Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.
Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.
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DOI：
10.1021/jacs.1c13434
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发表时间：
2022-03-16
影响因子：
15
通讯作者：
Gouverneur V
中科院分区：
文献类型：
--
作者：
Wang J;Horwitz MA;Dürr AB;Ibba F;Pupo G;Gao Y;Ricci P;Christensen KE;Pathak TP;Claridge TDW;Lloyd-Jones GC;Paton RS;Gouverneur V
不对称催化叠氮化对于获得对映体富集的含氮分子的重要性增加，但使用廉价叠氮化钠的方法仍然很少。这促使我们对氢键相转移催化（HB-PTC）在叠氮化钠对映选择性叠氮化反应中的应用进行了详细的研究。到目前为止，这种相转移歧管已被专门应用于不溶性金属碱金属氟化物的碳-氟键的形成。本文中，我们公开了在手性双脲催化剂的存在下，用叠氮化钠使衍生自β-氯胺的内消旋氮丙啶鎓亲电试剂不对称开环。新型氢键叠氮化合物的结构进行了分析计算，在固体状态下，通过X-射线衍射，并在溶液相，通过1H和14 N/15 N NMR光谱。使用N-异丙基化BINAM衍生的双脲，叠氮化物以三足方式与所有三个NH键的末端结合在能量上是有利的，这种安排让人想起相应的动态更刚性的三叉氢键键合的氟化物络合物。计算分析表明，导致主要对映体的最稳定的过渡态显示攻击从叠氮阴离子的氢键末端。所有三个H-键都保留在过渡态中;然而，如在不对称HB-PTC中所见，亲核试剂和单齿脲之间的H-键沿反应坐标沿着最显著地延长。动力学研究证实与周转率限制事件导致的手性离子对含有aziridinium阳离子和催化剂结合的叠氮阴离子，沿着与催化剂抑制所引起的积累的NaCl。本研究表明，HB-PTC可以作为一种活化模式，无机盐以外的金属碱金属氟化物的不对称合成中的应用。
Asymmetric catalytic azidation has increased in importance to access enantioenriched nitrogen containing molecules, but methods that employ inexpensive sodium azide remain scarce. This encouraged us to undertake a detailed study on the application of hydrogen bonding phase-transfer catalysis (HB-PTC) to enantioselective azidation with sodium azide. So far, this phase-transfer manifold has been applied exclusively to insoluble metal alkali fluorides for carbon–fluorine bond formation. Herein, we disclose the asymmetric ring opening of meso aziridinium electrophiles derived from β-chloroamines with sodium azide in the presence of a chiral bisurea catalyst. The structure of novel hydrogen bonded azide complexes was analyzed computationally, in the solid state by X-ray diffraction, and in solution phase by 1H and 14N/15N NMR spectroscopy. With N-isopropylated BINAM-derived bisurea, end-on binding of azide in a tripodal fashion to all three NH bonds is energetically favorable, an arrangement reminiscent of the corresponding dynamically more rigid trifurcated hydrogen-bonded fluoride complex. Computational analysis informs that the most stable transition state leading to the major enantiomer displays attack from the hydrogen-bonded end of the azide anion. All three H-bonds are retained in the transition state; however, as seen in asymmetric HB-PTC fluorination, the H-bond between the nucleophile and the monodentate urea lengthens most noticeably along the reaction coordinate. Kinetic studies corroborate with the turnover rate limiting event resulting in a chiral ion pair containing an aziridinium cation and a catalyst-bound azide anion, along with catalyst inhibition incurred by accumulation of NaCl. This study demonstrates that HB-PTC can serve as an activation mode for inorganic salts other than metal alkali fluorides for applications in asymmetric synthesis.
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影响因子：
3.2
作者：
Hasnaoui-Dijoux, Ghannia;Elenkov, Maja Majeric;Janssen, Dick B.
通讯作者：
Janssen, Dick B.
影响因子：
3.1
作者：
Bushmarinov, Ivan S.;Nabiev, Orudzh G.;Lyssenko, Konstantin A.
通讯作者：
Lyssenko, Konstantin A.
影响因子：
4.9
作者：
Escuer, Albert;Esteban, Jordi;Font-Bardia, Merce
通讯作者：
Font-Bardia, Merce
影响因子：
15
作者：
Hansen, KB;Leighton, JL;Jacobsen, EN
通讯作者：
Jacobsen, EN
影响因子：
15
作者：
Guerin, DJ;Miller, SJ
通讯作者：
Miller, SJ