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>

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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 border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Name of Material/ Equipment</td>
			<td style="width:71px;">Company</td>
			<td style="width:119px;">Catalog Number</td>
			<td style="width:167px;">Comments/Description</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Sonicator</td>
			<td style="width:71px;">VGT</td>
			<td style="width:119px;">1860QT</td>
			<td>Ultrasonic cleaner. Similar sonication devices may be used.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Dichloromethane</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">270997</td>
			<td>Anhydrous</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Boron trichloride solution&#160;</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">178934</td>
			<td>1M solution in DCM</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Acyl chloride</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">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 height="42">
			<td height="42" style="height:42px;width:216px;">Potassium alkynyltrifluoroborate salt</td>
			<td style="width:71px;">N/A</td>
			<td style="width:119px;">N/A</td>
			<td>Synthesized23 from terminal alkyne</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Ethyl acetate</td>
			<td style="width:71px;">ACP</td>
			<td style="width:119px;">E-2000</td>
			<td>ACS grade</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hexanes</td>
			<td style="width:71px;">ACP</td>
			<td style="width:119px;">H-3500</td>
			<td>ACS grade</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pentane</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">236705</td>
			<td>Anhydrous</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Magnesium sulfate</td>
			<td style="width:71px;">Sigma</td>
			<td style="width:119px;">M7506</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Filter paper</td>
			<td style="width:71px;">Whatman</td>
			<td style="width:119px;">1093 126</td>
			<td>Student grade. This speceific variety is not necessary.</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Silica Gel 60</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">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 ...

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Alkynes

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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

Preparation and Use of Samarium Diiodide (SmI2) in Organic Synthesis: The Mechanistic Role of HMPA and Ni(II) Salts in the Samarium Barbier Reaction

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of molecular iodine to samarium metal in THF.1,2-3 It is a mild and selective single electron reductant and its versatility is a result of its ability to initiate a wide range of reductions including C-C bond-forming and cascade or sequential reactions. SmI2 can reduce a variety of functional groups including sulfoxides and sulfones, phosphine oxides, epoxides, alkyl and aryl halides, carbonyls, and conjugated double bonds.2-12 One of the fascinating features of SmI-2-mediated reactions is the ability to manipulate the outcome of reactions through the selective use of cosolvents or additives. In most instances, additives are essential in controlling the rate of reduction and the chemo- or stereoselectivity of reactions.13-14 Additives commonly utilized to fine tune the reactivity of SmI2 can be classified into three major groups: (1) Lewis bases (HMPA, other electron-donor ligands, chelating ethers, etc.), (2) proton sources (alcohols, water etc.), and (3) inorganic additives (Ni(acac)2, FeCl3, etc).3
Understanding the mechanism of SmI2 reactions and the role of the additives enables utilization of the full potential of the reagent in organic synthesis. The Sm-Barbier reaction is chosen to illustrate the synthetic importance and mechanistic role of two common additives: HMPA and Ni(II) in this reaction. The Sm-Barbier reaction is similar to the traditional Grignard reaction with the only difference being that the alkyl halide, carbonyl, and Sm reductant are mixed simultaneously in one pot.1,15 Examples of Sm-mediated Barbier reactions with a range of coupling partners have been reported,1,3,7,10,12 and have been utilized in key steps of the synthesis of large natural products.16,17 Previous studies on the effect of additives on SmI2 reactions have shown that HMPA enhances the reduction potential of SmI2 by coordinating to the samarium metal center, producing a more powerful,13-14,18 sterically encumbered reductant19-21 and in some cases playing an integral role in post electron-transfer steps facilitating subsequent bond-forming events.22 In the Sm-Barbier reaction, HMPA has been shown to additionally activate the alkyl halide by forming a complex in a pre-equilibrium step.23
Ni(II) salts are a catalytic additive used frequently in Sm-mediated transformations.24-27 Though critical for success, the mechanistic role of Ni(II) was not known in these reactions. Recently it has been shown that SmI2 reduces Ni(II) to Ni(0), and the reaction is then carried out through organometallic Ni(0) chemistry.28
These mechanistic studies highlight that although the same Barbier product is obtained, the use of different additives in the SmI2 reaction drastically alters the mechanistic pathway of the reaction. The protocol for running these SmI2-initiated reactions is described.

Preparation and Use of Samarium Diiodide SmI2 in Organic Synthesis: The Mechanistic Role of HMPA and NiII Salts in the Samarium Barbier Reaction

A straightforward procedure for the preparation of samarium diiodide (SmI2) in THF is described. The role of two main additives namely hexamethylphosphoramide (HMPA) and Ni(acac)2 in Sm mediated reactions is demonstrated in the Sm-Barbier reaction.

二碘化钐的制备和使用（SMI<sub&gt; 2</sub&gt;）在有机合成中：HMPA和镍（II）盐的钐巴尔比耶反应的机理作用

Although initially considered an esoteric reagent, SmI2 has become a common tool for synthetic organic chemists. SmI2 is generated through the addition of ...

科研

化学

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

The traditional strategy for the introduction of chemical functionalities is the use of solid-phase synthesis by appending suitably modified phosphoramidite precursors to the nascent chain. However, the conditions used during the synthesis and the restriction to rather short sequences hamper the applicability of this methodology. On the other hand, modified nucleoside triphosphates are activated building blocks that have been employed for the mild introduction of numerous functional groups into nucleic acids, a strategy that paves the way for the use of modified nucleic acids in a wide-ranging palette of practical applications such as functional tagging and generation of ribozymes and DNAzymes. One of the major challenges resides in the intricacy of the methodology leading to the isolation and characterization of these nucleoside analogues.
	
	In this video article, we present a detailed protocol for the synthesis of these modified analogues using phosphorous(III)-based reagents. In addition, the procedure for their biochemical characterization is divulged, with a special emphasis on primer extension reactions and TdT tailing polymerization. This detailed protocol will be of use for the crafting of modified dNTPs and their further use in chemical biology.

The protocol described herein aims to explain and abridge the numerous obstacles in the way of the intricate route leading to modified nucleoside triphosphates. Consequently, this protocol facilitates both the synthesis of these activated building-blocks and their availability for practical applications.

核苷三磷酸 - 从合成到生化特征

The  traditional strategy for the introduction of chemical functionalities is the  use of solid-phase synthesis by appending suitably modified ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

超分子胶体的合成与表征

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. The complexes were tested for catalytic activity in arylation and Suzuki-Miyaura reactions. For each reaction investigated, at least one of the four complexes successfully catalyzed the reaction.

钯<em&gt;ñ</em&gt; - 杂环碳烯配合物：苯并咪唑盐的合成和碳 - 碳键合反应中的催化活性

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

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 ...

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. Their synthesis by conventional organic chemistry often requires tedious multi-step synthesis processes, with difficult control of the stereochemical outcome. We present a protocol to enzymatically synthetize amino alcohols starting from the readily available L-lysine in 48 h. This protocol combines two chemical reactions that are very difficult to conduct by conventional organic synthesis. In the first step, the regio- and diastereoselective oxidation of an unactivated C-H bond of the lysine side-chain is catalyzed by a dioxygenase; a second regio- and diastereoselective oxidation catalyzed by a regiodivergent dioxygenase can lead to the formation of the 1,2-diols. In the last step, the carboxylic group of the alpha amino acid is cleaved by a pyridoxal-phosphate (PLP) decarboxylase (DC). This decarboxylative step only affects the alpha carbon of the amino acid, retaining the hydroxy-substituted stereogenic center in a beta/gamma position. The resulting amino alcohols are therefore optically enriched. The protocol was successfully applied to the semipreparative-scale synthesis of four amino alcohols. Monitoring of the reactions was conducted by high performance liquid chromatography (HPLC) after derivatization by 1-fluoro-2,4-dinitrobenzene. Straightforward purification by solid-phase extraction (SPE) afforded the amino alcohols with excellent yields (93% to &#62;95%).

Chiral amino alcohols are versatile molecules for use as scaffolds in organic synthesis. Starting from L-lysine, we synthesize amino alcohols by an enzymatic cascade reaction combining diastereoselective C-H oxidation catalyzed by dioxygenase followed by cleavage of the carboxylic acid moiety of the corresponding hydroxyl amino acid by a decarboxylase.

酶联反应合成 l-赖氨酸手性氨基醇的研究

Amino alcohols are versatile compounds with a wide range of applications. For instance, they have been used as chiral scaffolds in organic synthesis. ...

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

Advancing synthetic capabilities is important for the development of nanoscience and nanotechnology. The synthesis of nanowires has always been a challenge, as it requires asymmetric growth of symmetric crystals. Here, we report a distinctive synthesis of substrate-bound Au nanowires. This template-free synthesis employs thiolated ligands and substrate adsorption to achieve the continuous asymmetric deposition of Au in solution at ambient conditions. The thiolated ligand prevented the Au deposition on the exposed surface of the seeds, so the Au deposition only occurs at the interface between the Au seeds and the substrate. The side of the newly deposited Au nanowires is immediately covered with the thiolated ligand, while the bottom facing the substrate remains ligand-free and active for the next round of Au deposition. We further demonstrate that this Au nanowire growth can be induced on various substrates, and different thiolated ligands can be used to regulate the surface chemistry of the nanowires. The diameter of the nanowires can also be controlled with mixed ligands, in which another &#34;bad&#34; ligand could turn on the lateral growth. With the understanding of the mechanism, Au nanowire-based nanostructures can be designed and synthesized.

We report a solution-based method to synthesize substrate-bound Au nanowires. By tuning the molecular ligands used during the synthesis, the Au nanowires can be grown from various substrates with different surface properties. Au nanowire-based nanostructures can also be synthesized by adjusting the reaction parameters.

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 ...

Synthesis and Characterization of Amphiphilic Gold Nanoparticles

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of their interactions with cell membranes, lipid bilayers, and viruses. The hydrophilic ligands make these particles colloidally stable in aqueous solutions and the combination with hydrophobic ligands creates an amphiphilic particle that can be loaded with hydrophobic drugs, fuse with the lipid membranes, and resist nonspecific protein adsorption. Many of these properties depend on nanoparticle size and the composition of the ligand shell. It is, therefore, crucial to have a reproducible synthetic method and reliable characterization techniques that allow the determination of nanoparticle properties and the ligand shell composition. Here, a one-phase chemical reduction, followed by a thorough purification to synthesize these nanoparticles with diameters below 5 nm, is presented. The ratio between the two ligands on the surface of the nanoparticle can be tuned through their stoichiometric ratio used during synthesis. We demonstrate how various routine techniques, such as transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and ultraviolet-visible (UV-Vis) spectrometry, are combined to comprehensively characterize the physicochemical parameters of the nanoparticles.

Amphiphilic gold nanoparticles can be used in many biological applications. A protocol to synthesize gold nanoparticles coated by a binary mixture of ligands and a detailed characterization of these particles is presented.

两栖金纳米粒子的合成与表征

Gold nanoparticles covered with a mixture of 1-octanethiol (OT) and 11-mercapto-1-undecane sulfonic acid (MUS) have been extensively studied because of ...

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for generating potential synthetic solutions. The programmable one-pot oligosaccharide synthesis approach is designed to empower fast oligosaccharide synthesis of large amounts using thioglycoside building blocks (BBLs) with the appropriate sequential order of relative reactivity values (RRVs). Auto-CHO is a cross-platform software with a graphical user interface that provides possible synthetic solutions for programmable one-pot oligosaccharide synthesis by searching a BBL library (containing about 150 validated and &#62;50,000 virtual BBLs) with accurately predicted RRVs by support vector regression. The algorithm for hierarchical one-pot synthesis has been implemented in Auto-CHO and uses fragments generated by one-pot reactions as new BBLs. In addition, Auto-CHO allows users to give feedback for virtual BBLs to keep valuable ones for further use. One-pot synthesis of stage-specific embryonic antigen 4 (SSEA-4), which is a pluripotent human embryonic stem cell marker, is demonstrated in this work.

This protocol demonstrates how to use the Auto-CHO software for hierarchical and programmable one-pot synthesis of oligosaccharides. It also describes the general procedure for RRV determination&#160;experiments and one-pot glycosylation of SSEA-4.

分层和可编程单罐寡糖合成

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for ...

A Femtoliter Droplet Array for Massively Parallel Protein Synthesis from Single DNA Molecules

Advances in spatial resolution and detection sensitivity of scientific instrumentation make it possible to apply small reactors for biological and chemical research. To meet the demand for high-performance microreactors, we developed a femtoliter droplet array (FemDA) device and exemplified its application in massively parallel cell-free protein synthesis (CFPS) reactions. Over one million uniform droplets were readily generated within a finger-sized area using a two-step oil-sealing protocol. Every droplet was anchored in a femtoliter microchamber composed of a hydrophilic bottom and a hydrophobic sidewall. The hybrid hydrophilic-in-hydrophobic structure and the dedicated sealing oils and surfactants are crucial for stably retaining the femtoliter aqueous solution in the femtoliter space without evaporation loss. The femtoliter configuration and the simple structure of the FemDA device allowed minimal reagent consumption. The uniform dimension of the droplet reactors made large-scale quantitative and time-course measurements convincing and reliable. The FemDA technology correlated the protein yield of the CFPS reaction with the number of DNA molecules in each droplet. We streamlined the procedures about the microfabrication of the device, the formation of the femtoliter droplets, and the acquisition and analysis of the microscopic image data. The detailed protocol with the optimized low running cost makes the FemDA technology accessible to everyone who has standard cleanroom facilities and a conventional fluorescence microscope in their own place.

The overall goal of the protocol is to prepare over one million ordered, uniform, stable, and biocompatible femtoliter droplets on a 1 cm2 planar substrate that can be used for cell-free protein synthesis.