To demonstrate the synthetic scalability of this methodology, several gram-scale syntheses were carried out under rhodium catalysis (condition A). As shown in Scheme 4A, the outcomes were almost maintained, paving a practical and economical way for large-scale production. In addition, the broad functional group tolerance provides abundant opportunities for further elaboration to access more complex spirooxindole scaffolds. For examples, the halogen functional groups were well tolerated, and aryl bromide/iodide could serve as a useful handle for a wide range of transition-metal-catalyzed cross-coupling reactions, such as Suzuki, Sonogashira, Heck and Rosenmund-von Braun couplings, to generate diversified spirooxindoles 43-48 (Scheme 4B). Besides, selective N-deprotection of products can be easily achieved (Scheme 4C): by treating product 3 with concentrated sulfuric acid at room temperature produced the Ts-deprotected product 49 in almost quantitative yield; by treating 3 with αchloroethyl chloroformate in CH2Cl2 at room temperature followed by reflux in MeOH, the remote N 1 -Bn protecting group was selectively removed to afford 50a almost quantitatively. The structure of 50a (free form) was assigned by X-ray diffraction analysis, which confirmed the selective remote N 1 -Bn deprotection (CCDC 2285029). Furthermore, application of the obtained N 1 -deprotected products as platform molecules for derivatizations to drug-derived molecules was also attempted. After verifying the feasibility of N-alkyl, propargyl and sulfonyl substitutions (40b/51, 52 and 53), different pharmacophores could be readily assembled to afford Cyclizine-, Sildenafil-, Imatinib-and Aripiprazole-derived spirooxindoles, respectively (54-57). These transformations demonstrated the potential synthetic utility of our protocol. Encouraged by the above success, the next step was to develop an asymmetric version for synthesis of optically active spirooxindole-piperazines. Initially, several well-established chiral rhodium catalysts, including Rh2(S-DOSP)4, Rh2(S-PTTL)4, Rh2(S-NTTL)4 and Rh2(R-BTPCP)4, were evaluated for the (5+1) cycloaddition of diazooxindole 1a with imidazolidine 2a. Unfortunately, product 3 was obtained with no stereocontrol (see Supporting Information and Table , entry 1). We then turned to Cu II /BOX catalytic system. Gratifyingly, the combination of Cu(OTf)2/Cy-BOX (L1) afforded product 4 in 60:40 e.r. (Table , entry 2). This result suggests that the rhodium-catalyzed process favors a metal-free ammonium ylide intermediate (II'), whereas the copper catalyst remains, at least to some extent, bound to the intermediate (II), in accord with related reports that metallocarbene-involved asymmetric reactions involving diazocarbene-ylide intermediates are highly metal-dependent, with copper being superior to rhodium. With this encouraging result, we then evaluated more BOX ligands (See Supporting Information for details). The Cy-SaBOX ligand L2 was better considering the higher yield and the same enantioselectivity (Table , entry 3), while the Cy-TOX ligand L3 resulted in lower enantioselectivity (Table , entry 4). When HFIP was used as solvent, the e.r. value was increased to 73:27 (Table , entry 5), which is probably due to the stabilizing effect of fluorinated alcohol on iminium cationic intermediate III. Low temperature was benificial for stereocontrol, leading to 77:23 e.r. (Table , entry 6). Increasing the steric hindrance at the bridged methylene of the bisoxazoline is generally beneficial for stereocontrol. Thus, a series of Cy-SaBOX ligands with bulky arms were synthesized and examined. Among them, 2-naphthylderived Cy-SaBOX L4 improved the e.r. value to 84:16 (Table , entry 7), and bulkier 3-phenanthrenyl-derived Cy-SaBOX L5 stood out as optimal, offering 81% yield and 86:14 e.r. (Table , entry 8). Other copper catalyst or co-solvent system led to no improvement (Table , entries 9-10).