| Acid-base chemistry is one of the most widely studied fields in chemistry. Depending upon the definition of an acid and base, almost all the chemical reactions can be characterized as the form of an acid-base reaction. Quantitatively describing the ability of a compound for gaining or losing a proton, equilibrium aciditiy (i.e. pKa), which is a very important parameter in Bronsted acid-base chemistry, bridges the gap between thermodynamics and kinetics. Historically, the studies on equilibrium acidity have led to a series of important discoveries. Nowadays, the concept of pKa has exhibited potential applications on diagnosing mechanism, designing catalyst and interpreting the origin of stereoselectivity. Meanwhile, the rapid development of computational chemistry makes the prediction of properties of compound, research on transition states and explaining mechanism of complicated reactions become a reality. Asymmetric organocatalysis, especially chiral Bronsted acids catalysis, has received significant attention since the last ten years. In this context, thousands of asymmetric transformations have been achieved. However, research interests focused on general rules behind specific reactions attract rather rare attention.Physical organic chemistry, which studies the interrelationships between structure and reactivity in organic molecules, is a powerful tool to address the above issues. Combination of experimental and computational chemistry, we attempted to narrow this gap from three aspects by virtue of pKa in this thesis.(1) pKa values of popular chiral phosphoric acids in DMSO were investigated computationally. An theoretical protocol (SMD/M06-2X/6-311++G(2df,2p)//B3LYP/6-31+G(d)) for accurate prediction of pKa was developed. The first pKa scale of chiral phosphoric acids was established on basis of pKa values for41acids. It was found that pKa values for BINOL phosphoric acids have linear correlation with the Hammett parameter of substituent group on3,3’position, which provided a facile method to predict pKa values for unknown phosphoric acids. Utilizing these pKa scales, an analysis between acidity and reaction activity&stereoselectivity was conducted. The study of acidity for phosphoric acids threw light on designing new organocatalysts.(2) Application of the above established method (SMD/M06-2X/6-311++G(2df,2p)//B3LYP/6-31+G(d)), a set of chiral Br(?)nsted acid catalysts were predicted in DMSO. It was found that this method can accurately predict pKa values for not only oxygen acids (O-H) but also nitrogen acids (N-H) in DMSO and Acetonitrile solutions. A pKa scale for containing more chiral acids was established, which makes the knowledge of acidities for different type Br(?)nsted acids reach a new stage. Three tactics based on pKa predictions were proposed to design new Br(?)nsted acid organocatalysts. Again, an analysis of how the acidities of catalysts influence the reaction activity-selectivity was carrid out at a wide range of pKa values.(3) In the light of acidity of substrate, an asymmetric organic catalyzed chemical transformation was designed to synthesize spirocyclic benzofuran-2-ones through double Michael addition. Three key factors were considered to design this reaction:(1) Acidity of hydrogen in3position at benzofuran-2-one (pKa:13.5) is equal to that of2-indolone protected by acetyl (13.5), and stronger than that of nitromethane (17.2) in DMSO.(2) N-CO2Et substituted2-indolone can react with dienones to gain spirocyclic indolones.(3) Nitromethane can add to dienones by a single Michael addition, and these products can be converted to cyclohexanones in the presence of strong base. A number of spirocyclic benzofuran-2-ones were successfully prepared in very good yields (up to99%), diastereoselectivities (up to19:1dr), and very good enantioselectivities (up to92%ee). The origin of stereoselectivity was attributed to favorable electrostatic interaction (δ+N-C-H…O) by performing density functional theory (DFT) calculations. |
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