【作者】 舒兴中；

【导师】 梁永民；

【作者基本信息】 兰州大学 ， 有机化学， 2010， 博士

【摘要】 第六周期的后过渡金属元素金、铂,它们除了过渡金属所具有的一般性质之外,还包含有特殊的lewis酸性,Furstner教授将其定义为π酸性。这种性质在活化过程中表现为对炔基官能团的强亲和性,也即在碳碳双键、碳杂双键以及杂原子孤电子对存在下优先发生对碳碳三键的配位,配位方式以单配位为主。在活化炔基的过程中,金、铂催化剂对π键的强极化能力使炔基上的电荷发生偏移,经过一系列的互变异构之后,得到各式各样的活性中间体。这些中间体能通过捕获亲核试剂来实现分子的去极化,也可通过分子内的骨架迁移来达到这一目的。另外,金、铂催化体系具有一定的互补性。前者的活性高,但酸性过强,往往会导致底物的分解；后者活性稍低,所需的反应温度较高、时间较长,但是性质相对温和。我们小组在金、铂催化的炔基活化领域也做了些研究,另外在N原子邻位sp3C-H活化方向也做了些探索性工作,主要包括以下四个部分：第一部分：金催化炔基环氧化合物环化、重排反应研究1.我们通过简单的金催化剂来实现炔基的活化,诱发分子内环氧官能团的亲核进攻,同时利用捕获分子间亲核试剂的方式来实现目标分子的去极化。反应通过简单的串联环化一步合成了2,5-二取代呋喃化合物。2.在实现了金催化炔基环氧与分子间亲核试剂的串联环化后,我们对炔基环氧的5并3氧翁离子中间体进行了进一步研究,发现在没有外在亲核试剂存在下,该中间体能诱发邻位基团的迁移或碳骨架的断裂。由此,我们通过金催化炔基环氧化合物的环化、1,2-烷基迁移实现了螺环吡喃酮的高效合成。在这个反应中,我们可以构建包括季碳在内的多个邻位手性碳。同时,对于迁移位置的碳来说,反应是高立体专一性的,可以维持该位置的立体构型不变。当我们采用非环体系来研究时,我们又发现了一类新颖的C-C键断裂骨架重组现象,在这一过程中,我们可以一步得到两个Z-式双键和一个羰基官能团,反应具有高立体、区域选择性。此外,对于α-羟基环氧的研究也得到了类似的C-C键断裂结果。第二部分：金催化的胺化氢胺化串联反应研究我们充分利用了金催化剂的酸性与π酸性,通过脱水胺化、氢胺化两步一锅反应,从简单易得的原料开始,实现了多取代吡咯化合物的合成。在经过对反应条件的细致优化后,我们对底物的适用性进行了研究,并且利用该方法对双毗咯化合物进行了合成。最后我们对反应机理加以实验认证,初步确认了机理的可行性。第三部分：铂催化炔酸酯类化合物的反应1.我们实现了Pt催化炔酸酯重排在环化反应中的应用,合成了一系列萘酚酯及苯并六元环结构。反应包含多种化学转化,如酯基重排、[1,5]-H迁移、[1,7]-H迁移以及6-π环化等等。在条件优化后,我们对底物的适用性以及保护基的影响进行了研究。在机理研究中,我们开展了D-代实验,验证了反应过程中H原子的转移轨迹。此外,反应具有高度的立体选择性,我们在研究中也对这种高选择性进行了阐述。2.我们研究了邻炔基醛酮类化合物与烯烃的环化反应,反应过程包含一类先前未被发现的重排现象。虽然普通炔基也能参与反应,但是炔酸酯可以给出更好的效果。在这里,关于酯基对反应的具体影响还有待进一步研究。在与1,5环辛二烯的反应中,反应可以选择性地发生在其中一个双键上,生成包含大环的多环骨架,同时还保留了相当多可修饰的活性官能团。另外,反应具有高立体、区域选择性。这些都为反应在今后的应用打下了良好的基础。第四部分：N原子邻位sp3 C-H的活化反应研究1.我们利用高价碘化合物PhI(OAc)2的氧化实现了N原子邻位sp3 C-H键的选择性官能团化。对于哌啶类衍生物来说,N原子经过氧化之后能成功实现α,β-位sp3 C-H键的双醋酸化,反应高立体选择性地得到cis-构型产物。然而对于四氢异喹啉化合物,由于反应能选择性在苄位生成相对稳定不含β-H的亚胺中间体,该中间体捕获亲核试剂之后便能得到一系列α-位官能团化产物；硝基烷烃、丙二酸酯以及酮酸酯都是很好的亲核试剂。另外,当我们使用丙二腈来研究偶联反应时,我们还得到了a-胺基腈产物。2.我们实现了交叉脱氢偶联(CDC)反应中三级胺向亚胺转化的第三条策略；首次在没有外加传统氧化剂的条件下,通过Pt(Ⅱ)促进的胺氧化、H转移过程,采用H+作为H受体来实现sp3C-H键的脱氢偶联。该体系除了能实现先前报道的例子之外,还成功实现了苯基哌啶、苯基四氢吡咯等的高选择性单官能团化。硝基化合物、活性亚甲基以及非活性酮在偶联反应中都能得到很好的应用。更多还原

【Abstract】 As the 6th period later transition elements, gold and platinum not only act as transition metals but also as lewis acids, which have been termed by Fiirstner asπ-acid. Theπ-acid shows high affinity for polarizingπ-bonds of the alkyne group, even in the presence of carbon-carbon, carbon-heteroatom double bonds or heteroatoms. After coordinating to gold and platinum, alkyne is polarized to active intermediates with dual cationic-carbenoid character, which react with nucleophiles or undergo the skeletal rearrangement to achieve the depolarization. On the other hand, the high active gold catalytic system exhibits high acidity, which always leads to the decomposition of starting material; whereas more mild platinum catalytic system needs higher temperature and longer reaction time.Recent years, we also have some studies in gold and platinum catalysis, furthermore we have a good starting in achieving the activation of sp3 C-H bond adjacent to nitrogen by oxidants or transition metals, as shown in the following 4 parts:Part I:Gold-catalyzed cycloisomerization and rearrangement of epoxy alkynes1. We have achieved the activation of alkynes by simple gold catalyst, which induced an intramolecular nucleophilic attack of an epoxide group to afford the oxonium ion intermediate. After capturing an intermolecular nucleophile, the depolarization of oxonium ion was achieved. Various 2,5-disubstituted furans have been synthesized according to this simple tandem process.2. Further studies on the intermediate oxonium ion, we found that the intermediate could induce the migration of an adjacent group or cleavage of adjacent bonds. Then we achieved the efficient synthesis of spiropyranones via gold-catalyzed cyclization/1,2-alkyl migration of epoxy alkynes. From this process, the construction of adjacent multiple stereocenters with a new quaternary carbon atom is achieved. The gold-catalyzed domino process is stereospecific with respect to the migrating carbon atom. A type of unusual C-C bond cleavage of epoxide systems has also been discovered, which can lead to the formation of two Z alkenes and a carbonyl functional group in one step with excellent stereoselectivity. The same C-C bond cleavage was also observed when an a-hydroxy epoxide was used.Part II:Gold-catalyzed tandem amination hydroamination reactionWe have well utilized the acidity andπ-acidity of gold catalyst to achieve the synthesis of poly-substituted pyrroles via tandem dehydration amination and hydroamination reactions. After a detailed optimization of reaction conditions, we studied the scope and the mechanism of this transformation. The bis pyrrole derivate was also synthesized from this method.Part III:Platinum-catalyzed reactions of propargylic esters1. Platinum-catalyzed rearrangement of propargylic ester has been applied in the cyclization reactions and various naphthalenyl acetates have been synthesized. The reaction might include the [1,3]-OAc shift, [1,5]-sigmatropic hydrogen shift and 6-πcyclization processes. After optimization of reaction conditions, we studied the scope of this reaction and the effect of different protective groups. The deuterium-labeling experiments were also carried out to reveal the mechanism. The high stereo-selectivity was also observed in this transformation.2. Platinum-catalyzed cyclization of o-alkynyl(oxo)benzenes with alkenes have been studied, where an interesting migration of the rigid structure of benzene was observed. Although ordinary alkynes could be applied in this reaction, the propargylic ester gave the best result. Further study was needed to reveal the detailed effect of ester group. When 1,5-cycloctadiene was used, large ring system was synthesized with one of the double bonds saved, which could be used for constructing more complex structures. The high stereo-and regioselectivity was also disclosed. Part IV:Studies on the activation of sp3 C-H bond adjacent to nitrogen1. A PhI(OAc)2 mediated selective functionalization of sp3 C-H bonds adjacent to a nitrogen atom has been achieved. When piperidine derivates were used, direct diacetoxylation of alpha and beta sp3 C-H adjacent to a nitrogen atom were observed to afford various cis-2,3-diacetoxylated piperidines. On the other hand, tetrahydroisoquinoline derivatives gave variousα-C-H functionalized products in the presence of PhI(OAc)2. Nitroalkanes, dialkyl malonates andβ-keto ester are active participants in this coupling reaction. Meanwhile, a-amino nitriles can also be obtained by oxidative coupling of amines with malononitrile.2. The third strategy for the transformation of tetra-amine to iminium in cross-dehydrogenative coupling (CDC) reactions has been achieved. The reaction proceeds efficiently via platinum mediated H-abstraction where H+ acts as the H-acceptor. No peroxides, hydrogen peroxide or other traditional oxidants is needed. Nitroalkanes as well as dialkyl malonate derivatives,β-keto esters and malononitrile are active participants in this coupling reaction. Both cyclic and acyclic non-activated simple ketones are good reactants in this reaction.更多还原