Synthesis Of Novel Spirobiindane-Derived Phosphoric Acids And Their Applications In Asymmetric Catalyic Reactions

Asymmetric organocatalysis has emerged as a frontier in the field of asymmetric catalysis. In this area, the design and synthesis of novel chiral catalyst has a very important meaning, since it directly affect the asymmetric induction and control of the reaction. This dissertation mainly focuses on the synthesis of a new class of chiral phosphoric acids with1,1’-Spirobiindane-7,7’-diol (SPINOL) as scaffold and their applications as organocatalysts in enantioselective transformations. The details are summarized as following:1. The racemic SPINOL was prepared in six steps from3-methoxybenzaldehyde via condensation, hydrogenation, bromination, cyclization, debromination, and demethylation, with an overall yield of30.4%. Then it was resolved by inclusion crystallization with N-benzylcinchonidinium chloride. With enantiopure (S)-SPINOL, a convenient route to6,6’-diaryl derivates was developed, including MOM protection of the hydroxyl group, ortho-iodination, deprotection, as well as the Suzuki coupling Finally, seven kind of SPINOL-derived phosphoric acids were obtained after a subsequent phosphorylation.2. A highly enantioselective aza-Friedel-Crafts reaction of indoles with N-sulfonyl imines promoted by SPINOL-derived phosphoric acids has been developed. Under the optimized conditions, a wide range of optically active3-indolyl methanamines were obtained in up to97%yield with up to>99%ee. The absolute configuration of products was determined to be S according to the X-ray single-crystal analysis, and a possible model for the asymmetric induction of our catalytic system was proposed. It’s the first application that the SPINOL-derived phosphoric acids were employed in organocatalysis.3. A highly enantioselective Biginelli reaction promoted by SPINOL-derived phosphoric acids has been developed. Under the optimized conditions with5mol%catalyst loading, a wide range of optically active dihydropyrimidinethiones (DHPMs) were obtained in up to98%yields with up to99%ee. The synthetic utility of this method was demonstrated by the synthesis of chiral precursors of two drugs, including (S)-L-771688and (S)-SQ32926.