SYNTHETIC AND MECHANISTIC STUDY OF ENANTIO- AND STEREOSELECTIVE HOUSE–MEINWALD REARRANGEMENT OF CONGESTED TRISUBSTITUTED SPIRO-EPOXIDES

Published Content: Jeedimalla, N.; Jacquet, C.; Bahneva, D.; Youte Tendoung, J.-J.; Roche, S. P. J. Org. Chem. 2018, 83, 12357.
The present thesis will be focused on the study of House-Meinwald Rearrangement (HMR) reactions for the congested trisubstituted spiro-epoxide molecules. Including their regio-selective, chemo-selective, enantio- selective selective and stereo-selectivity’s will be discussed in detailed by the mechanistic study approach of HMR reaction of trisubstituted spiro-epoxides.
Chapter 1 will present the efforts towards the biomimetic total synthesis of meroterpenoid natural product (+)-liphagal, which possess a recognizable biological activity. The shortcomings associated with its stereochemical assignment, and also the revision of stereochemical assignment of siphonodictyal B, through which the biosynthesis of (+)-liphagal was proposed were discussed.
Chapter 2 will focus on the study of regio and chemoselective HMR reaction. In addition, a three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β, β’-disubstituted benzylidene cycloalkanes using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Second, an epoxidation followed by the HMR of spiro-epoxides is reported to produce a number of α -arylated cycloalkanones upon the ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), demonstrating the difficulty to achieve the ring enlargement for electron deficient spiro-epoxides. On the other hand, via catalysis with aluminium trichloride the rearrangement proceeded typically in high yields and with remarkable regioselectivity. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enabled this method to be successfully extended to some chemo specific arene shifts and it can also synthesize aldehydes derivatives bearing a α-quaternary carbon.