Carbenes, diazirines

Most of the work concerning the modification of carbene reactivity has been performed on cyclodextrins (CD) with reactive alkyl carbenes. Diazirines have proven to be the most convenient precursors due to the small size of the three-membered ring and the volatility of the leaving group, molecular nitrogen. Diazirines are usually obtained from the corresponding ketone in two steps in a methanolic solution of ammonia, hydroxylamine-0-sulfonic acid (HOSA) is added yielding a diaziridine which then is oxidized to the diazirine, most conveniently with iodine. 

Diazirines are in most cases more easily available than linear diazo compounds. Moreover, their decomposition via true carbenes is free of side reactions, whereas linear diazo compounds in presence of H-donors may react by a cationic pathway. Only where reactions of linear diazo compounds are optimized for carbene formation do they give the same products as do decomposing diazirines. 

Two other fluorine-containing diazirines give similar results. Cyanofluorodiazirine (223) and fluoromethoxydiazirine (224) release nitrogen at 100 °C the carbenes formed can be trapped by tetrafluoroethylene to give cyclopropanes (65JHC371). Without a carbene trap alkenes are obtained. 

The same dichotomy was observed with hexafluorodimethylcarbene (228), formed by thermolysis of diazirine (227) at 150 °C. The carbene (228) can stabilize itself either intramolecularly to perfluoropropene (229), or intermolecularly by addition to multiple bonds. Oxirane (230) is formed with hexafluoroacetone, cyclopropene (231) with 2-butyne (66MI50800). 

Photolysis of dlazirines to nitrogen and carbenes is a general reaction and plays a greater role in carbene chemistry than photolysis of linear diazo compounds. Whereas the latter are often obtained only under the conditions of their thermal decomposition from suitable precursors, diazirines are obtainable in a pure state in most cases. Photolysis has the further advantage to permit nitrogen extrusion at atmospheric pressure, even with low-boiling materials. 

An extrapolation of product composition to zero pressure showed considerable but not complete absence of primary products. A second path to the primary products was assumed, leading from excited diazirine directly to the products without involving a carbene. 

In another experiment tritiated adamantane diazirine fixed to the hydrocarbon core of a membrane gave rise to carbene insertion into the catalytic subunit of ATP-ase. After protolytic degradation adjacent areas of the original structure became evident (80JBC(255)860). 

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... 

Substituted fluorocarbenes have been generated by several methods, but organometallic transfer reagents again are most useful synthetieally [64, 65, 66, 67, 68] (equations 25-27) Diazirines cleanly produce carbenes thermally [69, 71] or... 

Preliminary investigations on the formation of carbenes from diazirines have already been made available. Frey and Stevens recently reported the photolysis of cyclic diazomethane. Cyclic diazomethane was irradiated in the gaseous phase with light of wavelength... 

Halogen exchange of F is usually with chloro compounds however, replacement of bromine has enabled fluorodiazirines to be obtained (83JA6513 86TL419). Diazirine (2) was previously obtained by a difficult route involving F2. The relative ease of access to (2) enables a carbene whose reactivity is intermediate between that of electrophilic ( CF2) and nucleophilic ( C(OMe)2) carbenes to be studied. 

Diazirines (isomeric with diazoalkanes) also give carbenes ... 

During photolysis of [29] in an argon matrix doped with 4% CO, bands belonging to the ketene [31] were observed along with those of the carbene [30], Upon further warming to 40-45 K the carbene bands disappeared and were replaced with bands of the ketene [31], indicating a direct interaction of carbene (CF3)2C with CO. Photolysis of diazirine [29] in a matrix doped with 17% CO resulted in the appearance of only ketene [31] bands the carbene bands were not detected in this experiment. 

As was mentioned above, bis(trifluoromethyl)carbene [30] was not detected in matrix IR spectra of the products formed upon vacuum pyrolysis (500-1000°C, 10 Torr) of diazirine [29] or perfluoropropylene. 

Singlet halo(trifluoromethyl)carbenes [33a]-[33c], which were characterized by IR and UV spectroscopies and chemical trapping with HCl, have been generated from respective 3-halo-3-(trifluoromethyl)diazirines [34a]-[34c] frozen in an argon matrix at 12 K and irradiated with UV light at... 

In all cases the formation of carbenes was accompanied by partial photoisomerization of the precursor diazirines [53] into the corresponding diazo compounds [55] which possess a higher photochemical stability than the diazirines. 

The observed TRIR data are consistent with Scheme 4.1. Depletion of the diazirine and formation of the carbene occurs within the time resolution (50 ns) of the experiment. Subsequent decay of the carbene (J osbd = 3.0 X 10 s ) is observed at the same rate within experimental error ( 10%) that the a-lactone is produced ( osbd = 3.2 X 10 s ) and the final decay of the a-lactone (A bsd = 2.0 X 10 s ) occurs at the same rate as the acid chloride product is formed (A sbd = 1-8 X 10 s ). The position of the a-lactone band at 1910 cm is clearly indicative of ring-closed form 1 and in very good agreement with the signal observed at 10 K (1920 cm ) by Sander and co-workers. ... 

Finally, in some cases diradical negative ions can even be generated directly npon ionization of appropriate precnrsors. For example, nitrene and carbene anions can be formed by El of organic azides, diazo-compounds, and diazirines, whereas Branman and co-workers have reported the formation of oxyallyl anions by El of flnorinated acetyl componnds (Eq. 5.12). ... 

The conformational disorder and packing structure of diazirine 91N2 is shown on the left of Scheme 7.25. The formation of azine 92 can easily be explained by the head-to-head crystallization of the chloro-diazirine, which experiences close N---C1 interactions that ultimately bring the carbene carbon close to the diazirine nitrogen... 

Photolysis of diazirine 75 in N2 at 9 K produced carbene 76, whose IR and UV/Vis spectra fit predictions by DFT calculations. The IR spectra were most consistent with a carbene conformation with Cl aligned 90° to the adjacent C-CH bond. The carbene was found, by IR spectroscopy, to rearrange to chloroadamantene 77 slowly at 9 K in the dark. The rate of rearrangement was somewhat faster in Ar matrices at 9 K or at higher temperatures in N2. 

Diazirine is a cyclic isomer of diazomethane. According to the organometallic literature, scission of both C-N and N-N bonds can occur when diazirines interact with metal complexes. The formation of carbene ligands arises from selective cleavage of the C-N bond, whereas selective N-N bond scission results in the formation... 

Photoelimination of nitrogen from diazirines, for example, proceeds via carbene intermediates. 3-tert-Butyldiazirine (395) is converted into the cyclopropane 396 and the alkene 397 with the formation of the carbene insertion product being favored from the singlet state.328 3-Cyclopropyl-3-chlorodiazirine (398) has similarly been converted to the carbene 399 which undergoes both rearrangement to l-chlorocyclobutene(400)329 and addition... 

Some diazirines, particularly the 3-trifluoromethyl-3-aryldiazirines, can rearrange upon photolysis to a linear diazo derivative, similar in structure to the photosensitive end of the crosslinker PNP-DTP (Chapter 5, Section 3.12). These isomerized products themselves can be photolyzed to the reactive carbene. 

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