Olefins from carbonyls : Development of new phosphorus-based cross-coupling reactions

Abstract: Olefins, compounds containing C=C double bonds, are omnipresent in nature and serve as useful starting materials for various chemical modifications. Olefins are of crucial importance in Medicinal Chemistry and are also present in essential objects like dyes, polymers and plastics. Thus, developing methodologies for synthesizing olefins is at the heart of Organic Chemistry.In this regard, many reactions have been developed over the years for the production of olefins from different starting materials. To date only one reaction, namely the McMurry coupling, is available for constructing olefins from two carbonyls. This reaction is frequently applied in an academic context, but suffers many drawbacks that limit its wider use. This thesis offers innovative phosphorus-based methodologies for coupling two carbonyls into olefins. All the methods presented herein are based on a one-pot sequence in which a first carbonyl is transformed into a phosphaalkene (P=C double bond containing molecule) which, upon activation, reacts with a second carbonyl with formation of desired alkenes.The first two chapters of this thesis give a general overview on literature protocols for the formation of olefins, along with a comparison between P=C and C=C double bonds containing molecules.The third chapter is dedicated to the presentation of a new potential phosphorus-based coupling reagent. The studies presented in this chapter set the basis for the development of a new cross-coupling reaction of aldehydes to olefins.In the fourth chapter a new method for the one-pot synthesis of disubstituted alkenes from aldehydes is presented. The reactivity of phosphaalkene intermediates proved to be crucial in determining the reaction scope of the process. In the fifth chapter, a closer look into the E-Z stereoselectivity of the protocol is described.The following two chapters deal with more reactive phosphaalkenes. Studies on their chemical properties showed to be fundamental for developing an unprecedent cross-coupling of ketones and aldehydes to trisubstituted alkenes.In summary, this thesis represents the development of new phosphorus-based cross-couplings of carbonyls to olefins. Protocols for the stereoselective synthesis of disubstituted alkenes from two aldehydes, and trisubstituted olefins from ketones and aldehydes are presented. These innovative methodologies offer precious alternatives to the McMurry coupling.