Studies On Asymmetric Hetero-Diels-Alder Reaction Between Brassard Diene With Aldehydes

Diels-Alder reaction has been one of the cornerstone reactions in organicchemistry for the construction of six-membered rings and the formation ofcarbon-carbon binds. Asymmetric Hetero-Diels-Alder reaction (HDA) betweenelectron-rich diene with aldehydes can provide a series of dihydropyrans anddihydropyranones which are the important mediates in the synthesis of manynatural products. Most of researches focused on the HDA reaction betweenDanishefsky diene with aldehydes. There is no effective catalytic asymmetricsystem reported for the HDA reaction between Brassard diene with aldehydes tosynthesize δ-lactones. In this dissertation, the reactions between Brassard dienewith aldehydes were systematically studied and a series of encouraging resultswere obtained. Firstly, 24 chiral Schiff base ligands were prepared and evaluated for theasymmetric HDA reaction between Brassard diene with benzaldehyde. Theresults revealed that the ligand derived from 3,5-di-tert-butylsalicylaldehydewith (1R,2S)-2-amino-1,2-diphenyl-1-ethanol shows an excellent chiralinduction in the reaction. Under the optimized conditions, the cycloadduct wasobtained in good yield (76%) with excellent enantioseletivity (93%ee) in thepresence of 5 mol% chiral Ti complex. Ligand survey showed that the electronic and spatial effects of the -iii-范谦 四川大学博士论文substitutes in the lgands impacted on the enantioselectivity and reactivity theHDA reaction. Meantime, double-substitute ligands showed higherenationseletivities than single-substitute ligands in which 3-position substitutedhad more impacts than 5-position substituted on the enatioselectivity. Aftersubstrate survey, this catalytic system showed excellent chiral induction foraromatic aldehydes (87-99%ee) and rather disappointing chiral induction foraliphatic aldehydes (21%ee). Secondly, 11 chiral ligands containing BINOL and its derivatives werescreened in the asymmetric HDA reaction between Brassard diene withbenzaldehyde. The results revealed that (R)-BINOL shows higherenantioselectivity and reactivity than the others. Under the optimized conditions,the cycloadduct was obtained in moderate yield (40%) with highenantioselectivity (90%). After substrate survey, this catalytic system showedmoderate to excellent chiral induction for aromatic aldehydes (70-95%ee) andmoderate chiral induction for aliphatic aldehydes (75%ee). Finally, we studied the mechanism of the HDA reaction between Brassarddiene with benzaldehyde in the presence of the Schiff base-Ti complex. Theresults indicated that reaction temperature has influence on the reactionpathway: the reaction is mostly carried out at higher temperature (0 oC) by theDiels-Alder process and at lower temperature (-78 oC) by Mukaiyama Aldolprocess. Moreover, the reaction mediate was successfully separated from the-78 oC reaction solution and its structure was confirmed by NMR as aldolproduct. This is demonstrated that the lower temperature reaction pathway isMukaiyama Aldol process. And probable reaction transition state has beensupposed.