PART I. Transition Metal-Catalyzed Synthesis of Substituted Phenanthrenes PART II. Determination of Double-Bond Positions in Unsaturated Natural Products by Cross-Metathesis

Abstract

PART I. Transition Metal-Catalyzed Synthesis of Substituted Phenanthrenes

Yongseok Kwon Pharmaceutical Chemistry Major College of Pharmacy Graduate School of Seoul National University

Phenanthrenes are important structural motifs in medicinal chemistry and materials science. A number of synthetic strategies have been developed for the construction of the phenanthrene skeleton. Among these approaches, transition metal-catalyzed cycloisomerization of o-alkynylbiaryls has attracted much attention because it has the potential to allow efficient access to extensive structural variations. However, this strategy necessarily possesses regioselectivity problems

6-endo-dig vs 5-exo-dig depending on the metal catalyst and the substituents on the alkyne terminus. Therefore, transition metal-catalyzed cyclizations of o-propargylbiaryls and biaryl propargyl alcohols have been developed to provide an alternative and selective path for the synthesis of highly substituted phenanthrenes. A catalytic amount of indium salt (III) induced the hydroarylation of o-propargylbiaryls and subsequent exo-endo double bond isomerization to afford substituted phenanthrenes. The cyclization of biaryl propargyl alcohols effectively proceeds in the presence of platinum salt to construct phenanthrene skeletons with carbene functionality. The complete regioselectivity of both cyclization processes for six over seven membered rings has been achieved.

PART II. Determination of Double-Bond Positions in Unsaturated Natural Products by Cross-Metathesis

Yongseok Kwon Pharmaceutical Chemistry Major College of Pharmacy Graduate School of Seoul National University

Accurate identification of the double bond positions in long-chain olefins remains a challenge. The current analytical approaches for solving this problem depend on the use of mass spectrometry (MS). Conventional MS is inherently unreliable primarily due to rapid isomerization of the molecular ions. One solution to this problem involves the prior chemical derivatization of the analyte. This method has been commonly used by laboratories that do not specialize in MS. However, this approach suffers from several drawbacks including the need for a second derivatization step and possible interference from other functional groups on the analyte during derivatization. Therefore, a new chemical derivatization method for the determination of the double-bond positions in long-chain olefins has been developed. This method is based on a cross-metathesis (CM) reaction between the target compound and a simple olefin. Depending on the CM partner used, the resulting fragments possess distinctive physicochemical properties that are appropriate for LC/MS and GC/MS analysis. The position of the double bond can be deduced simply by comparing the changes in molecular mass. Both of the presented methods for LC/MS and GC/MS are equally reliable and applicable at a sub-milligram scale.