Carbene addition formation

Another means of in situ metal-carbene complex formation in an ionic liquid is the direct oxidative addition of the imidazolium cation to a metal center in a low oxidation state (see Scheme 5.2-2, route b)). Cavell and co-workers have observed oxidative addition on heating 1,3-dimethylimidazolium tetrafluoroborate with Pt(PPli3)4 in refluxing THF [32]. The Pt-carbene complex formed can decompose by reductive elimination. Winterton et al. have also described the formation of a Pt-car-bene complex by oxidative addition of the [EMIM] cation to PtCl2 in a basic [EMIM]C1/A1C13 system (free CP ions present) under ethylene pressure [33]. The formation of a Pt-carbene complex by oxidative addition of the imidazolium cation is displayed in Scheme 5.2-4. 

Metal-Catalyzed. Cyclopropanation. Carbene addition reactions can be catalyzed by several transition metal complexes. Most of the synthetic work has been done using copper or rhodium complexes and we focus on these. The copper-catalyzed decomposition of diazo compounds is a useful reaction for formation of substituted cyclopropanes.188 The reaction has been carried out with several copper salts,189 and both Cu(I) and Cu(II) triflate are useful.190 Several Cu(II)salen complexes, such as the (V-f-butyl derivative, which is called Cu(TBS)2, have become popular catalysts.191... 

Section D illustrates formation of carbenes from halides by a-elimination. The carbene precursors are formed either by deprotonation (Entries 14 and 17) or halogen-metal exchange (Entries 15 and 16). The carbene additions can take place at low temperature. Entry 17 is an example of generation of dichlorocarbene from chloroform under phase transfer conditions. 

Metallacycle Formation Involving Electrophilic Carbene Addition to a Benzene Ring of the PPh3 Ligand... 

An alternative to the synthesis of epoxides is the reaction of sulfur ylide with aldehydes and ketones.107 This is a carbon-carbon bond formation reaction and may offer a method complementary to the oxidative processes described thus far. The formation of sulfur ylide involves a chiral sulfide and a carbene or carbenoid, and the general reaction procedure for epoxidation of aldehydes may involve the application of a sulfide, an aldehyde, or a carbene precursor as well as a copper salt. This reaction may also be considered as a thiol acetal-mediated carbene addition to carbonyl groups in the aldehyde. 

These cycloadditions lead to the formation of three membered rings commonly seen in the carbene addition to double bonds. 

When 2,2-dichloro-3-phenylpropanal 203 is subjected to standard reaction conditions with chiral triazolium salt 75c, the desired amide is produced in 80% ee and 62% yield Eq. 20. This experiment suggests that the catalyst is involved in an enantioselec-tive protonation event. With this evidence in hand, the proposed mechanism begins with carbene addition to the a-reducible aldehyde followed by formation of activated car-boxylate XLII (Scheme 32). Acyl transfer occurs with HOAt, presumably due to its higher kinetic nucleophilicity under these conditions, thus regenerating the carbene. In turn, intermediate XLin then undergoes nucleophilic attack by the amine and releases the co-catalyst back into the catalytic cycle. 

Intramolecular carbene addition reactions have a special importance in the synthesis of strained ring compounds. Because of the high reactivity of carbene or carbenoid species, the formation of highly strained bonds is possible. The strategy for synthesis is to construct a potential carbene precursor, such as diazo compounds or di- or trihalo compounds, which can undergo intramolecular addition to the desired structure. Section E of Scheme 10.5 gives some representative examples. 

Carbene addition to C70 results in the formation of different monoadduct isomers [386]. Treatment with PhHgCCl2Br in reflmdng benzene produces a mixture of three isomers derived from addition to the C-l/C-2-bond, the C-5/C-6-bond and the C-7/C-8-bond in almost equimolar amoimts. Contrary to this result, addition of trichloroacetate yields almost exclusively the C-5/C-6-product [386]. 

Reactions of Cjq with metal carbene complexes also yield the [6,6] methano-fullerenes [392]. These adducts are probably not formed via a carbene addition, but via a formal [2-1-2] cycloaddition under formation of a metalla cyclobutane intermediate. The Fischer carbene complex [mefhyl(methoxymethylene)]pentacarbonyl chromium can be utilized to prepare l,2-mefhyl(methoxymethano)-fullerene in 20% yield [392]. A tungsten carbene complex was primarily used to initiate the formation of a polyacetylene polymer, but it was discovered that addition of to the complex-polymer-mixture improves the polymerization and dramatically increases the catalytic activity of the carbene complex [393]. can be integrated into the polymer via carbene addition. 

The most generally employed approach for the formation of cyclopropanes is the addition of a carbene or carbenoid to an alkene. In many cases, a free carbene is not involved as an actual intermediate, but instead the net, overall transformation of an alkene to a cyclopropane corresponds, in at least a formal sense, to carbene addition. In turn, the most traditional method for effecting these reactions is to employ diazo compounds, R R2 —N2, as precursors. Thermal, photochemical and metal-catalyzed reactions of these diazo compounds have been studied thoroughly and are treated separately in the discussion below. These reactions have been subjects of several comprehensive reviews,8 to which the reader is referred for further details and literature citations. Emphasis in the present chapter is placed on recent examples. 

Diazocarbonyl compounds, especially diazo ketones and diazo esters [19], are the most suitable substrates for metal carbene transformations catalyzed by Cu or Rh compounds. Diazoalkanes are less useful owing to more pronounced carbene dimer formation that competes with, for example, cyclopropanation [7]. This competing reaction occurs by electrophilic addition of the metal-stabilized carbocation to the diazo compound followed by dinitrogen loss and formation of the alkene product that occurs with regeneration of the catalytically active metal complex (Eq. 5.5) [201. 

As with the Aratani catalysts, enantioselectivities for cyclopropane formation with 4 and 5 are responsive to the steric bulk of the diazo ester, are higher for the trans isomer than for the cis form, and are influenced by the absolute configuration of a chiral diazo ester (d- and 1-menthyl diazoacetate), although not to the same degree as reported for 2 in Tables 5.1 and 5.2. 1,3-Butadiene and 4-methyl- 1,3-pentadiene, whose higher reactivities for metal carbene addition result in higher product yields than do terminal alkenes, form cyclopropane products with 97% ee in reactions with d-men thy 1 diazoacetate (Eq. 5.8). Regiocontrol is complete, but diastereocontrol (trans cis selectivity) is only moderate. 

Chiral Rh(II) oxazolidinones Rh2(BNOX)4 and Rh2(IPOX)4 (25a,b) were not as effective as Rh2(MEPY)4 for enantioselective intramolecular cyclopropanation, even though the steric bulk of their chiral ligand attachments (COOMe versus i-Pr or CH2Ph) are similar. Significantly lower yields and lower enantioselectivides resulted from dinitrogen extrusion from prenyl diazoacetate catalyzed by either Rh2(4.S -lPOX)4 or Rh2(4S-BNOX)4. This difference, and those associated with butenolide formation [91], can be attributed to the ability of the carboxylate substituents to stabilize the carbocation form of the intermediate metal carbene (3b), thus limiting the Rh2(MEPY)4-catalyzed reaction to concerted carbene addition onto both carbon atoms of the C-C double bond. 

The differences in deuterium and carbon isotope effects indicate the asymmetric transition state with more advanced carbon-carbon bond formation to the terminal Cl atom. The difference between deuterium isotope effects for HCI-S and Htmns hydrogens probably originates from experimental uncertainty. Theoretical calculations (B3LYP/6-31G, B3LYP/6-311+G ) for carbene addition to 1-butene were carried out for two modes with carbene approaching carbon atom Cl or C2. The best agreement for experimental isotope effects is for carbene attack on terminal carbon atom and the carbene-alkene separation in the transition state of 2.5 A. 

A few specific examples of cyclopropanation using the above methods are shown in Scheme 2.134. The naturally occurring insecticide /ra -chrisanthemic acid 396 served as an obvious target to check the viability of carbene addition as a preparative method. This compound was first synthesized (in the mixture with the cis isomer) by the monocyclopropanation of 2,5-dimethyl-2,4-hexadiene. Since then, numerous analogs of 396 were prepared by similar reactions. Some of the analogs are now widely used as efficient and ecologically safe pesticides. The formation of the tricyclic hydrocarbon 397 from 1,5-hexadiene proceeds as a sequence of inter- and intramolecular carbene transfer reactions. An initial carbene precursor, CHBr3, is actually employed here as an equivalent of a unique tetradentate Ci synthon The preparation of 398 via intramolecular [2 + 1] photocycloaddition is a typical example of the efficiency of this route for the construction of the polycyclic framework frequently encountered in the structures of natural compounds. 

The first reference to the formation of thiophenium ylids by carbene addition to thiophene appeared in 1972, when Durr and co-workers noted that pyrolysis of diazotetraphenylcyclopentadiene in thiophene resulted in a low yield of the ylid 14, although no information on the yield of the reaction or the physical or spectroscopic properties of 14 were given (72TL1257). 

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