釕金屬錯合物催化全碳鏈芳香丙炔醇經由釕金屬亞乙烯基/丙二烯錯合物合成雙環/參環有機化合物之反應

Sequential Allenylidene/Vinylidene Cyclization on Ruthenium for Stereoselective Construction of Bicyclic/Tricyclic Carbocycles from Aryl Propargyl Alcohol

馬浩瑋(Hao-Wei Ma)

指導教授 ： 林英智

國立臺灣大學/理學院/化學研究所/博士(2014年)

https://doi.org/10.6342/NTU.2014.02402

摘要

在本論文的第一部分中，我們探討釕金屬錯合物催化於鄰位含烯類碳鏈取代的芳香丙炔醇1,7-及1,8-烯炔化合物，藉由分子內環化反應形成聯繼(tandem)環化的產物。利用釕金屬催化劑[Ru]NCCH3+ ([Ru] = RuCp(PPh3)2) 與尾端烯類官能基內側具有甲基取代的1,7-烯炔化合物1在氯仿/甲醇的共溶劑中進行反應，可得到含有架橋的二次環化有機化合物15a。在單一溶劑系統(氯仿)中，相同的催化反應只會得到一次環化的烯炔中間物7。第一部分的環化中，可能經由尾端的烯類官能基親核性加成於釕金屬丙二烯中間物B的Cγ上，形成釕金屬亞乙烯基錯合物3。因尾端烯類官能基內側具有甲基取代，形成3的過程中有三級陽離子的生成能穩定中間體，使此環化反應得以進行。而第二次的環化則需在醇類與氯仿共溶劑的環境下，由第一次環化後仍保留的烯官能基親核性加成於亞乙烯基錯合物3的Cα上，之後醇類加成脫去釕金屬而得到二次環化有機物15a。1,8-烯炔化合物2，也可利用相同的催化反應條件得到類似的二次環化化合物13a。另一方面，我們也合成一系列芳香丙炔醇，於芳香環鄰位碳鏈烯類官能基末端有兩個甲基取代的化合物19, 20, 20’, 21，與釕金屬催化劑進行反應。當1,7-烯炔化合物19進行金屬催化反應時，可直接得到第二次環化後的有機產物23，反應機構則是類似於上述15a或13a的生成機制。但在這個催化過程中，並無法單離出釕金屬亞乙烯基錯合物O，推測可能是形成中間物O時，尾端的烯類官能基過於靠近Cα，因此快速的親核性加成於Cα後伴隨著金屬脫去產生催化後產物23。另外，也可使用類似的烯炔化合物20, 20’, 21與釕金屬催化劑進行環化反應得到相對應的二次環化產物24, 24’及25。最後，當使用尾端沒有任何甲基取代的芳香丙炔醇27或28，與釕金屬錯合物[Ru]-Cl反應，則不會有環化反應的發生，只會得到三苯基磷(PPh¬3¬)加成之釕金屬乙炔錯合物29, 30，釕金屬丙二烯錯合物31，或含甲氧基之釕金屬碳烯錯合物32。
第二部分中，則是針對一系列於四號位上有環己烷取代的1,6-烯炔有機化合物，與1,2-雙(聯苯代磷基)-乙烷釕金屬錯合物[Ru’]-Cl ([Ru’] = RuCp(dppe)) 的反應性做探討。首先，1,6-烯炔化合物33a與釕金屬錯合物在二氯甲烷中進行反應，可得到釕金屬丙二烯錯合物38。當溶劑系統改為甲醇，則會產生γ位甲氧基取代釕金屬亞乙烯基錯合物36a及含甲氧基釕金屬碳烯錯合物37之混合物。在鹼性條件下對36a於β碳上進行去質子化反應，可得到釕金屬乙炔基錯合物39，而此錯合物39在甲醇及四氟硼酸下，可再得到α碳上甲氧基加成之釕金屬碳烯錯合物37。另外，釕金屬亞乙烯基錯合物36a，在氧氣的參與下，具有新穎的反應性。錯合物36a在空氣及甲醇的條件下，可進行氧誘發環化反應而得到具有環接(spiro)的雙取代亞乙烯基錯合物40a。為了提高40a的產率，我們進行一系列的反應測試，發現在氧氣的慢慢導入及間-氯過氧苯甲酸(m-CPBA)的幫助之下，是最好的反應條件。除此之外，也進行了反應機制的探討，合成了帶有環氧基的丙炔醇41，並與釕金屬錯合物在甲醇中進行反應。然而，並沒有預期的氧誘導環化產物40a的產生，而是得到亞乙烯基錯合物42及環氧基開環後之釕金屬碳烯錯合物43混合物。而此二種錯合物在空氣中也不會有進一步的環化反應發生。為了討論釕金屬亞乙烯基錯合物更多反應性，將40a於四氟硼酸中進行質子化反應，可得到1,3-甲氧基位移之碳烯錯合物44及其結構異構物44’。接著，在鹼性條件下，44及44’混合物會完全反應產生中性釕金屬醯基錯合物45；並可以利用鹽酸將有機物部分以醛類的形式切下來得到有機化合物46。除此之外，尾端帶有甲基取代的1,6-烯炔化合物34及35，與釕金屬錯合物進行反應，則分別會經由5-exo-dig或6-exo-dig路徑產生環化後的釕金屬碳烯錯合物47及48，且在合環過程中，皆伴隨著三級碳陽離子的產生以穩定中間物。

關鍵字

釕金屬 ； 亞乙烯基錯合物 ； 丙烯基錯合物 ； 催化環化反應 ； 三級碳陽離子 ； 聯繼環化反應 ； 氧誘發環化 ； 環接化合物

並列摘要

The tandem cyclization reaction of phenyl propargyl alcohol 1, in which a 2-methyl-substituted allyl group is bound to the ortho-position of the phenyl ring, is catalyzed by [Ru]NCCH3+ ([Ru] = Cp(PPh3)2Ru) in a cosolvent of CHCl3/MeOH at 60 °C, to afford the cyclized compound 15a with two newly formed six-membered rings. In CHCl3 the catalytic reaction by [Ru]NCCH3+ stops at the isolable organic cyclization intermediate enyne 7. The first part of this tandem cyclization proceeds via an allenylidene complex B followed by a C-C bond formation between Cγ of the allenylidene ligand and the terminal carbon atom of the vinyl group generating the vinylidene complex 3, which can be isolated if [Ru]Cl is used. The presence of the methyl group on the internal vinyl carbon may serve to stabilize a proposed carbocation making the cyclization possible. The second part of the cyclization, which requires the presence of methanol, proceeds via addition of the olefin moiety on the six-membered ring to Cα of the vinylidene ligand of 3. This is followed by a demetalation process, affording the final product 15a. Tandem cyclization of analogous phenyl propargyl alcohol 2 with an additional methylene group also affords compound 13 with a sequentially formed seven-membered and six-membered ring. The similar catalytic cyclization reaction of 2 by [Ru]NCCH3+ in the first stage is also demonstrated to give 8 in high yield. Likewise, the vinylidene complex 4 is acquired from 2 with [Ru]Cl. A series of phenyl propargyl alcohol 19, 20, 20’ and 21 having two methyl groups on the terminal carbon of the ortho tethering chain were synthesized. The catalytic cyclization reaction of 19 by [Ru]NCCH3+ directly afford the second stage product 23. The formation of the tricyclic product 23 proceeds in the same way as we mentioned above. In this catalytic cycle, many attempts to isolate the vinylidene intermediate O failed. A fast addition of terminal olefinic moiety to Cα of the vinylidene ligand followed by a demetalation process yields the final product. Without the methyl group, two similar phenyl propargyl alcohols 27 and 28, in the reactions with [Ru]Cl, yield no cyclization product. Only the phosphonium acetylide complex 29, 30, the allenylidene complex 31 or the methoxy carbene complex 32 are obtained. All cyclic vinylidene complexes and organic compounds are characterized by NMR spectra.
Three 1,6-enyne compounds 33-35 each containing pendant olefinic groups, which have zero, one or two methyl groups, are prepared. Reaction of enyne 33a with [Ru’]Cl ([Ru’] = Cp(dppe)Ru) in CH2Cl2 yields the allenylidene complex 38. In MeOH, the same reaction gives a mixture of the γ-methoxyvinylidene complex 36a and the α-methoxycarbene complex 37. Deprotonation of 36a generate the acetylide complex 39, however, treatment of 39 with HBF4 in MeOH is readily followed by a methoxide addition to generate 37. Astonishingly, with the presence of two hydrogens at the terminal olefinic carbon, complex 36a undergoes a cyclization in air to give the vinylidene complex 40a containing a spiral ring system and mixed phosphine oxide of dppe as a minor product. Complex 40a is characterized by 1H, 13C, 31P, 1H-1H COSY, 1H-13C HSQC and 1H-13C HMBC NMR spectroscopy. Analogous complex 40a’ is directly obtained from the reaction of [Ru]Cl ([Ru] = Cp(PPh3)2Ru) with enyne 33a in MeOH in air. Protonation of 40a causes formation of the 1,3-migration product 44 and 44’. Moreover, base induced reaction of complexes 44 and 44’ leads to the neutral acyl complex 45. Finally, the spiral organic compound 46 with an aldehyde group is obtained from the reaction of 45 with HCl. In addition, the reactions of 1,6-enyne 34 with [Ru]Cl and [Ru’]Cl both proceed via a 5-exo-dig cyclization pathway to give the carbene complexes 47 and 47’, respectively. For the enyne 35 with one methyl groups at the internal carbon of the olefinic part, formation of the carbene complexes 48 or 49 may then involve a 6-exo-dig cyclization to give the tertiary carbocation, ultimately leading to 48 in methanol and 49 in CH2Cl2.

並列關鍵字

Ruthenium ； Vinylidene Complex ； Allenylidene Complex ； Carbocation ； Tandem cyclization ； Oxygen Induced Cyclization ； Spiro Ring

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