Chiral Metal Catalysts Synthesis And Application To Trapping Unstable Carbene In Mul-componet Reactions

Multi-component Reactions (MCRs), are the most effective synthetic strategy to constructmolecules of multifunctional groups in a single operation over the conventional step-by-stepmethodology. But the fulfillment of orderly self-assembly of all components and highstereoselectivity entail the combination of all different kinds of catalysts, which is referred toas cooperative strategy. This dissertation describes the development of two sorts of Br nstedacids as compatible cooperative catalysts in the realm of our ylide transformation research,and the attempt in Multi-component Michael-Michael Tandem Reactions.The introductory chapter offers a short review on the chemistry of carbene, diazocompounds, ylides, Multi-component reactions as well as cooperative catalysis strategy,which lays the background for the progressively continuous researches.In the chapter two, we have synthesized a series of chiral phosphoric acids, up to sixteen, withacceptable total yield50-60%, according to modified procedures. The improvedprotocol—more low temperature (-78℃) was adopted when we conducted directed ortholithiation and subsequent diiodides substitution—unclogs the bottleneck we are facing, thatsynthetic scale is rather limited because the process for preparation of diiodides is highlyexothermic and larger scale invariably gives rise to low yield. What′s more, we, for the firsttime, disclosed racemization of the final chiral product phosphoric acids and systematicallyascertained the mechanism. The racemization took place contaminant with deprotection ofmethoxymethyl group on substrates at100℃under acidic condition and it could beovercome at a lower temperature. While strong acidity and high polarity of chiral PAs denythe access to steady and convenient determination of their ee for both positive-phase columnchromatography and negative column chromatography, methylation modification we devisedmakes the determination come true. These findings will surely provide an instructive guidefor related researches.In the following section, we developed a route for producing more strong acidic chiralBr nsted acids1,1′-binaphthyl-2,2′-disulfonic acids, a kind of promising cooperative catalystsfor activating aldehydes and ketones in our reaction system. Unfortunately, the route is notapplicable to other3,3′positions substituted sulfonic acids, and the presence of substitutionsprevent the Newman–Kwart rearrangement and subsequent oxidation reactions. As a continuous interest in Multi-component reactions on ylide transformation, we report,in the final chapter, a progress utilizing substrates ethyl4-hydroxybut-2-enoate as Michaeldonors to realize intermolecular Michael-Michael tandem sequence—the reaction that has notbeen achieved before. In the asymmetric synthesis attempt, only about10%of enantiomericexcess of the three-component product obtained, though it is the first example ofintermolecular tandem reactions concerning our researches.