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

イノンの1の合成<ol><li>化学天秤を使用して、目的のカリウムalkynyltrifluoroborate塩（1.5当量）の0.15ミリモルを比較検討し、磁気撹拌棒を備えた清浄なバイアルに加える。 </li><li>針を取り付けたガラスジャーシリンジを使用して、ロボの0.3 M溶液を得バイアルに無水DCMの0.5ミリリットルを追加します。 注：これは新しい方法であるので、反応は、概念実証のために行われている。廃棄物を減らすために、それらは小規模で行われている。反応は、必要に応じて、より大きな収量を生成するためにスケーリングすることができる。 </li><li>ガラスシリンジを使用して、撹拌しながら、周囲温度（20℃）で反応容器に、1.0M三塩化ホウ素溶液の0.15ミリモル（1.5当量、150μl）を滴下する。キャップを交換してください。ホールドまたは反応液を超音波処理装置内の水ラインの下にあるようにキャップされた反応容器をクランプする。 20℃で30秒間、溶液および周波数oを超音波処理40 kHzのF。 </li><li>さらに20分間、室温（20℃）で反応液を撹拌した。 alkynyltrifluoroborate出発物質の性質に応じて、色の変化を観察する。日焼けする白または濃い茶色、赤色、または紫色の色の変化が一般的である。 </li><li>攪拌しながら周囲温度（20℃）でバイアルに、所望の塩化アシル（1.0当量）の0.1ミリモルを加える。代替的に、磁気攪拌棒及びアシルクロライド0.1ミリモルを充填したフラスコに、反応容器の内容物を移す。キャップを交換してください。 30分間、周囲温度（20℃）で反応液を撹拌した。 注：一般的に、非常に暗い色への変化は、反応が起こっていることの指標である。 </li><li>薄層クロマトグラフィー（TLC）34を使用すると、適切な塩化アシル標準と比較することにより、反応の進行をモニターする。 注記：出発物質の性質に応じて、反応が完結しない場合があります。 Acylは塩化出発材料は、この方法を用いてこれまでに調製ynonesのすべての最終生成物よりも高いランニングスポットとして観察されている。 <ol><li>小さなバイアル中で、酢酸エチル1mlの出発物質の塩化アシルの約10mgの希釈して塩化アシル標準を準備する。 </li><li> TLCスポッターを使用して、反応溶液及びTLCプレートのスタートラインに標準スポット。反応溶液及び標準の両方との共スポットが依然として反応液中に存在する出発材料が存在するかどうかを決定するために有用であり得る。 </li><li>試行錯誤によって、適切なTLC移動相を決定します。物品1aの製造のために、移動相は1:30の酢酸エチルからなる：イノン製品および塩化ベンゾイル約0.5と0.8のR f値でヘキサン結果、それぞれの出発材料。 </li><li> UV光の下で開発されたTLCプレートの可視化。目に見えるスポットをマークするために鉛筆を使用してください。 </li></ol></li></ol> 2.水性後処理<ol><li>反応容器に冷水（約5℃）1mlを加えて反応をクエンチした。パスツールピペットを用いて、クリーンな分液漏斗に溶液を移す。さらに10ミリリットルの冷水で分液漏斗の内容物を希釈し、15mlの酢酸エチル中に一度生成物を抽出。 </li><li>底の水層を捨て、水10mlおよび食塩水10mLで1時間で有機層1の追加の時間を洗う。きれいな三角フラスコに有機層を収集し、硫酸マグネシウムで乾燥した。重力濾過を用いての清浄な丸底フラスコに溶液を濾過する。 </li></ol>イノンの精製<ol><li>薄層クロマトグラフィーを用いて、生成物のフラッシュクロマトグラフィー精製に適した移動相を決定する。約0.5の保持因子（R f）は 、残りの開始から生成物を分離するために一般的に十分である材料とサイドの製品をる。 注：分離不良の場合には、より極性の低い溶媒系は ​​、生成物がより低いR f値を有するように使用することができる。出発物質の極性、ヘキサンに依存：5〜1：30の範囲内の酢酸エチル混合物1は、一般的に適切である。 </li><li>適切な移動相との湿式シリカを含むカラムを準備します。製品と溶離液の添加によりシリカを乱さないようにするために、カラムの頂部に砂の層を追加する。 </li><li> 40℃の浴温を120rpmに設定した回転にロータリーエバポレーターを使用して後処理液を蒸発させる。移動相の2ミリリットルでフラスコの内容物を溶解し、慎重にカラム上に均等にソリューションをロードします。シリカが濡れているが、溶媒ラインがシリカの高さを超えないようにしてください。いくつかの溶媒が生成物をシリカ上であるように溶出することができるようにします。移動相とリピートを少量加える。 </li><li> COLを埋めるステップ3.1で決定された移動相とUMN。製品1aの場合には、30：1ヘキサン：酢酸エチル混合物が適切である。精製プロセスをスピードアップするためにフラッシュクロマトグラフィーを用いて試験管内の画分を収集する。単に空気出口にチューブをアダプタに接続します。溶離液は、適切な速度でカラムを通って流れるように空気圧を調整します。 </li><li> TLCプレート上でのカラム画分のそれぞれを見つける。必要に応じて、参照として塩化アシル標準スポット。移動相はステップ1.8で適切と判断使用してTLCを開発する。生成物を塩化アシル標準より低いR fをを有することが期待されていることを指摘し、UV光下で可視の任意のスポットをマークする。 </li><li>大きな丸底フラスコに見えるスポットを含む全ての画分を収集します。出発材料より低いR fを有する複数のスポットが存在する場合、独立したフラスコ中で、それらを集める。ロータリーエバポレーターを用いて溶媒を蒸発させ、未定義の回収物を乾燥させる2時間高真空rを。 </li><li>必要に応じて、さらに電子不足塩化アシル出発物質から調製したイノンの生成物を精製するために、小さなカラム上ペンタン洗浄を行う。小規模では、これは、カラムとして、パスツールピペットを用いて行うことができる。 <ol><li>クロロホルム、DCM、ジエチルエーテル最小に生成物を溶解し、ペンタンで湿式シリカカラム上にロードする。カラムを通過ペンタンの1-2列の長さを溶出し、廃棄物のビーカーに集める。 </li><li>ジエチルエーテルもしくは酢酸エチルを使用ペンタンカラムから純粋なイノンの生成物を溶出。別のフラスコ中で溶離液を集めて蒸発し、最低2時間高真空下に置く。 NMR分光法によって特徴づけのための製品の約10 mgを得。 </li></ol></li></ol>イノンの4キャラクタリゼーション<ol><li> 1 H及び13 C NMR分光法を用いて、最終生成物の純度を特徴付けると評価する。34一般的に、カルボニル炭素の化学シフトは、13 C NMRスペクトルに177 ppmの近くに表示されます。イノン官能基の2のSP炭素は87と93 ppmの近くに特徴的なピークで表されます。 </li><li>イノン製品の特徴的なカルボニルピークを識別するために、赤外分光法34を使用してください。隣接する三重結合から電子の非局在化は、通常は1600と1650センチメートルの間で表示されるようにカルボニルピークの原因となる-1、化合物の電子特性に応じて。 </li><li>生成物の分子量を決定し、さらに、高分解能質量分析を使用してIDを検証。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=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は、対応するイノン製品を形成するために、塩化ベンゾイルとフェニルトリフルオロボレートとの反応のための条件を最適化するために行われるステップを示している。最初に、organodifluoroboranesになオルガノに変換することが知られている触媒を試験した。残念ながら、シリカゲル、35四塩化ケイ素、36及び三フッ化ホウ素31,32は、所望のイノン（ 表1、エントリー1-3）の形成を促進しなかった。塩素化ルイス酸触媒の使用が成功であることが判明した。所望イノン1aの低い収率は、塩化鉄（III）触媒（ 表1、エントリー4）の存在下で得られた。次に、塩化アルミニウム（III）は、フリーデル-クラフツアシル化においてオキソカルベニウムイオンの形成を促進するの十分に確立された能力の結果として調査した。塩化アルミニウム（III）触媒だったとき37-39所望の生成物を収率62％で得た。 EMPloyed。 さらなる最適化は、空気と水分が反応した（ 表1、エントリー5~7）の収率にほとんど影響を及ぼさないことが明らかになった。その結果、その後の反応は、空気の存在下で非乾燥したガラス器具中で行った。溶媒を最適化する試みは、ジクロロメタン（DCM）が反応した（ 表1、エントリー8-12）に特に適していることが明らかになった。塩化アルミニウム（III）によって触媒反応の結果の不一致は、代替触媒の探求を促した。市販のアルミニウム（III）六水和物は、反応条件（ 表1、エントリー13）の下では完全に不活性であった。これは、アルミニウム（III）塩化物水和物の生成反応を阻害することを示す良い指標である。三塩化ホウ素をより良く整合性（ 表1、エントリー14）と同様の収率を生じることが見出された。 カリウムalkynyltrifluの相互作用に三塩化ホウ素、より反応性organodichloroborane種とoroborateが形成されている。40この最初のステップが進行するイノンの塩化アシルと形成との反応のために重要である。 organotrifluoroborate塩をDCMに溶解しないので、反応は、不均一な混合物として行われる。三塩化ホウ素の添加後、溶液を反応に利用できるトリフルオロボレート塩の表面積を増加させることによって反応性ジクロロボラン種の形成を促進するために超音波処理される。反応混合物への超音波の適用は、キャビテーション気泡の生成を介して機械的な効果を引き起こす。超音波処理中、キャビテーションの崩壊は、高い温度および圧力の局所的な領域内の流体の結果で気泡41衝撃波固体トリフルオロボレート塩の運動エネルギーの増加をもたらす微細な乱流を作り出すことが産生される。超音波処理のプロモーション中のシステムのエネルギーの増加トリフルオロホウ酸塩のtesの断片化は、三塩化ホウ素と相互作用することが可能な表面積を増加させ得た。出発物質の前塩化アシルを加え、反応混合物の超音波処理は、より強制的な条件またはより長い反応時間を必要とすることなく、反応alkynyldichloroborane種の効率的な形成を確実にする。 図2はフェニルトリフルオロボレートが最適化された反応条件下での塩化アシルの様々な反応させた場合の結果を示している。中性芳香族（1B、1C）および脂肪族（1J-L）塩化アシルは、合成的に有用な収率で対応するynonesを提出。電子吸引基が比較的控えめな利回り（1H、1I、1メートル ）になりながら、電子供与基に（1D-G）を有するこれらのアシル塩化物は優れた収率を提供する。 Intere電子吸引基がオルト位 （1iを 、59％）にあるときstingly、有意な収量の増加は、類似のパラ位と比較して観察される塩化アシル（1時間 、30％）置換されている。 オルト位の置換基の立体相互作用することにより、芳香環の電子吸引文字を相殺する、平面外にカルボニル官能基を強制することができる。それは、4ブロモブチリルクロリドを収率39％で所望の生成物の1メートルを得反応したことは注目に値する。我々の知る限り、これが臭化アルキル官能基を​​許容するynonesの合成のための最初のプロトコルである。時折、出発物質の塩化アシルは、中性または電子不足である場合、脂肪族不純物はプロトンNMRに表示される。これにより、生成物を精製するために、ペンタン洗浄を必要とするかもしれない。可能ではあるが、それは最初の精製段階の間ペンタン洗浄を実行することは経済的ではないインスペンタンヘキサンと比較して高価である。そのようなパスツールピペットカラムとして小規模で個別に二次精製を完了すると、大幅に必要なペンタンの量を減少させる。 図3は、反応の収率にalkynyltrifluoroborate塩の同一性の効果を示す。一般に、芳香環上に電子供与性の置換基を有するフェニルトリフルオロホウ酸塩の誘導体が優れた収率（ 図2a-cは 、 図3a-c）の良好に所望のynonesを生成するために芳香族および脂肪族アシル塩化物と反応させる。脂肪alkynyltrifluoroborate塩は、反応性の低い基材であることが判明した。 hexynyl-とcyclopentylethynyltrifluoroborate塩が電子豊富塩化ベンゾイル誘導体（ 図4a、図5a）と反応させた際に適度な収率が得られている。 結論として、oを調製するための新規な方法アシル塩化物およびカリウムalkynyltrifluoroborate塩からfはynonesが開発されている。出発物質の塩化アシルとロボの性質に応じて適度なより優れた、この方法の範囲によってynonesの合成のために得られた収率。一般に、電子供与性の置換基を有する出発物質は、中性の電子吸引性官能基を有する出発物質よりも容易に反応を受ける。このアプローチの値は、メソッドの動作シンプルさと官能基許容範囲にある。この単純なワンポット反応が空気および水分を排除することなく、三塩化ホウ素の存在下、周囲温度で急速に進行する。この便利な方法は、塩化アシルとalkynyltrifluoroborate塩種々の優れた収率を適度にynonesの調製に使用することができる。

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.

初期の努力はフェニルトリフルオS1からイノン1aの調製および塩化ベンゾイル（ 図1）の周りに集中した。 表1の最適化ステップの反応には、種々のルイス酸のスクリーニング、溶媒、並びに水の影響の検討を含む行わ示し。次に、反応の範囲は、塩化アシル（ 図2）の種々の存在下で最適化された条件にフェニルアセチレントリフルオを提出することによって検討されている。優れた収率に適度なアシル塩化ビニル基材の性質に応じて得ることができる。反応の範囲はさらにalkynyltrifluoroborate塩のいくつかのさらなる実施例の調製を介して評価された。 図3は、開発の条 ​​件でynonesの調製に使用することができる他のalkynyltrifluoroborate塩の選択された例を示している。フェンの誘導体alkynyltrifluoroborate塩の脂肪族誘導体が、ささやかな収量を与える若干反応性が低いであることが証明されつつ、優れた収率に良いの対応イノン製品を与え置換基を供与するylacetyleneロボベアリン​​グ電子。 <img alt="図1" src="/files/ftp_upload/52401/52401fig1highres.jpg" /> 図1：フェニルトリフルオS1及び塩化ベンゾイルからイノン1aの調製スキームは、反応性中間体ジクロロボランの形成を含むイノン1aの調製のための条件を示す。 <img alt="図2" src="/files/ftp_upload/52401/52401fig2highres.jpg" /> 図2：イノン1aの代表的な1 H NMRスペクトルの化学シフト及び特性プロトンの相対的な統合が標識されている。 図3：イノン1aの代表13 C NMRスペクトル特性炭素の化学シフトは、ラベルが付いています。 <img alt="図4" src="/files/ftp_upload/52401/52401fig4highres.jpg" /> 図4：大気圧化学イオン化を介して得られるイノン1aの代表HRMSスペクトル [M + H]の測定されたm / z値+イオンが報告されている。 <img alt="図5" src="/files/ftp_upload/52401/52401fig5highres.jpg" /> 図5：アイデンティティを変化させることにより、製造された製品のための塩化アシルとphenylacetylenetrifluoroborate塩S1の反応構造と歩留まり。塩化アシルの出発材料で示されている。反応は、塩化アシルの1当量、1.5当量のカリウムphenylacetylenetrifluoroborate S1、および1.5当量の三塩化ホウ素を使用して実行した。 <img alt="図6" src="/files/ftp_upload/52401/52401fig6highres.jpg" /> 図6：塩化アシル構造とalkynyltrifluoroborate出発物質の同一性を変化させることによって製造された製品のための収率で、様々なalkynyltrifluoroboratesの反応が示されている。反応は、塩化アシルの1当量、2.5当量のカリウムorganotrifluoroborate塩および2.5当量の三塩化ホウ素を使用して実行した。 <table border="0" cellpadding="0" cellspacing="0"><tbody><tr><td> エントリー </td><td> ルイス酸 </td><td> ルイス酸（当量） </td><td> 条件 </td><td> 産出（％） </td></tr><tr><td> 1 B &lt;/ SUP&gt; </td><td> SiO 2の</td><td> 16.5 </td><td> CH 2 Cl 2を </td><td> 0 </td></tr><tr><td> 2 </td><td> SiCl 4を </td><td> 1 </td><td> CH 2 Cl 2を </td><td>トレース</td></tr><tr><td> 3 </td><td> BF 3·OEtで2 </td><td> 1 </td><td> CH 2 Cl 2を </td><td>トレース</td></tr><tr><td> 4 B </td><td>のFeCl 3 </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 24 </td></tr><tr><td> 5 C </td><td>のAlCl 3 </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 62 </td></tr><tr><td> 6 D </td><td>のAlCl 3 </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 66 </td></tr><tr><td> 7 E </td><td>のAlCl 3 </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 60 </td></tr><tr><td> 8 </td><td>のAlCl 3 </サブ&gt; </td><td> 1 </td><td> THF </td><td>トレース</td></tr><tr><td> 9 </td><td>のAlCl 3 </td><td> 1 </td><td>トルエン</td><td>トレース</td></tr><tr><td> 10 </td><td>のAlCl 3 </td><td> 2 </td><td>のClCH 2 CH 2 Clを</td><td> 33 </td></tr><tr><td> 11 </td><td>のAlCl 3 </td><td> 1 </td><td> DMSO </td><td>トレース</td></tr><tr><td> 12 </td><td>のAlCl 3 </td><td> 2 </td><td>アセトニトリル</td><td>トレース</td></tr><tr><td> 13 </td><td>のAlCl 3·6H 2 O </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 0 </td></tr><tr><td> 14 B </td><td> BCl 3を </td><td> 1.5 </td><td> CH 2 Cl 2を </td><td> 67 </td></tr><tr><td> 15 </td><td>のBBr 3 </td><td> 1 </td><td> CH 2 Cl 2を </td><td> 20 </td></tr></tbody></table><strongの&gt;表1：イノン1aのa の調製のための条件の最適化生成物の収率。 反応条件およびルイス酸触媒の変動に応じ1aは反応は、1当量の塩化ベンゾイルおよび1当量のカリウムphenylacetylenetrifluoroborate S1で実行した。B 1.5当量のS1、C無水条件。dの反応は、空気中で乾燥していないガラス製品中で行った。 電子無水条件+水1μL。

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.

アシル塩化物およびカリウムAlkynyltrifluoroborate塩からYnonesの金属を含まない合成

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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Unit 1

Carboxylic Acid Derivatives

Alkynes

SCIENTISTS IN ACTION

11.1K ビュー.  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.

ビデオ: 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.

二ヨウ化サマリウム（SMIの調製および使用<sub&gt; 2</sub&gt;）有機合成における：サマリウムバルビエ反応におけるHMPAとNi（II）塩の力学的役割

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

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.

ヌクレオシド三リン酸 - 合成からの生化学的特徴付けへ

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.

超分子コロイドの合成とキャラクタリゼーション

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.

パラジウム<em&gt; N</em&gt; - 複素環カルベン錯体：ベンズイミダゾリウム塩からの合成と炭素 - 炭素結合形成反応における触媒活性

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.

合成とオリゴ ペプチドの質量分析

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.

L リジンから光学活性アミノ アルコールの合成酵素連鎖反応

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.

アクティブな表面の成長メカニズムを介して基質結合 Au ナノワイヤの作製

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.

親和性金ナノ粒子の合成と特性化

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.

階層的でプログラム可能なワンポットオリゴ糖合成

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.