Carbenes diazo precursors

The electrophilic carbene carbon atom of Fischer carbene complexes is usually stabilised through 7i-donation of an alkoxy or amino substituent. This type of electronic stabilisation renders carbene complexes thermostable nevertheless, they have to be stored and handled under inert gas in order to avoid oxidative decomposition. In a typical benzannulation protocol, the carbene complex is reacted with a 10% excess of the alkyne at a temperature between 45 and 60 °C in an ethereal solvent. On the other hand, the non-stabilised and highly electrophilic diphenylcarbene pentacarbonylchromium complex needs to be stored and handled at temperatures below -20 °C, which allows one to carry out benzannulation reactions at room temperature [34]. Recently, the first syntheses of tricyclic carbene complexes derived from diazo precursors have been performed and applied to benzannulation [35a,b]. The reaction of the non-planar dibenzocycloheptenylidene complex 28 with 1-hexyne afforded the Cr(CO)3-coordinated tetracyclic benzannulation product 29 in a completely regio- and diastereoselective way [35c] (Scheme 18). 

It has been possible to record the IR and UV spectra of several derivatives of the carbene [75] - tetrachlorocyclopentadienylidene [80], indenylidene [81] and fluorenylidene [82] (Bell and Dunkin, 1985). These carbenes were formed by UV photolysis of the corresponding diazo precursors frozen in inert matrices and have a triplet ground state. The carbenes [80]-[82] react with CO in inert matrices at 30 K, but exhibit a lower reactivity than the carbene [75]. Furthermore, they were stabilized in a pure CO matrix at 12 K, whereas the free carbene [75] could not be detected under these conditions. The different reactivity towards CO between [75] and [80]-[82] may be associated with the different steric shielding of the carbene centres and with the different triplet-singlet gap as well. 

The only problem for the matrix-isolation of 21 consisted in the non-availability of a reasonable diazo precursor molecule suited for this technique. But since we already had experience with the preparation of 2,3-dihydrothiazol-2-ylidene46 (see below) by photofragmentation of thiazole-2-carboxylic acid we tried the same method with imidazole-2-carboxylic acid (20). Indeed, irradiation of 20 with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between carbene 21 and CO2. This is shown by the observation that the experimental IR spectrum fits only with the calculated spectrum of complex 21-CC>2 (calculated stabilization energy relative to its fragments 4.3 kcal mol-1). The type of fixation of CO2 to 21 is indicated in the formula S-21 C02. 

Table II lists all pertinent chemical shifts and coupling constants for the known phosphinocarbenes and their respective diazo precursors. The (phosphino)(silyl)carbenes are all characterized by high field chemical shifts for phosphorus ( 24 to 50 ppm) and silicon (-3 to -21 ppm), and low field chemical shifts for carbon (120 to 143 ppm) with large couplings to phosphorus (147 to 203 Hz).

Not much is known about the reactivity of the phosphinocarbene 2i. Problems arise, at least in part, from the high 1,3-dipolar reactivity of the diazo precursor li, which hides any carbene reactivity. Indeed, although li is stable in a toluene solution at 60°C for hours, the addition of an electron-poor olefin, such as a perfluoroalkyl-monosubstituted alkene, induces the exclusive formation of the thermodynamically more stable anti-isomer of the cyclopropane 14 (see Section V,B,3,a).36 This clearly demonstrates that the cyclopropanation reaction does not involve the carbene 2i, but that an initial [2 + 3]-cycloaddition occurs leading to the pyrazoline 13, which subsequently undergoes a classical N2 elimination.37... 

A variety of transition metal-carbene complexes have been prepared and characterized. None of these are known to efficiently effect intermolecular C-H insertion. An electrophilic iron carbcne complex can, however, participate in intramolecular C-H insertions (Section I.2.2.3.2.I.). More commonly, transition metal complexes are used to catalyze intramolecular C-H insertion starting with a diazo precursor. In these cases, the intermediate metal carbene complexes are not isolated. 

Since the discovery of the stable carbene la, many other (phosphino)(silyl) carbenes have been prepared, all of them using diazo precursors,but only a few of them are stable at room temperature. The silyl group at the carbene center can be replaced by an isoelectronic and isovalent phosphonio substituent without dramatic modibcation. Indeed, the stable (phosphino)(phosphonio)carbenes and were synthesized from the corresponding diazo precursors 2a and 2b... 

A disadvantage of diazo compounds is that they are quite polar, which endows them with a propensity to form dimers in the gas phase, even at concentrations as small as 1 5000. This feature becomes evident after their decomposition, which sometimes leads predominantly to carbene dimers (e.g., pentafulvalene in the case of diazocyclopentadiene" ), or adducts of the target carbene with its diazo precursor, as in the case of methylene, where the main products are CH2=NH and HCN." The problem disappears at very high guest/host ratios, but it is often impractical to achieve these. Fortunately, diazirines are less prone to dimerization in the gas phase. 

Highly electrophilic nitromethylenes [ CRN02 (R = H, CF3, COPh, C02R, CN, S02Ar)] are added to alkenes via Rh2 (OAc)4-catalyzed decomposition of the corresponding diazo precursors. The reaction works best with electron-rich, sterically undemanding alkenes (equation 106)225-227. The addition of chiral glycosylidene carbenes to electron-deficient... 

A number of appropriate diazo precursors have been subjected to tandem carbene cyclization-iso-munchnone intramolecular cycloaddition.129 Thus, (232a) was cyclized with rhodium acetate to provide a tricyclic tetrahydrofuran (232b) cyclized similarly and produced just one stereoisomer. 

When (trimethylsilyl)carbene (3a) is generated by photolysis of the diazo precursor 19 in an alcohol solution at room temperature, the rearrangement to the silene is so fast that only the addition products of the latter, but not the 0,H insertion product of the carbene, can be isolated (equation 4)34. The same holds true for photolysis in diethylamine38. 

The effect of ligands on the selectivity of carbenes generated by copper-catalyzed decomposition of diazo precursors has been recognized for a long time as proof of the participation of copper-carbene complexes (carbenoids) in these processes. 

The intramolecular O—H insertion reaction of a carbene has been successful in the synthesis of the oxygen-containing heterocycle 216 in quantitative yield (85JOC5223). Carbene generated by photolysis of diazo precursor 217 in protic solvents gives 2-phenyl-2,5-dihydroisobenzofuran competitively with insertion into the O —H bonds of the solvent (90JOC2325). 

The first case of an mrramolecular C-H carbenoid insertion was reported by Cane and Thomas in 1984 [12], with the special diazoacetate 17 forming the spirocyclic 5-lactone 18 in 45 % yield according to eq. (8). Doyle et al. recognized that this is a general methodology for the synthesis of y-butyrolactones [16], The reactivity of the C-H bond toward carbene insertion is increased in the vicinity of an ether functionality. Thus, the 3(2H)-furanone 20, as a useful building block in the total synthesis of (+)-muscarine, results in 40% yield from the diazo precursor compound 19 [17],... 

A range of (phosphino)(aryl)carbenes (20 R = i-Pr, c-hexyl V, W, X, Y, Z = various combinations of H, F, Me, CF3, NMe2) have been generated by photolysis of their diazo precursors. The substituent effects on carbene stability were investigated both experimentally and theoretically. The presence of an acceptor and also a spectator aryl substituent resulted in stable or at least persistent carbenes, which could be characterized by standard spectroscopic techniques, whereas a donor aryl ring produced a very fleeting carbene. 

Cycloalkenylidenes are most frequently generated by photolysis of the corresponding diazo precursors, and, in general, react as triplet carbenes. Thus, their [2 + 1] cycloadditions to Z-or -substituted alkenes can proceed with partial loss of configuration of the olefin (see Vol. El9b, pp793-803). 

Diazo precursors to organic carbenes can be induced to insert into relatively unactivated CH bonds by... 

Carbenes photogenerated from diazo precursors undergo proton transfer from alcohols to generate carbocations that are eventually trapped by nucleophiles [Eq. (11)] [106],... 

In spite of the fact that reactions of diazo compounds via carbenes are discussed in detail in Section 8.3 and later in this chapter, products formed from carbenes in general are summarized briefly here because the subject of Section 8.2 (dediazonia-tion mechanisms of diazo compounds to carbenes) is based to a significant extent on investigations of their reaction products. This short synopsis is mainly based on historically important investigations, although it also contains reactions in which the carbene or carbene-like precursor is not a diazo compound, but, for example, an alkyl halide. 

Inspection of Table 19 shows three carbene-carbenoid pairs, namely, CHPh, CHC1, and Ph C-Br. The most significant discrepancies exist in the reactivities of the intermediates formed from chlorodiazomethane and a-elimination on methylene chloride . The pronounced stereoselectivity observed in the a-elimination reaction giving rise to relatively large synlanti ratios is reduced to random addition when the halocarbenes are generated from the diazo precursors. The competition data with different olefins indicate that a considerably less reactive intermediate is formed in the a-elimination. 

Fluorodiazirines have also been used extensively as carbene photoprecursors for cryogenic matrix isolation " and laser flash photolysis studies. Photolysis of fluorophenoxydiazirine has made observation of the corresponding carbene directly observable in yet another fashion encapsulated in a hemicarcer-and. Diazirines have been used for studies in solution of carbene philicities as well as for synthesis of cyclopropanes and cyclopropenes.Of course, diazo compounds can also serve as carbene photoprecursors, but for carbenes such as difluorocarbene, the diazo precursor is either nonexistent or extremely unstable. 

---