1 ABSTRACT
This thesis describes the development of the concept of C-C bond forming conjugate addition/oxidative cyclisation reactions and their application in the total synthesis of natural polyphenols. The first part deals with the development of methodology for conjugate addition of main- group organometallic reagents to unsaturated carbonyl compounds coupled with in situ single electron transfer oxidation. The resulting radical undergoes stereoselective cyclisation, that can be followed by a second SET oxidation, leading to further cationic cyclisation. This methodology is ideally suited for the synthesis of furoindane stilbenolignans (FIS), a neglected and structurally distinct class of natural polyphenols. Using this process, racemic synthesis of a derivative of kompasinol A was achieved, confirming the relative configuration of FISs. In an effort to develop asymmetric route to FISs, an unprecedented direct conjugate addition of aryllithiums to ylidenemalonates mediated by diethers and diamines was discovered, leading to asymmetric synthesis of gnetifolin F and 11- deoxykompasinol A.
Based on X-ray evidence, a related annulation methodology consisting of direct conjugate addition/epoxide opening was shown to result in bridged lactones, instead of isomeric FISs. This finding led to an approach for the rapid assembly of the neopodophyllotoxin core. An asymmetric variant using organocatalytic Corey-Chaykovsky epoxidations was also explored. The nitrosative cleavage of ketone enolates, which was serendipitously discovered during the study of SET oxidation, was systematically explored in terms of scope and limitations. Through optimization it was developed into a useful method for anti-Beckmann cleavage of symmetrical as well as non-symmetrically substituted ketones.
