Studies On The Construction Of Two Types Of Chiral Quaternary Carbon And The Application In The Synthesis Of Sieboldine A And Lepadiformine

The quaternary carbon extensively exists in active natural products and other useful organic molecules. It is one of the major important and more challenges to enantioselectively construct this type of synthetic structure in Organic Chemistry. Based on this point of view, two synthetic methods for constructing the chiral quaternary carbon were developed and further applied to the total synthesis of some novel structural and active natural products. The following three parts are mainly included:1. Quinine/Selectfluor complex was designed and used to promote effectively the tadem semipinacol rearrangement of allyl alcohols. The reaction condition was firstly optimized and a series of allyl alcohols were subjected to the reaction. The a-quaternary-(3-fluor aldehydes could be obtained from 61% to 82% ee. Based on the Mosher' method, the absolute configuration of the typical product was determined. A reaction mechanism was proposed according to the controlling stereochemistry of the product.2. L-prolinamide/PPTS system was developed to catalyze Robinson annulation of 1,3-cyclohexanedione derivatives. Using this system, the functionalized carbon chain of Wieland-Wiescher ketone could be synthesized in high enantioselectivity, which was a useful synthon for structural diversity of total synthesis of natural product. A reaction mechanism was proposed according to the absolute configuration of the product.3. In exploration to the reaction of the intermolecular desymmetric method, the functionlized Hajos-Parrish- Eder-Sauer-Wiechert ketone could be synthesized in high enantioselectivity by L-proline/PPTS system, which was used for synthesis of the core structure of biological significant natural product, Sieboline A and (-)-Lepadiformine. Staring from the 1,3-cyclopentanedione, the key intermediate 4-14 efficiently synthesized through 3 steps in an overall 32% yield with 97% ee. The precursor of the tricycli skeleton of (-)-Lepadiformine C was synthesized through 2 steps in 65% yield by the intermediate above. This work is ongoing in our group.