Remarkable effects of lone pair-lone pair interactions on the extremely stereoselective [2 + 2] cycloaddition of azidoketene to chiral 3-imino-.beta.-lactams
Remarkable effects of lone pair-lone pair interactions on the extremely stereoselective [2 + 2] cycloaddition of azidoketene to chiral 3-imino-.beta.-lactams
复制标题
孤对-孤对相互作用对叠氮烯酮与手性 3-亚氨基-.β.-内酰胺的极其立体选择性 [2 2] 环加成的显着影响
DOI：
10.1021/ja00240a033
复制
发表时间：
1987
影响因子：
15
通讯作者：
N. Hatanaka
中科院分区：
文献类型：
--
作者：
I. Ojima;K. Nakahashi;S. Brandstadter;N. Hatanaka
叠氮酮在ri上的立体选择性[2+ 2]环加成。进行了s-3-亚胺-3-内酰胺1、2和3，IRA -i -3-亚胺-/3-内酰胺4和as-3-irninoazetidine 5。结果表明，1、2和3的立体选择性为99.5%，分别生成了双3-内酰胺9、14和19。反应4得到双-3-内酰胺20，de为62%；反应5得到3-内酰胺21，de为32%，诱导了相反方向的不对称。这些结果清楚地表明，除了传统的空间效应外，3-内酰胺氧与中间甜菜碱氧的孤对-孤对相互作用是叠氮酮具有极立体选择性的[2+ 2]环加成到1,2,3的关键因素。提出了这些立体选择性[2+ 2]环加成的可能机理。给出了3a的x射线晶体结构和3a、4、5的能量最小构象的模型-mm2-rotochem程序计算。烯酮类化合物的[2+ 2]环加成是合成3-内酰胺骨架最方便的方法之一，因此该反应已被用于多种3-内酰胺类抗生素的合成。在我们研究利用同手性3-内酰胺作为寡肽合成的关键中间体的过程中，4我们发现叠氮酮[2+ 2]环加成到具有同手性3-内酰胺骨架（la, lb）的苄基二胺具有极高的立体选择性，得到光学纯的双-3-内酰胺。5**虽然该反应的合成重要性是显而易见的，但我们根本无法根据通常的立体化学考虑，用dreding模型和CPK模型来合理化如此高的立体选择性，即亚胺的构象和烯酮的接近似乎有很大的自由，任何预测似乎都是武断的。因此，我们计划通过使用一系列同手性的二-3-亚胺-3-内酰胺3、zra«5-3-亚胺-3-内酰胺4和m-3-im-吲哚噻啶5作为底物来澄清控制这种独特的易于测量的[2+ 2]环加成的立体化学过程的关键因素，并发现出乎意料的强孤对-孤对相互作用（偶极-偶极相互作用和/或静电相互作用）控制了反应的立体化学。我们想在这里描述3-内酰胺羰基孤对作为极选择性[2+ 2]环加成的关键因素的显著作用。
The stereoselective [2+ 2] cycloadditions of azidoketene to ri. s-3-imino-3-lactams 1, 2, and 3, ira «i-3-imino-/3-lactam4, and as-3-irninoazetidine 5 were carried out. It was found that the reactions of 1, 2, and 3 proceeded with> 99.5% stereoselectivity to give bis-3-lactams 9, 14, and 19, respectively. The reaction of 4 gave a bis-3-lactam 20 with 62% de, and the reaction of 5 gave a 3-lactamazetidine 21 with 32% de inducing the asymmetry in the opposite direction. These results clearly indicate that, in addition to the conventional steric effects, the lone pair-lone pair interaction of 3-lactam oxygen with the intermediate betaine’s oxygen is the crucial factor for the extremely stereoselective [2+ 2] cycloadditionof azidoketene to 1, 2, and 3. Possible mechanisms for these stereoselective [2+ 2] cycloadditions are proposed. The X-ray crystal structure of 3a and the calculated energy-minimum conformations of 3a, 4, and 5 with model-mm2-rotochem programs are provided.The [2+ 2] cycloadditionof ketene species to¡ mines serves as one of the most convenient methods for the synthesis of the 3-lactam skeleton, and thus the reaction has been used for a variety of 3-lactam antibiotic syntheses. 3 In the course of our study on the use of homochiral3-lactams as key intermediates of oligopeptide syntheses, 4 we found that the [2+ 2] cycloaddition of azidoketene to a benzylideneamine bearing a homochiral 3-lactam backbone (la, lb) proceeded with extremely high stereoselectivity to give an optically pure bis-3-lactam. 5** Although the synthetic importance of the reaction was obvious, we could not rationalize such high stereoselectivity atall based on the usual stereochemical considerations by using Dreiding models and CPK models, viz., the conformationof the imine and the approach of the ketene seemed to have so much freedom that any predictions seemed arbitrary. Accordingly, we planned to clarify the crucial factors which governed the stereochemical course of this uniqueasym-metric [2+ 2] cycloaddition by using a series of homochiral di-3-imino-3-lactam 3, zra «5-3-imino-3-lactam 4, and m-3-im-inoazetidine 5 as substrates and found unexpectedly strong lone pair-lone pair interactions (dipole-dipole interaction and/or electrostatic interaction) which controlled the stereochemistry of the reaction. We would like to describe here remarkable effects of 3-lactam carbonyl lone pairs as a crucial factor for extremely selective [2+ 2] cycloadditions.