XJIPC OpenIR  > 资源化学研究室
Thesis Advisor卢崇道
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Name博士
Degree Discipline有机化学
Keyword极性反转 Α-碳基酯 磷杂brook重排 杂darzens反应 氮杂环丙烷

极性反转是有机合成中的一种有用的方法策略,通过极性反转可以实现亲电试剂与亲电试剂的反应。α-羰基酯作为一种官能团的羰基化合物,常用作亲电试剂参与反应。亚磷酸酯和六甲基亚磷酰三胺能够引发α-羰基酯的酮羰基的极性反转,本论文主要对此进行了研究。首先,研究了亚磷酸酯引发α-羰基酯极性反转与N-磺酰亚胺或N-二苯基次磷酰亚胺的三组分反应。碱作用下,亚磷酸酯与α-羰基酯的加成中间体发生 [1,2]-磷杂Brook重排生成α-磷酰氧基烯醇负离子,继而被亲电试剂捕捉,实现了α-羰基酯的极性反转。双(三甲基硅基)氨基钠作用下,亚磷酸二乙酯、α-羰基酯和N-磺酰亚胺三组分反应可以高收率和高非对映选择性地合成syn构型的α-磷酰氧基-β-氨基酸酯;双(三甲基硅基)氨基锂作用下,亚磷酸二乙酯、α-羰基酯和N-二苯基次磷酰亚胺三组分反应可以高收率和高非对映选择性地合成trans构型的2-氮杂环丙烷羧酸酯,反应中亚磷酸酯和α-羰基酯的联合使用表现出了Darzens试剂的性质,离去基团为磷酸酯基。这两个反应有着良好的底物适用性,α-芳基取代的α-羰基酯、芳基醛亚胺以及α-脂肪基团取代的α-羰基酯、脂肪醛亚胺均适用于此反应。其次,研究了亚磷酸酯引发α-羰基酯极性反转与手性N-叔丁基亚磺酰亚胺的反应。反应的产物为光学纯的2-氮杂环丙烷羧酸酯,但只有部分α-脂肪基团取代的α-羰基酯适用于此反应。再次,研究了六甲基亚磷酰三胺引发α-羰基酯的酮羰基极性反转与亚胺的反应。六甲基亚磷酰三胺和α-羰基酯的加成中间体可以被亚胺捕捉。N-磺酰亚胺或N-二苯基次磷酰亚胺捕捉时,均能高收率地合成trans构型的2-氮杂环丙烷羧酸酯。反应中,六甲基亚磷酰三胺和α-羰基酯的联合使用也表现出了Darzens试剂的反应性,离去基团为六甲基磷酰三胺。此反应的α-羰基酯底物受限,α-脂肪基团取代的α-羰基酯不适用于此反应。反应的非对映选择性受立体位阻影响明显,邻位取代苯基醛亚胺有助于提高反应的非对映选择性,而邻位取代苯甲酰基甲酸酯会降低反应的非对映选择性。最后,研究了亚磷酸酯引发α-羰基烯丙基酯极性反转后发生Ireland-Claisen重排的反应。在双(三甲基硅基)氨基锂、亚磷酸二甲酯和三甲基氯硅烷条件下,α-羰基烯丙基酯能够发生Ireland-Claisen重排,生成α-磷酰氧基羧酸酯产物。此反应有着优异的非对映选择性。

Other Abstract

Polarity reversal (umpolung) is a powerful strategy in organic synthesis, which makes the reaction between electrophiles and electrophilic reagents come true. α-Ketoesters, one class of ester-functionalized compounds containing carbonyl groups, are widely used in organic synthesis as electrophiles. This thesis mainly focuses on the studies of the umpolung of α-ketoesters initiated by phosphites/P(NMe2)3. Firstly, the reaction between α-ketoesters and N-sulfonyl aldimines (or N-diphenylphosphinyl aldimines) via umpolung triggered by phosphites was explored. Under alkaline condition, addition of phosphites to α-ketoesters, followed by [1,2]-phospha-Brook rearrangement, generated α-phosphonyloxy enolates which could be intercepted by electrophiles. In the presence of sodium bis(trimethylsilyl)amide, coupling reaction of diethyl phosphite, α-ketoesters and N-sulfonyl aldimines gave syn-α-phosphonyloxy-β-amino esters in high yields with excellent diastereoselectivities; In the presence of lithium bis(trimethylsilyl)amide, coupling reaction of diethyl phosphite, α-ketoesters and N-diphenylphosphinyl aldimines provided trans-aziridine-2-carboxylates in high yields with excellent diastereoselectivities. In the latter aziridination of N-diphenylphosphinyl aldimines, the combination of diethyl phosphite and α-ketoesters was used as a new kind of Darzens reagent, in which leaving group is phosphate. Both the two reactions shown broad substrate suitability and they were suitable for alkyl- and aryl-substituted α-ketoesters and aldimines.Next, the coupling of α-ketoesters with N-tert-butanesulfinyl aldimines initiated by phosphites was investigated. Chiral aziridine-2-carboxylates were accessible using this synthetic strategy, but only limited α-ketoesters were acceptable for this conversion.After that, P(NMe2)3-mediated aziridination of imines with α-ketoesters was examined. Adducts derived from P(NMe2)3 and α-ketoesters were successfully captured by imines. Both N-diphenylphosphinyl aldimines and N-sulfonyl aldimines afforded aziridine-2-carboxylates in high yields. In this transformation, P(NMe2)3 and α-ketoesters serves as Darzens reagent with a leaving group of hexamethylphosphoramide. The scope of the reaction is limited to α-ketoesters bearing α-aryl substituents and the diastereoselectivity depends on steric hindrance of substituents on the substrates.Finally, the Ireland-Claisen rearrangement of allylic α-ketoesters was explored. [1,2]-Aza-Brook/ Ireland-Claisen rearrangement of allylic α-ketoesters induced by nucleophilic addition of dimethyl phosphite enables the formation of α-phosphonyloxy carboxylates with high diastereoselectivities.

Document Type学位论文
Recommended Citation
GB/T 7714
蒋金. 亚磷酸酯/六甲基亚磷酰三胺引发α-羰基酯的极性反转反应研究[D]. 北京. 中国科学院大学,2017.
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