【作者】 邓友前；

【导师】 麻生明； 傅春玲；

【作者基本信息】 浙江大学 ， 有机化学， 2010， 博士

【摘要】 联烯是最简单的累积烯烃。联烯末端的四个位置有着良好的取代基装载能力,如果在联烯上引入官能团,就能调节、改变联烯的物理、化学性质,再通过改变反应条件,反应位点也可以选择性地发生在联烯的三个碳原子上。基于我们小组在单官能团化联烯、1,5-双联烯领域的研究成果以及已经实现的两个官能团化联烯的反应模式,本论文的工作目标就是(1)发展双官能团化联烯的反应；(2)进一步发展和完善官能团化联烯之间的反应模式并借鉴这些模式实现官能团化双联烯的反应模式；(3)研究基于2,3-联烯酸酯共轭加成反应的不对称烯丙基化反应。论文主要包括以下五大部分：第一部分：2-(甲氧羰基)-2,3-联烯醇的立体选择性消除反应首先合成了双官能团化联烯2-(甲氧羰基)-2,3-联烯醇,通过与草酰氯在不同条件下的反应,可以分别立体选择性地合成2-(甲氧羰基)-1(E),3-共轭烯炔和3-(甲氧羰基)-2-氯代-1,3(Z)-共轭二烯。通过与金属卤盐的加成-消除反应,有效制备了立体构型单一的3-(甲氧羰基)-2-卤代-1,3(Z)-共轭二烯,并通过偶联反应合成了各种取代的3-(甲氧羰基)-1,3(E)-共轭二烯。这些方法丰富了1,3-共轭烯炔和1,3-共轭二烯的立体选择性合成。第二部分：钯(II)-催化的2,3-联烯醇的分子间以及双联烯醇的环化反应1.发展了PdCl2/NaI催化的2,3-联烯醇的自身双分子偶联反应。从光学活性的底物出发,可以得到手性保持的光学活性产物。对比实验表明NaI的添加对反应的进行具有很重要的作用,我们提出了Pdl2为该反应活性催化物种的可能机理。2.首次实现了PdI2催化的同种不同联烯分子间的交叉偶联反应模式：2位取代的2,3-联烯醇通过钯氧化过程构筑2,5-二氢呋喃环骨架,而2位没有取代的2,3-联烯醇则生成了相应1,3-共轭二烯片段。我们发现添加剂BF3·Et20明显提高了反应产率。从光学活性的2位取代的2,3-联烯醇出发也可以得到手性保持的光学活性产物。3.在上述工作的基础上,我们第一次成功发展了官能团化双联烯的环化反应模式：Pd(Ⅱ)-催化的双联烯醇或联烯醇-联烯醇醋酸酯的环化反应单一立体选择性地得到五元并七或八元双环产物；以Novozym-435酶动力学拆分得到的光学活性联烯醇-联烯醇醋酸酯为底物时,产物手性得到保持。第三部分：Pd(Ⅱ)或Rh(Ⅰ)-催化的1,5-双联烯酮的环化反应1.发展了PdCl2(PhCN)2-催化的1,5-双联烯酮的环化反应,在温和条件下,催化剂的量只需1 mo1%就可以较好的选择性(89/11-99/1)得到一组五元并七元环的异构体,通过一定浓度盐酸的处理或直接柱层析就可得到单一3,4-并环呋喃化合物。2.实现了[RhCl(CO)2]2-催化的1,5-双联烯酮的环化反应,以丙酮为溶剂时在室温下反应可以优秀的产率得到单一的3,4-并环呋喃化合物。第四部分：路易斯碱催化或促进的双联烯酮的环化反应1.实现了在1 mol% PPh3催化下1,5-双联烯酮的环化反应,生成了六元环产物,但反应的立体选择性一般,以顺式产物为主。2.发展了催化量TBAF促进下的1,6-双联烯酮的环化反应,生成了七元环产物,反应的选择性较好(-95/5),以反式产物为主。第五部分：Pd(0)-催化的1,3-二烯醇镁盐的不对称烯丙基化反应在本小组工作的基础上,通过铁催化下格氏试剂对2,3-联烯酸酯的高区域和立体选择性的加成反应可以得到1,3-二烯醇镁盐中间体。我们对Pd(0)-催化的1,3-二烯醇镁盐的不对称烯丙基化反应做了初步研究,通过一系列的条件优化,实现了ee值从27%到56%的提高。更多还原

【Abstract】 Allenes are a class of compounds with a unique cumulated diene structual unit. The electron density and the reactivity of each carbon atom of the allene unit can be tuned by the introduction of functionalities or the changing of reaction conditions.Based on the studies of our group in the field of functionalized allenes, 1,5-bisallenes, and the cross-cyclization reaction of two functionalized allenes, my Ph.D. dissertation focuses on (1) the development of reactions of bifunctionalized allenes; (2) further development of the reactions involving two functionalized allenes and realization of the reaction mode of functionalized bisallenes; (3) the development of enantioselective allylation based on the iron-catalyzed conjugate addition of 2,3-allenoates and Grignard reagents.Part I:Highly stereoselective elimination reactions of 2-(methoxycarbonyl)-2,3-allenolsThe efficient stereoselective synthesis of conjugated enynes and conjugated 1,3-dienes are of current interest since they are very important intermediates in organic synthesis. Highly regio-and stereoselective reactions of readily available bifunctionalized allenes, i.e.,2-(methoxycarbony1)-2,3-allenols, with oxalyl chloride in the presence of Et3N or DMSO affords methyl 2-(ethynyl)alk-2(E)-enoates and 2-(1’-chlorovinyl)alk-2(Z)-enoates, respectively, in moderate to good yields. On the other hand,3-(methoxycarbonyl)-2-halo-1,3(Z)-dienes can be prepared highly stereoselectively via the SN2’-type addition-elimination reaction of 2-(methoxycarbonyl)-2,3-allenols with MX (Nal, LiBr-H2O, or LiCl·H2O). These products may easily undergo Negishi or Sonogashira coupling reactions to yield a series of stereodefined polysubstituted 1,3(E)-dienes.PartⅡ:Pd(Ⅱ)-catalyzed coupling-cyclization reaction of two 2,3-allenols and tandem-cyclization reaction of 1,ω-bisallenols1. We have developed a homodimeric coupling-cyclization reaction of 2,3-allenols using PdCl2/Nal as the catalyst, which provides an efficient route to 4-(1’,3’-dien-2’-y1)-2,5-dihydrofuran derivatives. By using the optically active 2,3-allenols, no racemization was observed under the standard reaction conditions, affording optically active products in good yields. Based on control experiment, it was founded that PdI2, generated in situ from PdCl2 and Nal, may be the catalytically active specie.2. We have developed the first example of transition metal-catalyzed dimeric coupling-cyclization reaction of two different 2,3-allenols using the PdI2 as the catalyst in the presence of BF3-Et2O providing an efficient route to 4-(1’,3’-dien-2’-yl)-2,5-dihydrofuran derivatives, in which the 2-substituted 2,3-allenols construct the 2,5-dihydrofuran ring while the 2-nonsubstituted 2,3-allenols provide the 1,3-diene unit at the 4-position by applying deliberate control of electronic and steric effects. Theβ-elimination process is believed to be mediated by the presence of Lewis acid.3. After the realization of intermolecular coupling-cyclization of 2,3-allenols, we paid our attention to the intramolecular cyclization reaction of 1,ω-bisallenols. In the presence of Pd(Ⅱ)-catalyst, the reaction of 1,ω-bisallenols can form 2,5-dihydrofuran-fused bicyclic skeletons. With "unsymmetric" substrates, the reaction may be realized by converting one hydroxyl group to acetate. Optically active bicyclic products may be easily prepared by applying the Novozym-435 catalyzed kinetic resolution and the tandem double cyclization of these optically active substrates.PartⅢ:Pd(Ⅱ)-or Rh(Ⅰ)-catalyzed tandem-cyclization reaction of 1.5-bis(1,2-allenylketone)s1. We have developed the PdCl2(PhCN)2-catalyzed tandem-cyclization reaction of 1,5-bis(1,2-allenylketone)s affording a mixture of two isomeric products with a ratio of 89/11 to 99/1. A single furo[3,4-c]furan product could be obtained after the treatment with hydrochloric acid or by column chromatography.2. We have realized the [RhCl(CO)2]2-catalyzed tandem-cyclization reaction of 1,5-bis(1,2-allenylketone)s in acetone providing an efficient route to furo[3,4-c]furans with high regioselectivity (>99/1).PartⅣ:Lewis base-catalyzed or promoted cyclization reaction of bis(1,2-allenylketone)s 1. We discovered the PPh3-catalyzed cyclization reaction of 1,5-bis (1,2-allenyl-ketone)s forming ethynyl substituted cyclohexane derivatives with moderate stereoselectivity for the cis-products.2. We have established a catalytic protocol of TBAF-promoted cyclization reaction of 1,6-bis(1,2-allenylketone)s forming ethynyl substituted cycloheptane derivatives with good stereoselectivity (-95/5) for the trans-products.Part V:Pd(0)-catalyzed enantioselective allylation of magnesium dienolateWe have studied the Pd(0)-catalyzed enantioselective allylation of magnesium dienolate formed from the iron-catalyzed conjugate addition of 2,3-allenoate with Grignard reagents. After some conditions screening, we have improved the ee value from 27% to 56%.更多还原