Hydrogen, carbene complexes

Chiral monodentate carbene complexes of Rh and Ir of the type [MCl(l,5-COD) (NHC)] (M = Rh, Ir) with the ligands 7-9 (Fig. 2.1) have been stndied as catalysts for the enantioselective hydrogenation of methyl-2-acetamido acrylate. Even though the activities were high, the enantiomeric excesses (ee) were poor [7, 8]. 

Although transition metal alkylidene complexes, i.e., carbene complexes containing only hydrogen or carbon-based substituents, were first recognized over 15 years ago, it is only relatively recently that Ru, Os, and Ir alkylidene complexes have been characterized. Neutral and cationic complexes of these Group 8 metals are known for both metal electron configurations d8 and d6. The synthesis, structural properties, and reactivity of these compounds are discussed in this section. 

Bu2P(CH2)5P Bu2 to form IrHCl[ Bu2P(CH2)2CH(CH2)2P Bu2], (54) (59). Compound 54 reversibly eliminates hydrogen on thermolysis at reduced pressure, yielding the Ir(I) carbene complex 55 ... 

In view of the possibility of a-hydrogen transfer to metal, it remains possible that the metathesizing carbene complex has structure II rather than III [Eq. (13)] ... 

Thermolysis of ruthenium carbene complexes leads to intramolecular r/> -bcnzylic C-H functionalization in the presence of a hydrogen-accepting olefin (Equation (35)).44,44a. 

The first rhodium-catalyzed reductive cyclization of enynes was reported in I992.61,61a As demonstrated by the cyclization of 1,6-enyne 37a to vinylsilane 37b, the rhodium-catalyzed reaction is a hydrosilylative transformation and, hence, complements its palladium-catalyzed counterpart, which is a formal hydrogenative process mediated by silane. Following this seminal report, improved catalyst systems were developed enabling cyclization at progressively lower temperatures and shorter reaction times. For example, it was found that A-heterocyclic carbene complexes of rhodium catalyze the reaction at 40°C,62 and through the use of immobilized cobalt-rhodium bimetallic nanoparticle catalysts, the hydrosilylative cyclization proceeds at ambient temperature.6... 

Styrene derivatives 68-71 (Fig. 30.17 Table 30.13) were hydrogenated with moderate to high selectivity using carbene complexes 13a and 13b [20]. 

Aqueous two-phase hydrogenations are dominated by platinum group metal catalysts containing water-soluble tertiary phosphine ligands. The extremely stable and versatile N-heterocyclic carbene complexes attracted only limited interest, despite the fact that such complexes were described in the literature [62-65]. Recently, it was reported that the water-soluble [RuXY(l-butyl-3-methylimi-dazol-2-ylidene) ( 76-p-cymene)]n+ (X=Ch, H20 Y = C1-, H20, pta) complexes preferentially hydrogenated cinnamaldehyde and benzylideneacetone at the C = C double bond (Scheme 38.5) with TOF values of 30 to 60 h 1 in water substrate biphasic mixtures (80 °C, lObar H2) [66]. 

Because hydrogen, alkyl, or aryl groups can compensate only to a limited extent the electron deficit of the carbene carbon atom, it is mainly the metal and its ligands which provide stabilization in this type of carbene complex. For this reason the reactivity of these compounds depends mainly on the nature and oxidation state of the metal and on the electronic properties of the remaining ligands. 

In many of the reported preparations of stable carbene complexes from alkyl complexes, alkyl groups without p-hydrogen (e.g. neopentyl, 2,2,2-trifluoroethyl, trimethylsilylmethyl, methyl, benzyl) were chosen in order to avoid p-elimination. There are, however, also examples of moderately stable, non-heteroatom-substituted alkylidene complexes with hydrogen in the -position to the metal (see, e.g.. Figure 3.8). 

Acid-catalyzed dealkoxylation is particularly suitable for the preparation of highly reactive, cationic iron(IV) carbene complexes, which can be used for the cyclopropanation of alkenes [438] (Figure 3.11). Several reagents can be used to catalyze alkoxide abstraction these include tetrafluoroboric acid [457-459], trifluoroacetic acid [443,460], gaseous hydrogen chloride [452,461], trityl salts [434], or trimethylsilyl triflate [24,104,434,441,442,460], In the case of oxidizing acids (e.g. trityl salts) hydride abstraction can compete efficiently with alkoxide abstraction and lead to the formation of alkoxycarbene complexes [178,462] (see Section 2.1.7). 

Alkynes react readily with a variety of transition metal complexes under thermal or photochemical conditions to form the corresponding 7t-complexes. With terminal alkynes the corresponding 7t-complexes can undergo thermal or chemically-induced isomerization to vinylidene complexes [128,130,132,133,547,556-569]. With mononuclear rj -alkyne complexes two possible mechanisms for the isomerization to carbene complexes have been considered, namely (a) oxidative insertion of the metal into the terminal C-Fl bond to yield a hydrido alkynyl eomplex, followed by 1,3-hydrogen shift from the metal to Cn [570,571], or (b) eoneerted formation of the M-C bond and 1,2-shift of H to Cp [572]. 

Most electrophilic carbene complexes with hydrogen at Cjj will undergo fast 1,2-proton migration with subsequent elimination of the metal and formation of an alkene. For this reason, transition metal-catalyzed cyclopropanations with non-acceptor-substituted diazoalkanes have mainly been limited to the use of diazomethane, aryl-, and diaryldiazomethanes (Tables 3.4 and 3.5). 

Also in macrocyclizations the conformation of the starting diene has an influence on the RCM/ADMET ratio. Substituents on the diene which form hydrogen bonds between each other or with the intermediate carbene complex, or external Lewis acids can have an important effect on the course of the reaction. Such effects, often subtle, might explain the variable results sometimes obtained in macrocyclizations [842], but make synthesis-planning and the formulation of general guidelines difficult. 

In acceptor-substituted carbene complexes with hydrogen at Cp fast hydride migration to the carbene will usually occur [1094,1095]. The resulting olefins are often formed with high stereoselectivity. 1,2-Hydride migration will also occur in P-hydroxy carbene complexes, ketones being formed in high yields (Table 4.2). Intramolecular 1,5-C-H insertion can sometimes compete efficiently with 1,2-insertion [1096]. 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

There have been many reports of the use of iridium-catalyzed transfer hydrogenation of carbonyl compounds, and this section focuses on more recent examples where the control of enantioselectivity is not considered. In particular, recent interest has been in the use of iridium A -heterocyclic carbene complexes as active catalysts for transfer hydrogenation. However, alternative iridium complexes are effective catalysts [1, 2] and the air-stable complex 1 has been shown to be exceptionally active for the transfer hydrogenation of ketones [3]. For example, acetophenone 2 was converted into the corresponding alcohol 3 using only 0.001 mol% of this... 

A -Heterocyclic carbene complexes of Ir(I) and Ir(III) have also demonstrated high reactivity in transfer hydrogenation reactions of ketones (Scheme 2) [4]. Complex 4 catalyzed the reduction of a range of ketones into the corresponding alcohols, including the reduction of pinacolone 7 into alcohol 8 with a low catalyst loading and short reaction time [5]. The chelating bis(Af-heterocyclic carbene) complex 5 was shown to catalyze the reduction of ketones, and in the case of the reduction of benzophenone 9 to alcohol 10, the reaction was complete within 4 min [6]. 

The same catalyst has also been used for the reduction of aldehydes to primary alcohols [7]. Several other iridium W-heterocyclic carbene complexes have been shown to be successful as catalysts for the transfer hydrogenation of ketones [8-12], including the interesting complex 6, where the cyclopentadienyl ring is tethered to the 77-heterocyclic carbene. Complex 6 was employed at low catalyst loading for the reduction of a range of ketones including the conversion of cyclohexanone 11 into cyclohexanol 12 [13]. 

The catalyst is also effective for the reduction of styrenes, ketones, and aldehydes. Cyclohexenone 16 was reduced to cyclohexanone 11 by transfer hydrogenation, and using a higher catalyst loading, styrene 17 was reduced to ethylbenzene 18. The elaboration of [Ir(cod)Cl]2 into the triazole-derived iridium carbene complex 19 provided a catalyst, which was used to reduce aUcene 20 by transfer hydrogenation [25]. 

A large number of reports have concerned transfer hydrogenation using isopropanol as donor, with imines, carbonyls-and occasionally alkenes-as substrate (Scheme 3.17). In some early studies conducted by Nolan and coworkers [36], NHC analogues of Crabtree catalysts, [Ir(cod)(py)(L)]PF,5 (L= Imes, Ipr, Icy) all proved to be active. The series of chelating iridium(III) carbene complexes shown in Scheme 3.5 (upper structure) proved to be accessible via a simple synthesis and catalytically active for hydrogen transfer from alcohols to ketones and imines. Unexpectedly, iridium was more active than the corresponding Rh complexes, but... 

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