**6. Miscellaneous**

In 2014, Yao and coworkers reported a novel Lewis acid La(OTf)3 as a co-catalyst in the NHC-catalyzed [4 + 2] annulation of 2-bromo-2-enals with isatin derivatives 112 (Scheme 25). This dual catalysis process was initiated by the addition of the NHC to 2-bromo-2-enals to give the Breslow intermediate, which then underwent a3 to d<sup>3</sup> umpolung and debromination to generate <sup>α</sup>,β-unsaturated acyl azolium intermediate without the addition of external oxidant. The <sup>α</sup>,β-unsaturated acyl azolium was then deprotonated at the γ-position to provide the vinyl enolate intermediate. Subsequently, the nucleophilic addition and intramolecular lactonization occurred between the vinyl enolate and isatin 112. Spirocyclic oxindole-dihydropyranones 113 were prepared in good yields and with excellent enantioselectivities. Similar to Chi's and Wang's report (vide supra), only 19–41% *ee* were observed in all cases in the absence of Lewis acid La(OTf)3 as a co-catalyst [78].

**Scheme 25.** NHC/La(OTf)3 strategy for the stereoselective synthesis of spirocyclic oxindole-dihydropyranones.

Ye and colleagues investigated the reactions of<sup>α</sup>,β-unsaturated carboxylic acids with isatin-derived ketamines under NHC catalysis. Initially, the desired spirocyclic oxindolodihydropyridinone product was isolated in low yield with only 7% *ee* in the absence of Lewis acid. Notably, the Lewis acid La(OTf)3 performed well to improve the yield and enantioselectivity [79]. In 2017, Huang and co-workers presented an enantioselective β-protonation of enals via a shuttling strategy (Scheme 26). A variety of Lewis acids have been screened and displayed a strong impact on the enantioselectivity. Finally, Cu(OTf)2 resulted in the highest yield and *ee* value. The Lewis acid could coordinate with enals and mercaptans 114 through not only stabilizing a homoenolate intermediate but also facilitating protonation by increasing the acidity of the thiol. In a word, the combination of a chiral *N*-heterocyclic carbene (NHC) catalyst and a strong Brønsted/Lewis acid cocatalyst solved the longstanding challenge of enantioselective remote β-protonation of homoenolates with excellent reactivity and enantioselectivity [80].

**Scheme 26.** Enantioselective β-protonation of enals via a shuttling strategy.
