Rhodium Carbene Research Articles

Geminal Aminocyanation Enabled by Ylide Mediated Rearrangement.

Herein, we describe experimental and computational studies to understand the features of oxycyanopyridinium ylides generated in situ from oxy-cyanopyridines and rhodium carbene. This chemistry has enabled the concomitant formation of both C-N and C-C bonds, providing a complementary approach for cyanation reactions. Density functional theory calculations indicate the sequential metal-bound ylide formation, rhodium-associated five-membered transition state, and 1,4-cyano group relocation. Moreover, the enantioselective rearrangement has been realized by using chiral dirhodium complexes as the catalysts.

Rhodium(II)‐Catalyzed Denitrogenative Transformations of N‐Sulfonyl‐1,2,3‐Triazoles

AbstractN‐Sulfonyl‐1,2,3‐triazoles are valuable precursors for the generation of α‐imino carbene intermediates in the presence of the metal catalysts, especially rhodium(II) complexes. Due to the presence of electrophilic carbene and nucleophilic nitrogen, these reactive intermediates can easily be incorporated into many annulations, cycloadditions, C−H or O/N/S−H bond insertions and functionalization reactions. A large number of pharmaceutically important nitrogen‐based building blocks can be constructed via this direct and atom‐economical carbene strategy. In this review, we have described the transformations of N‐sulfonyl‐1,2,3‐triazoles based on α‐imino rhodium(II) carbene intermediates.

Rhodium-Catalyzed One-pot Chemoselective Insertion-Rearrangement-Cyclization of Azavinyl Carbenes with 2-Aminobenzyl Alcohols.

Chemoselective insertion of in situ generated α-imino rhodium carbene onto the O-H bond of 2-aminobenzyl alcohols over the N-H bond followed by [1,3]-alky shift has been successfully accomplished for the synthesis of amine tethered ketone derivatives. The resultant product was further cyclized under acidic conditions to afford biologically important 3-aminoquinolines. Successful integration of chemoselective insertion-cum-rearrangement and cyclization in one pot offered access to various 3-aminoquinolines in a good yield. Conversion of 3-aminoquinolines into biological important motifs has also been demonstrated.

Chlorido-[(1,2,5,6-η)-cyclo-octa-1,5-diene](1-ethyl-4-isobutyl-1,2,4-triazol-5-yl-idene)rhodium(I).

A new neutral triazole-based N-heterocyclic carbene rhodium(I) complex [RhCl(C8H12)(C8H15N3)], has been synthesized and structurally characterized. The complex crystallizes with two mol-ecules in the asymmetric unit. The central rhodium(I) atom has a distorted square-planar coordination environment, formed by a cyclo-octa-1,5-diene (COD) ligand, an N-heterocyclic carbene (NHC) ligand, and a chlorido ligand. The bond lengths are unexceptional. A weak inter-molecular non-standard hydrogen-bonding inter-action exists between the chlorido and NHC ligands.

Construction of Ge-Stereogenic Center by Desymmetric Carbene Insertion of Dihydrogermanes.

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

(4-Butyl-1-ethyl-1,2,4-triazol-5-yl-idene)[(1,2,5,6-η)-cyclo-octa-1,5-diene](tri-phenyl-phosphane)rhodium(I) tetra-fluorido-borate.

In the title triazole-based N-heterocyclic carbene rhodium(I) cationic complex with a tetra-fluorido-borate counter-anion, [Rh(C8H12)(C8H15N3)(C18H15P)]BF4, which crystallizes with two cations and two anions in the asymmetric unit, the Rh center has a distorted square-planar coordination geometry with expected bond distances. Several nonclassical C-H⋯F hydrogen-bonding inter-actions help to consolidate the packing. Two of the F atoms of one of the anions are disordered over adjacent sites in a 0.814 (4):0.186 (4) ratio.

Synthesis of Isochromeno[3,4‐d]imidazoles via Rh(II)‐catalyzed [3+2] Annulation between 4‐Diazoisochroman‐3‐imines and Oximes

AbstractA series of isochromeno[3,4‐d]imidazoles were synthesized in good yields via Rh(II)‐catalyzed [3+2] annulation between 4‐diazoisochroman‐3‐imines and oximes. This method involves the formation of rhodium carbene intermediates and elucidates the unique reactivity of oximes under Rh(II) catalysis. Operationally simple and mild reaction conditions with broad substrate diversity, and readily accessible starting materials and rhodium catalyst are the merits of our reaction.

Dirhodium-Catalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles to 2,3-Dehydropiperazines.

The dirhodium(II)-catalyzed synthesis of a range of C2-substituted 2,3-dehydropiperazines using 1-mesyl-1,2,3-triazoles and β-haloalkylcarbamates is reported. The reaction is proposed to proceed through an α-imino rhodium carbene 1,3-insertion into N-H followed by a base-mediated cyclization. C-Substituted dehydropiperazines can also be conducted directly from terminal alkynes in a three-step, one-pot operation, forming the triazole in situ. This methodology has also been expanded to afford several 2,5-disubstituted 2,3-dehydropiperazines as well as a larger 4,5,6,7-tetrahydro-1H-1,4-diazepine derivative.

Synthesis of Bridged N,O‐Heterocyclic 1,6‐Epoxybenzo[c]azocines via Migration‐Annulation Cascade Reaction of α‐Imino Rhodium Carbenes

AbstractA rhodium‐catalyzed cascade migration‐annulation reaction of 1‐sulfonyl‐1,2,3‐triazole has been developed. As the key step, the 1,3‐sulfinate migration of α‐imino rhodium carbene yielded an extended zwitterion, which was intramolecularly trapped by aldehyde group furnishing bridged N,O‐heterocyclic 1,6‐epoxybenzo[c]azocine as the [5+2] cyclization product. This migration‐annulation strategy provides more flexibility for heterocycle synthesis and medium‐sized ring construction, especially for the construction of polycycles with complex skeletons.

Rh-Catalyzed [2,3]-Sigmatropic Rearrangement of Alkynyl Carbenes with Allyl Sulfides to Access Sulfide-Substituted 1,5-Enynes.

This study describes the development of Rh-catalyzed [2,3]-sigmatropic rearrangement of alkynyl carbenes with allyl sulfides. The protocol exhibits equitable functional group tolerance and allows the formation of a variety of synthetically valuable sulfide-substituted 1,5-enyne products. To the best of our knowledge, this is the first example of [2,3]-sigmatropic rearrangement of alkynyl carbenes. DFT analysis supports the involvement of rhodium carbene generation, sulfonium ylides formation, and [2,3]-sigmatropic rearrangement pathway.

Substituent-Controllable Cascade Regioselective Annulation of β-Enaminones with N-Sulfonyl Triazoles for Modular Access to Imidazoles and Pyrroles.

A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of N-sulfonyl-1,2,3-trizaoles with β-enaminones. The imidazole ring was formed through a 1,1-insertion of the N-H bond to α-imino rhodium carbene, followed by a subsequent intramolecular 1,4-conjugate addition. This occurred when the α-carbon atom of the amino group was bearing a methyl group. Additionally, the pyrrole ring was constructed by utilizing a phenyl substituent and undergoing intramolecular nucleophilic addition. The mild conditions, good tolerance towards functional groups, gram-scale synthesis capability, and ability to undergo valuable transformations of the products qualify this unique protocol as an efficient tool for the synthesis of N-heterocycles.

Catalyst Loading Controls Chemoselectivity: Unusual Effect in Rhodium(II) Carbene Insertion Reactions with Tetrahydrofuran

(E)-3-Arylidene-4-diazopyrrolidine-2,5-diones previously shown to yield two products in reactions with tetrahydrofuran mediated by rhodium carbenes—tetrahydrofur-2-yl-substituted product of C-H insertion and spirocyclic product of formal C-O insertion. Accidentally, it was noted that the ratio of the two products depends on the catalyst loading, and the phenomenon was investigated in detail. It was found to be of preparative significance: by solely changing the catalyst loading from 0.01 mol% to 10 mol%, one can obtain sound yields of either of the two products. Mechanistic and kinetic interpretation of this new phenomenon has been proposed.

Synthesis of 3‐Methylidene‐2,3‐dihydropyrroles via Formal 1,2‐Enamine Migration/Cyclization Cascade of Rhodium Carbenes

Abstract3‐Methylidene‐2,3‐dihydropyrroles with an ester or keto group at the C4 position were obtained in moderate to good yields from enamine‐tethered triazoles in the presence of a rhodium(II) catalyst. A formal 1,2‐enamine migration/cyclization cascade triggered by formation of an α‐amino carbene is proposed to illustrate the mechanism. The valuable exocyclic double bond showed distinctive reactivity, which is very useful for further introduction of functional groups. The dihydropyrrole is stable under neutral, weakly acidic, or weakly basic conditions.magnified image

Synthesis of 3-aminoquinolines from α-imino rhodium carbenes and 2-aminobenzaldehydes.

A facile and efficient synthetic method for 3-aminoquinolines has been reported. The straightforward process starts from easily available triazoles and 2-aminobenzaldehydes. Low catalyst loading and good functional group compatibility are the other two merits of this transformation. Easy decoration of the 3-aminoquinoline motifs enabled the convenient synthesis of bioactive molecules, demonstrating the potential of this protocol in organic synthesis.

Catalyst Controlled Site- and Stereoselective Rhodium(II) Carbene C(sp3)-H Functionalization of Allyl Boronates.

Rhodium(II) catalyst-controlled site- and stereoselective carbene insertion into the distal allylic C(sp3)-H bond of allyl boronates is reported. The optimum chiral catalyst for this reaction is Rh2(S-TPPTTL)4. The fidelity and asymmetric induction of this catalytic transformation allows for a highly diastereoselective and enantioselective C-C bond formation without interference from the allyl boronate functionality. The resulting functionalized allyl boronates are susceptible to stereoselective allylations, generating products with control of stereochemistry at four contiguous stereogenic centers.

Silyl-functionalised silver rhodium and iridium N-heterocyclic carbene complexes with promising cytotoxicity and antimicrobial potential

In the present study, we have synthesized Ag, Rh, and Ir complexes of a silyl-substituted NHC ligand in order to investigate their biological properties. Firstly, Ag-NHC ( 2 ) complex was synthesized by the interaction of Ag 2 O with benzimidazolium iodide ( 1 ). Rh- ( 3 ) and Ir-NHC ( 4 ) complexes were synthesized by the transmetalation reaction between Ag-NHC and [M(cod)Cl] 2 (M = Rh or Ir) dimers. The complexes were characterised by NMR spectroscopy and elemental analyses, and crystal structures of Rh- and Ir-NHC ( 3 and 4 ) were also reported. The cytotoxic effects of the complexes were tested on four human cancer cell lines and the antimicrobial activities of the complexes were tested against a panel of nine pathogenic microorganisms. The complexes performed comparable or better activity than standards, cisplatin and AgNO 3 .

Rh-Catalyzed Coupling Reactions of Fluoroalkyl N-Sulfonylhydrazones with Azides Leading to α-Trifluoroethylated Imines.

Herein we describe the pioneering Rh-catalyzed coupling reactions of a fluoroalkyl carbene with azides to access α-trifluoroethylated imines, where fluoroalkyl N-sulfonylhydrazones are used as fluoroalkyl diazo surrogates. Remarkably, using TMSN3 as the N source, two C-N bond formation products were obtained. Furthermore, the α-trifluoroethylated imine products could be easily reduced to the corresponding N-trifluoroethylated anilines. Experimental results and theoretical calculations justify a stepwise reaction pathway involving the formation of rhodium carbene, the addition of HN3, and C═N bond formation.

Hexafluoroisopropanol for the Selective Deactivation of Poisonous Nucleophiles Enabling Catalytic Asymmetric Cyclopropanation of Complex Molecules

In the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), nucleophilic and reactive reagents are prevented from interacting with a rhodium carbene, allowing asymmetric cyclopropanation to occur with high yield and stereoselectivity on a variety of compounds. A high-throughput screen was conducted on cyclopropanation with a complementary catalytic system in the presence of 90 different poisonous nucleophiles and varying amounts of HFIP (10 equiv, used as reaction solvent). The scope of both the aryl/heteroaryl diazoacetate and the olefin was expanded, and the study culminated in the enantioselective functionalization of complex molecules including API and natural products.

Synthesis and Characterisation of a Heterobimetallic N-heterocyclic Carbene Rhodium Ruthenium Complex as Catalyst for Transfer Hydrogenation

The heterobimetallic N-heterocyclic dicarbene (NHDC) rhodium ruthenium complex [Ru(OAc)(Mes-NHC-methyl-PPh2)(Mes-aNHC-methyl-PPh2)RhCl(cod)] (4) is obtained from a mixed normal/abnormal bis-NHC ruthenium complex via transmetallation by addition of [RhCl(cod)]2 in THF at 40 °C, applying Ag2O as base. Crystallization is achieved by layering a solution of 4 in THF with Et2O. The complex is applicable as a catalyst in the transfer hydrogenation (TH) reaction of acetophenone, exhibiting a turnover frequency (TOF) of 6 700 h−1 with 80% conversion after 25 min (0.10 mol% catalyst, iPrOH, 80 °C, 2.00 mol% NaiOPr). These results are compared to an analogous iridium ruthenium NHDC complex.

Rhodium‐Catalyzed Transannulation of N‐Sulfonyl‐1,2,3‐triazoles with Carboxylic Esters

AbstractA rhodium‐catalyzed transannulation of N‐sulfonyl‐1,2,3‐triazoles with carboxylic esters followed by acid‐mediated aromatization has been developed, affording a variety of 2,5‐disubstituted oxazole derivatives in good to high yields under mild reaction conditions. The present transformation is proposed to involve the intermolecular carbonyl ylide formation between in situ generated α‐imino rhodium carbene species and carboxylic esters, which undergoes the nucleophilic attack of the neighboring α‐imino moiety.magnified image