論文の公開元へStudies on Chemo- and Site-Selective C-H Amination of Aniline and Phenol Derivatives with Dirhodium Catalysts and Catalytic Asymmetric Synthesis of Inherently Chiral Calixarenes
概要
Development of methods for the construction of C-N bonds is still of great synthetic importance in current synthetic organic chemistry because C-N bonds are ubiquitously involved in functional materials and bioactive molecules. Metal-catalyzed nitrogen-group-transfer via C-H bond cleavage has become an important method for the construction of C-N bonds. While the cleavage of C-H bonds is position-limited in intramolecular reactions, control of chemo- and site-selectivity becomes an issue in intermolecular reactions. Dirhodium nitrene species have emerged as powerful intermediates for C(sp3)-H amination reactions. Electron rich C(sp3)-H bonds α to C-C multiple bonds and oxygen atoms, and tertiary C(sp3)-H bonds can be selectively converted to C-N bonds, even in intermolecular reactions, so far. In 2018, Kawabata et al. reported a general method for chemo- and site-selective C-H amination of anisole derivatives with dirhodium nitrene complexes. Under the condition, the aromatic C(sp2)-H amination selectively took place at the para position of the oxygen substituent in the presence of benzylic C(sp3)-H bonds and/or C(sp3)-H bonds α to ethereal oxygen. Based on this transformation, I studied three topics in this thesis as described below.
Chapter 2. Development of Chemo- and Site-Selective C-H Amination of N,N-dialkylanilines
As I expected C(sp2)-H amination of aniline derivatives, application of the reported procedure for C(sp2)-H amination of anisole derivatives, using Rh2(tpa)4 (tpa = triphenylacetate) as a catalyst and O-tosyl-N-trichloroetnoxycarbonylhydroxylamine (TrocNHOTs) as a nitrene source to N,N-dimethylaniline did not provide any C-H aminated products. Catalyst screening revealed that C-H amination of N,N-dimethylaniline catalyzed by Rh2(oct)4 (oct = n-octanoate) proceeded selectively at C(sp3)-H bonds α to the nitrogen atom, in the presence of aromatic C(sp2)-H bonds. The prominent feature under this condition is site-selectivity of the C(sp3)-H amination. C(sp3)-H amination of the N-methyl group of various N-alkyl-N-methylanilines (alkyl ≠ methyl) was observed exclusively even in the presence of potentially reactive benzylic and tertiary C-H bonds α to the nitrogen atom.
Chapter 3. Studies on Chemoselectivity in C-H Amination of Anisole and Aniline Derivatives
As interested in the difference of chemoselectivity between in C-H amination of anisole and in that of N,N-dimethylaniline, I studied effects of ligands on dirhodium complexes on the C-H amination reactions. In the case of C(sp3)-H amination of N,N-dimethylaniline, as the numbers of phenyl substituents on the α carbon to the carboxyl group of the ligands increased, the yield of the aminated product decreased. Based on the calculation about association of N,N-dimethylaniline and dirhodium complexes, the phenyl substituents of the ligands can stabilize coordination of substrate to the Rh by multiple C-H/π interactions, which would inhibit the catalytic cycle of the C-H amination. On the other hand, in the case of C(sp2)-H amination of anisole, as the numbers of phenyl substituents on the α carbon to the carboxyl group of the ligands increased, the yield of the aminated product increased. I assumed that the phenyl substituents on the ligands could stabilize the partial positive charge on the aromatic ring attacking to the dirhodium nitrene species in the transition state of C-N bond formation.
Chapter 4. Catalytic Asymmetric Synthesis of Inherently Chiral Calixarenes by Enantioselective C(sp2)-H Amination
Calixarenes are representative molecules in host-guest chemistry. Due to the bowl-shaped 3D structure, calixarenes have a non-classical chirality (named, inherent chirality) depending on the arrangement of achiral substituents. Because of the attractive chirality, some studies on applications of inherently chiral calixarenes (ICCs) to asymmetric catalysts and molecular recognition were reported. While several examples of asymmetric synthesis of ICCs were reported by virtue of chiral auxiliaries, there is only one report on catalytic asymmetric synthesis of ICCs utilizing enzymatic acylation reaction. In this chapter, catalytic desymmetrization of Cs-symmetric calix[4]arene derivatives by enantioselective C(sp2)-H amination was investigated. A chiral dirhodium complex constituting of amino acid derivatives catalyzed C(sp2)-H amination of a calix[4]arene derivative with the adequate substituents on upper and lower rims in high enantioselectivity (up to 87% ee).
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