A Ternary Complex Reagent for an Asymmetric Reaction of Lithium Ester Enolates with Imines
A Ternary Complex Reagent for an Asymmetric Reaction of Lithium Ester Enolates with Imines
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DOI：
10.1021/ja963581u
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发表时间：
1997-02
影响因子：
15
通讯作者：
Hiroki Fujieda;M. Kanai;T. Kambara;A. Iida;K. Tomioka
中科院分区：
文献类型：
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作者：
Hiroki Fujieda;M. Kanai;T. Kambara;A. Iida;K. Tomioka
锂酯烯醇盐是在碳-碳键形成中确立的、强有力的亲碳核试剂之一。1将试剂扩展应用于不对称反应一直是有机合成化学中的一个相当大的挑战。2实际上，在手性酯3及其等同物如恶唑啉4酰基恶唑烷酮5和酰基磺内酰胺6的开发方面已经取得了显著成就，尽管这些需要至少化学计量量的手性助剂。另一种有前途的方法依赖于手性外部配体，这为不对称反应开辟了催化途径。已报道使用化学计量量的手性氨基锂或手性胺作为与锂酯烯醇化物形成手性二元络合物的外部手性配体。[8]通过X射线晶体学和NMR研究证明了酮烯醇化锂和氨基锂的二元配合物。9，10然而，与在手性烯醇化锂与手性亚胺的不对称加成领域中记录的努力相比，在外部手性配体存在下将烯醇化锂酯不对称加成到偶氮甲碱基团上是相当不发达的。[11]我们参与了有机锂在手性外部配体的帮助下的化学计量和催化不对称反应的开发。12，13我们在此描述了锂酯烯醇化物2与亚胺3基于三元络合物试剂的化学计量和催化不对称反应，所述三元络合物试剂包含三种组分：手性醚配体（1），非手性氨基锂，和2，得到高对映体过量（ee）的相应β-内酰胺4。由异丁酸3-戊酯（2.0当量）和二异丙基氨基锂（LDA，2.2当量）与苯甲醛茴香胺亚胺3a在手性醚（1）（2.6当量）14的存在下在甲苯中在-20 ℃下反应7小时产生相应的β-内酰胺（S）-4aa15，95%。
Lithium ester enolate is among the established, powerful carbonucleophiles in the formation of carbon-carbon bonds. 1 The extended application of the reagent into asymmetric reactions has been a considerable challenge in synthetic organic chemistry. 2 Indeed, there have been significant achievements in the development of the chiral ester3 and its equivalents such as oxazoline, 4 acyloxazolidinone, 5 and acylsultam, 6 even though these require at least a stoichiometric amount of a chiral auxiliary. Another promising approach relies on a chiral external ligand, which opens a catalytic way to an asymmetric reaction. 7 The use of a stoichiometric amount of a chiral lithium amide or chiral amine has been reported as an external chiral ligand that forms a chiral, binary complex with a lithium ester enolate. 8 The binary complex of the lithium ketone enolatelithium amide has been demonstrated by X-ray crystallography and NMR studies. 9, 10 However, the asymmetric addition of the lithium ester enolate to the azomethine group in the presence of an external chiral ligand is quite undeveloped in comparison with efforts on record in the area of asymmetric addition of the chiral lithium enolate to a chiral imine. 11 We have been involved in the development of both stoichiometric and catalytic asymmetric reactions of organolithiums with the aid of chiral external ligands. 12, 13 We describe herein the stoichiometric and catalytic asymmetric reactions of lithium ester enolates 2 with imines 3 based on a ternary complex reagent, which comprises three components: a chiral ether ligand (1), an achiral lithium amide, and 2, giving the corresponding β-lactams 4 in high enantiomeric excess (ee).The reaction of lithium ester enolate 2a, generated from 3-pentyl isobutylate (2.0 equiv) and lithium diisopropylamide (LDA, 2.2 equiv), with benzaldehyde anisidine imine 3a in the presence of a chiral ether (1)(2.6 equiv) 14 in toluene at-20 C for 7 h gave the corresponding β-lactam (S)-4aa15 in 95%