ll Article Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes Wei Liu, Adam Vianna, Zengyu Zhang, ..., Mohand Melaimi, Guy Bertrand, Xiaoyu Yan [email protected] (G.B.) [email protected] (X.Y.) Highlights Breslow intermediates derived from mesoionic carbenes are super electron donors A mesoionic-carbene-catalyzed arylacylation of alkenes is described Facile construction of complex carbonyl compounds from simple substrates Breslow intermediates derived from mesoionic carbenes (BIMICs) are highly reductive species able to reduce iodoarenes under ambient condition. The reductive power of BIMICs allows for the use of mesoionic carbenes as powerful catalysts in the inter- and intramolecular arylacylation of alkenes. Liu et al., Chem Catalysis 1,1–11 June 17, 2021 ª 2021 Elsevier Inc. https://doi.org/10.1016/j.checat.2021.03.004 Please cite this article in press as: Liu et al., Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes, Chem Catalysis (2021), https://doi.org/10.1016/j.checat.2021.03.004 ll Article Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes Wei Liu,1 Adam Vianna,2 Zengyu Zhang,1 Shiqing Huang,1 Linwei Huang,1 Mohand Melaimi,2 Guy Bertrand,2,3,* and Xiaoyu Yan1,* SUMMARY The bigger picture Classical N-heterocyclic carbenes (NHCs), such as thiazolylidenes, N-Heterocyclic carbenes (NHCs) 1,2,4-triazolylidenes, and imidazol(in)-2-ylidenes, are powerful or- have been demonstrated to be ganocatalysts for aldehyde transformations through the so-called powerful organocatalysts for Breslow intermediates (BIs). The reactions usually occur via elec- carbonyl transformations via the tron-pair-transfer processes. In contrast, the use of BIs in single- so-called Breslow intermediates electron transfer (SET) pathways is still in its infancy, and the scope (BIs). Recently, NHC-catalyzed is limited by the moderate reduction potential of BIs derived from reactions via single-electron classical NHCs (ca. À1.0 V versus standard calomel electrode transfer (SET) pathways have been [SCE]). Here, we report that BIs from 1,2,3-triazolylidenes, a type developed but still suffer from the of mesoionic carbene (MIC), have a reduction potential as negative limitation of moderate reduction as À1.93 V versus SCE and thus are among the most potent organic potential of BIs. In this paper, reducing agents reported to date. They are reductive enough to taking advantage of highly undergo SET with iodoarenes, which allows the highly efficient inter- reductive MIC-derived BIs, we and intramolecular MIC-catalyzed arylacylation of styrenes and describe the three-component alkenes, respectively. coupling reaction of iodoarenes, alkenes, and aldehydes catalyzed INTRODUCTION by mesoionic carbenes (MICs). This reaction affords various Over the past decades, N-heterocyclic carbenes (NHCs) have been demonstrated to substituted ketones and even be powerful organocatalysts for aldehyde transformations.1–6 The umpolung of al- polycyclic ketones with readily dehydes by NHCs7 through the formation of nucleophilic Breslow intermediates available substrates. (BIs) was later extended to provide other reactive intermediates, such as acyl azo- liums, enolates, and homoenolates.8–12 These intermediates react with diverse elec- trophilic and nucleophilic coupling partners via electron-pair-transfer processes. In contrast, NHC-catalyzed reactions via single-electron transfer (SET) pathways are still in their infancy.13–15 In 2008, Studer and co-workers reported the NHC-catalyzed oxidation of aldehydes by TEMPO via a SET process (Figure 1).16 Other oxidants, such as nitroarenes, nitroalkenes, CX4,C2Cl6, and sulfonic carbamate, were also em- ployed to achieve oxidative reactions of aldehydes.17–21 Recently, an important breakthrough has been reported by Ohmiya, Nagao, and co-workers, who showed that redox-active esters could be employed as both SET oxidants and alkylating reagents.22,23 The same group also described a three-component alkylacylation re- action of alkenes via a radical relay strategy,24 andtheLigroupachievedtheNHC- catalyzed radical acylfluoroalkylation of olefins with the Togni reagent or polyfluor- oalkyl halides.25 Ye and co-workers described g-andε-alkylation with alkyl radicals, in which an activated alkyl halide was employed as SET oxidant and alkylating re- agent.26 Hongandco-workersreportedtheNHC-catalyzedradicalcouplingofalde- hydes and Katritzky pyridinium salts.27 However, as a result of the moderate reduc- tion potential of BIs derived from classical NHCs (ca. À1.0 V versus standard calomel electrode [SCE]),28–30 these SET catalyzed reactions required a relatively strong Chem Catalysis 1, 1–11, June 17, 2021 ª 2021 Elsevier Inc. 1 Please cite this article in press as: Liu et al., Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes, Chem Catalysis (2021), https://doi.org/10.1016/j.checat.2021.03.004 ll Article Figure 1. BIs for SET reactions (A) Reduction potential of known BIs and their SET partners. (B) Breslow intermediates derived from mesoionic carbenes (BIMICs). (C) Three-component MIC-catalyzed arylacylation of alkenes. oxidant to ensure the electron-transfer process, which dramatically limits the scope of the reactions. For much less oxidative substrates, BIs with more negative reduc- tion potentials are needed. Recently, we reported the formation of BIs derived from mesoionic carbenes (BIMICs) and their application to the catalytic H/D ex- change of aldehydes.31 This class of BIs was found to be far more electron rich than any others previously known and should thus be much more reductive. Herein, we describe the electrochemistry of BIMICs, which have a reduction potential as negative as À2.49 V versus Fc/Fc+ (calculated as À1.93 V versus SCE). The oxidation product, namely the radical form of a deprotonated BIMIC, was unambiguously characterized by a single-crystal X-ray diffraction study. This type of BI can be clas- sified as a new organic super electron donor32,33 and is reductive enough to undergo SET with iodoarenes. This is demonstrated by the highly efficient mesoionic carbene (MIC)-catalyzed arylacylation of alkenes. 1Department of Chemistry, Renmin University of China, Beijing 100872, People’s Republic of China RESULTS AND DISCUSSION 2UCSD-CNRS Joint Research Laboratory (UMI Initially, we investigated the electrochemistry of BIMIC 3a, which was prepared by 3555), Department of Chemistry and Biochemistry, University of California, San Diego, 34–37 addition of benzaldehyde to MIC 2a, generated by deprotonation of 1a (Fig- La Jolla, CA 92093-0358, USA ure 2A). The cyclic voltammogram of 3a shows an irreversible redox process be- 3Lead contact ∙ tween 3a and 4a with an anodic peak potential Epa = À2.49 V and a corresponding *Correspondence: [email protected] (G.B.), cathodic peak potential Epc = À2.59 V (Figure 2F). This is in agreement with an EC [email protected] (X.Y.) process38 in which the oxidation of 3a is immediately followed by the easy https://doi.org/10.1016/j.checat.2021.03.004 2 Chem Catalysis 1, 1–11, June 17, 2021 Please cite this article in press as: Liu et al., Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes, Chem Catalysis (2021), https://doi.org/10.1016/j.checat.2021.03.004 ll Article Figure 2. Synthesis and characterization of 3a and 4a∙ (A) Synthesis of 3a. ∙ (B) Synthesis of 4a . ∙ (C) Solid-state structure of 4a . ∙ (D) EPR of 4a (top, experimental; bottom, simulated). ∙ (E) Electron spin density of 4a . (F) Cyclic voltammograms of 3a in tetrahydrofuran (THF) (+(nBu)4NPF6 0.1 mol/L). ∙ (G) Cyclic voltammograms of 4a in THF (+(nBu)4NPF6 0.1 mol/L). + (H) Cyclic voltammograms of 4a in THF (+(nBu)4NPF6 0.1 mol/L). + *Refer to the redox of in-situ-generated impurity 1a. (Scan rate: 100 mV/s; E versus Fc/Fc .) Chem Catalysis 1, 1–11, June 17, 2021 3 Please cite this article in press as: Liu et al., Mesoionic carbene-Breslow intermediates as super electron donors: Application to the metal-free arylacylation of alkenes, Chem Catalysis (2021), https://doi.org/10.1016/j.checat.2021.03.004 ll Article Figure 3. Proposed reaction pathway for the MIC-catalyzed arylacylation of alkenes ∙ deprotonation of 3a to generate 4a .29 To confirm this redox process, we prepared ∙ + the radical form 4a by reducing the deprotonated BIMIC 4a with KC8 in tetrahydro- ∙ furan (Figure 2B). The structure of 4a was unambiguously characterized by X-ray diffraction analysis (Figure 2C) and electron paramagnetic resonance (EPR) (Fig- ure 2D). Compared with other acyl-carbene radicals derived from NHCs and CAACs,39–41 the C(carbene)–C(acyl) bond is slightly longer, whereas the dihedral angle between the carbene ring and the acyl moiety is larger. We performed density functional theory (DFT) calculations at the B3LYP-D3(BJ)/6-311G** level of theory to ∙ ∙ gain more insight into the electronic structure of 4a . The SOMO of 4a is mainly located on the p* orbital of the triazole ring and carbonyl group (see supplemental information), whereas the spin density is mainly located on N1 and N2 with some ∙ contribution on C2, C40, and O1 (Figure 2E). As expected, EPR spectra of 4a in ben- zene solution featured a strong signal centered at g = 2.003 with hyperfine coupling with two nitrogen nuclei (aiso = 6.68 G). In agreement with DFT calculations, the small hyperfine coupling constants indicate a strong delocalization of the unpaired elec- ∙ tron. The cyclic voltammogram of 4a also shows two irreversible peaks (one oxida- tion peak at À2.46 V and one reduction peak at À2.63 V), which affords further evi- ∙ dence of the process between 3a and 4a (Figure 2G). In addition, one set of reversible peaks at E1/2 = À1.53 V was observed, corresponding to the reversible ∙ process 4a /4a+.