Carbene complexes with acids

Ruthenium complexes B are stable in the presence of alcohols, amines, or water, even at 60 °C. Olefin metathesis can be realized even in water as solvent, either using ruthenium carbene complexes with water-soluble phosphine ligands [815], or in emulsions. These complexes are also stable in air [584]. No olefination of aldehydes, ketones, or derivatives of carboxylic acids has been observed [582]. During catalysis of olefin metathesis replacement of one phosphine ligand by an olefin can occur [598,809]. 

The most frequently used ylides for carbene-complex generation are acceptor-substituted diazomethanes. As already mentioned in Section 3.1.3.1, non-acceptor-substituted diazoalkanes are strong C-nucleophiles, easy to convert into carbene complexes with a broad variety of transition metal complexes. Acceptor-substituted diazomethanes are, however, less nucleophilic (and more stable) than non-acceptor-substituted diazoalkanes, and require catalysts of higher electrophilicity to be efficiently decomposed. Not surprisingly, the very stable bis-acceptor-substituted diazomethanes can be converted into carbene complexes only with strongly electrophilic catalysts. This order of reactivity towards electrophilic transition metal complexes correlates with the reactivity of diazoalkanes towards other electrophiles, such as Brpnsted acids or acyl halides. 

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. 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

I would emphasize that the reaction of the amino acid-carbene complex with boron tribromide represents a good possibility of again cleaving the carbenyl protective group under extremely mild conditions at —25°C. 

Even Lewis acid adducts of the acyl metalate 11 (Section 8.3.1.1, Scheme 8) proved effective in generating benzannulation products. The reaction of a trimethylsilyloxy chromium carbene complex with 3-hexyne to give the respective semi-silylated hydroquinone tricarbo-nylchromium complex in 35 % yield [30a] and the use of titanoxycarbene complexes [30b] constitute such examples. Thiocarbene complexes form hydrothioquinones in a Lewis acid supported benzannulation reaction [32]. 

Thermal cyclization reaction of Fischer carbene complexes with a, 3-unsaturated ketones and aldehydes led to 2,3-dihydrofurans, which were converted to the corresponding furans under various conditions, including treatment with silica gel, use of non-aqueous acid (HBF4 or CF3CO2H) or simply by heating <07AGE4136>. 

The additional adamantyl substituent on the phenol moiety was introduced by an acid catalysed reaction with 1-adamantol prior to the reduction step. The significance of this ligand is that it stabilises a Pd-alkyl group cis to the NHC ligand in a palladium(II) carbene complex. These transition metal carbene complexes with a cis alkyl ligand are still rare... 

Naturally, it is possible to synthesise a similar ligand system without central chirality and in fact without the unnecessary methylene linker unit. A suitable synthesis starts with planar chiral ferrocenyl aldehyde acetal (see Figure 5.30). Hydrolysis and oxidation of the acetal yields the corresponding carboxylic acid that is transformed into the azide and subsequently turned into the respective primary amine functionalised planar chiral ferrocene. A rather complex reaction sequence involving 5-triazine, bromoacetal-dehyde diethylacetal and boron trifluoride etherate eventually yields the desired doubly ferrocenyl substituted imidazolium salt that can be deprotonated with the usual potassium tert-butylate to the free carbene. The ligand was used to form a variety of palladium(II) carbene complexes with pyridine or a phosphane as coligand. 

In Fischer s original synthesis, carbyne complexes were obtained fortuitously as products of the reactions of carbene complexes with Lewis acids. For example, the methoxycarbene complex Cr(CO)5[C(OCH3)C6H5] reacts with the Lewis acids BX3 (X = Cl, Br, or I). 

This enhanced reactivity difference for thiolate addition has been attributed to the combination of two factors. The first is the favorable soft acid-soft base interaction for the reaction of the soft carbene complex with the soft thiolate ion which contrasts with the unfavorable hard acid (CH3COH)-soft base (EtS ) interaction in reaction (66). The second is the favorable hard acid-hard base interaction between the hard MeO with the hard methylbenzoate which contrasts with the unfavorable soft acid-hard base interaction in the reaction of the carbene complex with MeO. ... 

This methodology was successfully applied to other carbene complexes with relatively high values but for the more acidic complexes it fails because... 

In another example, the hydrogenation of the azapenam (55,6/ )-6-methoxy-2,2,6-trimethyl-l,4-diazabicyclo[3.2.0]heptan-7-one (154), prepared by reaction of a pentacarbonyl chromium carbene complex with liV-Boc-4,4-dimethylimidazoline, in the presence of 1.1 equiv. of racemic camphor sulfonic acid resulted in the cleavage of the Boc group and ring expansion of the azapenam to hexahydro-3,3,6-trimethyl-6-methoxy-5//-l,4-diazepin-5-one (155) in 71% yield <92JA5010>. It was pointed out that the ready availability of a variety of substituted chromium carbene complexes and imidazolines would make this a general route to this class of diazepine. 

Philip Kocienski published an elegant synthesis of racemic olean. The starting material is the THP ether of 4,4-dibromobutanol. In spite of the acid-sensitivity of the acetal, the formation of a carbene complex with titanium tetrachloride and zinc can be achieved. Its reaction with a corresponding ester leads to an enol ether, which cyclises to olean under acidic conditions. [217]... 

Evidence for the tetrahedral intermediate has been gained in some cases by the reaction of the Fischer carbene complex with a Lewis base. Some of these reactions generate Lewis acid-base adducts in which the the carbene carbon acts as the Lewis acid. For example, addition of quinuclidine to the classic Fischer carbene complexes [M(CO)5=CPh(OMe)] (M = Cr or W) generated stable adducts, as shown for the tungsten example in Scheme 13.7. ... 

Weaker acids also add to Os(=CR)Cl(CO)(PPh3)2, for example, acetic acid with Os(sCp-tolyl)Cl(CO)(PPh3)2 gives the cationic carbene complex with a dihapto acetato-Ugand, [Os(Ti2-02CCH3)(=CHp-tolyl)(CO)(PPh3)2]+ [12]. 

The first gold(I)-carbene complex with a gold-oxygen bond [Au(R2-imy)OC(0) CH3] (Fig. 2) was successfully applied for the addition of water to 3-hexyne in the presence of a Lewis acid as a co-catalyst [115]. 

JA5190). Upon deprotonation by bases, 285 (R = H) transforms to 286, and 285 (R = Me) goes to 287 because the C2 position is occupied. Protonation of 286 with triflic acid occurs at position 3 of the heteroring to form the benzothienyl carbene complex 288, and deprotonation reverts it to 286. This kind of process is a rarity for the uncomplexed benzothiophenes (81AHC171). 

Due to the high a-C,H acidity in the alkoxyethylidene complexes 6 (e.g.,piCa=8 (R=Me)) [ 16], transformations via an enolate analog are possible and have been used to introduce additional functionality into the carbene side chain to access various Fischer carbene complexes [3]. The a,/J-unsaturated complex 8 could be obtained from 6 (R=Et) by an aldol-type condensation with benzaldehyde 7 in the presence of triethylamine and trimethylsilyl chloride (Scheme 2) [17]. This reaction proceeds completely diastereoselectively to yield only the trans-isomer. Analogously, binuclear complexes have been prepared from 6 and 1,3-and 1,4-phthaldialdehyde in good yields [17]. This type of condensation has... 

A particular case of a [3C+2S] cycloaddition is that described by Sierra et al. related to the tail-to-tail dimerisation of alkynylcarbenes by reaction of these complexes with C8K (potassium graphite) at low temperature and further acid hydrolysis [69] (Scheme 24). In fact, this process should be considered as a [3C+2C] cycloaddition as two molecules of the carbene complex are involved in the reaction. Remarkable features of this reaction are (i) the formation of radical anion complexes by one-electron transfer from the potassium to the carbene complex, (ii) the tail-to-tail dimerisation to form a biscarbene anion intermediate and finally (iii) the protonation with a strong acid to produce the... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

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... 

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