Optimized Immobilization Strategy for Dirhodium(II) Carboxylate Catalysts for C−H Functionalization and Their Implementation in a Packed Bed Flow Reactor

Abstract

Herein we demonstrate ap acked bed flow reactor capable of achieving highly regio-and stereoselective CÀH functionalization reactions using an ewly developed Rh 2 (S-2-Cl-5-CF 3 TPCP) 4 catalyst. To optimize the immobilized dirhodium catalyst employed in the flowr eactor,w es ystematically study both (i)t he effects of ligand immobilization position, demonstrating the critical factor that the catalyst-support attachment location can have on the catalyst performance, and (ii)s ilica support mesopore length, demonstrating that decreasing diffusional limitations leads to increased accessibility of the active site and higher catalyst turnover frequency. We employt he immobilized dirhodium catalyst in as imple packed bed flow reactor achieving comparable yields and levels of enantioselectivity to the homogeneous catalyst employed in batch and maintain this performance over ten catalyst recycles.

Self-Adaptive Dirhodium Complexes in a Metal–Organic Framework for Synthesis of N–H Aziridines

“…As a consequence, all of these protocols require an extra prefunctionalization or modification for either the support or dirhodium carboxylates to perform the heterogenization process. Moreover, these catalysts often provide an “anchor-like” immobilization where only one ligand is connected to the support, which usually distorts the coordination environment of Rh sites and thus affects the reactivity and reproducibility. , Furthermore, most of the supports used in the heterogenization process are rigid materials such as silica, in which three-dimensional active sites hardly adapt their molecular structures to a reacting substrate through noncovalent interaction, thereby limiting catalytic performances of heterogenized dirhodium catalysts . Therefore, the development of a facile way to obtain heterogenized dirhodium carboxylates in a flexible but nonstationary microenvironment with self-adaptive catalytic behaviors is urgently needed. − …”

Mechanistically Guided Workflow for Relating Complex Reactive Site Topologies to Catalyst Performance in C–H Functionalization Reactions

“…Introducing an ortho -Cl substituent to the C1 phenyl ring of TPCP ligands was previously found to have a dramatic effect on site-selectivity in the dirhodium-catalyzed C–H functionalization of 1-bromo-4-pentylbenzene, with Rh 2 ( S -2-Cl-5-BrTPCP) 4 ( B ) affording optimal C2:Bn site-selectivity (20.2:1 rr) and enantioselectivity (90% ee) . Seeking to further understand catalyst performance and improve upon this result, we designed and synthesized a diversified library of Rh 2 ( S - o -ClTPCP) 4 catalysts (see the Supporting Information (SI)) . Notably, complexes with additional aryl rings were synthesized via 4-fold Pd-catalyzed cross-coupling from the parent dirhodium complexes, Rh 2 ( S -2-Cl-5-BrTPCP) 4 ( I ) and B (Scheme a)…”

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

“…Immobilization and flow reactor technology has also been successfully developed for the same purpose. 84 These results have provided promising strategies for relevant catalyst design and process development.…”

“…In this context, catalytic enantioselective carbene insertion to aliphatic C(sp 3 )-H and heteroaryl C(sp 2 )-H bonds for direct construction of chiral carbon centers has been paid considerable attention due to the protocol applicability to modify complex molecules and/or enable site-selective C-H functionalization by means of chiral transition-metal complex catalysts, chiral ligands, and/or chiral substrates. 24,39,[81][82][83][84]314,383,384 Catalyst-and substrate-control strategies are usually applied for regioselective and stereoselective C-H functionalization by carbene insertion with diverse carbene source compounds. This section will summarize the advance in transition-metal-catalyzed enantioselective direct C-H functionalization through carbene insertion by the categories of C-H bonds.…”

“…The immobilization strategy has recently been further optimized for dirhodium( ii ) carboxylate catalysts for C–H functionalization by Davies and Jones, et al 84 The new dirhodium complex Rh 2 ( S -2-Cl-5-CF 3 TPCP) 4 was synthesized and exhibited a better catalytic activity for the secondary C–H functionalization of 4-bromopentylbenzene ( 578 ) with trifluoroethyl 4-bromophenyldiazoacetate ( 1b ) compared to Rh( ii ) complex catalysts Rh 2 ( S-o -ClTPCP) 4 and Rh 2 ( S -2-Cl-5-BrTPCP) 4 . 84 There are two possible C–H bonds that can be functionalized in 578 : the electronically favored benzylic C–H bond and the sterically favored terminal methylene (C2)C–H bond. The effect of the substituents on the aryl moieties was obvious on the aligment of ligand in the dirhodium tetrakis(1,2,2-triarylcyclopro-panecarboxylate) catalysts of type Rh 2 (TPCP) 4 and their catalytic activity for C–H functionalization by carbene insertion.…”