Paul Mathias, Peckelsen Katrin, Thomulka Thomas, Martens Jonathan, Berden Giel, Oomens Jos, Neudörfl Jörg-M, Breugst Martin, Meijer Anthony J H M, Schäfer Mathias, Berkessel Albrecht
Department of Chemistry, Cologne University, Greinstrasse 4, 50939, Cologne, Germany.
Institute for Molecules and Materials, FELIX Laboratory, Radboud University, Toernooiveld 7, 6525, ED, Nijmegen, The Netherlands.
Chemistry. 2021 Feb 5;27(8):2662-2669. doi: 10.1002/chem.202003454. Epub 2020 Dec 1.
Breslow intermediates (BIs) are the crucial nucleophilic amino enol intermediates formed from electrophilic aldehydes in the course of N-heterocyclic carbene (NHC)-catalyzed umpolung reactions. Both in organocatalytic and enzymatic umpolung, the question whether the Breslow intermediate exists as the nucleophilic enol or in the form of its electrophilic keto tautomer is of utmost importance for its reactivity and function. Herein, the preparation of charge-tagged Breslow intermediates/keto tautomers derived from three different types of NHCs (imidazolidin-2-ylidenes, 1,2,4-triazolin-5-ylidenes, thiazolin-2-ylidenes) and aldehydes is reported. An ammonium charge tag is introduced through the aldehyde unit or the NHC. ESI-MS IR ion spectroscopy allowed the unambiguous conclusion that in the gas phase, the imidazolidin-2-ylidene-derived BI indeed exists as a diamino enol, while both 1,2,4-triazolin-5-ylidenes and thiazolin-2-ylidenes give the keto tautomer. This result coincides with the tautomeric states observed for the BIs in solution (NMR) and in the crystalline state (XRD), and is in line with our earlier calculations on the energetics of BI keto-enol equilibria.
布雷斯洛中间体（BIs）是在N-杂环卡宾（NHC）催化的极性翻转反应过程中，由亲电醛形成的关键亲核氨基烯醇中间体。在有机催化和酶促极性翻转反应中，布雷斯洛中间体是以亲核烯醇形式还是以其亲电酮互变异构体形式存在的问题，对于其反应活性和功能至关重要。本文报道了由三种不同类型的NHC（咪唑烷-2-亚基、1,2,4-三唑啉-5-亚基、噻唑啉-2-亚基）和醛衍生的带电荷标记的布雷斯洛中间体/酮互变异构体的制备。通过醛单元或NHC引入铵电荷标记。电喷雾电离质谱红外离子光谱法得出明确结论：在气相中，咪唑烷-2-亚基衍生的BI确实以二氨基烯醇形式存在，而1,2,4-三唑啉-5-亚基和噻唑啉-2-亚基均给出酮互变异构体。这一结果与在溶液（核磁共振）和晶体状态（X射线衍射）中观察到的BI互变异构状态一致，并且与我们早期关于BI酮-烯醇平衡能量学的计算结果相符。
