The Study Of Semipinacol Rearrangement Reaction: Construction Of Several Quaternary Carbon Sterencenters

As is well-known, quaternary carbon centers exist widely in active natural products and drug molecules, so construction of quaternary carbon centers has always been a focal point in organic chemistry. However, construction of them, especially all-carbon quaternary centers, remains one of the most challenging subjects. Semipinacol rearrangment reactions have been proven to be highly efficient methods to construct quaternary carbon centers. Moreover, semipinacol rearrangment reactions are widely applied to the synthesis of natural products. Our research group has been working on semipinacol rearrangement reactions for a long time. In this thesis, we constructed multi-functional chiral oxo-quaternary carbon centers by fluorination, chlorination, bromination/semipinacol rearrangement. In addition, we also developed copper-catalyzed trifluoromethylation/semipinacol rearrangement reaction of allylic alcohols. The reaction enables the construction of oxo-quaternary and all-carbon quaternary centers.Part I:The study of enantioselective chlorination, bromination/semipinacol rearrangement reactions. As early as2003, our group reported racemic halogenation/semipinacol rearrangement reactions. In2004and2006,(±)-Lycoramine and (±)-Galanthamine were synthesized using this method as a key reaction. However, the catalytic asymmetric halogenation/semipinacol rearrangement of allylic alcohols has not been reported. In2011, we developed a novel asymmetric halogenation/semipinacol rearrangement reaction of allylic alcohols catalyzed by (DHQD)2PYR and (DHQ)2PYR for the first time. This reaction is valuable since two adjacent stereocenters, one of which is the chiral oxo-quaternary carbon, were constructed effectively and two types of β-haloketo compounds (X=Br, Cl) were readily obtained. Moreover, the desired (+) and (-) enantiomers of the products were also readily obtained.Part II:The study of enantioselective fluorination/semipinacol rearrangement reaction. In2005, our group has reported the use of quinine as promoter could effect the asymmetric fluorination/semipinacol rearrangement of allylic alcohols, generating a range of chiral a-all-carbon quaternary (3-fluoro-aldehydes in moderate ee and yield, however, a suitable catalytic method has not been reported before our group. In2012, we developed a novel asymmetric fluorination/semipinacol rearrangement reaction catalyzed by (DHQD)2PYR and (DHQ)2PYR for the first time. This reaction is valuable since a series of chiral a-oxo-quaternary carbon (3-fluoroketones have been constructed. Moreover, both enantiomers of the products were readily obtained.Part III:The study of copper-catalyzed trifluoromethylation/semipinacol rearrangement reaction. Organic compounds bearing a trifluoromethyl group have useful properties for agricultural, functional materials, and pharmaceutical applications. However, there is no strategy for the preparation of α-quaternary carbon β-trifluoromethylcarbonyl compounds, which are potentially useful in organofluorine chemistry. In2013, we developed a novel copper-catalyzed trifluoromethylation/semipinacol rearrangement reaction of allylic alcohols. This tandem reaction is valuable since a series of α-quaternary β-trifluoromethyl ketones were readily obtained.