Aymmetric Formal[3+3] Annulation Of 2-Enoyl-Pyridine N-Oxides With Acetone

Michael-aldol tandem reaction as an effective method is widely used in organic synthesis for constructing cyclic compounds.The chiral cyclohex-2-enone scaffolds are widely discoved in natural products and biologically active molecules.In this context,various synthetic methods for chiral cyclohex-2-enone have developed rapidly in the past two or three decades.However,the synthesis of highly enantioselective chiral cyclohex-2-enone with high efficiency and simplicity is still attracted tremedous attention from chemists.Meanwhile,2-enoyl-pyridine N-oxides as one of the most popular substrates has been extensively explored in the asymmetric transformations due to the good coordination ability of the pyridine N-oxides,moreover,the multiple reactive sites of 2-enoyl-pyridine N-oxides,including carbonyl and carbon-carbon double bonds,made it become a versatile building block in asymmetric synthesis.Based on the above background,the asymmetric formal[3+3]annulation of 2-enoyl-pyridine N-oxide with acetone was chose as a model reaction to construct chiral 3,5-diaryl-cyclohex-2-enone derivatives.In the synthetic route of chiral cyclohex-2-enone derivatives,a natural amino acid salt catalyst,L-phenylalanine potassium,have been found as efficient catalyst in asymmetric formal[3+3]annulation between 2-enoyl-pyridine N-oxide derivatives with acetone,a series of chiral 3,5-diaryl-cyclohex-2-enone derivatives can be easily accessed through a dehydration process in the presence of silica gel.Easily available acetone and 2-enoyl-pyridine N-oxides were used as starting materials,and a simple natural amino acid salt was used as a catalyst.This procedure provided a simple and straightforward method to construct chiral 3,5-diaryl-cyclohex-2-enone derivatives.Based on the X-ray crystal structure analysis of product and the control experiments,we proposed the possible mechanism of the reaction.This thesis includes three parts.In the first part,the synthesis of chiral cyclohex-2-enones and asymmetric reactions of 2-enoyl-pyridine N-oxides were reviewed.The second part shows the enantioselective formal[3+3]annulation of acetone to 2-enoyl-pyridine N-oxides.The third part is the experimental part.