Applications of guanidines as novel multifunctional organocatalysts and studies of new synthetic routes towards chiral bicyclic guanidinium salts

摘要

During the first part of the research work, the main emphasis was given to the exploration of neglected nucleophilic properties of guanidines. Initially, a gamma-selective Morita-Baylis-Hillman (MBH) reaction of alpha-,gamma-disubstituted allenoate esters was investigated. Among tested nucleophiles, bicyclic guanidines 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) showed the best results. Allenic alcohols were obtained as products in good to excellent yields even with electron rich aromatic aldehydes. These products were shown to be useful intermediates for the synthesis of densely substituted heterocycles. Au(I)-catalyzed cycloisomerization of allenic alcohols afforded dihydrofurans and applying tributyl phosphine led to the formation of pyrones. Further investigations led to the development of a TBD-catalyzed diastereoselective synthesis of densely substituted trifluoromethylated oxetanes from gamma-substituted allenoate esters and trifluoromethyl-aryl ketones. This approach represents the first convenient intermolecular entry to fully substituted oxetanes by using a non-photochemical cycloaddition reaction. The bicyclic guanidine TBD has also been shown to catalyze complex four- or even five-step reaction cascades between gamma-substituted allenoates/beta-alkynoates and aldehydes. This work exemplifies the multifunctional nature of guanidines, as TBD acted not only as a Brønsted, but also as a Lewis base. The dioxine-products possess four newly formed stereogenic centers and are obtained in excellent diastereoselectivities and high yields. A logical continuation of all the projects presented in the first part of the thesis would be the development of corresponding enantioselective variants of the discovered reactions. For this purpose, chiral derivatives of [4.4.0]- and [3.3.0]-bicyclic guanidines had to be prepared and studied for their catalytic activity. Within the framework of this work the emphasis was given to a guanylation approach using di(1H-imidazol-1-yl)methanimine. Although the control of regioselectivity represents a yet to be solved challenge, the new approach possesses a great potential due its robustness, scalability and reproducibility. As a matter of fact, it was successfully applied for the synthesis of a chiral derivative of TBD.