Author: Ji, Jianxin
Title: Catalytic asymmetric addition reactions leading to carbon-carbon bond formation : phenyl and alkenyl transfer to aldehydes and alkynylation of [alpha]-amino ester
Degree: Ph.D.
Year: 2004
Subject: Hong Kong Polytechnic University -- Dissertations
Asymmetric synthesis
Phenyl compounds -- Synthesis
Alkenes -- Synthesis
Department: Department of Applied Biology and Chemical Technology
Pages: ix, 129 p. : ill. ; 30 cm
Language: English
Abstract: Catalytic asymmetric addition reactions of nucleophiles to carbonyl and imine electrophiles are important processes in asymmetric synthesis. Such addition reactions are intrinsically efficient in the production of a wide range of valuable enantiomerically pure compounds since a new chiral center and a new carbon-carbon bond are established in a single operation. The quest for efficient catalytic systems and chiral ligands plays a crucial role in expanding the utility of this strategy. Furthermore, for the practical applications of useful catalytic asymmetric synthesis, it is highly desirable to develop convenient methods for the preparation of effective chiral ligands. Over the past two decades, catalytic asymmetric addition reactions employing enolsilanes (aldol addition), allyl-stannanes (allylation), and dialkylzinc (alkylation) have proved to be remarkably effective and products with excellent enantiomeric excesses have been achieved for different types of C=X electrophiles. Compared to the above well-established reactions, however, catalytic asymmetric alkenyl, phenyl and alkynyl transfers to carbonyl and imine compounds are substantially less developed in spite of their importance in organic synthesis. In this study, we have developed a convenient, one-step synthesis of optically active tertiary aminonaphthols, which have been found to be very effective chiral ligands in catalytic asymmetric phenyl and alkenyl transfers to aldehydes. A novel and efficient synthetic methodology of Ag (I) and Cu (I)/(II)-catalyzed alkynlation of 帢-amino ester has also been developed. Chiral ligand 1-((S)-phenyl(((1'S)-1'-phenylethyl)methylamino)methyl)-2-naphthol was synthesized by direct condensation of the corresponding aldehyde, naphthol and secondary amine. A successful application of this chiral ligand in the enaritioselective alkenylzinc addition to aldehydes was achieved and a variety of (E)-allyl alcohols were obtained in high yields and ee's (92%-99%). Considering that a bulkier group at the newly generated chiral center could increase the rigidity of the ligand which may be beneficial for chiral induction, a novel chiral tertiary aminonaphthoi ligand 1((S)-1'-naphthyl(((1"S)-1"-phenylethyl)methylamino)methyl)-2-naphthol was designed and prepared by the one-step procedure which we have developed. This ligand was employed in the phenyl boronic acids-diethyl zinc-aryl aldehydes system and a variety of chiral diaryl methanols were achieved in high chemical yields with excellent enantioselectivities. To the best of our knowledge, this is the first example of a ligand devoid of planar- and axial-chirality which is able to generate high enantioselectivites in phenyl transfer reactions. Especially noteworthy is that (R)-ortho-methyl benzhydrol, which was obtained in 99% ee, is the direct precursor of Orphenadrine, an anticholinergic and antihistamiriic agent. 帣, 帠-Alkynyl 帢-amino acid derivatives are a special class of nonproteinogenic amino acids which possess important biological activities. We have not only developed the first catalytic synthesis of 帣, 帠-alkynyl 帢-amino acid derivatives but have also extended the applications of Ag alkynilide in organic synthesis by showing the feasibility of direct addition of terminal alkynes to 帢-imino ester in the presence of a catalytic amount of Ag (I) salts under mild reaction conditions. Cu (I)/(II) salts were also found to be effective catalysts in the above reaction system. Furthermore, moderate ee (67%) was achieved in the experiment for asymmetric version of this novel synthetic methodology.
Rights: All rights reserved
Access: open access

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