【作者】 杨维清；

【导师】 冯小明；

【作者基本信息】 四川大学 ， 有机化学， 2005， 博士

【摘要】 Diels-Alder反应是有机化学中建构六员环和碳碳键生成最为重要的反应之一。在这类反应中,硅醚二烯与羰基化合物的不对称Hetero-Diels-Alder（HDA）反应生成光学活性的二氢吡喃酮衍生物的研究尤为引人注目。其中又以Danishefsky二烯与羰基化合物的反应研究最为详尽。而取代的Danishefsky的HDA反应则报道较少。由Trans-4-methoxy-2-trimethylsiloxy-penta-1,3-diene与羰基化合物的反应生成二氢吡喃酮衍生物的研究近乎空白。本研究以手性钛络合物为催化剂,系统研究了此二烯与醛及活化酮的不对称Hetero-Diels-Alder反应,获得一系列的创新性研究成果。 1.作者首先发现了联萘酚在反应体系中是有效的。据此又合成了九种联萘酚衍生的配体及其它几种配体。系统考察了联萘酚衍生的配体中基团的电子效应和空间位阻效应,发现联萘酚与Ti（OiPr）₄的络合物催化二烯与苯甲醛的HDA反应表现出最好的不对称诱导能力。经过对中心金属、配体与金属的比例、溶剂、添加剂、催化剂用量、底物浓度和反应温度等的细致优化后,确定了最佳反应条件。底物扩展证明,催化体系对芳香醛、杂芳香醛、脂肪醛以及αβ-不饱和醛都具有优良的手性诱导能力,获得83.99%ee。对于对硝基苯甲醛获得了99%收率和99%的选择性。对链状的脂肪醛都取得了大于90%的立体选择性,这是在现有文献报道中不多见的。活化酮在重新优化后的反应条件下,也取得了很好的结果（94-99%ee）。更多还原

【Abstract】 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.更多还原