Name: metal-free synthesis of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts
Uploaded: 2015-02-24T14:00:00.000+00:00
Duration: 9 min 58 s
Description: Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

This work was supported by the UOIT start-up fund. We thank Mr. Matthew Baxter (UOIT) for his assistance in the laboratory.

1.合成Ynone的<ol><li>用分析天平，称量0.15毫摩尔所需钾alkynyltrifluoroborate盐（1.5当量），并加入到一个干净的小瓶中装有磁力搅拌棒。 </li><li>用装有针头的玻璃注射器柱塞，加入0.5毫升无水DCM中的小瓶，得到三氟的0.3M的溶液。 注:由于这是一个新的方法，反应已经进行了概念验证。为了减少浪费，他们已经在小范围内进行的。该反应可以按比例根据需要，以产生更大的产量。 </li><li>用玻璃注射器，加入0.15的1.0M的三氯化硼溶液毫摩尔（1.5当量，150微升）中的溶液，以在环境温度（20℃）搅拌下的反应容器中。更换帽。持或夹紧封端反应容器，使反应溶液低于水线的超声波仪。超声处理在20℃的溶液中30秒，频率ø˚F40千赫。 </li><li>在室温下搅拌（20℃）下另外20分钟反应溶液中。取决于alkynyltrifluoroborate起始材料的性质，观察颜色变化。从白色到黄褐色或黑褐色，红色或紫色颜色的变化是常见的。 </li><li>加入0.1毫摩尔的在所需的酰基氯（1.0当量），以在环境温度下的管形瓶（20℃）并搅拌。可替代地，将反应容器的内容物转移到装有磁力搅拌棒的烧瓶和0.1毫摩尔的酰氯。更换帽。在环境温度搅拌（20℃）下进行30分钟的反应液中。 注意:通常情况下，改变到非常暗的颜色是指示该反应的发生。 </li><li>使用薄层色谱（TLC）34监测反应通过用合适的酰氯标准进行比较的进展。 注意:根据所用原料的性质，反应可能不完全。在一个缸氯化物起始材料已被观察到了更高的运行点比对所有使用该方法制备迄今ynones的最终产品。 <ol><li>通过稀释大约10毫克的酰基氯为起始材料用1ml乙酸乙酯的小瓶制备的酰基氯的标准。 </li><li>用TLC点样器，当场在TLC板上的起跑线的反应溶液和标准。的共点与两个反应溶液和标准可能是有用的，以确定是否存在仍然起始原料存在于反应溶液中。 </li><li>通过试验和误差确定合适的薄层色谱的流动相。对于物品1a的制备，流动相组成为1:30的乙酸乙酯:己烷的结果在大约0.5和0.8的ynone产物和苯甲酰氯的 R F值分别原料。 </li><li>可视化在UV光下的开发TLC板上。用铅笔标注任何可见的斑点。 </li></ol></li></ol> 2.水后处理<ol><li>淬火通过添加1毫升的冷水（约5℃）到反应容器中的反应。使用巴斯德吸管，将溶液转移到一个干净的分液漏斗中。进一步稀释的分液漏斗中的内容，用10ml冷水和提取产物一旦在15ml乙酸乙酯中。 </li><li>弃去底部的水层，并用10毫升水和1的时间，用10ml盐水洗涤有机层1的额外时间。收集有机层到一个干净的锥形瓶中，并用硫酸镁干燥。过滤该溶液成利用重力过滤干净圆底烧瓶中。 </li></ol> 3.净化Ynone的<ol><li>采用薄层色谱法，确定一个合适的流动相对于所述产物的快速色谱法纯化。约0.5的保留因子（R f）为通常足以产物从任何剩余开始分离荷兰国际集团的材料和副产物。 注意:在分离度不佳的情况下，一个极性较小的溶剂系统可以用于使得该产品具有较低的Rf 值为 。因起始原料，一己烷的极性:1至5:在30〜乙酸乙酯混合物1一般是合适的。 </li><li>制备的含二氧化硅柱用合适的流动相湿。加了一层砂到塔的顶部，以便在加入产物和洗脱液，以避免扰乱二氧化硅。 </li><li>蒸发使用旋转蒸发器与浴温在40℃和旋转设定为120转的后处理溶液。溶解烧瓶的内容物在2 ml的流动相，并仔细均匀加载溶液上柱。确保该二氧化硅是湿但溶剂线不超过二氧化硅的高度。允许一些溶剂洗脱，使得产品的二氧化硅。添加少量的流动相重复。 </li><li>填写山坳UMN与在步骤3.1中确定的流动相;在物品1a的情况下，一个30:1的己烷:乙酸乙酯混合物是适当的。收集用快速色谱法以加速纯化过程在试管的级分。简单的适配器与管的空气出口连接。调节空气压力，使得洗脱液流过该柱以合适的速率。 </li><li>在TLC板上发现每一柱组分的。任选地，当场酰氯标准作为参考。用流动相认为适当步骤1.8开发TLC。马克在紫外光下可见的任何点，并指出，产品预计有较低的 R F比酰氯标准。 </li><li>收集含有可见的斑点成一个大圆底烧瓶中的所有分数。如果一个以上的点具有较低的 R F比起始材料存在，收集它们在单独的烧瓶中。用旋转蒸发器蒸除溶剂并干燥理解过程收集到的材料R为高电平真空两小时。 </li><li>如果需要的话，为了进一步纯化，从缺电子酰氯起始材料制备的ynone产品上执行一个小柱戊烷洗涤。在小规模，这可以使用巴氏吸管作为列执行。 <ol><li>溶解在最小量的氯仿中，DCM或二乙醚和负载的产品到硅胶柱上用戊烷湿。戊烷通过该柱洗脱1-2柱的长度，并收集到废烧杯中。 </li><li>洗脱使用乙醚或乙酸乙酯的戊烷塔的纯ynone产物。收集洗脱液在一个单独的烧瓶中，蒸发，并在高真空下放置了至少两小时。得到大约10毫克产物用于表征通过NMR光谱。 </li></ol></li></ol> Ynone 4.表征<ol><li>表征和评估使用1 H和13 C NMR谱的最终产品的纯度。34典型地，羰基碳的化学位移出现近177 ppm的在13 C NMR光谱。该ynone官能团的两个碳原子的SP由邻近87和93 ppm的特征峰来表示。 </li><li>用红外光谱仪34来识别ynone产物的特征羰峰。从相邻的三键电子离域通常会导致羰峰出现之间1600 1650 -1，这取决于该化合物的电子特性。 </li><li>确定产物的分子量，并使用高分辨率质谱进一步验证的身份。34 </li></ol>

<ol>
	<li>Bannwarth, P., Valleix, A., Gr&#233;e, D., Gr&#233;e, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flexible+Synthesis+of+Pyrimidines+with+Chiral+Monofluorinated+and+Difluoromethyl+Side+Chains.">Flexible Synthesis of Pyrimidines with Chiral Monofluorinated and Difluoromethyl Side Chains.</a> J. Org. Chem. 74, 4646-4649 (2009).</li><li>Karpov, A. S., Merkul, E., Rominger, F., M&#252;ller, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Concise+Syntheses+of+Meridianins+by+Carbonylative+Alkynylation+and+a+Four&#8208;Component+Pyrimidine+Synthesis.">Concise Syntheses of Meridianins by Carbonylative Alkynylation and a Four&#8208;Component Pyrimidine Synthesis.</a> Angew. Chem. Int. Ed. 44, 6951-6956 (2005).</li><li>Arcadi, A., Aschi, M., Marinelli, F., Verdecchia, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pd-catalyzed+regioselective+hydroarylation+of+&#945;-(2-aminoaryl)-&#945;,+&#946;-ynones+with+organoboron+derivatives+as+a+tool+for+the+synthesis+of+quinolines:+experimental+evidence+and+quantum-chemical+calculations.">Pd-catalyzed regioselective hydroarylation of &#945;-(2-aminoaryl)-&#945;, &#946;-ynones with organoboron derivatives as a tool for the synthesis of quinolines: experimental evidence and quantum-chemical calculations.</a> Tetrahedron. 64, 5354-5361 (2008).</li><li>Lee, C. G., Lee, K. Y., Lee, S., Kim, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemical+transformation+of+Baylis&#8211;Hillman+adducts:+the+reaction+of+methyl+3-arylamino-2-methylene-3-phenylpropanoates+in+polyphosphoric+acid.">Chemical transformation of Baylis&#8211;Hillman adducts: the reaction of methyl 3-arylamino-2-methylene-3-phenylpropanoates in polyphosphoric acid.</a> Tetrahedron. 61, 1493-1499 (2005).</li><li>Kirkham, J. D., Edeson, S. J., Stokes, S., Harrity, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Ynone+Trifluoroborates+toward+Functionalized+Pyrazoles.">Synthesis of Ynone Trifluoroborates toward Functionalized Pyrazoles.</a> Org. Lett. 14, 5354-5357 (2012).</li><li>Mohamed Ahmed, M. S., Kobayashi, K., Mori, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+construction+of+pyrazoles+and+isoxazoles+with+palladium-catalyzed+four-component+coupling.">One-pot construction of pyrazoles and isoxazoles with palladium-catalyzed four-component coupling.</a> Org. Lett. 7, 4487-4489 (2005).</li><li>Awuah, E., Capretta, A. <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+Flavones+via+a+Microwave-Assisted,+One-Pot+Sonogashira&#8722;+Carbonylation&#8722;+Annulation+Reaction.">Access to Flavones via a Microwave-Assisted, One-Pot Sonogashira&#8722; Carbonylation&#8722; Annulation Reaction.</a> Org. Lett. 11, 3210-3213 (2009).</li><li>She, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Trisubstituted+Isoxazoles+by+Palladium+(II)-Catalyzed+Cascade+Cyclization&#8211;Alkenylation+of+2-Alkyn-1-one+O-Methyl+Oximes.">Synthesis of Trisubstituted Isoxazoles by Palladium (II)-Catalyzed Cascade Cyclization&#8211;Alkenylation of 2-Alkyn-1-one O-Methyl Oximes.</a> J. Org. Chem. 77, 3627-3633 (2012).</li><li>Corey, E., Helal, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+electronic+effects+of+remote+substituents+on+the+oxazaborolidine-catalyzed+enantioselective+reduction+of+ketones.">Novel electronic effects of remote substituents on the oxazaborolidine-catalyzed enantioselective reduction of ketones.</a> Tetrahedron Lett. 36, 9153-9156 (1995).</li><li>Matsumura, K., Hashiguchi, S., Ikariya, T., Noyori, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+transfer+hydrogenation+of+&#945;,+&#946;-acetylenic+ketones.">Asymmetric transfer hydrogenation of &#945;, &#946;-acetylenic ketones.</a> J. Am. Chem. Soc. 119, 8738-8739 (1997).</li><li>Midland, M. M., McDowell, D. C., Hatch, R. L., Tramontano, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+of.+alpha.,.+beta.-acetylenic+ketones+with+B-3-pinanyl-9-borabicyclo+[3.3.+1]+nonane.+High+asymmetric+induction+in+aliphatic+systems.">Reduction of. alpha.,. beta.-acetylenic ketones with B-3-pinanyl-9-borabicyclo [3.3. 1] nonane. High asymmetric induction in aliphatic systems.</a> J. Am. Chem. Soc. 102, 867-869 (1980).</li><li>Logue, M. W., Moore, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cuprous+trimethylsilylacetylide.+Preparation+and+reaction+with+acid+chlorides.">Cuprous trimethylsilylacetylide. Preparation and reaction with acid chlorides.</a> J. Org. Chem. 40, 131-132 (1975).</li><li>Normant, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organocopper+(I)+Compounds+and+Organocuprates+in+Synthesis.">Organocopper (I) Compounds and Organocuprates in Synthesis.</a> Synthesis. , 63-80 (1972).</li><li>Logue, M. W., Teng, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium-catalyzed+reactions+of+acyl+chlorides+with+(1-alkynyl)+tributylstannanes.+A+convenient+synthesis+for+1-alkynyl+ketones.">Palladium-catalyzed reactions of acyl chlorides with (1-alkynyl) tributylstannanes. A convenient synthesis for 1-alkynyl ketones.</a> J. Org. Chem. 47, 2549-2553 (1982).</li><li>Nahm, S., Weinreb, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=N-Methoxy-N-methylamides+as+effective+acylating+agents.">N-Methoxy-N-methylamides as effective acylating agents.</a> Tetrahedron Lett. 22, 3815-3818 (1981).</li><li>Baba, T., Kizuka, H., Handa, H., Ono, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reaction+of+ketones+or+aldehydes+with+1-alkynes+over+solid-base+catalysts.">Reaction of ketones or aldehydes with 1-alkynes over solid-base catalysts.</a> Appl. Catal., A. 194, 203-211 (2000).</li><li>Brown, H. C., Garg, C. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+procedure+for+the+chromic+acid+oxidation+of+alcohols+to+ketones+of+high+purity.">A simple procedure for the chromic acid oxidation of alcohols to ketones of high purity.</a> J. Am. Chem. Soc. 83, 2952-2953 (1961).</li><li>Nishimura, T., Onoue, T., Ohe, K., Uemura, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium+(II)-catalyzed+oxidation+of+alcohols+to+aldehydes+and+ketones+by+molecular+oxygen.">Palladium (II)-catalyzed oxidation of alcohols to aldehydes and ketones by molecular oxygen.</a> J. Org. Chem. 64, 6750-6755 (1999).</li><li>Pu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+alkynylzinc+additions+to+aldehydes+and+ketones.">Asymmetric alkynylzinc additions to aldehydes and ketones.</a> Tetrahedron. 59, 9873-9886 (2003).</li><li>Kim, W., Park, K., Park, A., Choe, J., Lee, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pd-Catalyzed+Selective+Carbonylative+and+Non-carbonylative+Couplings+of+Propiolic+Acid:+One-Pot+Synthesis+of+Diarylalkynones.">Pd-Catalyzed Selective Carbonylative and Non-carbonylative Couplings of Propiolic Acid: One-Pot Synthesis of Diarylalkynones.</a> Org. Lett. 15, 1654-1657 (2013).</li><li>Kobayashi, T., Tanaka, M., Sakakura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Palladium(ii)+Complex-catalysed+Formation+of+a-Keto+Acids+via+Double+Carbonylation+of+Organic.">Palladium(ii) Complex-catalysed Formation of a-Keto Acids via Double Carbonylation of Organic.</a> Halides J. Chem. Soc., Chem. Commun. , 837-838 (1985).</li><li>Mohamed Ahmed, M. S., Mori, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carbonylative+Sonogashira+coupling+of+terminal+alkynes+with+aqueous+ammonia.">Carbonylative Sonogashira coupling of terminal alkynes with aqueous ammonia.</a> Org. Lett. 5, 3057-3060 (2003).</li><li>Vieira, A. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nucleophilic+Addition+of+Potassium+Alkynyltrifluoroborates+to+d-Glucal+Mediated+by+BF3&#183;+OEt2:+Highly+Stereoselective+Synthesis+of+&#945;-C-glycosides.">Nucleophilic Addition of Potassium Alkynyltrifluoroborates to d-Glucal Mediated by BF3&#183; OEt2: Highly Stereoselective Synthesis of &#945;-C-glycosides.</a> Org. Lett. 10, 5215-5218 (2008).</li><li>Darses, S., Genet, J. -. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potassium+organotrifluoroborates:+new+perspectives+in+organic+synthesis.">Potassium organotrifluoroborates: new perspectives in organic synthesis.</a> Chem. Rev. 108, 288-325 (2008).</li><li>Darses, S., Genet, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potassium+trifluoro+(organo)+borates:+new+perspectives+in+organic+chemistry.">Potassium trifluoro (organo) borates: new perspectives in organic chemistry.</a> Eur. J. Org. Chem. 2003, 4313-4327 (2003).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+Protected+Boronic+Acids+That+Expand+the+Versatility+of+the+Suzuki+Coupling+Reaction.">Organotrifluoroborates: Protected Boronic Acids That Expand the Versatility of the Suzuki Coupling Reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Stefani, H. A., Cella, R., Vieira, A. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+organotrifluoroborates+chemistry.">Recent advances in organotrifluoroborates chemistry.</a> Tetrahedron. 63, 3623-3658 (2007).</li><li>Matteson, D. S., Kim, G. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asymmetric+alkyldifluoroboranes+and+their+use+in+secondary+amine+synthesis.">Asymmetric alkyldifluoroboranes and their use in secondary amine synthesis.</a> Org. Lett. 4, 2153-2155 (2002).</li><li>Dumas, A. M., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Synthesis of Acyltrifluoroborates. Org. Lett. 14, 2138-2141 (2012).</li><li>Dumas, A. M., Molander, G. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amide&#8208;Forming+Ligation+of+Acyltrifluoroborates+and+Hydroxylamines+in+Water.">Amide&#8208;Forming Ligation of Acyltrifluoroborates and Hydroxylamines in Water.</a> Angew. Chem. Int. Ed. 51, 5683-5686 (2012).</li><li>Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+of+Dialkyl+Ethers+from+Organotrifluoroborates+and+Acetals.">Synthesis of Dialkyl Ethers from Organotrifluoroborates and Acetals.</a> J. Am. Chem. Soc. 131, 18057-18059 (2009).</li><li>Vo, C. -. V. T., Mitchell, T. A., Bode, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expanded+substrate+scope+and+improved+reactivity+of+ether-forming+cross-coupling+reactions+of+organotrifluoroborates+and+acetals.">Expanded substrate scope and improved reactivity of ether-forming cross-coupling reactions of organotrifluoroborates and acetals.</a> J. Am. Chem. Soc. 133, 14082-14089 (2011).</li><li>Zeng, J., Vedachalam, S., Xiang, S., Liu, X. -. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+C-Glycosylation+of+Organotrifluoroborates+with+Glycosyl+Fluorides+and+Its+Application+to+the+Total+Synthesis+of+(+)-Varitriol.">Direct C-Glycosylation of Organotrifluoroborates with Glycosyl Fluorides and Its Application to the Total Synthesis of (+)-Varitriol.</a> Org. Lett. 13, 42-45 (2010).</li><li>Lehman, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+student's+lab+companion:+laboratory+techniques+for+organic+chemistry:+standard+scale+and+microscale.">The student's lab companion: laboratory techniques for organic chemistry: standard scale and microscale.</a> Pearson College Div. , (2008).</li><li>Molander, G. A., Cavalcanti, L. N., Canturk, B., Pan, P. -. S., Kennedy, 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=Efficient+Hydrolysis+of+Organotrifluoroborates+via+Silica+Gel+and+Water.">Efficient Hydrolysis of Organotrifluoroborates via Silica Gel and Water.</a> 74, 7364-7369 (2009).</li><li>Molander, G. A., Ellis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organotrifluoroborates:+protected+boronic+acids+that+expand+the+versatility+of+the+Suzuki+coupling+reaction.">Organotrifluoroborates: protected boronic acids that expand the versatility of the Suzuki coupling reaction.</a> Acc. Chem. Res. 40, 275-286 (2007).</li><li>Calloway, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+Syntheses.">The Friedel-Crafts Syntheses.</a> Chem. Rev. 17, 327-392 (1935).</li><li>Gore, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel-Crafts+acylation+reaction+and+its+application+to+polycyclic+aromatic+hydrocarbons.">The Friedel-Crafts acylation reaction and its application to polycyclic aromatic hydrocarbons.</a> Chem. Rev. 55, 229-281 (1955).</li><li>Groves, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Friedel&#8211;Crafts+acylation+of+alkenes.">The Friedel&#8211;Crafts acylation of alkenes.</a> Chem. Soc. Rev. 1, 73-97 (1972).</li><li>Kim, B. J., Matteson, D. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conversion+of+alkyltrifluoroborates+into+alkyldichloroboranes+with+tetrachlorosilane+in+coordinating+solvents.">Conversion of alkyltrifluoroborates into alkyldichloroboranes with tetrachlorosilane in coordinating solvents.</a> Angew. Chem. 116, 3118-3120 (2004).</li><li>Thompson, L., Doraiswamy, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sonochemistry:+science+and+engineering.">Sonochemistry: science and engineering.</a> Ind. Eng. Chem. Res. 38, 1215-1249 (1999).</li></ol>

The authors declare that they have no competing financial interests.

表1示出了采取优化条件为苯乙炔三氟与苯甲酰氯反应，形成相应的ynone产物的步骤。最初，公知的organotrifluoroborates转换为organodifluoroboranes催化剂进行了测试。不幸的是硅胶，35四氯化硅，36和三氟化硼31,32没有促进形成所需ynone的（ 表1，条目1-3）。使用证明含氯路易斯酸催化剂，以获得更大的成功。在铁（III），氯化催化剂（ 表1，条目4）的存在下获得所需的ynone 1a的低收率。接着，铝（III），氯化了研究，作为其既定的能力，以促进在弗里德尔-克拉夫茨酰化oxocarbenium离子形成的结果。37-39需要的产物，产率62％时获得的铝（III），氯化催化剂为EMPloyed。 进一步的优化显示，空气和水分对反应的收率（ 表1，条目5-7）几乎没有影响。其结果是，随后的反应在非干燥的玻璃器皿中进行在空气的存在。尝试优化溶剂透露二氯甲烷（DCM）是特别适合的反应（ 表1，条目8-12）。在反应铝（III）氯化物催化的结果不一致促使替代性催化剂的探索。市售的铝（III），氯化六水合物是在反应条件（ 表1，条目13）下完全失活。这是一个很好的指标，铝（III），氯化水合物的形成抑制该反应。三氯化硼被发现产生类似的产量具有更好的一致性（ 表1，条目14）。 当钾alkynyltriflu互动oroborate用三氯化硼，更活泼的organodichloroborane物种形成。40该初始步骤是用于与酰氯的ynone并形成进行该反应的关键。因为organotrifluoroborate盐不溶于DCM中，将反应发生的非均相混合物。另外三氯化硼后，将溶液超声处理顺序通过增加三氟盐的可用以使该表面积，以促进形成反应二氯硼物种。超声波在反应混合物中的应用程序将导致通过空化气泡的产生机械影响。期间超声处理，空化气泡塌陷在流体导致高的温度和压力的局部区域41中冲击波产生的创建导致增加在固体三氟盐的动能微观湍流。期间超声促销系统中的能量的增加对三氟盐TES碎片而增加的表面积与三氯化硼交互。将反应混合物之前加入酰基氯为起始材料的超声处理保证了有效形成反应alkynyldichloroborane物种，而不需要更多的强制条件或更长的反应时间。 图2示出了当苯乙炔三氟用优化的反应条件下的各种酰氯的反应，所得到的结果。中性芳族（1B，1C）和脂族（1J-1）酰氯提供相应ynones在合成有用的产率。这些酰氯带有电子基团（1D-G）提供了良好的收益，而吸电子基团导致相对温和的收益率（1H，1I，1M）。有兴趣的朋友stingly，当吸电子基团位于邻位 （1I，59％），一显著产量增加相比于类似的对位观察取代的酰基氯（1H，30％）。该取代基中的邻位位置上的空间相互作用可能迫使羰基官能团出的平面，从而抵消了芳香环的吸电子性质。值得一提的是，4-溴丁酰氯反应，得到39％收率的所需产物1m上。据我们所知，这是第一个协议ynones合成容忍烷基溴官能团。偶尔，当酰基氯原料是中性或缺电子，脂族杂质出现在质子NMR。这可能需要一个戊烷洗涤以进一步提纯产物。虽然有可能，这是不经济的第一纯化S期期间执行戊烷洗因斯戊烷是昂贵相比己烷。二次纯化以较小规模分别完成诸如巴斯德吸管柱显著降低戊烷所需的量。 图3示出的alkynyltrifluoroborate盐的身份对反应产率的影响。在通常情况下，芳环上的苯基乙炔三氟盐轴承的给电子取代基的衍生物反应，用芳族和脂族酰基的氯化物，以产生所需的ynones良好至优良产率（2A-2C，3A-C）。脂族alkynyltrifluoroborate盐证明是较低反应性的底物。当hexynyl-和cyclopentylethynyltrifluoroborate盐进行反应与富电子苯甲酰氯衍生物（4α，5α）适度的产量已经被获得。 总之，新方法的编写Øf起酰基氯化物和钾alkynyltrifluoroborate盐ynones已经研制成功。通过该方法的范围从温和到优良取决于酰氯的性质获得ynones的合成收率和三氟起始原料。在一般的那些起始物承载给电子取代基进行反应更容易地比起始材料轴承中性和吸电子官能团。这种方法的价值在于方法的操作简便性和官能团的耐受性。这种直接的，一锅反应在环境温度下在三氯化硼的存在下迅速进行，而不排斥空气和湿气的。这种简便的方法可以采用ynones的制剂谦虚良好的收益从各种酰氯和alkynyltrifluoroborate盐。

The intention of this video is to demonstrate a straightforward approach for the preparation of compounds containing an ynone functional group from convenient starting materials. Ynones are valuable building blocks in organic chemistry that have been shown to have biomedical and material significance. Ynones are precursors to valuable organic functional groups including pyrimidines,1,2 quinolones,3 furans,4 pyrazoles,5,6 flavones,7 oximes,8 and chiral propargylic alcohols.9-11 A more convenient method for the preparation of ynones has been sought as a result of the drawbacks of traditional methods including poor functional group tolerance and tedious synthetic routes.
The reaction of metal12,13 and metalloid14 acetylides with acyl chlorides is one common route for the preparation of ynones. Alternatively, the synthesis of ynones from acyl chloride can be achieved via two-step procedures using Weinreb amides and organolithium or Grignard reagents.15 Another prevalent approach includes the addition of organolithium or Grignard reagents to an aldehyde, which is followed by the oxidation of a secondary alcohol to the corresponding ketone.16-19 Poor functional group tolerance of metal acetylides and the need to purify synthetic intermediates after each step are main deficiencies of the aforementioned methods. Transition-metal-catalyzed carbonylative couplings have recently emerged as an alternative approach for the preparation of ynones.20-22 Unfortunately, in addition to cost and toxicity associated with transition metals, metal-catalyzed carbonylative reactions often require elevated CO pressures and suffer from the presence of an undesired Sonogashira coupling byproduct. Given their utility in organic synthesis as well as the drawbacks associated with traditional synthetic methods, the development of a more straightforward method for the preparation of ynones is appealing.
Potassium organotrifluoroborate salts have recently emerged as versatile reagents in organic synthesis. Advantages including ease of preparation,23 inherent stability, low toxicity, and good functional group tolerance have made organotrifluoroborate salts attractive synthetic reagents.24-27 Organotrifluoroborate salts have been used primarily as a bench-stable equivalent of boronic acids for palladium-catalyzed Suzuki-Miyaura coupling.26 Recently, following a seminal work by Matteson and co-workers,28 Bode, Molander and others have highlighted the utility of organotrifluoroborates as reagents in non-metal catalyzed reactions.29-33 The field of transition-metal-free reactions of trifluoroborates is still in its infancy stage. Given the great potential for use of organotrifluoroborate salts in non-metal catalyzed organic synthesis, we sought to develop a novel method for the preparation of ynones from acyl chlorides and alkynyltrifluoroborate salts.

<table><tbody><tr><td>Sonicator</td><td>VGT</td><td>1860QT</td><td>Ultrasonic cleaner. Similar sonication devices may be used.</td></tr><tr><td>Dichloromethane</td><td>Sigma</td><td>270997</td><td>Anhydrous</td></tr><tr><td>Boron trichloride solution&amp;nbsp;</td><td>Sigma</td><td>178934</td><td>1 M solution in DCM</td></tr><tr><td>Acyl chloride</td><td>Sigma</td><td>Various</td><td>Acyl chlorides from other suppliers such as Alfa Aesar may be used. Caution: refer to MSDS for safety information.</td></tr><tr><td>Potassium alkynyltrifluoroborate salt</td><td>N/A</td><td>N/A</td><td>Synthesized&lt;sup&gt;23 &lt;/sup&gt;from terminal alkyne</td></tr><tr><td>Ethyl acetate</td><td>ACP</td><td>E-2000</td><td>ACS grade</td></tr><tr><td>Hexanes</td><td>ACP</td><td>H-3500</td><td>ACS grade</td></tr><tr><td>Pentane</td><td>Sigma</td><td>236705</td><td>Anhydrous</td></tr><tr><td>Magnesium sulfate</td><td>Sigma</td><td>M7506</td><td></td></tr><tr><td>Filter paper</td><td>Whatman</td><td>1093 126</td><td>Student grade. This speceific variety is not necessary.</td></tr><tr><td>Silica Gel 60</td><td>EMD</td><td>1.11567.9026</td><td>Particle size 0.040-0.063</td></tr></tbody></table>

metal-free synthesis of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride.

最初的努力都集中围绕由苯乙炔三氟S1和苯甲酰氯（ 图1）的制备ynone 1a的。 表1示出了优化步骤来执行，包括各种路易斯酸，溶剂，以及检查的水对反应的影响的筛选。接着，将反应的范围已探索通过提交苯乙炔三氟到优化条件下在各种酰氯的存在（ 图2）。温和至优异的产量可取决于酰氯衬底的性质而获得。该反应的范围已进一步通过alkynyltrifluoroborate盐的几个其他示例的准备进行评价。 图3示出了可以在开发的条件下ynones的制备可以采用其他alkynyltrifluoroborate盐中的例子。啉衍生物ylacetylene三氟轴承电子捐赠取代给予相应的ynone产品优良率，而alkynyltrifluoroborate盐的脂肪族衍生物被证明是略少反应，得到适度的产量。 <img alt="图1" src="/files/ftp_upload/52401/52401fig1highres.jpg" /> 图1:示出了用于ynone 1a的制备包括形成反应性中间体二氯硼烷的条件从苯乙炔三氟S1和苯甲酰氯方案制备Ynone 1a的 。 <img alt="图2" src="/files/ftp_upload/52401/52401fig2highres.jpg" /> 图2:ynone 1a的代表1 H NMR谱的化学位移和特性的质子的相对积分来标记。 图3:ynone 1a的代表。13 C NMR光谱特性的碳的化学位移被标记。 <img alt="图4" src="/files/ftp_upload/52401/52401fig4highres.jpg" /> 图4: 通过常压化学电离得到ynone 1a的代表性的HRMS光谱的[M + H]所述的测定m / z值+离子被报告。 <img alt="图5" src="/files/ftp_upload/52401/52401fig5highres.jpg" /> 图5:phenylacetylenetrifluoroborate盐S1反应与酰基氯的结构和产率通过改变身份生产的产品。酰基氯的原料的图示。反应运行与1当量的酰氯，1.5当量钾phenylacetylenetrifluoroborate S1中，与1.5当量的三氯化硼。 <img alt="图6" src="/files/ftp_upload/52401/52401fig6highres.jpg" /> 图6:不同alkynyltrifluoroborates与酰氯的结构和产率通过改变alkynyltrifluoroborate原料的身份生产的产品的反应如下所示。反应运行与1当量的酰氯，2.5当量钾organotrifluoroborate盐和2.5当量的三氯化硼。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> 输入 </td><td> 路易斯酸 </td><td> 路易斯酸（当量） </td><td> 条件 </td><td> 产量（％） </td></tr><tr><td> 1 B &lt;/ SUP&gt; </td><td> SiO 2的</td><td> 16.5 </td><td> 的 CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 2 </td><td> 四氯化硅</td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td>跟踪</td></tr><tr><td> 3 </td><td> BF 3·OET 2 </td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td>跟踪</td></tr><tr><td> 4 B </td><td> 氯化铁</td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 24 </td></tr><tr><td> 5℃ </td><td> 3氯化铝</td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 62 </td></tr><tr><td> 6天</td><td> 3氯化铝</td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 66 </td></tr><tr><td> 7ê </td><td> 3氯化铝</td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 60 </td></tr><tr><td> 8 </td><td> 3氯化铝</子&gt; </td><td> 1 </td><td> THF </td><td>跟踪</td></tr><tr><td> 9 </td><td> 3氯化铝</td><td> 1 </td><td>甲苯</td><td>跟踪</td></tr><tr><td> 10 </td><td> 3氯化铝</td><td> 2 </td><td> CLCH 2的CH 2 Cl </td><td> 33 </td></tr><tr><td> 11 </td><td> 3氯化铝</td><td> 1 </td><td> DMSO </td><td>跟踪</td></tr><tr><td> 12 </td><td> 3氯化铝</td><td> 2 </td><td>乙腈</td><td>跟踪</td></tr><tr><td> 13 </td><td>氯化铝3·6H 2 O </td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 0 </td></tr><tr><td> 14 B </td><td> BCL 3 </td><td> 1.5 </td><td> 的 CH 2 Cl 2 </td><td> 67 </td></tr><tr><td> 15 </td><td> BBR 3 </td><td> 1 </td><td> 的 CH 2 Cl 2 </td><td> 20 </td></tr></tbody></table><stro纳克&gt;表1:产品的优化条件，供的ynone 1a 上的制备产率 1a的反应条件和路易斯酸催化剂的变化时。 一个反应是运行用1当量苯甲酰氯和1当量的钾phenylacetylenetrifluoroborate S1。B 1.5当量S1。Ç无水条件D中的反应物在空气下的非干燥的玻璃器皿进行即无水条件+1微升水中。

Watch this Scientific Journal Video about Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts at JoVE.com

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

Ynones从酰氯和钾Alkynyltrifluoroborate盐无金属合成

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups ...

metal-free-synthesis-ynones-from-acyl-chlorides-potassium

Research

Education

JoVE Journal

JoVE Core

Chemistry

Organic Chemistry

Unit 1

Carboxylic Acid Derivatives

Alkynes

SCIENTISTS IN ACTION

11.1K 次观看.  University of Ontario Institute of Technology. The goal of this manuscript is to demonstrate a straightforward method for the preparation of ynones from acyl chloride and potassium alkynyltrifluoroborate salt starting materials. The one-pot reaction proceeds rapidly in the presence of boron trichloride without exclusion of air and moisture.

视频: Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

高价碘鎓炔基三氟甲磺酸酯的生成Cyanocarbenes的合成应用

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

科研

化学

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 &#176;C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

协议的合成<em&gt;邻</em&gt; -trifluoromethoxylated苯胺类化合物

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond&#8211;forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

A two step one-pot protocol for the umpolung of ketone enolates to enolonium species and addition of a nucleophile to the &#945;-position is described. Nucleophiles include chloride, azide, azoles, allyl-silanes, and aromatic compounds.

Enolonium 种极性转换酮功能化的两步协议

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

Application of Elemental Lanthanides in the Selective C-F Activation of Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the possibility of accessing unique fluorine-containing molecules, which are difficult to obtain by other synthetic pathways. Among various metals, which can undergo C-F activation, lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide metals are strong reducing agents with a redox potential Ln3+/Ln&#160;of approximately -2.3 V, which is comparable to the value of the Mg2+/Mg&#160;redox couple. In addition, lanthanide metals display a promising functional group tolerance and their reactivity can vary along the lanthanide series, making them suitable reagents for fine-tuning reaction conditions in organic and organometallic transformations. However, due to their oxophilicity, lanthanides react readily with oxygen and water and therefore require special conditions for storage, handling, preparation, and activation. These factors have limited a more widespread use in organic synthesis. We herein present how dysprosium metal - and by analogy all lanthanide metals - can be freshly prepared under anhydrous conditions using glovebox and Schlenk techniques. The freshly filed metal, in combination with aluminum chloride, initiates the selective C-F activation in trifluoromethylated benzofulvenes. The resulting reaction intermediates react with nitroalkenes to obtain a new family of difluoroalkenes.

This protocol describes the preparation of elemental lanthanides under inert atmosphere and their application in a selective C-F activation process involving trifluoromethylated benzofulvenes.

元素镧在选择性 c-F 活化 Trifluoromethylated Benzofulvenes 中的应用提供各种 Difluoroalkenes 的访问

The selective activation of one carbon-fluorine bond in polyfluorinated aromatic molecules or in trifluoromethyl-containing substrates offers the ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

基于末端碘氧化炔烃的 1-Iodoalkynes、12-Diiodoalkenes、11、2 Triiodoalkenes 的 Chemoselective 制备

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC&#8211;NHC &#8220;Wanzlick&#8221; dimer and the synthesis of the related stable organic &#8220;olefin&#8221; radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick&#8217;s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed &#8220;Wanzlick dimer&#8221; and the reduced stable organic radical.

分离游离卡本内斯、其混合二聚体和有机自由基

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the ...

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

The conjugate addition of organometallic reagents to &#945;,&#946;-unsaturated carbonyls represents an important method to generate C&#8211;C bonds in the preparation of all-carbon quaternary centers. Though conjugate additions of organometallic reagents are typically performed utilizing highly reactive organolithium or Grignard reagents, organozinc reagents have garnered attention for their enhanced chemoselectivity and mild reactivity. Despite numerous recent advances with more reactive diorganozinc and mixed diorganozinc reagents, the generation of all-carbon quaternary centers via the conjugate addition of functionalized monoorganozinc reagents remains a challenge. This protocol details a convenient and mild &#8220;one-pot&#8221; preparation and copper mediated conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to afford a broad scope of all-carbon quaternary centers in generally excellent yield and diastereoselectivity. Key to the development of this technology is the utilization of DMA as a reaction solvent with TMSCl as a Lewis acid. Notable advantages to this methodology include the operational simplicity of the organozinc reagent preparation afforded by the utilization of DMA as a solvent, as well as an efficient conjugate addition mediated by various Cu(I) and Cu(II) salts. Moreover, an intermediate silyl enol ether can be isolated utilizing a modified workup procedure. The substrate scope is limited to cyclic unsaturated ketones, and the conjugate addition is impeded by stabilized (e.g., allyl, enolate, homoenolate) and sterically encumbered (e.g., neopentyl, o-aryl) monoorganozinc reagents. Conjugate additions to five- and seven-membered rings were effective, albeit in lower yields compared with six-membered ring substrates.

A simple and practical protocol for the efficient conjugate addition of functionalized monoorganozinc bromides to cyclic &#945;,&#946;-unsaturated carbonyls to furnish all-carbon quaternary centers was developed.

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 ...

Acidity of 1-Alkynes

<h4></h4>
The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa &#8212; the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1left" src="/files/ftp_upload/11833/11833_PT_Figure_1_left.svg" style="text-align: center; height: 75px;" /> 
			Ethane 
			(pKa&#160;= 51)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure1middle" src="/files/ftp_upload/11833/11833_PT_Figure_1_Middle.svg" style="text-align: center; height: 50px;" /> 
			 
			Ethene 
			(pKa&#160;= 44)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			
			<img alt="Figure1right" src="/files/ftp_upload/11833/11833_PT_Figure_1_Right.svg" style="text-align: center; height: 20px;" /> 
			 
			&#160;
			Ethyne 
			(pKa&#160;= 25)
			</td>
		</tr>
	</tbody>
</table>
With a pKa difference of 26 units, acetylene is 1026 times more acidic than ethane. Similarly, a difference of 19 pKa units makes it 1019 times stronger than ethene.
<h4>Hybridization effect</h4>
The pronounced increase in the acidity of terminal alkynes relative to the other hydrocarbons can be explained by considering the stability of the corresponding carbanions formed by deprotonation. Note that, in the nomenclature of organic compounds, the suffix &#34;-ide&#34; indicates that the molecule is a negatively charged ion.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2top" src="/files/ftp_upload/11833/11833_PT_Figure_2_top.svg" style="text-align: center; height: 80px;" /> 
			ethanide&#160;(an alkyl anion) 
			sp3&#160;lone pair, 25% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2middle" src="/files/ftp_upload/11833/11833_PT_Figure_2_middle.svg" style="text-align: center; height: 60px;" /> 
			ethenide&#160;(a vinylic anion) 
			sp2&#160;lone pair, 33% &#8220;s&#8221; character</td>
		</tr>
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure2bottom" src="/files/ftp_upload/11833/11833_PT_Figure_2_bottom.svg" style="text-align: center; height: 40px;" /> 
			acetylide&#160;(an acetylenic anion) 
			sp&#160;lone pair, 50% &#8220;s&#8221; character</td>
		</tr>
	</tbody>
</table>
The stability of the carbanion depends on the nature of the hybridized orbital occupied by the lone pair of electrons. As shown above, in ethane&#160;the lone pair resides in an sp3 orbital, while in ethene&#160;it occupies the sp2 orbital and an sp orbital in the case of acetylene. The sp3, sp2, and sp orbitals have 25%, 33%, and 50% &#34;s&#34; character, respectively. Since &#34;s&#34; orbitals are closer to the positively charged nucleus, a hybrid orbital with a higher &#34;s&#34; character will effectively stabilize the negative charge. Thus, the acetylide ions will be the most stable and readily formed in the presence of a suitable base.
<h4>Choosing a suitable base</h4>
In general, for a base to deprotonate an acid, the pKa of the base&#39;s conjugate acid must be at least 10 pKa units greater than that of the acid.
<img alt="Figure3" src="/files/ftp_upload/11833/11833_Figure_3v2.svg" style="text-align: center; height: 80px;" />
Terminal alkynes have a pKa of 25. Therefore, an appropriate base would be one where the conjugate acid has a pKa that is at least 35. Recall that for an acid-base reaction, the equilibrium favors the formation of weaker acids and bases from stronger acids and bases.
stronger acids + stronger bases <img alt="arrow" src="/files/ftp_upload/11833/arrow.png" style="text-align: center; height: 13px;" />weaker acids + weaker bases
With sodium amide as the base, terminal alkynes form sodium acetylide and ammonia as the conjugate acid. Since the pKa of ammonia is greater than 25, the equilibrium favors the formation of sodium acetylide, making sodium amide a strong enough base for the deprotonation reaction.
<img alt="Figure4" src="/files/ftp_upload/11833/11833_Figure_4.svg" style="text-align: center; height: 100px;" />
Apart from sodium amide, sodium hydride, butyllithium, and lithium diisopropylamide (LDA) are other commonly used bases to form acetylide ions.
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;">
			<img alt="Figure5left" src="/files/ftp_upload/11833/11833_PT_Figure_5_left.svg" style="height: 25px;" />
			Sodium hydride
			</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5middle" src="/files/ftp_upload/11833/11833_PT_Figure_5_middle.svg" style="text-align: center; height: 60px;" /> 
			Butyllithium (n-BuLi)</td>
			<td style="border-style: solid; border-color: black; color: black; text-align: center;"><img alt="Figure5right" src="/files/ftp_upload/11833/11833_PT_Figure_5_right.svg" style="text-align: center; height: 60px;" /> 
			Lithium diisopropylamide (LDA)</td>
		</tr>
	</tbody>
</table>
In the presence of sodium hydroxide as the base, terminal alkynes form sodium acetylide and water as the conjugate acid. However, since the pKa of water is less than 25, the equilibrium favors the reactants. Therefore, sodium hydroxide is not a suitable base to form acetylide ions.
<img alt="Figure6" src="/files/ftp_upload/11833/11833_Figure_6.svg" style="text-align: center; height: 110px;" />
<h4>Synthesis of organometallic reagents </h4>
The relative acidity of terminal alkynes finds application in the synthesis of organometallic compounds when treated with Grignard or organolithium reagents. These are examples of transmetalation reactions involving the transfer of a metal atom from one carbon to another, thereby forming new metal&#8211;carbon bonds. However, they can also be interpreted as acid&#8211;base reactions that favor the formation of weaker acids and bases.
<img alt="Figure7top" src="/files/ftp_upload/11833/11833_Figure_7v3.svg" style="text-align: center; height: 225px;" />
<div></div>

Acidity of Terminal Alkynes: Formation of Acetylide Anions

1-炔烃的酸度


The acidic strength of hydrocarbons follows the order: Alkynes &#62; Alkenes &#62; Alkanes. The strength of an acid is commonly expressed in units of pKa ...

教育

有机化学

炔烃

关键术语与概念

Preparation of Alkynes: Alkylation Reaction

<h4>Introduction</h4>
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
<img alt="Figure1" src="/files/ftp_upload/11834/11834_PT_Figure_1.svg" style="text-align: center; height: 50px;" />
The reaction takes place in two steps:
1. The first step is the deprotonation of the terminal alkyne by the strong base forming an acetylide ion.
<img alt="Figure2" src="/files/ftp_upload/11834/11834_PT_Figure_2.svg" style="text-align: center; height: 50px;" />
2. The second step is a nucleophilic substitution reaction in which the acetylide ion reacts with the alkyl halide to form a new C&#8211;C bond.
<img alt="Figure3" src="/files/ftp_upload/11834/11834_PT_Figure_3.svg" style="text-align: center; height: 50px;" />
<h4>Reaction Mechanism &#8212;SN2 pathway </h4>
Acetylide ions are strong bases and can also function as good nucleophiles. The substitution reaction follows an SN2 pathway where the nucleophilic acetylide ion attacks the electrophilic carbon of the primary alkyl halide from the backside.
<img alt="Figure4" src="/files/ftp_upload/11834/11834_PT_Figure_4.svg" style="text-align: center; height: 250px;" />
Since this is a concerted process, the nucleophilic attack and the departure of the leaving group takes place simultaneously to form the product with an inverted stereochemistry at the reaction center.
The reaction works best with unhindered alkyl halides like methyl halide and other primary halides. With secondary and tertiary alkyl halides, acetylide ions act as strong bases, in which case E2 elimination is the preferred pathway.
<h4>Application in organic synthesis </h4>
Alkylation of simple terminal alkynes is a useful method to extend the length of the carbon chain. Acetylene, a terminal alkyne, can be converted to a higher internal alkyne by repeated alkylation as shown below:
<img alt="Figure5" src="/files/ftp_upload/11834/11834_PT_Figure_5.svg" style="text-align: center; height: 50px;" />

炔烃的制备:烷基化反应

Introduction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for ...

Preparation of Alkynes: Dehydrohalogenation

<h4>Introduction</h4>
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
<img alt="Figure1" src="/files/ftp_upload/11835/11835_PT_Figure_1.svg" style="text-align: center; height: 200px;" />
<h4>Reaction Mechanism &#8211; E2 pathway</h4>
Vicinal dihalides
In the first elimination step, the strong base abstracts the proton from the dihalide that is oriented anti to the leaving group. Since E2 reactions follow a concerted pathway, the abstraction of a proton and departure of the halide leaving group occur simultaneously to form a haloalkene.
<img alt="Figure2" src="/files/ftp_upload/11835/11835_PT_Figure_2.svg" style="text-align: center; height: 90px;" />
In the second elimination reaction, another equivalent of the strong base reacts with the haloalkene in a similar fashion to give the desired alkyne.
<img alt="Figure3" src="/files/ftp_upload/11835/11835_PT_Figure_3.svg" style="text-align: center; height: 90px;" />
Geminal dihalides
Likewise, geminal dihalides, when treated with two equivalents of a sodium amide, undergo double dehydrohalogenation to give alkynes.
<img alt="Figure4" src="/files/ftp_upload/11835/11835_PT_Figure_4.svg" style="text-align: center; height: 90px;" />
<img alt="Figure5" src="/files/ftp_upload/11835/11835_PT_Figure_5.svg" style="text-align: center; height: 90px;" />
Terminal dihalides 
Dehydrohalogenation of terminal dihalides yields terminal alkynes as the final product. In the presence of a strong base like sodium amide, terminal alkynes get converted to acetylide ions. In such cases, a third equivalent of the base is required to complete the dehydrohalogenation of the remaining haloalkene.
<img alt="Figure6" src="/files/ftp_upload/11835/11835_PT_Figure_6.svg" style="text-align: center; height: 70px;" />
Protonation of the acetylide ions with water or an aqueous acid completes the reaction.
<img alt="Figure7" src="/files/ftp_upload/11835/11835_PT_Figure_7.svg" style="text-align: center; height: 50px;" />
<h4>Application in Organic Synthesis</h4>
Dehydrohalogenation of vicinal dihalides is a useful intermediate step in the conversion of alkenes to alkynes. For example, chlorination of 1-propene gives 1,2-dichloropropane &#8211; a vicinal dihalide, which upon double dehydrohalogenation yields 1-propyne.
<img alt="Figure8" src="/files/ftp_upload/11835/11835_PT_Figure_8.svg" style="text-align: center; height: 60px;" />
Similarly, alkynes can also be synthesized from ketones via dehydrohalogenation of geminal dihalides. For example, treatment of acetone with phosphorous pentachloride yields 2,2-dichloropropane &#8211; a geminal dihalide, which undergoes double dehydrohalogenation to give 1-propyne.
<img alt="Figure9" src="/files/ftp_upload/11835/11835_PT_Figure_9.svg" style="text-align: center; height: 80px;" />

炔烃的制备:脱卤化氢

Introduction
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ...