Asymmetric Synthesis Of Indole-Based C-N Axially Chiral Skeleton

Atropisomerism is a property exhibited by molecules where bond rotation is restricted.The axial chirality is different from the central chirality.The axial chiral compounds have no stereocenter,but there is a pair of enantiomers that are mirror images of each other.The axially chiral compounds widespread appearance in naturally occurring biologically active compounds and also play a significant role in acting as chiral ligands or organocatalysts.Therefore,the asymmetric synthesis of various types of axial chiral compounds has received extensive attention.The research in this thesis mainly focuses on the asymmetric synthesis of novel C-N axial chirality based on N-indole sulfonamides.The new axially chiral N-indole sulfonamdies were constructed by different strategies with high diastereoselectivity or enantioselectivity.The main contents in this thesis are summarized as follows:1.NaClO-promoted atroposeletive couplings of 3-substituted indoles with amino acid derivatives.Axially chiral N-indole sulfonamdies were constructed by the NaClO-promoted coupling of 3-substituted indoles with chiral amino acid-based sulfonamdies.The diastereoselective was achieved by chiral induction of chiral amino acids and ortho-position resistance of C-N bonds.The stability of this structurally interesting atropisomers is highly relied on the C3-substituents of indoles and side chains of amino acid derivatives.2.An atroposelective coupling of indoles with chiral amino acid-based sulfonamides mediated by hypohalides is described.The strategy has the advantages of mild conditions,simplicity and efficiency.A series of 2-amido-3-haloindoles with a C-N chiral axis are delivered using this strategy.The C3 halogen atoms can facilitate further transformation.Various functionalities,such as carbonyl,phosphine,aryl and alkenyl groups,can be introduced into C3 position of indoles.These structurally diverse and axially chiral indole derivatives can find further synthetic utilities.It can be exemplified with an axially chiral phosphine,which serves as a ligand in Pd-catalyzed cross couplings.3.Enantioselective synthesis of axially chiral indoles containing two C-N chiral axis via asymmetric Suzuki-Miyaura coupling.Under the catalytic system of Pd and chiral phosphine ligands,the asymmetric construction of axially chiral indoles containing two C-N chiral axis was achieved for the first time by asymmetric Suzuki-Miyaura coupling reaction.A series of structurally diverse axially chiral indoles containing two C-N chiral axis were prepared using our established method.In addition,we have carried out detailed studies on the racemization phenomenon(half-life,rotational energy barrier,chiral axis rotation)of this novel double C-N bond axially chiral compound.