When unsymmetrical imidazolidine 2r possessing significant N-steric effect was used, unfortunately, there was almost no regioselectivity (4ar). Gratifyingly, imidazolidine 2s with obvious N-electronic difference resulted in good regioselectivity (4as). The structure of 4ab was unambiguously assigned by X-ray structure analysis (CCDC 2327804). Encouraged by the above success, we speculate that a Lewis acid catalyzed (6+3) cycloaddition of BCBs with hexahydropyrimidines should be feasible, because it has been well demonstrated by our group that hexahydropyrimidines exhibit similar reactivity to imidazolidines and can be considered as 1,6-dipole precursors. This would be a straightforward method for the construction of synthetically challenging bicyclo[6.1.1]decane scaffolds. We then focused on the Lewis acid catalyzed (6+3) cycloaddition of BCBs with hexahydropyrimidines (Scheme 4). Gratifyingly, the expected 2,6-diazabicyclo[6. product 5a was obtained in 74% yield when 2-naphthyl BCB ketone 1a and N-PMP substituted hexahydropyrimidine 3a were used as model substrates under the same reaction conditions. Subsequently, a series of BCB ketones were examined (5a-t). In these cases, 1-naphthyl, (hetero)aryl, alkyl and alkenyl BCB ketones all reacted smoothly to afford the target products 5b-r in moderate to excellent yields (48-87%). The structure of 5b was confirmed unambiguously by X-ray structure analysis (CCDC 2327802). For the less electrophilic BCB Weinreb amide 1x, the (6+3) cycloadduct 5s was detected by 1 H NMR analysis in traces only under B(C6F5)3 or Sc(OTf)3 catalysis. The sterically more demanding phenylsubstituted BCB ketone 1y was suitable for this (6+3) cycloaddition, giving rise to the desired product 5t in 64% yield. Next, several hexahydropyrimidines, including N-aryl, N-benzyl and C-substituted ones, were tested, all of which led to their corresponding products in acceptable yields (5u-z). As shown in Scheme 5A, the robustness of the protocol was further demonstrated by a gram-scale reaction of BCB ketone 1a with imidazolidine 2a, and the outcome was almost maintained, paving a practical and economical way for large-scale production. Moreover, the obtained product 4aa could be employed as a handle for diverse downstream transformations to access a variety of medium-bridged ring systems by condensation (6), allylation (7), Wittig olefination (8) and reduction (9), as shown in Scheme 5B. In addition, the N-PMP cleavage of 4aa under oxidative conditions was also explored, but 4aa totally decomposed and no major product was detected. Gratifyingly, selective N-debenzylation of 4al could be easily achieved (Scheme 5C). By treating 4al with α-chloroethyl chloroformate in CH2Cl2 at room temperature followed by reflux in MeOH, the remote N 1 -Bn protecting group was selectively removed to 10, while the free N 1 -H group of 10 inhibited the proximal N 2 -Bn deprotection under the same or even harsh reaction conditions. Interestingly, when the free N 1 -H group of 10 was substituted, treatment of 11 with α-chloroethyl chloroformate in 1,2-dichloroethane (DCE) at 80 o C followed by reflux in MeOH smoothly deprotected the proximal N 2 -Bn group to 12. Thus, after a second N 2 -H substitution of 12, various 13 bearing different N-pharmacophores including sulfonyl and triazole groups could be readily assembled. The structure of 13b was assigned by X-ray structure analysis, which unambiguously confirmed the N 1 /N 2 -Bn deprotection sequence (CCDC 2338181). These transformations demonstrated the potential synthetic utility of our protocol.