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Brook重排介导的三组分反应对手性α-季碳-α-羟基-β-氨基酸酯类化合物的合成研究
蒋九龙
Subtype硕士
Thesis Advisor卢崇道
2014-05-30
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline有机化学
KeywordBrook重排 三组分反应 Α-季碳-α-羟基-β-氨基酸酯
Abstract

手性α-季碳-α-羟基-β-氨基酸酯是一类重要的分子结构片段,广泛存在于具有重要生物活性的分子中,目前这类结构的合成方法有限,而且已经报道的合成方法都有各自的局限性。本论文发展了一种通过Brook重排介导的三组分反应,高效、立体选择性构建α-季碳-α-羟基-β-氨基酸酯的合成方法。论文首先研究了α-芳基-α-羟基-β-氨基酸酯的合成方法,以芳基格氏试剂、硅基乙醛酸酯、叔丁基亚磺酰醛亚胺三组分作为合成起始原料,并添加三氟化硼乙醚作为活化亚胺的路易斯酸,高立体选择性、高产率(dr>20:1:0:0,产率最高可达98%)地合成了α-芳基-α羟基-β-氨基酸酯。然后对金属试剂做了扩展性研究,开发了以甲基锂为亲核试剂,进行上述反应可以高立体选择性、高产率(dr值最高可达20:1:0:0以上,产率最高可达93%)地合成α-甲基-α-羟基-β-氨基酸酯。另外,使用叔丁基亚磺酰酮亚胺作为亲电捕捉剂,成功的构建了α,β-双季碳手性中心。需要指出的是,通过不同的金属试剂引发的反应,在使用相同绝对构型的手性叔丁基亚磺酰亚胺时,得到不同绝对构型的产物。根据反应产物的绝对构型信息,推测了反应过程中可能的立体化学控制。

Other Abstract
α-Quaternary α-hydroxyl-β-amino esters are important building blocks in natural products and biologically active agents, such structures have anticancer, anti-Gram-positive and -negative bacteria activity. General and straightforward method for enantioselective synthesis of α-quaternary α-hydroxyl-β-aminoesters are badly needed but seldom reported. This thesis describes an efficient method for the enantioselective synthesis of α-quaternary α-hydroxyl-β-aminoesters via Brook rearrangement-mediated three-component reactions. We have developed a novel three-component coupling reaction of aryl Grignard reagents, silyl glyoxylates and N-tert-butanesulfinyl imines for constructing α-aryl-α-hydroxyl-β-aminoesters. These reactions exhibit excellent yields (up to 98%) and outstanding diastereoselectivity (dr > 20:1:0:0). By replacing the Grignard reagent with other organometallic reagents, we have developed a new method for the synthesis of α-methyl-α-hydroxyl-β-aminoesters by employing methyllithium. These reactions also display excellent yields (up to 93%) and outstanding diastereoselectivity (dr > 20:1:0:0). In addition,using N-tert-butanesulfinyl imines derived from acetophenons led to α-hydroxy-β-amino esterspossessing vicinal stereogenic quaternary carbon centersin in good yield with excellent diastereoselectivity. It is noted that the reactions induced by the different metal reagents with the same absolute configuration of chiral N-tert-butanesulfinyl imines would give different absolute configuration of the products. We propose and discussed the possible stereocontrolled pathway of the reactions through the stereochemical outcome of products.
Document Type学位论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/3425
Collection资源化学研究室
Affiliation中国科学院新疆理化技术研究所
Recommended Citation
GB/T 7714
蒋九龙. Brook重排介导的三组分反应对手性α-季碳-α-羟基-β-氨基酸酯类化合物的合成研究[D]. 北京. 中国科学院大学,2014.
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