Gold And Platinum-catalyzed Reactions Of Alkyne And Activation Reactions Of Sp~3 C-H Bond Adjacent To Nitrogen

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.