Pd(?)-Catalysed Acetoxime Directed C-H Functionalization Of Alcohols

Controlling site-specific functionalization of C-H bonds has always been a challenge and the key point;however,harnessing a directing group to enable site-selective C-H functionalization is one of the most successful strategies.Due to the widespread existence of hydroxy group in natural products and bioactive molecules,and its important role in funcational group transformations,it is necessary to explore and develop the novel directing group and protecting group for the C-H functionalization of alcohols.In this thesis,we mainly studied palladium(II)-catalyzed acetoxime directed ortho-olefination and arylation of aromatic alcohols.Benzyl alcohols are important versatile synthetic precursors in synthetic chemistry,and usually are the omnipresent component of many natural products and drug molecules.Herein,we addressed a simple and potential exo-oxime ether directing group for direct C-H functionalization of benzyl alcohols at ortho-positions.Phenethyl alcohols were also effective,despite of relatively remote coordination.Moreover,the crystal of six-membered exo-palladacycle intermediate was successfully prepared.Finally,we demonstrated the utility of ortho-C-H olefination by total synthesis of a rare fungal metabolite—3-deoxyisoochacinic acid from commercial available 2-benzylocybenzyl alcohol in five steps.Inspired by our previous results,we further developed the first example of acetoxime directed ortho-arylation of masked aromatic alcohol derivatives via the possible six-and seven-membered exo-palladacycle intermediate.A variety of acetoxime ethers could be coupled with a diverse range of arylboronic acid pinocol esters giving direct access to bioactive biaryls containing a benzyloxy motif under ligand accelerated palladium catalysis.Impressively,either acetoxime could be subsequently removed without a separation,or functionalized hydroxylamine derivatives could be obtained.