Studies On Asymmetric Hetero-Diels-Alder Reaction Of Trans-4-methoxy-2-trimethylsiloxy-penta-1,3-diene With Aldehydes And Activated Ketones

Diels-Alder reaction has been one of the cornerstone reactions in organic chemistry for the construction of six-membered rings and the formation of carbon-carbon bonds. Asymmetric Hetero-Diels-Alder reaction (HDA) between electron-rich diene with aldehydes can provide a series of dihydropyrans and dihydropyranones which are one of the most important intermediates in the synthesis of many natural products. Most of researches focused on the HDA reaction between Danishefsky diene with aldehydes. To date, there have been some examples of synthesis of substituted dihydropyrones, while the synthesis of 2,6-disubstituted dihydropyrones has not yet been fully studied. There is no effective catalytic asymmetric system reported for the HDA reaction of Trans-4-methoxy-2-trimethylsiloxy-penta-1,3-diene with Aldehydes and activated Ketones In this dissertation, the reactions were systematically studied and a series of encouraging results were obtained.Firstly, 9 chiral ligands derivated from BINOL were prepared and evaluated for the asymmetric HDA reaction between the diene with benzaldehyde. The results revealed that BINOL shows an excellent chiral induction in the reaction. Under the optimized conditions, the cycloadduct was obtained in good yield (70%) with excellent enantioseletivity (99%ee) in thepresence of 20 mol% chiral Ti complex.Ligand survey showed that the electronic and spatial effects of the substitutes on BINOL impacted on the enantioselectivity and reactivity the HDA reaction. Aromatic, heteroaromatic, conjugated, aliphatic aldehydes and pyruvates afforded the corresponding products in moderate to high isolated yields(61-99%) with considerably high ee values(83-99% ee).Secondly, we discovered that 4A molecular sieves could greatly promote this reaction. It was suggested that 4A molecular sieves may be supplied with water slowly.Thirdly, a positive nonlinear effect was obviously observed.Finally, we studied the mechanism of the HDA reaction between the diene with benzaldehyde in the presence of the BINOL-Ti complex. The HDA reactions catalyzed by the chiral Ti(IV) complex proceeded via the Mukaiyama aldol pathway. Moreover, the reaction mediate was obtained and its structure was confirmed by by *H, 13C NMR and HRMS analysises.