Stereoconvergent Conjugate Additions and Novel Transformations of Configurationally Labile Molecules

I. Formation of Dienolates as a Novel Mode of Racemization in Stereoconvergent 1,4-Additions The first example of a stereoconvergent reaction that takes advantage of an acidic −proton to racemize the −position through a dienol or dienolate, followed by a stereoconvergent intermolecular conjugate addition was achieved. The first part of this chapter highlights the challenges associated with this type of transformation: sufficient acidity of the −proton to rapidly form the dienolate, as well as, catalyst controlled addition of the nucleophile are significant hurdles to this type of transformation. The second part of this chapter describes the successful addition of arylboronic acids to −stereogenic butenolide derivatives. These reactions are catalyzed by commercially available hydroxy[(S)-BINAP]-rhodium(I) dimer to afford new, stereochemically complex −butyrolactone derivatives. The reaction products provide functionality amenable to further manipulation and can lead to products with up to three contiguous stereocenters. During these studies, the formation of complex cyclopropane derivatives was serendipitously discovered. In the third part of this chapter, efforts to optimize the nitromethane addition to −halo alkylidene −ketoesters to afford densely functionalized cyclopropanes is disclosed. II. Diastereoselective Organocatalytic Addition of α-Angelica Lactone to β-Halo-α-ketoesters A quinidine-catalyzed diastereoselective addition of α-angelica lactone to β-halo-α-ketoesters is reported. The α-angelica lactone displays unusual regioselectivity in this reaction, acting as a nucleophile at the α-position to provide fully substituted glycolic esters with three contiguous stereocenters. Subsequent diastereoselective hydrogenation provides an additional stereocenter within the lactone. III. Hydroxylamine as a Green Precursor for Nitrene and Diimide Formation In the first part of this chapter, efforts toward the Rh-catalyzed aziridination of olefins with hydroxylamine, tosyl chloride, and carbon dioxide are described. Under the defined conditions, we are able to access tosylated aziridines. Despite extensive efforts to optimize this reaction, this reaction remains plagued by low conversions and undesired side reactions. During the course of this project, we observed that reaction conditions lead to the formation of diimide, a highly reactive intermediate known to reduce olefins. By omitting the Rh-catalyst, we can selectively reduce olefins with safe and cheap reagents. The second part of this chapter discusses efforts to optimize the operationally simple diimide reduction of C=C double bonds with hydroxylamine salts, tosyl chloride, and sodium bicarbonate.Doctor of Philosoph