Alkyl from carbene complexes

Few examples of preparatively useful intermolecular C-H insertions of electrophilic carbene complexes have been reported. Because of the high reactivity of complexes capable of inserting into C-H bonds, the intermolecular reaction is limited to simple substrates (Table 4.9). From the results reported to date it seems that cycloalkanes and electron-rich heteroaromatics are suitable substrates for intermolecular alkylation by carbene complexes [1165]. The examples in Table 4.9 show that intermolecular C-H insertion enables highly convergent syntheses. Elaborate structures can be constructed in a single step from readily available starting materials. Enantioselective, intermolecular C-H insertions with simple cycloalkenes can be realized with up to 93% ee by use of enantiomerically pure rhodium(II) carboxylates [1093]. 

The reaction of alkyl-substituted tungsten-carbene complexes of the type (88b) have been reported by Macomber to react with alkynes to give dienes of the type (319). One mechanism that has been proposed to account for this product is a 3-hydride elimination from the metallacyclobutene intermediate (320) and subsequent reductive elimination in the metal hydride species (321). An additional example of this type of reaction has been reported by Rudler, also for an alkyl tungsten carbene complex. Chromium complexes have not been observed to give diene products of this type the reaction of the analogous chromium complex (88a) with diphenylacetylene gives a cyclobutenone as the only reported product (see Scheme 31). Acyclic products are observed for both tungsten and chromium complexes in their reactions with ynamines. These reactions produce amino-stablized carbene complexes that are the result of the formal insertion of the ynamine into the metal-carbene bond. ... 

Many other organometaUic compounds also react with carbonyl groups. Lithium alkyls and aryls add to the ester carbonyl group to give either an alcohol or an olefin. Lithium dimethyl cuprate has been used to prepare ketones from esters (41). Tebbe s reagent, Cp2TiCH2AlCl(CH2)2, where Cp = clyclopentadienyl, and other metal carbene complexes can convert the C=0 of esters to C=CR2 (42,43). 

Chromium carbene complexes like 13, which are called Fischer carbene complexes, can conveniently be prepared from chromium hexacarbonyl 11 and an organolithium compound 12, followed by an O-alkylation step ... 

From Alkyl-Substituted Fischer Carbene Complexes. 23... 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Alkylation of an anionic acylmetallate is the second step in the classic Fischer synthesis of carbene complexes. The same type of reaction can be performed with stable neutral acyl complexes, producing cationic carbene compounds. Compound 17 has been prepared from a ruthenium acetyl complex by direct methylation and by protonation with subsequent methylenation (45) ... 

Methylation of the dihaptothioacyl complex 22 affords compound 23 containing a bidentate carbene ligand, which on reaction with chloride ion leads to the neutral monodentate carbene complex 24 (50,51). The chelate carbene complex 26 is generated in a novel interligand reaction from the thiocarboxamidothiocarbonyl cation 25. The thiocarbonyl carbon acts as the electrophilic component in this reaction, and 26 is further alkylated to a bidentate dicarbene species (52). 

With the long alkyl chain substitutions on the A-heterocyclic carbenes, lamella-structured silver(i) carbene complexes 27a and 27b (Figure 14) were isolated.74 It is interesting to note that the synthetic procedures for the two complexes are the same except for the use of different solvents of crystallization. The dinuclear 27a was obtained from recrystallization in dichloromethane- -hexane while the tetranuclear 27b was obtained from acetone. The structure of 27a could be interpreted as the dimeric form of [Ag(carbene)Br] bridged by intermolecular Ag-Br interactions. The Ag-G bond has a distance of 2.094(5) A. The tetranuclear 27b, on the other hand, could be regarded as two monocationic bis(carbene)silver(i) bridged by an [Ag2Br4]2 anion, with the presence of short Ag(cationic)-Ag(anionic) contact (3.0038(18) A) and comparable Ag-G bond distances (2.0945(5), 2.138(13) A). A related... 

The carbene complexes generated by desulfurization of thioacetals with the titanoce-ne(II) species react with internal alkynes to produce the conjugated dienes 79 with high stereoselectivity (Scheme 14.34) [77]. The process appears to involve syn-elimination of P-hydride from the alkyl substituent that originates from the carbene complex after the formation of titanacyclobutene 80. 

A further general route to heteroatom-substituted carbene complexes is based on the a-abstraction of nucleophiles from alkyl complexes (electrophilic abstraction Figure 2.13). 

The intermediate vinylketene complexes can undergo several other types or reaction, depending primarily on the substitution pattern, the metal and the solvent used (Figure 2.27). More than 15 different types of product have been obtained from the reaction of aryl(alkoxy)carbene chromium complexes with alkynes [333,334]. In addition to the formation of indenes [337], some arylcarbene complexes yield cyclobutenones [338], lactones, or furans [91] (e.g. Entry 4, Table 2.19) upon reaction with alkynes. Cyclobutenones can also be obtained by reaction of alkoxy(alkyl)carbene complexes with alkynes [339]. 

Many non-heteroatom-substituted carbene complexes have been prepared from alkyl complexes by a-abstraction, for which two mechanistically different pathways must be considered (Figure 3.3) ... 

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). 

Dimethylsulhde can be eliminated from a-(dimethylsulfonium)alkyl complexes simply by heating (Figure 3.15). The resulting, very reactive, electrophilic iron carbene complexes cannot usually be isolated but are generated directly in the presence of a suitable reactant, e.g. an olefin. Cationic nickel [475] and tungsten [476] carbene complexes have been prepared by similar routes. 

Fig. 3.16. Generation of reactive, cationic iron(lV) carbene complexes from a-(phenyl-thio)alkyl complexes [470,482].

Protonation of alkenyl complexes has been used [56,534,544,545] for generating cationic, electrophilic carbene complexes similar to those obtained by a-abstraction of alkoxide or other leaving groups from alkyl complexes (Section 3.1.2). Some representative examples are sketched in Figure 3.27. Similarly, electron-rich alkynyl complexes can react with electrophiles at the P-position to yield vinylidene complexes [144,546-551]. This approach is one of the most appropriate for the preparation of vinylidene complexes [128]. Figure 3.27 shows illustrative examples of such reactions. 

As already discussed (Section 3.1.1) the elimination of, for instance, neopentane from penta(neopentyl)tantalum corresponds to an a-deprotonation of one alkyl ligand by another, the latter being eliminated as neopentane. Hence in the reverse reaction the carbene carbon atom of the (nucleophilic) carbene complex must formally deprotonate the incoming alkane with simultaneous electrophilic attack of the metal at the newly formed, carbanionic alkyl group (Figure 3.36). 

However, with substrates prone to form carbocations, complete hydride abstraction from the alkane, followed by electrophilic attack of the carbocation on the metal-bound, newly formed alkyl ligand might be a more realistic picture of this process (Figure 3.38). The regioselectivity of C-H insertion reactions of electrophilic transition metal carbene complexes also supports the idea of a carbocation-like transition state or intermediate. 

Electrophilic carbene complexes generated from diazoalkanes and rhodium or copper salts can undergo 0-H insertion reactions and S-alkylations. These highly electrophilic carbene complexes can, moreover, also undergo intramolecular rearrangements. These reactions are characteristic of acceptor-substituted carbene complexes and will be treated in Section 4.2. 

The usefulness of this reaction for the preparation of heterocycles under mild conditions became apparent in 1978, when chemists from Merck, Sharp Dohme reported the synthesis of bicyclic 3-lactams by intramolecular carbene N-H insertion [1179]. Intramolecular N-alkylation of P-lactams by carbene complexes is one of the best methods for preparation of this important class of antibiotic and many P-lactam derivatives have been prepared using this methodology [1180 -1186] (Table 4.11). Intramolecular N-H insertion can also be used to alkylate amines [1187-1189], y-lactams [1190], and carbamates [1191-1193] (Table 4.11). 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

An intramolecular alkyl group transfer occurs upon warming up solutions of the ate-complex 180 generated by transmetalation of 1-lithio-l-methoxyethene 56 (equation 76)405,406 Tungsten and chromium carbene complexes 181 and 182, respectively, have been isolated from l-lithio-l,2-dimethoxyethene (equation 11... 

The carbene complexes can also be formed by direct oxidative addition of ze-rovalent metal to an ionic liquid. The oxidative addition of a C-H bond has been demonstrated by heating [MMIM]BF4 with Pt(PPh3)4 in THF, resulting in the formation of a stable cationic platinum carbene complex (Scheme 15) (189). An effective method to protect this carbene-metal-alkyl complex from reductive elimination is to perform the reaction with an imidazolium salt as a solvent. 

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