Dirhodium Tetracarboxylate Research Articles

Quantum Chemical Interrogation of Reactions Promoted by Dirhodium Tetracarboxylate Catalysts─Mechanism, Selectivity, and Nonstatistical Dynamic Effects.

ConspectusRh2L4 catalysts have risen in popularity in the world of organic synthesis, being used to accomplish a variety of reactions, including C-H insertion and cyclopropanation, and often doing so with high levels of stereocontrol. While the mechanisms and origins of selectivity for such reactions have been examined with computational quantum chemistry for decades, only recently have detailed pictures of the dynamic behavior of reacting Rh2L4-complexed molecules become accessible. Our computational studies on Rh2L4 catalyzed reactions are described here, with a focus on C-H insertion reactions of Rh2L4-carbenes. Several issues complicate the modeling of these reactions, each providing an opportunity for greater understanding and each revealing issues that should be incorporated into future rational design efforts. First, the fundamental mechanism of C-H insertion is discussed. While early quantum chemical studies pointed to transition structures with 3-center [C-H-C] substructures and asynchronous hydride transfer/C-C bond formation, recent examples of reactions with particularly flat potential energy surfaces and even discrete zwitterionic intermediates have been found. These reactions are associated with systems bearing π-donating groups at the site of hydride transfer, allowing for an intermediate with a carbocation substructure at that site to be selectively stabilized. Second, the possible importance of solvent coordination at the Rh atom distal to the carbene is discussed. While effects on reactivity and selectivity were found to be small, they turn out not to be negligible in some cases. Third, it is shown that, in contrast to many other transition metal promoted reactions, many Rh2L4 catalyzed reactions likely involve dissociation of the Rh2L4 catalyst before key chemical steps leading to products. When to expect dissociation is associated with specific features of substrates and the product-forming reactions in question. Often, dissociation precedes transition structures for pericyclic reactions that involve electrons that would otherwise bind to Rh2L4. Finally, the importance of nonstatistical dynamic effects, characterized through ab initio molecular dynamics studies, in some Rh2L4 catalyzed reactions is discussed. These are reactions where transition structures are shown to be followed by flat regions, very shallow minima, and/or pathways that bifurcate, all allowing for trajectories from a single transition state to form multiple different products. The likelihood of encountering such a situation is shown to be associated again with the likelihood of formation of zwitterionic structures along reaction paths, but ones for which pathways to multiple products are expected to be associated with very low or no barriers. The connection between these features and reduced yields of desired products are highlighted, as are the means by which some Rh2L4 catalysts modulate dynamic behavior to produce particular products in high yield.

Elucidating the Electronic Nature of Rh-based Paddlewheel Catalysts from 103 Rh NMR Chemical Shifts: Insights from Quantum Mechanical Calculations.

The tremendous importance of dirhodium paddlewheel complexes for asymmetric catalysis is largely the result of an empirical optimization of the chiral ligand sphere about the bimetallic core. It was only recently that a H(C)Rh triple resonance 103 Rh NMR experiment provided the long-awaited opportunity to examine - with previously inconceivable accuracy - how variation of the ligands impacts on the electronic structure of such catalysts. The recorded effects are dramatic: formal replacement of only one out of eight O-atoms surrounding the metal centers in a dirhodium tetracarboxylate by an N-atom results in a shielding of the corresponding Rh-site of no less than 1000 ppm. The current paper provides the theoretical framework that allows this and related experimental observations made with a set of 19 representative rhodium complexes to be interpreted. In line with symmetry considerations, it is shown that the shielding tensor responds only to the donor ability of the equatorial ligands along the perpendicular principal axis. Axial ligands, in contrast, have no direct effect on shielding but may come into play via the electronic -effect that they exert onto the neighboring equatorial sites. On top of these fundamental interactions, charge redistribution within the core as well as the electronic -effect of ligands of different donor strengths is reflected in the recorded 103 Rh NMR shifts.

Bifunctionality of dirhodium tetracarboxylates in metallaphotocatalysis

Metallaphotocatalysis has been recognized as a pivotal catalysis enabling new reactivities. Traditional metallaphotocatalysis often requires two or more separate catalysts and exhibits flaw in cost and substrate-tolerance, thus representing an await-to-solve issue in catalysis. We herein realize metallaphotocatalysis with a bifunctional dirhodium tetracarboxylate ([Rh2]) alone. The [Rh2] shows an photocatalytic activity of promoting singlet oxygen (1O2) oxidation. By harnessing its photocatalytic activity, the [Rh2] catalyzes a photochemical cascade reaction (PCR) via combination of carbenoid chemistry and 1O2 chemistry. The PCR is characterized by high atom-efficiency, excellent stereoselectivities, mild conditions, scalable synthesis, and pharmaceutically interesting products. DFT calculations-aided mechanistic study rationalizes the reaction pathway and interprets the origin of stereoselectivities of the PCR. The products show inhibitory activity against PTP1B, being promising in the treatment of type II diabetes and cancers. Overall, here we show the bifunctional [Rh2] merges Rh-carbenoid chemistry and 1O2 chemistry.

Enantioselective Synthesis of Triarylmethanes via Intermolecular C-H Functionalization of Cyclohexadienes with Diaryldiazomethanes.

Rhodium-catalyzed C-H functionalization of cyclohexadiene derivatives with diaryldiazomethanes followed by oxidation with DDQ provides ready access to triarylmethanes. Two chiral dirhodium tetracarboxylates, Rh2(S-PTAD)4 and Rh2(S-TPPTTL)4, were found to be the optimum chiral catalysts for these transformations. This method showcases the ability of diaryldiazomethanes to perform intermolecular C-H insertion with high enantioselectivity and good yields. The method has a broad substrate scope, leading to triarylmethane products with a variety of aryl and heteroaryl substituents, including benzofuran and pyridine heterocycles.

Site-Selective C–H Functionalization of N-Aryl and N-Heteroaryl Piperidines, Morpholines, and Piperazines Controlled by a Chiral Dirhodium Tetracarboxylate Catalyst

Site-Selective C–H Functionalization of <i>N</i>-Aryl and <i>N</i>-Heteroaryl Piperidines, Morpholines, and Piperazines Controlled by a Chiral Dirhodium Tetracarboxylate Catalyst

Rhodium(II)-Catalyzed Enantioselective Intermolecular Aziridination of Alkenes.

C4-Symmetrical dirhodium(II) tetracarboxylates are highly efficient catalysts for the asymmetric intermolecular aziridination of substituted alkenes with sulfamates. The reaction proceeds with high levels of efficiency and chemoselectivity to afford aziridines with excellent yields of up to 95% and enantiomeric excesses of up to 99%. The scope of the alkene aziridination includes mono-, di-, and trisubstituted olefins as well as the late-stage functionalization of complex substrates. The reaction can be performed on a gram-scale with a catalyst loading of 0.1 mol %. Our DFT study led us to propose a two-spin-state mechanism, involving a triplet Rh-nitrene species as key intermediate to drive the stereocontrolled approach and activation of the substrate.

Design, Synthesis, and Evaluation of Extended C4–Symmetric Dirhodium Tetracarboxylate Catalysts

Design, Synthesis, and Evaluation of Extended C₄–Symmetric Dirhodium Tetracarboxylate Catalysts

Copper(II) Acetate-Induced Oxidation of Hydrazones to Diazo Compounds under Flow Conditions Followed by Dirhodium-Catalyzed Enantioselective Cyclopropanation Reactions.

A tandem system comprising in-line diazo compound synthesis and downstream consumption in a rhodium-catalyzed cyclopropanation reaction has been developed. Passing hydrazone through a silica column absorbed with Cu(OAc)2-H2O/N,N-dimethylaminopyridine oxidized the hydrazone to generate an aryldiazoacetate in flow. The crude aryldiazoacetate elutes from this column directly into a downstream cyclopropanation reaction, catalyzed by the chiral dirhodium tetracarboxylates, Rh2(R-p-Ph-TPCP)4 and Rh2(R-PTAD)4. This convenient flow to batch method was applied to the synthesis of a range of 1,2-diarylcyclopropane-1-carboxylates in high yields and with high levels of enantioselectivity.

Rhodium‐Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes

AbstractThe reaction of 2‐siloxycyclo‐1,3‐dienes with E‐vinyldiazoacetates in the presence of the bulky chiral dirhodium tetracarboxylate catalyst, Rh2(R‐p‐PhTPCP)4 results in an enantioselective [4+2] cycloaddition, in which three new stereogenic centers are formed. The [4+2] cycloadducts are generated as single diastereomers with high enantiocontrol (95–98 % ee). When the diene contains an additional stereogenic center, effective kinetic resolution can be achieved.

Rhodium-Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes.

The reaction of 2-siloxycyclo-1,3-dienes with E-vinyldiazoacetates in the presence of the bulky chiral dirhodium tetracarboxylate catalyst, Rh2 (R-p-PhTPCP)4 results in an enantioselective [4+2] cycloaddition, in which three new stereogenic centers are formed. The [4+2] cycloadducts are generated as single diastereomers with high enantiocontrol (95-98 % ee). When the diene contains an additional stereogenic center, effective kinetic resolution can be achieved.

In Situ Kinetic Studies of Rh(II)-Catalyzed Asymmetric Cyclopropanation with Low Catalyst Loadings

Dirhodium tetracarboxylates are versatile catalysts for the reactions of donor/acceptor carbenes. They catalyze a variety of transformations, including enantioselective intermolecular cyclopropanat...

Dirhodium tetracarboxylates as catalysts for selective intermolecular C-H functionalization.

C-H Functionalization has become widely recognized as an exciting new strategy for the synthesis of complex molecular targets. Instead of relying on functional groups as the controlling elements of how molecules are assembled, it offers a totally different logic for organic synthesis. For this type of strategy to be successful, reagents and catalysts need to be developed that generate intermediates that are sufficiently reactive to functionalize C-H bonds but still capable of distinguishing between the different C-H bonds and other functional groups present in a molecule. The most well-established approaches have tended to use substrates that have inherently a favored site for C-H functionalization or rely on intramolecular reactions to control where the reaction will occur. A challenging but potentially more versatile approach would be to use catalysts to control the site-selectivity without requiring the influence of any directing group. One example that is capable of achieving such transformations is the C-H insertion chemistry of transient metal carbenes. Dirhodium tetracarboxylates have been shown to be especially effective catalysts for these reactions. This review will highlight the development of these dirhodium catalysts and illustrate their effectiveness to control both site-selective and stereoselective C-H functionalization of a wide variety of substrates.

Reactions of Rh2(CH3COO)4 with thiols and thiolates: a structural study.

The structural differences between the aerobic reaction products of Rh2(AcO)4 (1; AcO- = CH3COO-) with thiols and thiolates in non-aqueous media are probed by X-ray absorption spectroscopy. For this study, ethanethiol, dihydrolipoic acid (DHLA; a dithiol) and their sodium thiolate salts were used. Coordination of simple thiols to the axial positions of Rh2(AcO)4 with Rh-SH bonds of 2.5-2.6 Å keeps the RhII-RhII bond intact (2.41 ± 0.02 Å) but leads to a colour change from emerald green to burgundy. Time-dependent density functional theory (TD-DFT) calculations were performed to explain the observed shifts in the electronic (UV-vis) absorption spectra. The corresponding sodium thiolates, however, break up the Rh2(AcO)4 framework in the presence of O2 to form an oligomeric chain of triply S-bridged Rh(III) ions, each with six Rh-S (2.36 ± 0.02 Å) bonds. The RhIII...RhIII distance, 3.18 ± 0.02 Å, in the chain is similar to that previously found for the aerobic reaction product from aqueous solutions of Rh2(AcO)4 and glutathione (H3A), {Na2[Rh2III(HA)4]·7H2O}n, in which each Rh(III) ion is surrounded by about four Rh-S (2.33 ± 0.02 Å) and about two Rh-O (2.08 ± 0.02 Å). The reaction products obtained in this study can be used to predict how dirhodium(II) tetracarboxylates would react with cysteine-rich proteins and peptides, such as metallothioneins.

Bottom‐Up Synthesis of Acrylic and Styrylic RhII Carboxylate Polymer Beads: Solid‐Supported Analogs of Rh2(OAc)4

We have developed a short and efficient bottom‐up synthesis of acrylic and styrylic polymer beads containing dirhodium(II) tetracarboxylates. The solid supported dirhodium(II) tetracarboxylate catalysts were synthesized in as little as two steps overall from dirhodium tetratrifluoroacetate and commercially available carboxylic acids, making the bottom‐up approach a viable alternative to the post‐modification approach commonly used. The dirhodium(II) tetracarboxylate polymer beads have a convenient size (ca. 100 µm), are easy to handle, and can be considered solid‐supported analogs of Rh2(OAc)4. Beads generated from dirhodium(II) tetracarboxylates with four polymerizable carboxylate ligands displayed the best catalytic performance and compared favorably to Rh2(OAc)4 in benchmarked cyclopropanation reactions. The results imply that the cumbersome synthesis of monomeric dirhodium(II) tetracarboxylates with mixed ligands systems can be avoided and that immobilized dirhodium(II)‐catalysts with a higher degree of crosslinking is a viable option to catalysts linked in an anchor‐like fashion. We demonstrate recovery and recycling, and a potential use of the beads as catalysts in a cyclopropanation reaction towards the insecticide chrysanthemic acid.

Ternary complexes consisting of chiral rhodium(II) tetracarboxylates, derivatives of amino acid and triphenylphosphine: The 31P NMR study

Thirteen ternary complexes of optically pure chiral rhodium(II) tetracarboxylates with chiral ligands and triphenylphosphine, formed in situ in CDCl3 solution, were examined by nuclear magnetic resonance spectroscopy. As chiral substrates, two dimeric rhodium tetracarboxylates, derivatives of Mosher's acid and N-phthaloyl tert-leucine, were used. Two chiral amines, N,N-dimethyl-butan-2-amine and N,N-dimethyl-1-phenylethanamine, and some derivatives of methionine, selenomethionine, S-methylcysteine, leucine and proline, were applied as chiral ligands, both optically pure and racemic. An achiral component of ternary complexes, triphenylphosphine, acted as a 31P NMR probe.Ternary complexes containing optically pure ligands revealed 31P NMR signals (233 K, CDCl3) within the range from ca. −24 to −36 ppm, appearing as doublets due to 1J(103Rh,31P) coupling constants of ca. 90 Hz. For some combinations of racemic ligand and dirhodium tetracarboxylate, the signals appeared as quartets due to the presence of two diastereomeric ternary complexes. In these cases, diastereomeric dispersion varied from 14 to 88 Hz. Such signal splitting was not observed for the corresponding complexes of optically pure ligands. The presence of bulky substituents in rhodium tetracarboxylate increases diastereomeric dispersion. These results suggested that ternary complexes in question, in combination with 31P NMR technique, can serve, in some cases, as a means of the optical purity analysis of chiral ligands.

Catalyst-Controlled Selective Functionalization of Unactivated C-H Bonds in the Presence of Electronically Activated C-H Bonds.

A new chiral dirhodium tetracarboxylate catalyst, Rh2( S-2-Cl-5-BrTPCP)4, has been developed for C-H functionalization reactions by means of donor/acceptor carbene intermediates. The dirhodium catalyst contains four ( S)-1-(2-chloro-5-bromophenyl)-2,2-diphenylcyclopropane-1-carboxylate ligands, in which all four 2-chloro-5-bromophenyl groups are on the same face of the catalyst, leading to a structure, which is close to C4 symmetric. The catalyst induces highly site selective functionalization of remote, unactivated methylene C-H bonds even in the presence of electronically activated benzylic C-H bonds, which are typically favored using earlier established dirhodium catalysts, and the reactions proceed with high levels of diastereo- and enantioselectivity. This C-H functionalization method is applicable to a variety of aryl and heteroaryl derivatives. Furthermore, the potential of this methodology was illustrated by sequential C-H functionalization reactions to access the macrocyclic core of the cylindrocyclophane class of natural products.

Comparison of Reactivity and Enantioselectivity between Chiral Bimetallic Catalysts: Bismuth–Rhodium- and Dirhodium-Catalyzed Carbene Chemistry

This paper describes the influence of replacement of one of the rhodium atoms by bismuth in a chiral dirhodium tetracarboxylate catalyst on asymmetric induction in the cyclopropanation and C–H functionalization chemistry of trichloroethyl aryldiazoacetates. The chiral ligand used in this study is S-tert-butylsulphonylprolinate (S-TBSP), which was used in the first highly enantioselective dirhodium tetracarboxylate catalyst. Even though the replacement of a Rh atom with a Bi atom has changed the electronic properties of the system, the RhBi complexes have several similarities to the corresponding Rh2 catalysts, with regard to their reactions with donor/acceptor carbenes. The asymmetric induction with RhBi(S-TBSP)4 is very similar to that achieved with Rh2(S-TBSP)4. The major differences between the two systems are the rates of reactions with the Rh2 complexes reacting much faster, and the scope of the C–H functionalization with Rh2 complexes capable of catalyzing reactions with a much wider range of substr...

Highly Chemo‐ and Stereoselective Catalyst‐Controlled Allylic C−H Insertion and Cyclopropanation Using Donor/Donor Carbenes

AbstractThe highly chemo‐, enantio‐, and diastereoselective catalyst‐controlled intramolecular allylic C−H insertion and cyclopropanation of donor/donor carbenes are reported. The RuII/Pybox complex selectively catalyzed the intramolecular allylic C−H insertion, providing vinyl‐substituted dihydroindoles with greater than 20:1 chemoselectivity and up to greater than 99 % ee. Chiral dirhodium(II) tetracarboxylates, however, selectively promoted the intramolecular cyclopropanation, giving rise to cyclopropane‐fused tetrahydroquinoline derivatives in excellent yields with greater than 99:1 chemoselectivity and up to 97 % ee.

Highly Chemo- and Stereoselective Catalyst-Controlled Allylic C-H Insertion and Cyclopropanation Using Donor/Donor Carbenes.

The highly chemo-, enantio-, and diastereoselective catalyst-controlled intramolecular allylic C-H insertion and cyclopropanation of donor/donor carbenes are reported. The RuII /Pybox complex selectively catalyzed the intramolecular allylic C-H insertion, providing vinyl-substituted dihydroindoles with greater than 20:1 chemoselectivity and up to greater than 99 % ee. Chiral dirhodium(II) tetracarboxylates, however, selectively promoted the intramolecular cyclopropanation, giving rise to cyclopropane-fused tetrahydroquinoline derivatives in excellent yields with greater than 99:1 chemoselectivity and up to 97 % ee.

Mechanism and Diastereoselectivity of [3+3] Cycloaddition between Enol Diazoacetate and Azomethine Imine Catalyzed by Dirhodium Tetracarboxylate: A Theoretical Study

The mechanism and diastereoselectivity of the dirhodium‐catalyzed [3+3] cycloaddition reaction between an enol diazoacetate and an azomethine imine in toluene to produce bicyclic pyrazolidinone derivatives have been investigated by DFT at the M06‐GD3/6‐311+G(2d,2p) [Rh‐RSC+4f]//M06‐GD3/6‐31G(d,p) [Rh‐RSC+4f] level combined with the solvation SMD model. The results revealed that the reaction process, beginning with the rhodium–carbene active intermediate, occurs in two steps: Vinylogous addition (C–N bond forming) and intramolecular six‐numbered ring closure (C–C bond forming), with the second step being rate‐limiting. Furthermore, the origin of the diastereoselectivity was investigated by orbital composition analysis, distortion/interaction analysis, and natural bond orbital calculations and found to be a result of steric and electronic effects.