An [(NHC)(NHCEWG)RuCl2(CHPh)] Complex for the Efficient Formation of Sterically Hindered Olefins by Ring‐Closing Metathesis

NHC with EWGs for RCM : Ruthenium complexes with two N‐heterocyclic carbenes (NHCs), one of them substituted with electron‐withdrawing groups (EWGs), are highly efficient (pre)catalysts for the synthesis of tetrasubstituted olefins and trisubstituted olefins by ring‐closing metathesis reactions (RCM, see scheme).

     

Tandem Ring‐Opening–Ring‐Closing Metathesis for Functional Metathesis Catalysts

Use of a tandem ring‐opening–ring‐closing metathesis (RORCM) strategy for the synthesis of functional metathesis catalysts is reported. Ring opening of 7‐substituted norbornenes and subsequent ring‐closing metathesis forming a thermodynamically stable 6‐membered ring lead to a very efficient synthesis of new catalysts from commercially available Grubbs’ catalysts. Hydroxy functionalized Grubbs’ first‐ as well as third‐generation catalysts have been synthesized. Mechanistic studies have been performed to elucidate the order of attack of the olefinic bonds. This strategy was also used to synthesize the ruthenium methylidene complex.     

Oxidation‐Triggered Ring‐Opening Metathesis Polymerization

Eight new N‐Hoveyda‐type complexes were synthesized in yields of 67–92 % through reaction of [RuCl₂(NHC)(Ind)(py)] (NHC=1,3‐bis(2,4,6‐trimethylphenylimidazolin)‐2‐ylidene (SIMes) or 1,3‐bis(2,6‐diisopropylphenylimidazolin)‐2‐ylidene (SIPr), Ind=3‐phenylindenylid‐1‐ene, py=pyridine) with various 1‐ or 1,2‐substituted ferrocene compounds with vinyl and amine or imine substituents. The redox potentials of the respective complexes were determined; in all complexes an iron‐centered oxidation reaction occurs at potentials close to E=+0.5 V. The crystal structures of the reduced and of the respective oxidized Hoveyda‐type complexes were determined and show that the oxidation of the ferrocene unit has little effect on the ruthenium environment. Two of the eight new complexes were found to be switchable catalysts, in that the reduced form is inactive in the ring‐opening metathesis polymerization of cis‐cyclooctene (COE), whereas the oxidized complexes produce polyCOE. The other complexes are not switchable catalysts and are either inactive or active in both reduced and oxidized states.     

A Facile Route to Backbone‐Tethered N‐Heterocyclic Carbene (NHC) Ligands via NHC to aNHC Rearrangement in NHC Silicon Halide Adducts

The reaction of 1,3‐diisopropylimidazolin‐2‐ylidene (iPr₂Im) with diphenyldichlorosilane (Ph₂SiCl₂) leads to the adduct (iPr₂Im)SiCl₂Ph₂ 1 . Prolonged heating of isolated 1 at 66 °C in THF affords the backbone‐tethered bis(imidazolium) salt [(^aHiPr₂Im)₂SiPh₂]²⁺ 2 Cl^? 2 (“^a” denotes “abnormal” coordination of the NHC), which can be synthesized in high yields in one step starting from two equivalents of iPr₂Im and Ph₂SiCl₂. Imidazolium salt 2 can be deprotonated in THF at room temperature using sodium hydride as a base and catalytic amounts of sodium tert‐butoxide to give the stable N‐heterocyclic dicarbene (^aiPr₂Im)₂SiPh₂ 3 , in which two NHCs are backbone‐tethered with a SiPh₂ group. This easy‐to‐synthesize dicarbene 3 can be used as a novel ligand type in transition metal chemistry for the preparation of dinuclear NHC complexes, as exemplified by the synthesis of the homodinuclear copper(I) complex [{^a(ClCu?iPr₂Im)}₂SiPh₂] 4 .     

Ring‐Closing Metathesis Reactions: Interpretation of Conversion–Time Data

Conversion–time data were recorded for various ring‐closing metathesis (RCM) reactions that lead to five‐ or six‐membered cyclic olefins by using different precatalysts of the Hoveyda type. Slowly activated precatalysts were found to produce more RCM product than rapidly activated complexes, but this comes at the price of slower product formation. A kinetic model for the analysis of the conversion–time data was derived, which is based on the conversion of the precatalyst (Pcat) into the active species (Acat), with the rate constant k_act, followed by two parallel reactions: 1) the catalytic reaction, which utilizes Acat to convert reactants into products, with the rate k_cat, and 2) the conversion of Acat into the inactive species (Dcat), with the rate k_dec. The calculations employ two experimental parameters: the concentration of the substrate (c(S)) at a given time and the rate of substrate conversion (?dc(S)/dt). This provides a direct measure of the concentration of Acat and enables the calculation of the pseudo‐first‐order rate constants k_act, k_cat, and k_dec and of k_S (for the RCM conversion of the respective substrate by Acat). Most of the RCM reactions studied with different precatalysts are characterized by fast k_cat rates and by the k_dec value being greater than the k_act value, which leads to quasistationarity for Acat. The active species formed during the activation step was shown to be the same, regardless of the nature of different Pcats. The decomposition of Acat occurs along two parallel pathways, a unimolecular (or pseudo‐first‐order) reaction and a bimolecular reaction involving two ruthenium complexes. Electron‐deficient precatalysts display higher rates of catalyst deactivation than their electron‐rich relatives. Slowly initiating Pcats act as a reservoir, by generating small stationary concentrations of Acat. Based on this, it can be understood why the use of different precatalysts results in different substrate conversions in olefin metathesis reactions.     

A Light‐Activated Olefin Metathesis Catalyst Equipped with a Chromatic Orthogonal Self‐Destruct Function

A sulfur‐chelated photolatent ruthenium olefin metathesis catalyst has been equipped with supersilyl protecting groups on the N‐heterocyclic carbene ligand. The silyl groups function as an irreversible chromatic kill switch, thus decomposing the catalyst when it is irradiated with 254 nm UV light. Therefore, different types of olefin metathesis reactions may be started by irradiation with 350 nm UV light and prevented by irradiation with shorter wavelengths. The possibility to induce and impede catalysis just by using light of different frequencies opens the pathway for stereolithographic applications and novel light‐guided chemical sequences.     

Bis(Cyclic Alkyl Amino Carbene) Ruthenium Complexes: A Versatile,Highly Efficient Tool for Olefin Metathesis

The state‐of‐the‐art in olefin metathesis is application of N‐heterocyclic carbene (NHC)‐containing ruthenium alkylidenes for the formation of internal C=C bonds and of cyclic alkyl amino carbene (CAAC)‐containing ruthenium benzylidenes in the production of terminal olefins. A straightforward synthesis of bis(CAAC)Ru indenylidene complexes, which are highly effective in the formation of both terminal and internal C=C bonds at loadings as low as 1 ppm, is now reported.     

N‐Heterocyclic Carbene,High Oxidation State Molybdenum Alkylidene Complexes: Functional‐Group‐Tolerant Cationic Metathesis Catalysts

We synthesized the first N‐heterocyclic carbene (NHC) complexes of Schrock’s molybdenum imido alkylidene bis(triflate) complexes. Unlike existing bis(triflate) complexes, the novel 16‐electron complexes represent metathesis active, functional‐group‐tolerant catalysts. Single‐crystal X‐ray structures of two representatives of this novel class of Schrock catalysts are presented and reactivity is discussed in view of their structural peculiarities. In the presence of monomer (substrate), these catalysts form cationic species and can be employed in ring‐closing metathesis (RCM), ring‐opening metathesis polymerization (ROMP), as well as in the cyclopolymerization of α,ω‐diynes. Monomers containing functional groups, which are not tolerated by the existing variations of Schrock’s catalyst, e.g., sec‐amine, hydroxy, and carboxylic acid moieties, can be used. These catalysts therefore hold great promise in both organic and polymer chemistry, where they allow for the use of protic monomers.     

Neutral and Cationic Molybdenum Imido Alkylidene N‐Heterocyclic Carbene Complexes: Reactivity in Selected Olefin Metathesis Reactions and Immobilization on Silica

The synthesis and single‐crystal X‐ray structures of the novel molybdenum imido alkylidene N‐heterocyclic carbene complexes [Mo(N‐2,6‐Me₂C₆H₃)(IMesH₂)(CHCMe₂Ph)(OTf)₂] ( 3 ), [Mo(N‐2,6‐Me₂C₆H₃)(IMes)(CHCMe₂Ph)(OTf)₂] ( 4 ), [Mo(N‐2,6‐Me₂C₆H₃)(IMesH₂)(CHCMe₂Ph)(OTf){OCH(CF₃)₂}] ( 5 ), [Mo(N‐2,6‐Me₂C₆H₃)(CH₃CN)(IMesH₂)(CHCMe₂Ph)(OTf)]⁺ BAr_F^? ( 6 ), [Mo(N‐2,6‐Cl₂C₆H₃)(IMesH₂)(CHCMe₃)(OTf)₂] ( 7 ) and [Mo(N‐2,6‐Cl₂C₆H₃)(IMes)(CHCMe₃)(OTf)₂] ( 8 ) are reported (IMesH₂=1,3‐dimesitylimidazolidin‐2‐ylidene, IMes=1,3‐dimesitylimidazolin‐2‐ylidene, BAr_F^?=tetrakis‐[3,5‐bis(trifluoromethyl)phenyl] borate, OTf=CF₃SO₃^?). Also, silica‐immobilized versions I1 and I2 were prepared. Catalysts 3 – 8 , I1 and I2 were used in homo‐, cross‐, and ring‐closing metathesis (RCM) reactions and in the cyclopolymerization of α,ω‐diynes. In the RCM of α,ω‐dienes, in the homometathesis of 1‐alkenes, and in the ethenolysis of cyclooctene, turnover numbers (TONs) up to 100 000, 210 000 and 30 000, respectively, were achieved. With I1 and I2 , virtually Mo‐free products were obtained (<3 ppm Mo). With 1,6‐hepta‐ and 1,7‐octadiynes, catalysts 3 , 4 , and 5 allowed for the regioselective cyclopolymerization of 4,4‐bis(ethoxycarbonyl)‐1,6‐heptadiyne, 4,4‐bis(hydroxymethyl)‐1,6‐heptadiyne, 4,4‐bis[(3,5‐diethoxybenzoyloxy)methyl]‐1,6‐heptadiyne, 4,4,5,5‐tetrakis(ethoxycarbonyl)‐1,7‐octadiyne, and 1,6‐heptadiyne‐4‐carboxylic acid, underlining the high functional‐group tolerance of these novel Group 6 metal alkylidenes.     

Redox‐Switchable Ring‐Closing Metathesis: Catalyst Design,Synthesis, and Study

High yielding syntheses of 1‐(ferrocenylmethyl)‐3‐mesitylimidazolium iodide ( 1 ) and 1‐(ferrocenylmethyl)‐3‐mesitylimidazol‐2‐ylidene ( 2 ) were developed. Complexation of 2 to [{Ir(cod)Cl}₂] (cod=cis,cis‐1,5‐cyclooctadiene) or [Ru(PCy₃)Cl₂(?CH‐o‐O‐iPrC₆H₄)] (Cy=cyclohexyl) afforded 3 ([Ir( 2 )(cod)Cl]) and 5 ([Ru( 2 )Cl₂(?CH‐o‐O‐iPrC₆H₄)]), respectively. Complex 4 ([Ir( 2 )(CO)₂Cl]) was obtained by bubbling carbon monoxide through a solution of 3 in CH₂Cl₂. Spectroelectrochemical IR analysis of 4 revealed that the oxidation of the ferrocene moiety in 2 significantly reduced the electron‐donating ability of the N‐heterocyclic carbene ligand (ΔTEP=9 cm^?1; TEP=Tolman electronic parameter). The oxidation of 5 with [Fe(η⁵‐C₅H₄COMe)Cp][BF₄] as well as the subsequent reduction of the corresponding product [ 5 ][BF₄] with decamethylferrocene (Fc*) each proceeded in greater than 95 % yield. Mössbauer, UV/Vis and EPR spectroscopy analysis confirmed that [ 5 ][BF₄] contained a ferrocenium species, indicating that the iron center was selectively oxidized over the ruthenium center. Complexes 5 and [ 5 ][BF₄] were found to catalyze the ring‐closing metathesis (RCM) of diethyl diallylmalonate with observed pseudo‐first‐order rate constants (k_obs) of 3.1×10^?4 and 1.2×10^?5 s^?1, respectively. By adding suitable oxidants or reductants over the course of a RCM reaction, complex 5 was switched between different states of catalytic activity. A second‐generation N‐heterocyclic carbene that featured a 1′,2′,3′,4′,5′‐ pentamethylferrocenyl moiety ( 10 ) was also prepared and metal complexes containing this ligand were found to undergo iron‐centered oxidations at lower potentials than analogous complexes supported by 2 (0.30–0.36 V vs. 0.56–0.62 V, respectively). Redox switching experiments using [Ru( 10 )Cl₂(?CH‐o‐O‐iPrC₆H₄)] revealed that greater than 94 % of the initial catalytic activity was restored after an oxidation–reduction cycle.     

Synthesis of Carbazole Alkaloids by Ring‐Closing Metathesis and Ring Rearrangement–Aromatization

Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring‐closing metathesis (RCM) and ringrearrangement–aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2‐diallyl 3‐oxindole derivatives through a 1,2‐allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel class of spirocyclopentene‐3‐oxindole derivatives, which underwent a novel RRA reaction to afford carbazole derivatives. The synthetic sequence to carbazoles was shortened by combining the RCM and RRA steps in an orthogonal tandem catalytic process. The utility of this methodology was further demonstrated by the straightforward synthesis of carbazole alkaloids, including amukonal derivative, girinimbilol, heptaphylline, and bis(2‐hydroxy‐3‐methylcarbazole).     

Oxidative Addition of 2‐Halogenoazoles—Direct Synthesis of Palladium(II) Complexes Bearing Protic NH,NH‐Functionalized NHC Ligands

The chemistry of N‐heterocyclic carbenes (NHCs) is dominated by N,N′‐dialkylated or ‐diarylated derivatives. Such NHC ligands are normally obtained by C2‐deprotonation of azolium cations or by reductive elimination from azol‐2‐thiones. A simple one‐step procedure is described that leads to complexes with NH,NH‐functionalized NHC ligands by the oxidative addition of 2‐halogenoazoles to complexes of zero‐valent transition metals.     

Temporary Silicon‐Tethered Ring‐Closing Metathesis: Recent Advances in Methodology Development and Natural Product Synthesis

Temporary silicon‐tethered ring‐closing metathesis represents an important cross‐coupling strategy for the formation of medium‐sized silacycles. These intermediates are valuable synthons in organic synthesis due to their propensity to undergo a facile refunctionalization through protodesilylation, oxidation, silane‐group transfer or transmetallation. A particularly attractive utility of this methodology is an application in the synthesis of biologically important natural products. The purpose of this review article is to highlight the recent progress in methodology development and its strategic application toward the target‐directed synthesis.     

[IrCl2Cp*(NHC)] Complexes as Highly Versatile Efficient Catalysts for the Cross‐Coupling of Alcohols and Amines

A comparative study on the catalytic activity of a series of [IrCl₂Cp*(NHC)] complexes in several C–O and C–N coupling processes implying hydrogen‐borrowing mechanisms has been performed. The compound [IrCl₂Cp*(I^nBu)] (Cp*=pentamethyl cyclopentadiene; I^nBu=1,3‐di‐n‐butylimidazolylidene) showed to be highly effective in the cross‐coupling reactions of amines and alcohols, providing high yields in the production of unsymmetrical ethers and N‐alkylated amines. A remarkable feature is that the processes were carried out in the absence of base, phosphine, or any other external additive. A comparative study with other known catalysts, such as Shvo's catalyst, is also reported.     

Total Synthesis of (+)‐Cryptocaryalactone and of a Diastereoisomer of (+)‐Strictifolione via Ring‐Closing Metathesis (RCM) and Olefin Cross‐Metathesis (CM)

Ring‐closing metathesis (RCM) and olefin cross‐metathesis (CM) reactions were used as the key steps for the synthesis of (+)‐cryptocaryalactone ( 1 ) and the first synthesis of the diastereoisomer 3 of (+)‐strictifolione, starting from the commercially available L ‐malic acid (=(2S)‐2‐hydroxybutanedioic acid).