What Are the Radical Intermediates in Oxidative N‑Heterocyclic Carbene Organocatalysis?

The oxidation of the Breslow intermediate resulting from the addition of an N-heterocyclic carbene (NHC) to benzaldehyde triggers a fast deprotonation, followed by a second electron transfer, directly affording the corresponding acylium at E > −0.8 V (versus Fc/Fc+). Similarly, the oxidation of the cinnamaldehyde analogue occurs at an even higher potential and is not a reversible electrochemical process. As a whole, and contrary to previous beliefs, it is demonstrated that Breslow intermediates, which are the key intermediates in NHC-catalyzed transformations of aldehydes, cannot undergo a single electron transfer (SET) with mild oxidants (E < −1.0 V). Moreover, the corresponding enol radical cations are ruled out as relevant intermediates. It is proposed that oxidative NHC-catalyzed radical transformations of enals proceed either through SET from the corresponding electron-rich enolate or through coupled electron–proton transfer from the enol, in any case generating neutral capto-dative radicals. Relevant electrochemical surrogates of these paramagnetic species have been isolated.

当N-杂环卡宾（N-heterocyclic carbene, NHC）与苯甲醛加成生成的布雷斯洛中间体（Breslow intermediate）发生氧化反应时，会触发快速脱质子过程，随后伴随第二次电子转移，直接生成对应酰鎓离子（acylium），其氧化电势E > -0.8 V（相对于二茂铁/二茂铁正离子Fc/Fc+）。类似地，肉桂醛类似物的氧化反应所需电势更高，且不属于可逆电化学过程。总体而言，与此前学界的普遍认知相悖，本研究证实：作为醛类NHC催化转化核心中间体的布雷斯洛中间体，无法与温和氧化剂（电势E < -1.0 V）发生单电子转移（single electron transfer, SET）过程。此外，相关研究排除了对应烯醇自由基阳离子作为有效中间体的可能性。本研究提出，烯醛的氧化型NHC催化自由基转化过程，既可通过对应富电子烯醇负离子的单电子转移路径进行，也可通过烯醇的电子-质子耦合转移路径完成，两种路径均会生成中性capto-dative自由基。目前已成功分离得到这类顺磁性物种的相关电化学替代物。