Tanigawa, H., Yamamoto, T., Yoshida, Z. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Copper(I)-Promoted+Michael-Addition+Reaction+of+Organozincs+of+Esters,+Nitriles,+and+&#945;-Amino+Acids.">Copper(I)-Promoted Michael-Addition Reaction of Organozincs of Esters, Nitriles, and &#945;-Amino Acids.</a> Angewandte Chemie International Edition. 28 (3), 351-353 (1989).</li><li>Fulton, T. J., Alley, P. L., Rensch, H. R., Ackerman, A. M., Berlin, C. B., Krout, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Access+to+Functionalized+Quaternary+Stereocenters+via+the+Copper-Catalyzed+Conjugate+Addition+of+Monoorganozinc+Bromide+Reagents+Enabled+by+N,N-Dimethylacetamide.">Access to Functionalized Quaternary Stereocenters via the Copper-Catalyzed Conjugate Addition of Monoorganozinc Bromide Reagents Enabled by N,N-Dimethylacetamide.</a> The Journal of Organic Chemistry. 83 (23), 14723-14732 (2018).</li><li>Krasovskiy, A., Malakhov, V., Gavryushin, A., Knochel, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+Synthesis+of+Functionalized+Organozinc+Compounds+by+the+Direct+Insertion+of+Zinc+into+Organic+Iodides+and+Bromides.">Efficient Synthesis of Functionalized Organozinc Compounds by the Direct Insertion of Zinc into Organic Iodides and Bromides.</a> Angewandte Chemie International Edition. 45 (36), 6040-6044 (2006).</li><li>Huo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+Efficient,+General+Procedure+for+the+Preparation+of+Alkylzinc+Reagents+from+Unactivated+Alkyl+Bromides+and+Chlorides.">Highly Efficient, General Procedure for the Preparation of Alkylzinc Reagents from Unactivated Alkyl Bromides and Chlorides.</a> Organic Letters. 5 (4), 423-425 (2003).</li><li>Still, W. C., Kahn, M., Mitra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+Chromatographic+Technique+for+Preparative+Separations+with+Moderate+Resolution.">Rapid Chromatographic Technique for Preparative Separations with Moderate Resolution.</a> The Journal of Organic Chemistry. 43 (14), 2923-2925 (1978).</li><li>Knopff, O., Alexakis, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tandem+Asymmetric+Conjugate+Addition-Silylation+of+Enantiomerically+Enriched+Zinc+Enolates.+Synthetic+Importance+and+Mechanistic+Implications.">Tandem Asymmetric Conjugate Addition-Silylation of Enantiomerically Enriched Zinc Enolates. Synthetic Importance and Mechanistic Implications.</a> Organic Letters. 4 (22), 3835-3837 (2002).</li></ol>

本文提出了利用温和的功能化单有机酶在简单有效的共轭加成反应中合成β-季酮14的方法.通过使用极性、无菌溶剂 DMA 和 TMSCl 观察到了出色的产量和显著提高的催化剂效率. DMA 有助于单有机酸的形成, 促进锌直接插入随时可用的烷基溴创建一个广泛的功能化试剂16。
单有机溴化物的形成是该议定书中最重要的一步。在催化剂与 tmscl 具有适当...

碳碳键的形成可以说是有机化学中最重要、最有力的转变。有机金属试剂在α、β-不饱和碳基中的共轭添加包括构建 C-C 键的最通用的方法之一, 特别是在具有挑战性的全碳第四纪中心的生成中, 2. 尽管结合添加有机金属试剂对第四纪中心的形成至关重要, 但很少有方法解决将敏感官能团纳入这些反应的挑战。事实上, 在大多数这些转化中, 高反应性的有机硅、Grignard 或二有机酶试剂是首选的亲核物质。然而, 这些反应性有机金属与许多敏感官能团不兼容, 从而限制了α、β不饱和碳基和有机金属试剂的复杂性, 往往需要使用保护基团或多步骤合成中的替代策略。
单有机锌试剂是一类极具吸引力的有机金属试剂, 因其温和的反应性和增强的功能基团相容性而受到广泛关注.6. 尽管单有机酶具有特殊的官能团耐受性和从有机卤化物中制备的微不足道的物质, 但很少有单有机酶试剂在与β、β取代α、β-不饱和碳基的共轭中分离的例子。第四纪中心7,8,9。此外, 这些转变通常需要化学计量量的有毒氰化物试剂, 有一份报告显示了最小的催化剂周转10,11, 12,13. 我们研究的目的是建立一种简单实用的催化方法, 将功能化的单有机酶试剂结合到α、β-不饱和的碳基中, 以产生全碳第四纪中心。为此, 我们开发了一个协议, 利用n,n-二甲基乙酰胺 (dma) 作为溶剂与氯三甲基硅烷 (tmscl) 作为刘易斯酸, 使 "一锅" 铜催化 (20 摩尔%)将功能化的单有机酶试剂结合到α、β-不饱和的碳基中, 在高产14的情况下产生广泛的全碳第四纪中心.
与文献报道的方法相比, DMA 作为溶剂的应用有几个显著的优点。DMA 提高了锌插入有机卤化物的效率, 从而避免了对在空灵溶剂系统中使用的锂离子等昂贵和吸湿添加剂的要求。这也扩大了直接插入锌的范围, 从敏感的、往往是商业上无法获得的有机碘化物扩大到更稳定和更容易获得的有机硼16。本文详细介绍的协议产生来自不同有机硼化物的烷基单有机臭氧抑制剂 (2), 用于原位形成反应性立方复合物, 在共轭加成反应中参与循环α、β-不饱和酮 (图 1)。DMA 还使反应能够使用更便宜、毒性更小的铜来源, 如 Cubbr·Dms, 消除其他报告10、11、12、13中使用 cucn 产生的化学计量有毒废物。我们的标准反应条件提供了广泛的β-四元酮 (5) 与通过水解中硅烷醇醚 (4) 获得的5、六和七元环共轭受体。经改进的手术观察, 中间硅酰烯醇醚具有一定的稳定性, 可在良好的收率下进行分离。

<table>
	<tbody>
		<tr>
			<td>Ammonium Chloride</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Biotage Isolera One Flash Chromatography System</td>
			<td>Biotage</td>
			<td>ISO-ISW</td>
			<td>UV/vis detection (254, 280, 200-400nm)</td>
		</tr>
		<tr>
			<td>Chloroform-D, (D, 99.8%)</td>
			<td>Cambridge Isotope Laboratories</td>
			<td>DLM-7</td>
			<td></td>
		</tr>
		<tr>
			<td>Copper (I) bromide dimethyl sulfide complex , 99%</td>
			<td>Sigma Aldrich</td>
			<td>230502</td>
			<td>Air and moisture sensitive</td>
		</tr>
		<tr>
			<td>Diethyl Ether, anhydrous, 99%</td>
			<td>EMD Chemicals</td>
			<td>MEX01906</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>Ethyl 4-bromobutyrate</td>
			<td>Oakwood</td>
			<td>139400</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethyl Acetate, 99.9%</td>
			<td>Fisher</td>
			<td>E145-500</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>Glacial Acetic Acid</td>
			<td>Oakwood</td>
			<td>O35907</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>HCl</td>
			<td></td>
			<td></td>
			<td>1 M aq</td>
		</tr>
		<tr>
			<td>Hexanes, 98.5%</td>
			<td>EMD Chemicals</td>
			<td>HX0299</td>
			<td>ACS</td>
		</tr>
		<tr>
			<td>HP 6890 Series GC</td>
			<td>HP</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>HP-1 GC Column</td>
			<td>Agilent</td>
			<td>19091-60312</td>
			<td>0.2 mm x 0.33 um, 12 m, 7 inch cage</td>
		</tr>
		<tr>
			<td>Iodine</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Magnesium Sulfate, anhydrous, 98%</td>
			<td>EMD Chemicals</td>
			<td>MX0075</td>
			<td></td>
		</tr>
		<tr>
			<td>Mehtyl enone</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>N,N-Dimethylacetamide, anhydrous, 99%</td>
			<td>Alfa Aesar</td>
			<td>A10924</td>
			<td>Dried over 3 &#197;ms</td>
		</tr>
		<tr>
			<td>Silica gel</td>
			<td>VWR</td>
			<td>86306-350</td>
			<td>60 &#197;, 40-60 um</td>
		</tr>
		<tr>
			<td>Sodium Bicarbonate</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium Chloride</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tetra-n-butylammonium fluoride</td>
			<td>Oakwood</td>
			<td>O43479</td>
			<td>1 M in THF</td>
		</tr>
		<tr>
			<td>Thin-layer chromatography plates</td>
			<td>EMD Milipore</td>
			<td>115341</td>
			<td>6.5 x 2.2 cm2, 60 g F254 precoated plates (9.5-11.5 um particle size)</td>
		</tr>
		<tr>
			<td>Trimethyl silyl chloride, 99%</td>
			<td>Sigma Aldrich</td>
			<td>386529</td>
			<td>Air sensitive</td>
		</tr>
		<tr>
			<td>Zinc</td>
			<td></td>
			<td></td>
			<td>Powder, HCl-washed</td>
		</tr>
	</tbody>
</table>

efficient synthesis of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc bromides

在α、β-不饱和碳基中共轭添加有机金属试剂是在制备全碳第四纪中心时产生 C-c 键的重要方法。虽然有机金属试剂的共轭添加通常是使用高活性的有机硅或 Grignard 试剂进行的, 但有机锌试剂因其增强的化学选择性和温和的反应性而备受关注。尽管最近在活性二有机酶和混合二有机还原试剂方面取得了许多进展, 但通过共轭添加功能化单有机臭氧试剂生成全碳第四纪中心仍然是一个挑战。该协议详细介绍了一种方便而温和的 "一锅" 制剂和铜介导的共轭连接单有机酸溴到循环α, β不饱和碳基提供了广泛的全碳季中心在一般范围内的全碳季中心优异的产量和选择性。该技术发展的关键是利用 DMA 作为反应溶剂, TMSCl 作为 lewis 酸。这种方法的显著优点包括利用 DMA 作为溶剂提供的有机试剂制备操作简单, 以及由各种 Cu (I) 和 Cu (II) 盐介导的高效共轭添加。此外, 中间硅酰乙烯醚可以通过改进的处理程序进行分离。基板范围仅限于循环不饱和酮, 共轭添加受到稳定 (如烯丙基、烯酸、同烯酸酯) 和严格固定 (例如, 新戊基、 o-芳基) 单有机酸试剂的阻碍。在五元和七元环中加入共轭是有效的, 尽管与六元环基板相比, 产率较低。

共轭添加剂产品乙基 4-(1----3-氧环己基) 丁酸 (21) 使用此高效的一锅协议, 作为一种透明无色油 (1.0372 克, 4.583 mmol, 92% 收率) 进行分离。1图 2和图 3显示了 h 和13c 核磁共振光谱, 以确定其结构和纯度。在 1h 谱分析中, 特别值得注意的是存在两个质子 ab 四重奏在 2.15 ppm, 这表明非全应学 c2 氢原子...

Watch this Scientific Journal Video about Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides at JoVE.com

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

提出了一种将功能化的单有机酶溴有效地结合在环α、β-不饱和碳基中的全碳第四纪中心的简单实用的协议。

功能化单有机硼化合物共轭法高效合成全碳第四纪中心

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the ...

我们的协议详细说明了方便的单锅制备和铜介质结合添加功能化单有机溴化物到循环α-β-不饱和碳化物，以合成高产四元中心。这种方法的一大优势是使用二甲基乙酰胺，以便利有机体形成，从广泛可访问的功能化有机溴化物。首先，在火焰干燥的50毫升施伦克反应瓶中加入锌、灰尘、DMA和碘，在阿贡下加入搅拌棒。在环境温度下搅拌悬浮液，直到棕橙色完全消散为灰色悬架。在灰色悬浮液中加入乙基4-布罗莫丁酸酯。将烧瓶浸入 80 摄氏度的油浴中，进行剧烈搅拌，直到通过气相色谱或 GC 分析观察有机溴化物的消耗。将一次性玻璃巴斯德移液器短暂浸入反应混合物中，然后从烧瓶中取出。用约0.5毫升的二乙醚冲洗至含有约0.5毫升饱和氯化铵的两毫升小瓶中。大力摇动小瓶，通过GC分析有机层。将单有机丁试剂冷却至环境温度后，该试剂可以在惰性气氛下储存数小时至过夜，对结合剂添加产品的产量影响最小。对于单有机糖酸溴化物结合加入α-β不饱和酮首先冷却有机蛋白悬浮液在冰水浴约五分钟。然后加入溴二甲基硫化物铜和额外的DMA，搅拌反应10分钟。接下来在冷却的悬浮液中加入氯三甲基硅烷，然后是3-甲基-2-环丙酮。大约 30 分钟后取出冷却浴，并监测反应，直到 TLC 分析消耗 α-β 不饱和酮长达 24 小时。将醋酸加入已完成的联结加反应，将中间硅醇醚水解到酮产品中。通过 TLC 分析，以 15 分钟的时间间隔监控水解的进度。如果硅醇醚在一小时后仍然存在，添加四丁基酰氟化，以方便完全水解，TLC 就明显可见一下。在反应瓶中加入一个摩尔盐酸，混合好。然后将反应内容转移到250毫升分离漏斗中。用二乙醚和水冲洗烧瓶，将冲洗剂加入分离漏斗。轻轻摇动漏斗的内容，在每次混合之间通风，让层分开。将底部水层排入 125 毫升 Erlenmeyer 烧瓶中，然后将有机层排入单独的 250 毫升 Erlenmeyer 烧瓶中。将水层返回分离漏斗，用四个单独的二乙醚部分提取，将每个有机萃取物添加到含有机的 Erlenmeyer 烧瓶中。将组合有机萃取物加入分离漏斗，用饱和水性碳酸氢钠清洗。将水洗排入含水厄伦迈尔烧瓶中。现在用饱和的氯化钠清洗组合的有机萃取物。将第二次水洗排入含水厄伦迈尔烧瓶后，将最后的有机层排入干的 250 毫升 Erlenmeyer 烧瓶中。使用玻璃褶皱的布赫纳漏斗将硫酸镁和真空过滤器上的有机层干燥成 250 毫升的圆形底瓶。用一小部分额外的二乙醚冲洗褶皱上的固体。使用旋转蒸发器在减压下将滤液集中。将残留在高真空下的烧瓶放置至少 10 分钟。使用脱制氯仿分析质子 NMR 的粗残留样品。为了通过自动闪光色谱干燥装载原油，将原油溶解在最小量的二乙醚中。然后将此洗脱转移到预包装的硅胶盒中。将减压到装载柱底部约五分钟，以去除多余的溶剂。使用预包装的硅胶柱在六烷中采用乙酸乙酸酯梯度来吸出样品，收集试管中的铜柱废水。与以前一样使用 TLC 分析检测分数纯度。在焦油圆底瓶中混合并冲洗所有含有所需四元酮的馏分。最后，在降低压力下将溶液集中在旋转蒸发器上，并在高真空下去除最终挥发物至少30分钟。获得烧瓶的最终质量，并使用脱发氯仿分析质子 NMR 净化产品的样品。结合添加产品乙基4丁酸酯被隔离为透明无色油使用这种有效的单锅协议。对质子和碳 NMR 光谱的分析证实了其结构和纯度。质子光谱分析中特别值得注意的是，在2.15 ppm的化学移位下存在一个双质子AB四重奏，表明二质子C2氢旋转成双。化学移位为 0.94 ppm 的三质子单表示 Z1 四元甲基组。利用这种简单高效的单锅协议，准备了一系列具有β四元中心的环酮添加产品，以优异的收益率。所有反应产品都通过质子和碳 NMR 以及高分辨率质谱分析，并发现纯度高。除了加入酯、氮和卤化物功能外，该反应协议还为使用奇性α、β不饱和酮时具有各种环尺寸和高水平的立体选择性的产品提供。从这些例子中可以明显看出，受青睐的途径涉及将有机片段传递到与非氢组相反的烷面，其位于α-β不饱和酮的伽马和增量位置。由于单有机子试剂的当量降低，验证有机物完全插入锌非常重要。本程序中使用的试剂和溶剂通常易燃且毒性较轻。应在烟罩中使用适当的个人防护设备进行反应。

Research

JoVE Journal

Chemistry

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

微波辅助分子内Diels-Alder反应的功能化萘/变色染料的合成脱氢

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to ...

科研

化学

Synthesis and Characterization of Functionalized Metal-organic Frameworks

功能化的合成与表征金属 - 有机骨架

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Synthetic Methodology for Asymmetric Ferrocene Derived Bio-conjugate Systems via Solid Phase Resin-based Methodology

合成方法通过固相树脂为基础的方法不对称二茂铁产生的生物共轭系统

Early detection is a key to successful treatment of most diseases, and is particularly imperative for the diagnosis and treatment of many types of cancer. ...

Facile and Efficient Preparation of Tri-component Fluorescent Glycopolymers via RAFT-controlled Polymerization

通过RAFT控制聚合轻便和高效制备三组分荧光Glycopolymers

Synthetic glycopolymers are instrumental and versatile tools used in various biochemical and biomedical research fields. An example of a facile and ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

蛋白质生物缀合物的合成<em&gt;通过</em&gt;半胱氨酸马来酰亚胺化学

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

寡 peptoids 的合成及质谱分析

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

Synthesis of Substrate-Bound Au Nanowires Via an Active Surface Growth Mechanism

通过活性表面生长机制合成基片束缚金纳米线

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a ...

Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides

苷 2 ', 3 ' -二醇酯对双糖苷合成的选择性O-糖基化

Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties, have been known as a valuable group of natural products having ...

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

乙腈绿色 Steglich 酯化合成酯的研究

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the ...

Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers

通过结晶驱动生物降解块共聚物的自组装合成单分散圆柱状纳米粒子

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock ...