Carbenes, formyl

Very few reactions of carbenes with heterocyclic systems containing more than one hetero atom have been studied. They are confined to variants of the Reimer-Tiemann formylation of thiazoles, pyra-zoles, iminazoles, and indolizines/ and ring expansion does not appear to have been observed. 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

The preparative value of this compound lies in the surprising fact that bis(l,3-diphenylimidazolidinylidenc-2) behaves in many reactions ie.g., with aromatic aldehydes,2,7 and with carbon acids 2 7-fJ) as if it dissociated to form a nucleophilic carbene. The hydrolytic cleavage of these derived imidazolidine derivatives makes possible the preparation of formyl compounds, so that the amino olefin can be considered as a potential carbonyla-tion reagent. In many reactions it is not necessary to isolate... 

For a review of carbene methods for introducing formyl and acyl groups into organic molecules, see Kulinkovich, O.G. Russ. Chem. Rev., 1989, 58, 711. 

Abstract This chapter focuses on carbon monoxide as a reagent in M-NHC catalysed reactions. The most important and popular of these reactions is hydro-formylation. Unfortunately, uncertainty exists as to the identity of the active catalyst and whether the NHC is bound to the catalyst in a number of the reported reactions. Mixed bidentate NHC complexes and cobalt-based complexes provide for better stability of the catalyst. Catalysts used for hydroaminomethylation and carbonyla-tion reactions show promise to rival traditional phosphine-based catalysts. Reports of decarbonylation are scarce, but the potential strength of the M-NHC bond is conducive to the harsh conditions required. This report will highlight, where appropriate, the potential benefits of exchanging traditional phosphorous ligands with iV-heterocyclic carbenes as well as cases where the role of the NHC might need re-evaluation. A review by the author on this topic has recently appeared [1]. 

Of interest is the fact that the H2 required for the reduction of formyl to methoxide in reaction (73) is thought (428, 429) to come from a second zirconium moiety, ZrH2. The H2 reduction to coordinated hydroxymethyl in Eq. (72) could presumably go via a mononuclear H2M(CHO) intermediate, but such a reaction has not been demonstrated, nor has the final hydrogenolysis step via a presumed H2M(CH2OH) intermediate. Loss of water from this to give a carbene HM=CH2 (431, 432) followed by further reactions with H2 and CO, provides speculative pathways to higher hydrocarbons (417, 419a, 430, 433). 

To summarize briefly, our approach involves initial attack by a relatively nucleophilic metal hydride on coordinated CO. Such reactivity has been demonstrated repeatedly for main-group metal hydrides perhaps the most elegantly worked-out system involves CpRe(C0)2(N0)+ (Cp = Tl-C H ) which, under varying conditions, can be converted to an entire range of products containing CO at different stages of reduction, including formyl, carbene, hydroxymethyl and methyl species (Scheme l). Reactions lead-... 

The major product isolated from the reaction of secondary amines with dichloro-carbene the reaction under phase-transfer conditions is the A-formylamine [12-14], The isolated yields are considerably higher (Table 7.14) than those recorded for classical procedures and are not inhibited by steric effects [15]. Diphenylamine is converted into its A-formyl derivative in low yield by conventional procedures and, although application of the phase-transfer catalysed procedure increases the yields, the E- and Z-l,2-bis(diphenylamino)-l,2-dichloroethenes are also obtained as byproducts of the reaction [13],... 

It is reasonable to assume that the initial step in the cycloaddition reaction is an electrophilic attack by the carbene on the nitrogen atom to form the A -ylid. Where proton shift is possible, cyclization does not occur and the A-ylid produces the N-formyl compound (Scheme 7.30) [36]. 

CO formation on copper electrodes appears to be accompanied by hydride formation as well [103]. In Sch. 3, the surface bound CO is reduced by a hydride transfer reaction to form a formyl species as shown in step 2. There are precedents in organometallic chemistry for late transition metal hydrides reducing bound CO [105-109]. Protonation of the adsorbed formyl in step 3 results in the formation of a hydroxy carbene species [110, 111]. This hydroxycarbene species could be considered to be an adsorbed and rearranged form of formaldehyde, and the reduction of formaldehyde at a copper electrode has been reported to form hydrocarbons [102]. However, reduction of... 

As shown in Figures 1.6b,c, Z and 44C substituents either lower the 2p-spn gap or leave it about the same. In either case, the ground state for Z- or 44C -substituted carbenes is expected to be T. See recent investigations of phenyl carbene, C6H5CH, [164] ethynyl carbene, HC=C—CH [165] carboxylate-substituted carbenes, R—C—C02R [166] and formyl carbene, H—C—C(0)H [167]. 

Possible routes (i) hydrolysis of thioformyl or similar derivative (ii) dealkylation of M=CHOR carbenes Scheme 1. Some synthetic approaches to transition metal formyl complexes. 

Scheme 113 Chiral /V-heterocyclic carbene-catalyzed kinetic resolution of cw-4-formyl-...

Li and coworkers have previously found that in the presence of an /V-hetero-cyclic carbene catalyst m-4-formyl-(3-lactams underwent the ring expansion reaction to afford succinimide derivatives [242]. More recently, they reported the kinetic resolution version of this transformation attempted with a chiral /V-heterocyclic carbene (Scheme 113), leading to m-4-formyl-(3-lactams with moderate ee of 64% [243]. 

Scheme 61, yielded thiazole 200 as the major product, along with minor amounts of carbinol 201 [152]. On the other hand, treatment of the imine formed from 199 and p-methoxyphenylamine with catalytic tetrabutylammonium cyanide, produced suc-cinimide derivative 202. In both cases, the process is initiated by nucleophilic attack to the carbaldehyde C=0 (or azomethine s C=N) group, which is followed up by an anionic rearrangement. A variation of the above process using as catalysts /V-heterocyclic carbenes (NHC) derived from base treatment of azolium, imidazo-lium, or triazolium salts, has also been developed to access gem-disubstituted succinimides [153, 154]. Unfortunately, an attempt of kinetic resolution of racemic 4-formyl (3-lactams by using chiral NHC resulted in moderate selectivities only [154]. 

Pyrolysis of Meldrum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione) 362 proceeds by loss of acetone and CO2 to give ketene. Because of the ready availability of the starting material and the ease with which it can be functionalized at the acidic 5-position, pyrolysis of Meldrum s acid derivatives has been widely studied. Pyrolysis of the 5-formyl and 5-acyl derivatives 363 gives formyl or acylketenes 364, which can be trapped in a number of ways170-171. in many cases, loss of acetone and CO2 is accompanied by loss of CO to give a carbene, and this is illustrated by FVP of 365 at 560 °C which affords the Q -diketone 368 by way of ketene 366 and carbene 367172. 

Formamides are usually not deprotonated a to nitrogen but at the formyl group [227-231], The resulting carbamoyl lithium derivatives (R2NCOLi), which can also be generated from deprotonated amines [351] or amides [352] and carbon monoxide, react with electrophiles E+ to yield the expected products (R2NCOE), despite the carbene character and consequent low stability of these intermediates [179, 351] (Scheme 5.39, see Section 5.4.7). Palladium-catalyzed versions of the reaction have been reported [353, 354],... 

Hilf, C. Bosold, F. Harms, K. Lohrenz, J. C. W. Marsch, M. Schimeczek, M. Boche, G. Carbene structure of stable acyl (formyl) anion equivalents. Chem. Ber. 1997, 130,1201-1212. 

Azahomoadamantane derivatives are known as potential biologically active compounds and several synthetic routes to this skeleton have been reported.113 The reaction of 5-methyl-4-azahomoadamant-4-ene (211) with dichlorocarbene resulted in the formation of 4-formyl-5-methylene-4-azahomoadamantane (214) in 66% yield.114 The isolation of this material is consistent with a mechanism involving carbene addi-... 

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