Development of phosphine oxide and arsine oxide organocatalysis

Abstract

In the field of organic chemistry, phosphine oxides and arsine oxides have generally been viewed as undesirable nuisances since their major origin is the reaction by-products or result from undesired oxidation of a phosphine or arsine catalyst or ligand. This is especially true in the context of organic synthesis sequence such as Wittig reactions and Mitsunobu reactions where a stoichiometric amount of a phosphine oxide or arsine oxide, typically triphenylphosphine oxide or triphenylarsine oxide, is produced alongside the desired product. Although the great utility of these two reactions can be found many places in organic synthesis over the years due to their general reliability, easily available operability and predictable stereoselectivity, their use can sometimes be impractical in product isolation step where target molecule need to be separated from a complex reaction mixture containing large amounts of by-products. Thus, the use of those phosphine oxides and arsine oxides as Lewis base organocatalyst is regarded as meaningful topic, especially in one-pot reaction where in situ generated phosphine oxide or arsine oxide by-product can be used as catalyst in subsequent step. This thesis aims to cast phosphine oxides and arsine oxides in a more favourable light by summarizing our effort in the development of their use as organocatalysts. Triphenylphosphine oxide is a weak Lewis base that is reported to active trichlorosilane. We further develop the use of it in selective -reduction of conjugated polyunsaturated ketones, selective alpha-halogenation and two-pot, five-step sequence in generation of 3-phenyl-2,3,4,5-tetrahydro-1H-2-benzazepine where triphenylphosphine oxide by-product is used as catalyst for two times in subsequent reactions (chapter 2). 3-Methyl-1-phenyl phospholene oxide is another weak Lewis base that can active aryl isocyanate. We further develop the use of it in secondary amine formation, tertiary amine formation and amide formation reactions (chapter 3). Triphenylarsine oxide, a kind of even weaker Lewis base compared with triphenylphosphine oxide, can active both aryl and alkyl isocyanate. We further develop the use of it in intra-molecular imine formation reaction (chapter 4).