Allyl functionalization of achmatowicz rearragement products and synthetic methodology development with NHC-copper catalysts

Abstract

This thesis consists of four chapters, describing the development of new synthetic methodology and syntheses of natural products deratives: chapter one is focused on the methodology development and new synthetic methods to natural product deratives; chapters two and three is the new synthetic methodology with NHC Copper catalysts; chapter four is the summary and outlook for my thesis. Chapter one decribes the allylic functionalization development of a new catalytic method with Palladium catalysts for Achmatowicz rearrangement (AchR). The development of two novel complimentary oxa-[3+2] cycloaddition reactions was discussed, which allowed a rapid and highly efficient assembly of structurally interesting polycyclic furopyranones. The mechanism of this reaction was also proposed based on experimental results. The palladium catalyst involved Tsuji-Trost allylation followed by intramocular oxa-Michael cyclization and only produced the product with one configuration. In another case, quinine-mediated cascade cyclization occurred through a diastereoselective intermolecular Michael addition and subsequent S_N2-type cycloacetalization by dual activation. Chapter two describes the highly regioselective and stereospecific Cu-Catalyzed deoxygenation of epoxides to alkenes. The deoxygenation of epoxide has been developed for many years, but rare catalytic reactions were mentioned, and no reaction mechanism was discussed. Two copper salts [Cu(TFA)₂ and IMesCuCl] were identified as the earth abundant, inexpensive but effective catalysts together with diazo malonate for chemo/regioselective and stereospecific deoxygenation of various epoxides with tolerance of common functional groups (such as alkene, ketone, ester, PMB, Bn, TBS, TIPS). In particular, the regioselectivity al-lowed for the first time mono-deoxygenation of diepoxides to alkenylepoxide. DFT mechanistic studies showed that the deoxygenation occurred through collapsing the free ylide, unfavoring the possible pathway via cycloreversion of possible oxetane or Cu-tetrahydrofuran. In chapter three, the research continued on NHC copper catalysts. Ring expansion of oxetanes and azetidines was rarely reported. However, this could be a very effective method for the synthesis of tetrahydrofurans and pyrrolidines. The asymmetric ring expansion of oxetanes with diazo compounds was reported, but the substrate scope was quite limited. Ring expansion of azetidines with diazo compounds had only one example and no asymmetric version has been reported. We successfully developed a new NHC ligand combined with copper could successfully accomplish these two reactions with high yield and good enantioselectivity.

Date of Award	2018
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology