Construction Of Tetrasubstituted Carbon Stereocenters By Gold And Mercury Lewis Acid Catalysis

The exploration of the new reactivity of metal catalysts to activate relatively inert substrates for the catalytic asymmetric construction of fully substituted carbon stereocenters is an important task in modern organic chemistry. In view of this, under the guidance of HSAB theory, this thesis focuses on investigating the potential of Au(I) and Hg(Ⅱ) in activating soft bases with low reactivity under mild condition, for the development of new methodologies to construct tetrasubstituted carbon stereocenters. It turns out that although Au(I) and Hg(Ⅱ) are isoelectronic to each other, there existed significant difference as for their capacity in activating allyltrimethylsilane and diazooxindole. For instance, while cationic Hg(Ⅱ) can activate allyltrimethylsilane efficiently via coordinating to its double bond to form nucleophilic diallylmercury intermediate under room temperature, no obvious interaction is observed for the commonly used cationic Au(Ⅰ) catalyst. On the other hand, in the asymmetric cyclopropanation of diazooxindole with alkenes, the in situ generated Au(I) carbenoid intermediate shows higher reactivity than that derived from Hg(Ⅱ). These findings contributes to the first example of Hg(Ⅱ)-catalyzed asymmetric Sakurai-Hosomi, and the first catalytic asymmetric Au(Ⅰ)- and Hg(Ⅱ)-mediated olefin cyclopropnantion reaction. These new protocols allow efficient access to 3-allyl-3-hydroxyl oxindoles and 3-spirocyclopropyl oxindoles, prominent strucutral motif in natural products and pharmaceutically active compounds.(1) Hg(Ⅱ)-catalyzed Sakurai-Hosomi reaction of isatin and allylsilanesA new pathway to activate allyltrimethylsilane by Lewis acid is developed. The interaction of Hg(OTf)2 or Hg(ClO4)2·3H2O with the double bond of allyltrimethylsilane leads to the formation of a more reactive nucleophilic diallylmercury, along with TMSOTf or TMSClO4, which can be used for subsequent addition to aldehyde, isatin and their derived imines. The in situ formed TMSOTf or TMSClO4 is found to assist the release of the product and regeneration of the mercury catalyst. With this aid, the catalyst loading can be effectively fowered down to 0.1 mol%, which also reprersents one of the lowest catalyst loadings in Sakurai-Hosomi reaction. By employing commercially available (S)-Difluorophos as ligand, up to 97% ee can be achieved for such transformation.(2) Hg(Ⅱ)-catalyzed asymmetric cyclo pro pa nation of diazooxindole with styrenesThe first example of Hg(Ⅱ)-catalyzed cyclopropanation reaction of diazo reagent with alkenes is reported. It is found that the soft Lewis acidity of Hg(Ⅱ) allows the decomposition of diazooxindole, a type of donor-acceptor reagent with relatively low reactivity, under room temperature. Under the catalysis of(R)-Difluorophos/Hg(OTf)2, high stereoselectivities are achieved for the cyclopropanation between diazooxindole and mono-substituted stryenes, albeit with lower selectivities for the disubstituted ones. Furthermore, the presence of methyl or benzyl substituents on the nitrogen atom of diazooxindole has no obvious influence on the selectivity. Control experiments indicates the ligand-accelerated charactertic of the reaction, and the Lewis acidity of Hg(Ⅱ) can be nicely modulated by ligand is also observed for the first time.(3) Au(I)-cataryzed asymmetric cyclopropanation of diazooxindole with alkenesThe first example of highly stereoselective Au(Ⅰ)-catalyzed asymmetric olefin cyclopropanation is achieved. The Ding’s spiroketal bisphosphine (SKP)/Au(I) catalysts enable the cyclopropanation of diazooxindoles and a broad range of alkenes, including both cis and trans 1,2-disubstituted as well as trisubstituted ones, to synthesize spirocyclopropyl oxindoles with full control of stereoselectivity. It should be noted that although transition-metal catalyzed asymmetric cyclopropanation of diazo reagent with alkenes has been identified as a powerful way for the preparation of polysubstituted chiral cyclopropanes, no general method for the compatibility of both cis and trans alkenes was reported. The powerfulness of SKP/Au(Ⅰ) catalyst has also been demonstrated for the construction of two adjacent quarternary carbon stereocenters and mono-or difluoromethyl substituted cyclopropanes. Different from Hg(Ⅱ) catalysis, the existence of N-H bond is essential for achieving such high stereoselectivities and a wider scope of alkenes is also found for Au(Ⅰ) catalysis.