Diazo carbene precursors

Ifcobs is directly proportional to pyridine concentration. Therefore a plot of kobs vs. [pyridine] is linear, with a slope (k ) equal to the second order rate constant for ylide formation, and an intercept (k0) equal to the sum of all processes that destroy the carbene in the absence of pyridine (e.g.) intramolecular reactions, carbene dimerization, reactions with solvent, and, in the case of diazirine or diazo carbene precursors, azine formation. 

Clearly, rearrangements do occur in the excited states of diazirine and diazo carbene precursors. Kinetic studies of carbenic rearrangements need to consider the possible intervention of RIES when absolute rate constants are partitioned between competitive rearrangement pathways on the basis of product distributions.28... 

Certain transition metal complexes catalyze the decomposition of diazo compounds. The metal-bonded carbene intermediates behave differently from the free species generated via photolysis or thermolysis of the corresponding carbene precursor. The first catalytic asymmetric cyclopropanation reaction was reported in 1966 when Nozaki et al.93 showed that the cyclopropane compound trans- 182 was obtained as the major product from the cyclopropanation of styrene with diazoacetate with an ee value of 6% (Scheme 5-56). This reaction was effected by a copper(II) complex 181 that bears a salicyladimine ligand. 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

The non-nitrogenous carbene precursor (102) was used for the photochemical generation of the carbene (103) without complications due to reactions of diazirine or diazo species. In the presence of alkenes, carbene (103) gave rise to cyclopropanes and in the absence of alkenes was proposed to undergo [1,2]-C shift to form (104), which suffered retro-Diels-Alder reaction to give a triene. 

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. 

Throughout this chapter, we have almost always ignored the role of the carbene precursor. Carbenes are generally made from diazo compounds, or from a variety of surrogate diazo compounds including diazirines, tosylhydrazone salts, and aziridyl imines, all of which probably decompose through nonisolable diazo compounds. Not surprisingly, it turns out that diazo compounds have a rich chemistry of their own, especially when irradiated. Moreover, that chemistry often closely resembles the reactions of carbenes. Much of intramolecular carbene chemistry is, in fact, diazo compound chemistry. 

The reaction scheme to realize the coupling necessary to generate the persistent carbene precursor 122 is illustrated in Scheme 9.39. " Diazo groups are generally labile, and, hence, these groups are usually introduced at the last step of the... 

Linear and 2D branched poly(diarylcarbene) systems95 were much pursued as prototypical potential magnetic systems (Fig. 8). For example, Iwamura and coworkers developed synthetic methodologies to put many diazo sites (photochemical carbene precursor sites) into proper connectivity to photogenerate all or most of the carbene sites. Itoh and coworkers developed methods to obtain and analyze HS ESR spectra of polycarbenes and polycarbene ions.96 Although... 

Carbene precursors (a) Diazo compounds Diazocarbonyl derivatives... 

Recently, new photochemical carbene precursors which differed from diazo compounds and diazirines have been reported [62, 63], Platz et al. synthesized a photosensitive precursor 86 to phenylsulfanylcarbene 87 (Scheme 4.39) [62], The photolysis of 86 in the presence of 2,3-dimethyl-2-butene yielded the [2 +1] cycloadduct 88 in 80% yield. In contrast, Jenks et al. reported that S,C-ylides of malonates were photochemical precursors of carbene 90 [63]. Thus, the S,C-ylide 89 was irradiated at 254 nm in acetonitrile with 10% cyclohexene to give 91 in 44% yield (Scheme 4.40). 

In most of their reactions these ylides behave formally as carbene precursors. Iodonium ylides in this capacity have a resemblance to diazo compounds with which they often compare favourably. Many of their reactions proceed better under photochemical conditions. 

Human corticosteroid binding globulin (CBG) has been the target for photoaffinity labeling by the carbene precursor, [6,7-3H]-21-diazo-21-deoxycorticosterone (Compound V)... 

Dichlorocarbene is a typical singlet ground-state carbene which is commonly used for cydopropanation reactions, since it gives satisfactory yields in many cases, but in general, carbene synthesis implies a metal catalyst (usually copper) together with a diazo compound as the carbene precursor. In (he particular case of the O -H insertion reaction, sulfur dioxide has been reported as being an efficient catalyst for the insertion of carbalkoxycarbenes generated from diazoesters. 

The ester group in II is suggestive—although it is not a proof—of the intermediacy of a ketene, and ketene production in diazocarbonyl chemistry usually implies a Wolff rearrangement. The construction of a three-carbon chain on the other side of the ketone is a confirmation of this prediction. In turn, the Wolff rearrangement requires an a-keto carbene precursor that is the fate of diazo compounds exposed to ultraviolet light (wavelength lower than 3200 A). All this is translated into the mechanism depicted in Scheme 43.1. 

Free carbene 429 generated by photolysis or thermolysis of the diazo compound cyclizes into the sulfonium ylide, which undergoes a thia-Stevens rearrangement to 430 in 19% yield. The same result was obtained using the corresponding p-tosylhydrazone sodium salt as a carbene precursor (83JA6096). Rh(II)-catalyzed decomposition of sulfur-containing diazo... 

One of the most general approaches has already been mentioned and exemplified by equation 10.16. In this approach, diazoalkanes are used as free carbene precursors. These are photochemically or thermally decomposed to the free carbene, which reacts with a low-valent, mid- to late transition metal complex to give the alkylidene. Although general, this method suffers from the difficulty in handling often unstable diazo compounds. 

Monoaryldiazomethanes, readily prepared by a number of methods, are the carbene precursors most frequently used for the synthesis of arylcyclopropanes. When such diazo compounds are decomposed photochemically, thermally, or by using various transition-metal salts in the presence of an alkene, arylcyclopropanes are formed. The yield is often quite high, but in a number of cases cyclopropane formation has been hampered by competing reactions, of which, disregarding intramolecular reactions, azine formation, stilbene formation, and hydrogen abstraction followed by dimerization are the most predominant. Many aspects related to the use of diazomethane derivatives as carbene precursors have been thoroughly discussed by Wentrup. ... 

The majority of reactions using polycyclic aromatic diazo compounds as carbene precursors involve fluorenylidene itself, substituted fluorenylidenes and diazafluorenylidenes, but a handful of studies have also reported investigation of the reactivity of benzocycloheptenylidenes. Furthermore, there are some reports on the addition of other three-ring diarylcarbenes to C-C double bonds. In most cases, the decomposition of the diazo compounds has been carried out photochemically. 

The most versatile carbene precursors are a-diazocarbonyl compounds such as diazoacetic acid esters because they are readily prepared, easy to handle and much more stable than ordinary diazoalkanes [10,38]. Nevertheless, one should always be aware of the potential hazards of diazo compounds in general [39],but if the necessary precautions are taken, they can be safely handled even on an industrial scale [18]. The most frequently used reagent is commercially available ethyl diazoacetate. Besides a-diazocarbonyl reagents, diazomethane [40,41 ] and a y-diazoacrylate derivative [42] have been used in enantioselective Cu-cata-lyzed cyclopropanations but the scope of these reactions has not been studied systematically. It has been shown in certain cases that diazo compounds can be replaced by other carbene precursors such as iodonium ylides, sulfonium yUdes, or lithiated sulfones [8,43],but successful applications of these reagents in enantioselective Cu-catalyzed reactions have not been reported yet. 

The metal-carbene complex 8.8 may be called a carbene precursor in analogy to precursors in photolytic carbene formation from diazo compounds. 

Three-membered rings with two heteroatoms are usually encountered as reagents. Diazirines are useful carbene precursors - they are generally more stable that the equivalent isomeric diazo compounds, though they are sometimes explosive in the pure state. They can be prepared by oxidation of diaziridines which in turn are available via the condensation of a ketone or aldehyde with ammonia and chloramine. Chlorodiazirines, from the reaction of amidines with hypochlorite, will undergo Sn2 or Sn2 displacement reactions." ... 

In the 1950s and 1960s chemists learned how to generate carbenes from haloform, diazirine and diazo compound precursors as transient intermediates in solution. [1,5,6] The chemists of this era identified the products of carbene reactions and learned how to make these reactions synthetically useful. They postulated a framework for carbenes (Scheme 1) with ground or low lying triplet states which is still the starting point in all mechanistic discussions. 

Diazo compounds, precursors to carbenes, were prepared by the oxidation with active manganese(IV) oxide (or mercury(II) oxide) of the corresponding hydrazones which in turn were obtained from the corresponding ketones by the reaction with anhydrous hydrazine (or hydrazine monohydrate). This method was employed for the introduction of the diazo groups in most of our compounds... 

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