posted on 2022-02-11, 17:34authored byWei Gong, Xinfa Chen, Wenqiang Zhang, Kent O. Kirlikovali, Bing Nan, Zhijie Chen, Rui Si, Yan Liu, Omar K. Farha, Yong Cui
One
of the most widely employed strategies to produce chiral molecules
involves the asymmetric hydrogenation of functionalized olefins using
rhodium catalysts. Despite their excellent performance, the exact
identity of the active Rh species is still ambiguous as each site
may plausibly feature one or two phosphorus ligands. In this work,
we used a sequential postsynthetic modification approach to successfully
incorporate single-site Rh species into a zirconium-based metal–organic
framework comprised of chiral spinol-based ligands. These Rh species
feature one phosphorus ligand per Rh, which contrasts with the molecular
analogue that contains two phosphorus ligands per Rh site. Following
extensive characterization of the Rh-monophosphorus material using
techniques including solid-state NMR and extended X-ray absorption
fine-structure (EXAFS) spectroscopy, we studied their catalytic performance
in the asymmetric hydrogenations of enamides and α-dehydroamino
acid esters and observed excellent yields and enantioselectivities
(up to 99.9% ee). Notably, the Rh-monophosphorus catalyst is 5 times
more active than the homogeneous Rh-biphosphorus control, which we
attributed to the higher activity of the single-site Rh-monophosphorus
species and the confined MOF cavities that can enrich reactants. In
addition, we observed a unique topology-dependent behavior in which
linker expansion leads to the formation of a novel Zr-MOF with a distinct
4,8-connected net that cannot be phosphorylated, presumably due to
intense tensile strain and steric repulsion present within this framework.
Finally, we demonstrate the utility of this single-site Rh-monophosphorus
catalyst in the gram-scale synthesis of (R)-cinacalcet
hydrochloride, a first-in-class drug in the therapy of secondary hyperparathyroidism
and parathyroid carcinoma, with 99.1% ee.