Copper-Catalyzed Synthesis of Heterocyclic Rings via Alkene Difunctionalization
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Alkene DiaminationAlkene diamination is an important strategy in synthetic chemistry. It gives access to 1,2-vicinal diamines, and in the method disclosed in this chapter, 1,2-diamino-3-alcohols. These scaffolds are useful in many medicinally active compounds. Herein, we describe how earth abundant copper salts are applied in the synthesis of isoxazolidine rings using alkenes. These products can be converted to the 1,3-diamino alcohols. The isoxazolidine products were obtained in a very good diastereoselectivity. The mild reaction conditions enabled a wider amine scope including alkyl and arylamines, benzamides, sulfonamides and anilines. Carbamate-functionalized substrates were uniquely active for the first time in our copper chemistry. Oxidation potential of selected amides and amines were measured and correlated to some nitrogen radical chemistry observed in our diamination attempt of 1,1-disubstituted alkenes. The measured oxidation potentials also helped to rationalize previous observations reported by our group and others. A copper promoted aminooxygenation and dioxygenation of alleneols and allenylamines was achieved. No additional oxidant was needed. The resulting vinyl esters were transformed into α-aminoketones and acetoxyketones. A new methodology has been developed for the synthesis of 2-arylpyrrolidines using copper-catalysis and the shelf stable trifluoroborate salts with alkenylamine substrates. The reaction tolerated different tosamide and amide type substrates. Both aryl and alkyl substituted trifluoroborate salts were reactive as well.