Diastereoselectivity In The Sulfa-Michael Addition Of Thiophenol Or Thiols To Nitroalkenes

The Sulfa-Michael addition (SMA) has proven to be the most powerful strategy in constructing the sulfur-carbon bond and has the potential to introduce two stereogenic centers in one synthetic step when appropriately a,p-disubstituted nitroalkenes are employed as Michael acceptors. However, only limited reports directed toward the diastereoselective control in the preparation of substituted β-nitro sulfides which serve as versatile building blockings for the synthesis of biologically active sulfur-containing compounds.The diastereoselectivity in the triethylamine-catalyzed sulfa-Michael addition of nitroalkenes and thiols was investigated. The sulfa-Michael addition is kinetic control at the beginning and thermodynamic control at the end for less bulky reactants. Thus, kinetic and thermodynamic-controlled adducts can be obtained as major products by controlling the reaction time in those cases. Linear nitroalkenes generally produce anti-adducts as major kinetic products due to favorable steric and stereoelectronic effects, but the diastereoselectivity decreases obviously with steric increase of the substituent located in the vicinal olefinic carbon to the nitro group, even leading to syn-adducts as major kinetic products.1-Nitrocyclohexene gives rise stereospecifically to kinetic cis-adduct, which epimerizes into more stable trans-adduct as major product through the thermodynamic equilibrium. However, the Michael additions involving bulky reactants are generally slow, resulting in the direct generation of thermodynamic adducts. The configurations of syn-and anti-adducts were determined by the H-H coupling constants of vicinal hydrogens and the 13C chemical shifts via the y-gauche effect.In order to reveal the origin of the diastereoselectivity especially for bulky reactants, the reaction of nitroalkenes with thiolate anion followed by protonation at-78℃ was investigated. Then a rational half-chair transition state model for nitronate anion intermediate protonation were proposed by tuning the steric hindrance in both nitroalkenes and thiols. The conformational stability is governed by a chelation effect of lithium and stereoelectronic effect (lithium-oxygen σ* acceptor orbital antiperiplanar to lone pair orbital of the sulfur atom).Additionally,1,3-and 1,5-sulfonyl migrations under thermal conditions have been studied in this dissertation. And both N-arenesulfonylphenothiazine and N-arenesulfonylphenoxazine underwent sulfonyl migration to afford the corresponding aminoaryl sulfone derivatives in modest yield under mild, thermal (160℃ for 2-4 hours) and neutral conditions. Then a homolytic cleavage and intermolecular radical-radical coupling reaction mechanism was proposed via intercrossing experiments.