Dirhodium(II) tetrakis[methyl 2-oxaazetidine-4-carboxylate]: a chiral dirhodium(II) carboxamidate of exceptional reactivity and selectivity

[formula: see text] A new chiral azetidinone-carboxylate ligand for dirhodium(II) catalysis enhances reactivity toward diazo decomposition and selectivity toward cyclopropanation enabling diazomalonates, vinyldiazoacetates, and aryldiazoacetates to be effectively used with a dirhodium(II) carboxamidate catalyst.     

Catalysts with mixed ligands on immobilized supports. Electronic and steric advantages

[reaction: see text] Immobilized dirhodium(II) catalysts having mixed chiral ligands enhance reactivity (AH = azetidinone) and influence stereoselectivity in cyclopropanation and carbon-hydrogen insertion reactions.     

Olefin cyclopropanation with aryl diazocompounds upon catalysis by a dirhodium(II) complex

A dirhodium(II) complex with N-perfluorooctylsulfonylprolinate ligands is found to catalyze the cyclopropanation of olefins with simple aryl diazomethanes. In contrast to previously reported dirhodium(II) catalysts, the present complex works well not only with very electron-rich olefins such as enol ethers, but also with styrenes. Consequently, the present catalyst allows to prepare functionalized diarylcyclopropanes in moderate yields with good diastereoselectivity for the cis product, whereas the enantioselectivity of the reaction appears negligible.     

Axial coordination of NHC ligands on dirhodium(II) complexes: generation of a new family of catalysts

An efficient new methodology for the arylation of aldehydes is disclosed which uses dirhodium(II) catalysts and N-heterocyclic carbene (NHC) ligands. Complexes of Rh 2(OAc) 4 with one and two NHCs attached on the axial positions were successfully isolated, fully characterized, and used as catalysts in the reaction. The saturated monocomplex ((NHC 5)Rh 2(OAc) 4) 31 was shown to be the most active catalyst and was particularly efficient in the arylation of alkyl aldehydes. DFT calculations support participation of complexes with one axial NHC in the reaction as the catalysts active species and indicate that hydrogen bonds involving dirhodium unit, reactants, and solvent (alcohol) play an important role on the reaction mechanism.     

Simple strategy for the immobilization of dirhodium tetraprolinate catalysts using a pyridine-linked solid support

Dirhodium tetracarboxylates are readily immobilized on agitation in the presence of highly cross-linked polystyrene resins with a pyridine attachment. A systematic study demonstrates that the polymer backbone, the linker, the terminal pyridine group, and the catalyst structure all contribute to the efficiency of dirhodium catalyst immobilization. The immobilization is considered to be due to the combination of ligand coordination and encapsulation. The dirhodium tetraprolinate catalysts, Rh2(S-DOSP)4 (1a), Rh2(S-TBSP)4 (1b), and Rh2(S-biTISP)2 (2), are all efficiently immobilized. The resulting heterogeneous complexes are very effective catalysts for asymmetric cyclopropanation between methyl phenyldiazoacetate and styrene, and under optimized conditions they can be recycled five times with virtually no loss in enantioselectivity. The three-phase test studies indicated that a very slow reaction occurs when both the catalyst and the diazo compound were immobilized, but the slow rate precluded the likelihood that the cyclopropanation was predominately occurring by a release-and-capture mechanism.     

Dirhodium(II) tetrakis(perfluorobutyrate)-catalyzed 1,4-hydrosilylation of alpha,beta-unsaturated carbonyl compounds

The use of dirhodium(II) catalysts in the 1,4-hydrosilylation of alpha,beta-unsaturated ketones and aldehydes was explored. Dirhodium(II) tetrakis(perfluorobutyrate), Rh2(pfb)4, proved to be the catalyst of choice for this process, providing the corresponding silyl enol ethers in high yields.     

"Matched/mismatched" diastereomeric dirhodium(II) carboxamidate catalyst pairs. Structure-selectivity correlations in diazo decomposition and hetero-Diels-Alder reactions

Homo-ligated dirhodium(II) carboxamidates provide well-defined structural frameworks with which to investigate catalyst-controlled multiple asymmetric induction ("match/mismatch" effects). Diastereomeric pairs of methyl 2-oxoimidazolidine-4(S)-carboxylate ligands containing 2-phenylcyclopropane (4S,2'S,3'S-HMCPIM and 4S,2'R,3'R-HMCPIM) and N-benzenesulfonylproline (4S,2'S-HBSPIM and 4S,2'R-HBSPIM) attachments at the 1-N-acyl site have been prepared; the resulting (cis-2,2)-Rh(2)L(4) compounds have been produced in good yields, and the X-ray crystal structure of each dirhodium(II) compound has been obtained. The incorporation of additional stereocenters into the dirhodium(II) ligands leads to recognizable levels of double asymmetric induction for C-H insertion, cyclopropanation, and hetero-Diels-Alder cycloaddition applications. The configurationally "matched" cases provide modest increases in enantioselectivity for intramolecular C-H insertion reactions relative to the model catalyst Rh(2)(MPPIM)(4), but applications of the configurationally mismatched catalysts result in significant lowering of enantioselectivity. The Rh(2)(BSPIM)(4) catalysts show the highest degree of differential selectivity. Hetero-Diels-Alder reactions show inverse behavior from the configurationally matched and mismatched Rh(2)L(4) catalysts to that found in the metal carbene transformations.     

Amplification of asymmetric induction in sequential reactions of bis-diazoacetates catalyzed by chiral dirhodium(II) carboxamidates

[reaction: see text] Two sequential intramolecular carbon-hydrogen insertion or cyclopropanation reactions of bis-diazoacetates using chiral dirhodium(II) carboxamidate catalysts are reported. The initial metal carbene transformation forms an excess of one enantiomer that with the second transformation further enhances stereocontrol (kinetic amplification). Diastereoselectivity and enantioselectivity for product formation are controlled by the catalyst.     

Selectivity in reactions of allyl diazoacetates as a function of catalyst and ring size from gamma-lactones to macrocyclic lactones

Catalytic reactions of diazoacetates tethered through zero, one, two, and three ethylene glycol units to an allyl group have been investigated for chemoselectivity, diastereoselectivity, and enantioselectivity. Results from cyclopropanation, carbon-hydrogen insertion, and oxonium ylide generation are compared from reactions of achiral and chiral catalysts of copper(I) and dirhodium(II) carboxylates and carboxamidates. Relative to results from intermolecular reactions of ethyl diazoacetate with allyl ethyl ether, intermolecular reactions show a diversity of selectivities including preference for the opposite configurational arrangement from the one preferred in corresponding intermolecular cyclopropanation reactions. Enantioselectivities for cyclopropanation are dependent on the catalyst ligands in a manner that reflects divergent trajectories of the carbon-carbon double bond to the reacting carbene center. Enantioselectivity increases as a function of ring size with chiral copper catalysts, but the reverse occurs with chiral dirhodium(II) carboxamidates. Mechanistic implications, including those related to the conformation of the reacting metal carbene, offer a new dimension to understanding of enantioselectivity in catalytic asymmetric cyclopropanation reactions.     

Making expensive dirhodium(II) catalysts cheaper: Rh(II) recycling methods

Dirhodium(II) catalysts have been widely used as a remarkable tool in organic synthesis, ultimately resulting in a myriad of transformations and formation of a wide variety of compounds, every so often intermediaries in drug synthesis. Aiming at a more sustainable chemistry, several methods suitable for the reutilisation of expensive dirhodium complexes have been developed. Herein, we provide a combined overview of the available methods for recovering and reusing dirhodium(II) metal complexes in catalysis, covering homogeneous catalysis as well as heterogenisation methods.     

Kinetic and stereoselectivity effects of phosphite ligands in dirhodium catalysis

A phosphite additive that can act as an axial ligand for a dirhodium tetracarboxylate catalyst improves the enantioselectivity of silane insertion of a diazo substrate. A kinetic study enables measurement of the catalytic rate constant for the catalyst bound to an axial ligand. Although a single axial ligand has an inhibitory effect on reactivity at the distal rhodium center, axially-bound catalysts are the predominant active species in solution for phosphite concentrations above 6 mol % under our reaction conditions. We examine changes in product enantioselectivity as a function of ligand to shed light on the structure and kinetics of product formation steps.     

Enantio- and diastereoselective synthesis of cis-2-aryl-3-methoxycarbonyl-2,3-dihydrobenzofurans via the Rh(II)-catalyzed C-H insertion process

[formula: see text] The enantioselective intramolecular C-H insertion reaction of aryldiazoacetates has been explored with use of dirhodium(II) carboxylate catalysts, which incorporate N-phthaloyl- or N-benzene-fused-phthaloyl-(S)-amino acids as chiral bridging ligands. Dirhodium tetrakis[N-phthaloyl-(S)-tert-leucinate], Rh2(S-PTTL)4, has proven to be the catalyst of choice for this process, providing exclusively cis-2-aryl-3-methoxycarbonyl-2,3-dihydobenzofurans in up to 94% ee.     

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetric induction could be achieved using either (R)-pantolactone as a chiral auxiliary or chiral dirhodium tetracarboxylate catalysts. For meta- or para-substituted aryl- or heteroaryldiazoacetates the optimum catalyst was Rh₂(R-p-Ph-TPCP)₄. In the case of ortho-substituted aryl- or heteroaryldiazoacetates, the optimum catalyst was Rh₂(R-TPPTTL)₄. For a highly enantioselective reaction with the ortho-substituted substrates, 2-chloropyridine was required as an additive in the presence of either 4 Å molecular sieves or 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Under the optimized conditions, the cyclopropanation could be conducted in the presence of a variety of heterocycles, such as pyridines, pyrazines, quinolines, indoles, oxadiazoles, thiophenes and pyrazoles.

The dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation has been applied to the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates.     

Redox-active dirhodium(II,II) species covalently entrapped into a methylmethacrylate backbone

A novel class of polymers was obtained by insertion of dirhodium(II,II) metal systems into a methacrylate backbone; the synthesis was realized by free radical polymerization of an appropriate methacrylate-functionalized dirhodium polymer precursor, namely [Rh2(form)2(MA-COO)2](form =N,N'-di-p-tolylformamidinate)(MA-COO = 2-(methacroyloxy)ethyl-phthalate), with methylmethacrylate (MMA); the new copolymers, in solution, show reversible CO-absorption, connected to the axial reactivity of dirhodium(II,II) species.     

Carbonylative Suzuki coupling and alkoxycarbonylation of aryl halides using palladium supported on phosphorus‐doped porous organic polymer as an active and robust catalyst

Developing highly active catalysts with the combined advantages of molecular and solid catalysis is considered as the “Holy Grail” in the area of catalysis research. Herein, a phosphorus‐doped porous polymer‐immobilized palladium was successfully developed as an efficient, robust, and recyclable catalyst for the carbonylative Suzuki coupling and alkoxycarbonylation reactions of aryl halides. Rather than just as an immobilizing molecular catalyst, palladium supported on phosphorus‐doped porous organic polymer exhibits even better catalytic performances than that of its analogue homogeneous catalysts in both carbonylation reactions. Moreover, the catalyst can be easily separated and reused for at least 5 times without significant loss in reactivity. Importantly, the catalyst was highly stable under carbonylation reaction conditions, and no palladium nanoparticle was observed even after the 5th reuse.     

Polar phase hydroformylation: the dramatic effect of water on mono- and dirhodium catalysts

The addition of 30% water (by volume) to acetone creates a remarkably effective polar phase solvent system for a dicationic dirhodium tetraphosphine hydroformylation catalyst. The initial turnover frequency (TOF) increases by 265% (to 73 min-1) for the hydroformylation of 1-hexene relative to the initial TOF in pure acetone (20 min-1). The aldehyde linear to branched (L:B) ratio increases to 33:1, and alkene isomerization and hydrogenation side reactions are essentially eliminated. Comparisons with monometallic rhodium catalysts based on PPh3, Bisbi, Naphos, and Xantphos ligands demonstrate that this polar-phase bimetallic catalyst is one of the fastest and most selective hydroformylation systems known under these mild conditions (90 degrees C, 6.2 bar H2/CO). The monometallic catalysts also show rate enhancements (although considerably smaller) in water-acetone, but Rh-Xantphos does show a large increase of 115%, with considerably reduced alkene isomerization side reactions. The dramatic effect of water on the dirhodium catalyst system is believed to be due to simple inhibition of the fragmentation of the catalytically active species into inactive mono- and bimetallic complexes.     

Total synthesis of (S)-(+)-imperanene. Effective use of regio- and enantioselective intramolecular carbon-hydrogen insertion reactions catalyzed by chiral dirhodium(II) carboxamidates

The total synthesis of (S)-(+)-imperanene, a natural product found in Chinese medicine, has been completed in 12 steps from a commercially available cinnamic acid. The key step is highly enantioselective carbon-hydrogen insertion from a diazoacetate using a chiral dirhodium(II) carboxamidate catalyst. An elimination process essential to the construction has been optimized to avoid intramolecular Friedel-Crafts alkylation.     

Catalytic asymmetric synthesis of 1,1'-spirobi[indan-3,3'-dione] via a double intramolecular C-H insertion process

A highly efficient one-pot construction of optically active 1,1'-spirobi[indan-3,3'-dione] derivative (up to 80% ee) has been achieved by exploiting the double intramolecular C-H insertion reaction of dimethyl 2,2'-methylenebis(alpha-diazo-beta-oxobenzenepropanoate) under the influence of dirhodium(II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate] as a catalyst.     

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

Herein we demonstrate a packed bed flow reactor capable of achieving highly regio- and stereoselective C−H functionalization reactions using a newly developed Rh₂(S-2-Cl-5-CF₃TPCP)₄ catalyst. To optimize the immobilized dirhodium catalyst employed in the flow reactor, we systematically study both (i) the effects of ligand immobilization position, demonstrating the critical factor that the catalyst-support attachment location can have on the catalyst performance, and (ii) silica support mesopore length, demonstrating that decreasing diffusional limitations leads to increased accessibility of the active site and higher catalyst turnover frequency. We employ the immobilized dirhodium catalyst in a simple 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.     

Design of a Heterogeneous Catalyst Based on Cellulose Nanocrystals for Cyclopropanation: Synthesis and Solid‐State NMR Characterization

Heterogeneous dirhodium(II) catalysts based on environmentally benign and biocompatible cellulose nanocrystals (CNC‐Rh₂) as support material were obtained by ligand exchange between carboxyl groups on the CNC surface and Rh₂(OOCCF₃)₄, as was confirmed by solid‐state ¹⁹F and ¹³C NMR spectroscopy. On average, two CF₃COO^? groups are replaced during ligand exchange, which is consistent with quantitative analysis by a combination of ¹⁹F NMR spectroscopy and thermogravimetry. CNC‐Rh₂ catalysts performed well in a model cyclopropanation reaction, in spite of the low dirhodium(II) content on the CNC surface (0.23 mmol g^?1). The immobilization through covalent bonding combined with the separate locations of binding positions and active sites of CNC‐Rh₂ guarantees a high stability against leaching and allows the recovery and reuse of the catalyst during the cyclopropanation reaction.