釕金屬錯合物催化含醚類與環丙基之烯炔之聯繼環化反應

Abstract

本篇論文中，我們探討釕金屬錯合物催化含醚類與環丙基之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。利用釕金屬錯合物[Ru]Cl ([Ru] = Cp(PPh3)2Ru) 與尾端烯類官能基內側具有甲基取代的化合物1反應，可生成七環含氧的釕金屬亞乙烯錯合物2。此外，利用此亞乙烯錯合物2在乙腈中加熱或將化合物1和[Ru]NCCH3+ PF6－在氯仿中加熱至60 oC可得到一次環化烯炔中間物5。相同的反應在甲醇與氯仿之共溶劑的環境下，經由甲氧基親核性加成可獲得二次環化的環接 (spiro)有機產物6。另一方面，使用末端烯類官能基具有兩個甲基取代之化合物7與[Ru]Cl進行反應，得到錯合物8。錯合物8是具有新形成之六環之非鏡像異構物，其中主要異構物的烯基與其鄰位之炔基互為反向之形式，簡稱為反式。推測造成選擇性的主要原因為立體障礙，反應機制中，經由六元環船型之過渡態，若烯類尾端兩個甲基與環丙烯位於同向，則具較大的立體障礙，導致反式異構物成為主要產物。將化合物2和[Ru]NCCH3+ PF6－在氯仿中加熱至60 oC亦可獲得一次環化烯炔中間物9 （反式：順式 = 3：1）。化合物2或烯炔中間物9與[Ru]NCCH3+ PF6－在甲醇與氯仿之共溶劑的反應條件下，可獲得聯繼環化反應之產物10。 此外，在不含有甲基取代的1,8-烯炔化合物11與[Ru]Cl的反應中，並不會產生碳-碳鍵生成的產物。反之得到釕金屬環丙基亞丙烯基錯合物12與鏻鹽 (phosphonium)加成之釕金屬乙炔錯合物13。有趣的是，藉由將反應加熱至40 oC，可獲得三元環擴環生成五元環之亞乙烯基錯合物16。若化合物11與[Ru]Cl在甲醇作為溶劑下進行反應，則會獲得環氧碳烯錯合物17。為了探討形成17之反應機構，我們在二氯甲烷作為溶劑的條件下探討1,3-二元醇18與[Ru]Cl的反應。在二氯甲烷作為溶劑的條件下，18與[Ru]Cl反應可生成未脫水之環氧碳烯錯合物19與錯合物17的混合物（19：17 = 2 : 1）。然而，錯合物 19並無法藉由脫水形成錯合物17，因此可以斷定錯合物17的形成必須經由亞丙烯基錯合物作為中間物來獲得。總體而言，我們利用在烯烴上取代的甲基，使反應選擇走向連續環化形成雙環化合物或環丙基擴環而形成五元環。

We study chemical reactions of [Ru]Cl ([Ru] = Cp(PPh3)2Ru) with three 1,8-enyne compounds containing cyclopropyl group (1, 7 and 11) in which the triple bond is associated with propargylic alcohol and the olefinic group has various substituted methyl groups. The reaction of [Ru]Cl and 1, containing one methyl group added to the internal carbon of the allyl group, affords the vinylidene complex 2 with a newly formed seven-membered ring. Furthermore, tandem cyclization reaction of 1 in MeOH/CHCl3 catalyzed by [Ru]NCCH3+PF6－ at 60 oC leads to the product 6 with spiro-cyclopropyl ring, formed possibly via sequential allenylidene vinylidene cyclization followed by a nucleophilic addition of alkoxide. In CHCl3, the catalytic reaction by [Ru]NCCH3+ PF6－ gives the isolable organic cyclization intermediate enyne 5. Treatment of the propargylic alcohol 7 containing two terminal methyl groups at the O-allylic group, with [Ru]Cl yields a mixture of two diastereomers of the vinylidene complex 8 containing a newly formed six-membered ring in a ratio of ca. 10:1. Among diastereoisomers only the anti-isomer is isolated for complex 8. The cyclization reaction is proposed to proceed via the formation of a six-membered ring boat-like transition state with bulkiest group in the pseudo-equatorial position to reduce the 1,3-diaxial interactions. The catalytic reaction by [Ru]NCCH3+PF6－ in CHCl3 at 60 oC affords anti-9 and syn-9 in a ratio of 3:1. The thermal energy increases amount of product syn-9. The subsequent cyclization carried out in a cosolvent of ROH/CHCl3 at 60 oC affords bicyclic product 10. In the reaction of [Ru]Cl with 11, containing no methyl group, no C−C bond formation is observed. The reaction of 11with [Ru]Cl in the presence of NH4PF6 in CH2Cl2 affords a mixture of the allenylidene complex 12 and phosphonium acetylide 13. Interestingly, thermal treatment of 11 leads to a ring expansion of the cyclopropyl group, giving the vinylidene complex 16 with a five-membered ring. This ring expansion proceeds by C-C bond formation between Cβ of the cumulative double bond and a methylene group of the cyclopropyl ring. Reaction of 1,3-diol 18 with [Ru]Cl in CH2Cl2 yields a mixture of the alkoxy carbene 17 and 19 in a ratio of 1:2. The spontaneous dehydration of 19 to 17 by elevating temperature is failed. Fortunately, complex 17 could be the only product when the reaction is carried out in MeOH. Overall, tandem cyclizations of two 1,8-enynes with methyl-substituents have been achieved. Ring-expansion of a cyclopropyl group in a 1,8-enyne with no methyl-substituent is also accomplished.