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><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.

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

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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

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.

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

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

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.

の合成のためのプロトコル<em&gt;オルソ</em&gt; -trifluoromethoxylatedアニリン誘導体

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 種によるケトン類の極性転換を高機能化 2 段階のプロトコル

&#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.

様々 な Difluoroalkenes にアクセスを提供する Trifluoromethylated Benzofulvenes の選択的 C F の活性化で元素ランタノイドのアプリケーション

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.

1-Iodoalkynes、1, 2-Diiodoalkenes、末端アルキンの酸化ヨウ素化に基づく 1,1,2 Triiodoalkenes の化学選択的準備

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.

無料カルベン、混合二量体および有機ラジカルを分離します。

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.

官能化 Monoorganozinc 臭化物の共役添加による全炭素4級センターの効率的な合成

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-アルキンの酸性度


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 ...

有機化学

ユニット １

アルキン類

KEY TERMS AND CONCEPTS

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;" />

アルキンの調製:アルキル化反応

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;" />

アルキンの調製:脱ハロゲン化水素

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

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

要約

さらに動画を探す

この動画の章

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

の合成のためのプロトコル

Enolonium 種によるケトン類の極性転換を高機能化 2 段階のプロトコル

様々な Difluoroalkenes にアクセスを提供する Trifluoromethylated Benzofulvenes の選択的 C F の活性化で元素ランタノイドのアプリケーション

1-Iodoalkynes、1, 2-Diiodoalkenes、末端アルキンの酸化ヨウ素化に基づく 1,1,2 Triiodoalkenes の化学選択的準備

無料カルベン、混合二量体および有機ラジカルを分離します。

官能化 Monoorganozinc 臭化物の共役添加による全炭素4級センターの効率的な合成

1-アルキンの酸性度

アルキンの調製:アルキル化反応

アルキンの調製:脱ハロゲン化水素

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

要約

さらに動画を探す

この動画の章

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

の合成のためのプロトコル

Enolonium 種によるケトン類の極性転換を高機能化 2 段階のプロトコル

様々 な Difluoroalkenes にアクセスを提供する Trifluoromethylated Benzofulvenes の選択的 C F の活性化で元素ランタノイドのアプリケーション

1-Iodoalkynes、1, 2-Diiodoalkenes、末端アルキンの酸化ヨウ素化に基づく 1,1,2 Triiodoalkenes の化学選択的準備

無料カルベン、混合二量体および有機ラジカルを分離します。

官能化 Monoorganozinc 臭化物の共役添加による全炭素4級センターの効率的な合成

1-アルキンの酸性度

アルキンの調製:アルキル化反応

アルキンの調製:脱ハロゲン化水素

様々な Difluoroalkenes にアクセスを提供する Trifluoromethylated Benzofulvenes の選択的 C F の活性化で元素ランタノイドのアプリケーション