Aerobic Oxidation/Annulation Cascades through Synergistic Catalysis of RuCl₃ and N‐Heterocyclic Carbenes

Abstract

Cooperative catalysis combining a transition metal with an N-heterocyclic carbene is challenging due to strong binding of NHCs towards late transition metals. We report the first example of synergistic catalysis by a chiral NHC and a coordinatively unsaturated ruthenium compound. RuCl was found to mediate efficient aerobic oxidation of homoenolates generated from enals and the N-heterocyclic carbene. The resulting α,β-unsaturated acylazolium intermediate reacts selectively with 1,3-dicarbonyl compounds or ketones at either the β- or γ-carbon, yielding polysubstituted chiral lactones in high yield and with excellent enantioselectivity (up to 98 % yield, 94 % ee). This protocol can be applied to structurally sophisticated substrates.

N‐Heterocyclic Carbene/Copper Cooperative Catalysis for the Asymmetric Synthesis of Spirooxindoles

“…Ac hiral copper complex of NHC might form [15k] and participate in the control of stereochemistry,together with the chiral NHC catalyst. On the basis of our experimental results and recent studies, [10][11][12]14,15] ap lausible catalytic cycle is proposed for the [3+ +3] annulation reaction (Figure 1). Initially,t he alkyne group of substrate 2a coordinates with aC u I /NHC-3d complex that is formed from Cu(CH 3 CN) 4 PF 6 and NHC precatalyst 3d under basic conditions and has been identified in the standard reaction by ESI-MS spectroscopy (see the Supporting Information), giving active species I.Acopperallenylidene intermediate (III or III' ')i sg enerated from sequential deprotonation and decarboxylation of I.T hereafter, the NHC-homoenolate IV (which represents azolium homoenolate species V in their mesomeric form), generated from the addition of organocatalyst NHC-3d to the enal 1a through ac oncomitant organocatalytic cycle (right), would intercept copper-allenylidene intermediate III to generate an intermediate VI,w hich then undergoes O-acylation cyclization and protonation to furnish the final product 4a and to regenerate the organocatalyst NHC-3d and the copper catalyst.…”

“…NHCs are routinely used as strongly coordinating ligands due to their strong propensity for binding to transition metals with high affinity. [8] As such, the combination of these nucleophilic organocatalysts with transition metals [9] typically leads to the deactivation of either or both of the two catalysts.B yn ow, several groups have figured out solutions to such problems through careful evaluations of catalytic systems,a nd the combination of NHCs with palladium, [10] ruthenium, [11] and copper [12] catalysts has enabled av ariety of unprecedented asymmetric reactions (Scheme 1b). Remarkably,s everal pioneering reports from Scheidt, [10a] Liu, [10b,c] and co-workers have demonstrated synergy between NHC and p-allylpalladium in catalysis.Since then, cooperative catalysis with NHC and palladium, as reported by Glorius and co-workers,h as provided unique approaches to access chiral ring systems by trapping extended Breslow intermediates with p-allylpalladium species.…”

“…Va riation of the ratio of NHC precatalyst 3d to Cu(CH 3 CN) 4 PF 6 from 2:1t o1 :2 led to ad ramatically diminished yield with as lightly attenuated enantioselectivity (entries [8][9][10]. In the absence of either of copper, NHC precatalyst, or base,the reaction did not occur, thus indicating that both copper and the NHC were required to promote the transformation (entries [11][12][13].…”

Enantio‐ and Diastereoselective Hydrofluorination of Enals by N‐Heterocyclic Carbene Catalysis

“…However,o nce a-fluorination is accelerated by increasing the concentration of the enolate,t he b-protonation will inevitably be compromised because of the low concentration of protons.A sar esult, complications might arise from b-fluorination or direct oxidation of the homoenolate.W e recently found that oxidation of homoenolates to a,bunsaturated esters predominates when the concentration of protons in the reaction system is low. [11] This finding is consistent with reports that F + is an effective oxidant for Breslow-type enols or homoenolates,e ven under an inert atmosphere. [9,12] To address these issues,w ep ropose introducing suitable proton-and fluorine-transfer agents,aswell as NHC turnover agents,which might help accomplish adelicate kinetic balance for the desired b-protonation-a-fluorination cascade.…”

Enantio‐ and Diastereoselective Hydrofluorination of Enals by N‐Heterocyclic Carbene Catalysis

“…[9] However,t heir protocols cannot be extended to b-protonation because of the absence of ap roton source in the reaction. [11] This finding is consistent with reports that F + is an effective oxidant for Breslow-type enols or homoenolates,e ven under an inert atmosphere. Thesecond challenge is premature esterification of the acyl azolium intermediate prior to a-fluorination.…”