Stereocenters (thio) Urea Catalyst For Catalytic Asymmetric Heteroatom Michael Addition Reaction Theory

One of the entitative attributes of nature is chirality. Most of molecules in organism are chiral. Chiral compounds are used in organic chemistry, biochemistry and material chemistry widely. Enantioselective organocatalysis as a new concept emerged at the 21st century have been developing into an important tool for constructing of complex molecular skeletons because of its high-efficiency and high selective sensitivity. Enantioselective organocatalysis can offer extensively applied future for medicine, chemistry, material and biology. So, the experimental and theoretical investigations of organocatalytic asymmetric reactions will be of important theoretical and practical values. Theoretical studies of organocatalytic asymmetric reactions not only can understand the reaction mechanism fully from the molecular level but also can explain the experimental phenomenons. It also can make the function of organocatalyst and the origin of enantioselectivity for the catalyzed reaction clear.In this dissertation, we studied the Hetero-Michael reactions catalyzed by multi-stereocentral (thio)urea catalyst and squaramide-catalyst. Theoretical studies by computational methods can explain the reaction mechanism and the essential effect of the catalyst from micromechanism. The results can provide a theoretical direction for developing new type, high effective organocatalysts and novel organocatalytic asymmetric reactions.The valuable results in this dissertation can be summarized as follows:Our DFT calculations provide a first theoretical investigation on enantioselective sulfa-Michael addition reaction of theoacid and trans-β-nitrostyrene catalyzed by N-Sulfinyl urea in CPME solvent. The results show that there are two pathways for the reaction yielding the products. Pathway A which gives (R)-configuration product is favored over the pathway B which yields (S)-configuration product. The enantioselectivity of the sulfa-Michael addition reaction is controlled by the C-S bond-formation step. The rate determining steps are different in two pathways. In pathway A the step of conformational change from r2 to r2-1 is the rate-determining step, which is the proton transfer from the amino group of the catalysts to theα-carbon of the nitrothiolate in pathway B. The ee value we obtain is in agreement with the experimental data. From the calculation of the sulfa-Michael reaction of thiobenzoic acid and trans-β-nitrostyrene which need more sterical demand, we predict that the reaction has enantioselectivity used N-Sulfinyl urea as the catalyst. The present results will stimulate not only the development of novel organocatalyst for sulfa-Michael addition but also the expansion of the scope of N-Sulfinyl urea catalysis.The hetero-Michael reaction of dimethyl phosphate with nitroalkene catalyzed by a squaramide-organocatalyst is investigated using density functional theory (DFT) calculations. The catalysis proceed is by single functional activation. The tertiary amide of the catalyst activates nucleophilic substrate by transformation of proton. However, the electrophilic substrate is not activated.The results show that there are two channels for the reaction between dimethyl phosphate and nitroalkene. Channel A which gives (R)-configuration product is favored over the channel B which yields (S)-configuration product. The rate determining steps are different in two channels. In channel A the step of C-P bond formation is the rate-determining step, which is the proton transfer from the amino group of the catalysts to theα-carbon in channel B. The barriers of the two rate-determining steps are close. But channel A is the favored channel in the first step and in the second step of proton transfer the energy of R-TS1 is lower than that of S-TS1. So (R)-configuration product is preponderant. The enantioselectivity for the reaction is also calculated. The ee value we obtained is in agreement with the experimental fact. The present results will stimulate the expansion of the scope of squaramide catalysis.