Chiral metal–organic frameworks (MOFs) constitute a unique class of multifunctional hybrid materials and are envisioned as a versatile tool for various enantioselective applications, including the separation of optical isomers and the promotion of catalytic enantioselective reactions. Despite some pioneering works on catalytic enantioselective reactions promoted by chiral MOFs, there is still a need for practical catalysts and many fundamental issues must be answered; such as pin-pointing the site of the reaction and expedition of the reaction rate to the level of that in homogeneous media. We have designed and synthesized a chiral metal–organic framework, (S)-KUMOF-1 (Cu2(S)-1)2(H2O)2, 1 = 2,2′-dihydroxy-6,6′-dimethyl(1,1′-biphenyl)-4,4′-dicarboxylate) of which a non-interpenetrating NbO type framework provides a spacious pore (2 × 2 × 2 nm3) and is equipped with potential catalytic sites exposed into the pore. Since the functional group on the organic links, biphenols in this MOF, can be modified further on demand, this MOF can serve as a platform for new heterogeneous catalysis. Two reactions, the carbonyl-ene reaction with modified MOF after replacement of the protons on biphenol on the organic links with Zn(II) and the hetero-Diels–Alder reaction with Ti(IV), respectively, were studied. In this manoeuver, we observed that the reaction occurs entirely inside the pores and the reaction rate of the heterogeneous reaction by this specific MOF is comparable to that of its homogeneous counterpart. In addition, it is also observed that the enantioselectivities are significantly improved by extra steric bias provided from the frames of the MOF. These observations reinforce the legitimacy of the strategy of using a chiral MOF as a highly enantioselective heterogeneous catalyst.