Diazirines carbene precursors

Diazirines, carbene precursors, have slowly gained in importance since Smith and Knowles (1973, 1975) first made 3-H-3-aryIdiazirines and suggested that they would make useful reagents. Three useful classes of diazirines are given in Table 3.1. 

Diazirine, fluoromethoxy-nitrogen extrusion, 7, 224 Diazirine, methylvinyl-rearrangement, 7, 221 Diazirines addition reactions to Grignard compounds, 7, 2 0 as carbene precursors, 7, 236 IR spectra, 7, 203 microwave spectrum, 7, 199 molecular spectra, 7, 202-204 nitrogen extrusion, 7, 223 NMR, 7, 202 photoconversion to diazoalkanes, 7, 234 photoisomerization, 7, 221 photolysis, 7, 225-227 quantum chemical investigations, 7, 197 reactions... 

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. 

Knowledge of the intramolecular product distribution may allow for the partitioning of k between competitive intramolecular reactions, but one must be certain that noncarbenic routes to the products do not compete with the carbenic pathways. In particular, we must be concerned with the possible intervention of RIES (cf. Section m.C), especially when diazirines or diazoalkanes are the carbene precursors. Again, corrections for RIES can be made to quantitate the carbenic routes see, for example, the discussion of the cyclobutylhalocarbene rearrangements (Section m.C.1). 

Additional evidence for a second intermediate in supposed carbene reactions comes from numerous studies.17-29 In the earliest experimental approach, the carbene precursor, frequently a diazirine, was photolyzed in the presence of increasing quantities of an alkene, which trapped the carbene with the formation of a cyclopropane (5 in Scheme 1). If carbene 2 were the sole product-forming intermediate, as depicted in Scheme 1, then the ratio of its alkene addition product (5) to its 1,2-H shift rearrangement product (4) would vary linearly with alkene concentration Eq. 9. 

In the absence of direct evidence for CACs other second intermediates have been proposed to rationalize the curvature observed in correlations of addn/rearr vs. [alkene], A particularly viable candidate is an excited state (or species derived therefrom) of the carbene precursor, a suggestion that is quite apposite when the precursor is a photolytically decomposed diazirine. 

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... 

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. 

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. 

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). 

A similar method has been used to synthesize spirocyclic glycosyl diaziridines and diazirines (e.g., 66 and 67), which are used as glycosylidene carbene precursors. The diaziridine is made by reaction of the sulfonylated oxime 65 with ammonia, followed by oxidation to the diazirine with iodine (Scheme 23). 

Two examples of the applicability of anomeric carbenes were reported by VaseUa et al. [167,168]. The first demonstrated the utility of olefinic substrates such as Al-phenylmaleimide, acrylonitrile and dimethylmaleate for the formation of glycosidic cyclopropanes. The carbene precursor in this example was the glucose-derived diazirine. As shown in Scheme 7.55, the use of dimethylmaleate produced a mixture of diastereomers with a combined yield of 72%. Although not presented as a schematic, the second and more dramatic example was used to functionalize fullerenes. 

With the intent to selectively derivatize CyD oligosaccharides,80 Abelt enlisted nitrogenous carbene precursors as labile guests.81 The involvement of supramolecular carbenes could be inferred based on intramolecular products stemming from 1,2-H shifts. Of course, 3//-diazirines that possess a-C-H bonds, like 3-methyl-3-phenyl-3//-diazirine (6) (Scheme 2), are susceptible to rearrangements in the excited state (RIES) that mimic the results of carbene 1,2-H shifts,82 e.g., 6 —>10 (Scheme 2). 

The main challenge was to imbue CyDs and FAUs with a carbene precursor that is compatible with the hosts and the standard IC preparation. The sodium salt 49 must be kept moisture-free and, therefore, is incompatible with CyDs and FAUs, since both contain adventitious water molecules. Besides, CyD ICs are prepared from aqueous solutions Likewise, FAU ICs are prepared by loading the zeolite with a pentane solution of the guest salt 49 is insoluble in pentane. Therefore, a 3/7-diazirine,132 the previously unknown 3-azinortricyclane (3-azitricyclo[2.2.1.02,6]heptane, 45),133 was again needed as a precursor134 in lieu of the unsuitable Bamford-Stevens reagent 49. Products formed during the photolysis of diazirine 45 were initially assumed to stem from carbene 46 (Scheme 11). 

Generation of Alkyl and Cycloalkyl Carbenes - Photolysis or thermolysis of a series of alkylchlorodiazirines (16) (Scheme 7) in the presence of alkenes, such as tetramethylethene, results in 1,2-H shifts, giving the corresponding vinyl chorides (18), in competition with additions of the carbenes (17) to the alkenes, yielding cyclopropanes (19). The mechanism of these reactions is discussed in the light of results obtained from photoacoustic calorimetry, and the ratio of vinyl chloride to cyclopropane seems to depend on the excited states of the carbene precursors and also on carbene-alkene complexes. Similar reactions of related diazirines have been investigated by flash photolysis. 

So far, however, the attractive potentialities of diazirines to act as carbene precursors have not been exploited to the full. In the steroid field, ketones have been transformed to olefins via diazirines 172 yielded the A -compound preferentially. Pyrolysis of spirodiazirine 173 at 320°C yielded 96% dehydroadamantane 174. ... 

Diazirine was used as the carbene precursor in an experiment to make diazomethane from methylene and nitrogen in the gas phase. As shown by means of labeled nitrogen, there was 4% diazomethane formation. During the past 10 years thermal as well as photochemical decomposition of 3-chloro- and 3-bromodiazirine has been investigated in detail. Compounds 175 and 176 as well as analogous compounds are easily obtained by reaction of amidines with hypohalites according to Graham. ... 

Diazirine was used as the carbene precursor in an experiment to make diazomethane from methylene and nitrogen in the gas phase. As shown by means of labeled nitrogen, there was 4% diazomethane formation.185... 

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." ... 

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