Diazo precursors

Phloroglucinol is Hsted in the Colourindex as Cl Developer 19. It is particularly valuable in the dyeing of acetate fiber but also has been used as a coupler for azoic colors in viscose, Odon, cotton (qv), rayon, or nylon fibers, or in union fabrics containing these fibers (157). For example, cellulose acetate fabric is treated with an aromatic amine such as (9-dianisidine or a disperse dye such as A-hydroxyphenylazo-2-naphthylamine and the amine diazotizes on the fiber the fabric is then rinsed, freed of excess nitrite, and the azo color is developed in a phloroglucinol bath at pH 5—7. Depending on the diazo precursor used, intense blue to jet-black shades can be obtained with excellent light-, bleach-, and mbfastness. 

Whether these advances come from the study of zinc carbenoids, other organo-metallic sources, diazo precursors or as yet unrecognized sources of methylene transfer, it is our hope that this chapter will serve as a helpful starting point to guide future explorers of this fascinating landscape. 

The broad use of this rearrangement for thiepin synthesis has been demonstrated by its application in the preparation of thermolabile 3-benzo- and 1-benzothiepins. Thus, thermolabile ethyl 3-benzothiepin-2-carboxylate (5) can be generated from the diazo precursor by the action of a palladium catalyst at — 10°C and low temperature ( — 40°C) chromatography.5... 

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 presence of a two-electron donor ligand in the organometallic substrate that can be readily displaced by the CRR fragment of the diazo precursor is required. Alternatively, a coordinatively unsaturated species may be a suitable reactant. 

The exclusive and quantitative formation of oxepins upon Pd-catalyzed decomposition of 4-diazomethyl-4-methyl-4 //-pyrans (Entry 11) contrasts with the results of the CuCl-promoted reaction which affords a 2 1 mixture of oxepin (by 1,2-C migration) and 4-methylene-4//-pyran (by 1,2-H migration) under otherwise identical conditions 381J. When the methyl group at C-4 of the diazo precursor is replaced by H, the metal-catalyzed route to thiepins is no longer viable Pd- or Cu(I)-catalyzed decomposition of 4-diazomethyl-4//-thiopyrans invariably leads to 4-methylene-4H-thiopyrans 378 (Entry 10). Only the proton-catalyzed decomposition of these diazo compounds affords the desired thiepin, albeit in low yield 378). 

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. 

These reactions are covered in other chapters of Volume 11 (Chapters 11.06 and 11.07). This part deals only with examples which are in connection with other sections of this chapter. Additions of metallocarbenoids to unsaturated partners have been extensively studied. Most of the initial studies have involved the transition metal-catalyzed decomposition of cr-carbonyl diazo compounds.163,164 Three main reaction modes of metallocarbenoids derived from a-carbonyl diazo precursor are (i) addition to an unsaturated C-C bond (olefin or alkyne), (ii) C-H insertion, and (iii) formation of an ylid (carbonyl or onium).1 5 These reactions have been applied to the total synthesis of natural... 

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).

Pertinent Chemical Shifts (in ppm) and Coupling Constants (in Hz) for the Phosphinocarbenes and their Diazo Precursors... 

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... 

In a similar fashion, o-phenylenecarbenonitrene (47) was generated by photolysis of the azido-diazo precursor 47-DN (Scheme 10) and identified by IR spectroscopy with the help of calculations. Further irradiation caused a ring opening of carbenonitrene 47 to its isomer 48, which was formed as a mixture of Z,Z and E,E isomers. The same isomerization can be achieved thermally, and from the kinetic analysis in the temperature range 40-50 K, the activation energy was found to be 5.1 kcal/mol [108]. 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

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... 

Carbenoid sources other than those derived from diazo precursors for catalytic cyclopropanation reactions are currently limited. Inter- and intramolecular catalytic cyclopropanation using iodonium ylide have been reported. Simple olefins react with iodonium ylides of the type shown in equations 83 and 84, catalysed by copper catalysts, to give cyclopropane adducts in moderate yield127 128. In contrast to the intermolecular cyclopropanation, intramolecular cyclopropanation using iodonium ylides affords high yields of products (equations 85 and 86). The key intermediate 88 for the 3,5-cyclovitamin D ring A synthon 89 was prepared in 80% yield as a diastereomeric mixture (70 30) via intramolecular cyclopropanation from iodonium ylide 87 (equation 87)1 0. 

The best stereoselectivity can be obtained by combining the appropriate choice of diazo precursor, alkene and catalyst. More recent work has provided some good examples where stereoselectivities up to 95% have been achieved (equations 116 and 126-128)I6, 7 M82. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

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. 

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