A New Type Of Chiral Sulfinamide Monophosphine Ligands: Synthesis And Application

Chiral phosphine ligands play the important role in the field of asymmetric transition metal catalysis. Over the past decades, many privileged chiral phosphines based on ferrocene, binaphthyl, biphenyl, spiro and other backbones have been developed, but most of their synthesis pose considerable drawbacks, such as expensive starting materials, long synthetic route, limited structure-diversity, complicated chiral separation and so on. Therefore, the design and synthesis of novel chiral phosphines is still highly desirable. The main work of this thesis focuses on the design and synthesis of novel chiral phosphines-Ming-phos, as well as their applications in asymmetric transition metal catalysis. The specific research contents include the following three aspects:(1) The design and synthesis of a new type of chiral sulfinamide monophosphine ligands-Ming-PhosWe developed a new type of chiral sulfinamide phosphine ligand, so-called Ming-Phos, which could be easily made from inexpensive commercially available starting materials (i.e. tert-butanesulfinamide 2,200 CNY/kg). Two sets of diastereomeric Ming-Phos ligands could be obtained in good yields with high diastereoselectivity and wide structural diversity by changing the organometallic reagents. The absolute configurations of the two sets of Ming-Phos ligands were established by single-crystal X-ray diffraction analysis. The salient features of these new chiral ligands, including their simple structure, air stability, the practical preparation from readily available starting materials, and easy modification, render these ligands very attractive.(2) Au(I)-catalyzed asymmetric cycloaddition reactionsThe feature of gold(Ⅰ) complexe’s linear coordination renders enantioselective gold catalysis a very challenging task. The new type of chiral sulfinamide monophosphine ligands (Ming-Phos) showed good performance in asymmetric gold catalyzed cycloaddition reactions. For the asymmetric cycloaddition reaction of 2-(1-alkynl)-alk-2-en-l-ones with nitrones, both enantiomers could be furnished in high yields with excellent diastereo- and enantioselectivity by the employment of (R, Rs)-M5 and (S, Rs)-M5, respectively. In addition, either diastereomer of the fluorinated chiral ligands (R, Rs)-M16 and (S, Rs)-M16 also showed good performance in highly enantioselective gold-catalyzed intermolecular [3+2] cycloaddition of readily available N-allenamides with nitrones, delivering both enantiomers of synthetically useful optically active isoxazolidines in good yields with high regio- and enantioselectivities, respectively. Meanwhile, we discover that the acidic N-H bond of the ligand plays an important role in enhancement of enantioselectivity.(3) Cu(Ⅰ)-catalyzed azomethine ylides with β-Trifluoromethyl β,β-disubstituted enones intermolecular [3+2] asymmetric cycloaddition reactionWe reported the first example of highly enantioselective [3+2] cycloaddition reaction of imino esters with β-trifluoromethyl β,β-disubstituted enones. This is also the most efficient route to synthesize the pyrrolidines with all carbon quaternary trifluoromethylated stereocenter, the common skeleton in pharmaceutical and agrochemical. The salient features of this transformation include high efficiency, high diastereoselectivity and enantioselectivity, novel ligand and inexpensive copper catalyst, outstanding functional group tolerance and diverse transformations. In this chemistry, a new binding mode of Ming-Phos was observed, acting as a O, P ligand, which is quite different with the binding mode to gold.