Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

The sensitized photoexcitation of 2-diazocyclopentane-1,3-diones in the presence of THF leads to the insertion of the terminal N-atom of the diazo group into the α-С–Н bond of THF, producing the associated N-alkylhydrazones in yields of up to 63–71%. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products with up to 90–97% yield.

Recently a new light-induced reaction of diazo compounds with retention of the diazo group nitrogen atoms in the structure of the reaction products was discovered by our group.The sensitized photoexcitation of heterocyclic diazoketones -diazotetrahydrofuranones resulted in the formation of N-alkyl-substituted hydrazones and other nitrogen-containing compounds [27- 30].This photochemical process is assumed to proceed through the triplet excited states of diazoketones via 'insertion' of the terminal nitrogen atom of the diazo group into the С-Н bond of the organic substrates [27,30].
Hence it was principally demonstrated that by carefully varying the irradiation conditions one can direct the photochemical reaction of diazo compounds at the alternative way, which provides the retention of 'dinitrogen' in the structure of molecule formed.It is reasonable that a question arises on the scope and limitations of this new light-induced reaction of diazo compounds.
The main objective of our current research was to elucidate the possibility of using carbocyclic diazodiketones in this photochemical process.For this purpose, diazocyclopentanediones 1a-g were tested in the study including unsubstituted diazocyclopentanedione 1a, tricyclic diazodiketones 1b-e with CH 2and O-bridges in their structure, diazoindandione 1f, diazocyclopentenedione 1g, and as a С-Н donor tetrahydrofuran was employed in the study (Figure 1).
To determine the most efficient conditions for this reaction with diazodiketones 1, three sensitizers, acetophenone, benzophenone, and Michler's ketone, with different levels of triplet state energy were tested.Furthermore, to clearly demonstrate the difference of light-induced reactions of diazo compounds 1 in the triplet and singlet excited states, the direct photolysis of diazodiketones 1a-c without sensitizers was also examined.
Analysis of the UV spectra of diazodiketones 1 shows that they have four absorption bands: two intense ones at 216-222 and 248-250 nm, and two bands with very week intensities at 311-316 nm (215 < ε < 290) and 363-367 nm (30 < ε < 49) (see Supporting Information File 1, Table S1).By analogy with the literature data [40], the absorption bands in the short wavelength region (216-250 nm) are attributed to π-π* electronic transitions, whereas the long wavelength bands are most likely caused by n-π* transitions.Based on the position of the long wavelength bands (363-367 nm) the energy of the singlet excited state 1 S 1 of diazodiketones 1 can be estimated at about 78-79 kcal/mol [41].
The characteristics of the absorption bands of the sensitizers used in this study (acetophenone, benzophenone and Michler's ketone) demonstrate that they show appropriate absorption of the actinic light at the irradiation conditions of diazodiketones 1 (Supporting Information File 1, Table S2).
The irradiation of tricyclic diazodiketone 1b in the presence of 1 equiv of benzophenone in THF solution led to the formation of hydrazone 2b in a yield of 32% (Table 1, entry 4), whose structure was unambiguously established by X-ray analysis (Figure 2).To increase the yields of hydrazones 2, an effort was undertaken to optimize the photochemical reaction conditions by varying the wavelength of irradiation, sensitizer, as well as the ratio of sensitizer/diazodiketone 1b (Table 1, entries 4-9).
As can be seen from the data in Table 1 the most effective sensitizer for the light-induced reaction studied in the series of acetophenone, benzophenone, and Michler's ketone was found to be benzophenone.The application of acetophenone reduced the yield of hydrazone 2b by about 1/4 as compared to benzophenone (from 52 to 40%; Table 1, entries 6 and 8).With Michler's ketone, a complex product mixture was obtained, from which it was impossible to isolate pure compounds.
When varying the ratio of sensitizer/diazodiketone 1b, the best result was obtained with a 10-fold excess of benzophenone (Table 1, entry 7; 71% yield).Application of a 4-fold excess of this sensitizer diminished the yield of hydrazone 2b to 52% (Table 1, entry 6).In going from short wavelength (λ > 210 nm) to longer wavelength (λ > 310 nm) irradiation, the yield of hydrazone 2b remained practically unchanged, however the reaction time considerably increased from 1.3 to 6.5 h; Table 1, entries 4 and 5).
The reactions of tricyclic diazodiketone 1c and diazoindandione 1f in the presence of benzophenone as sensitizer proceeded in a similar way to diazo compound 1b under the Scheme 1: Photochemical cycloelimination of furans from hydrazones 2d,e.optimal conditions affording hydrazones 2c,f in yields of 63 and 52%, respectively (Table 1, entries 10 and 13).
Additional experiments showed that hydrazone 3 was not formed on sensitized photoexcitation of diazocyclopentenedione 1g in the presence of the C-H-donor THF (Scheme 1).
Thus one can conclude that product 3 is generated by a light-induced cycloelimination of furan from the initially generated tricyclic hydrazones 2d,e.
Hence it was established that the sensitized photoexcitation of diazodiketones 1a-d,f in THF solution proceeds through the insertion of the terminal N-atom of the diazo group in the α-С-Н-bond of THF with the formation of the appropriate hydrazones 2a-d,f and the most effective sensitizer for this reaction was found to be benzophenone.The structure of 2-oxocyclobutanecarboxylic acid 4a and the methyl esters 5a-c was established by spectroscopic data ( 1 Н, 13 С NMR, and HRMS), and in case of 4a and 5a, also confirmed by comparison with the known literature data [46][47][48].
Scheme 2: Different pathways of diazodiketones 1 light-induced reactions in the singlet (reaction I) and triplet (reaction II) excited states.
It was found that 2-oxocyclobutanecarboxylic acid 4a and ester 5a were easily hydrolyzed in the presence of H 2 O or during chromatography on silica gel to produce glutaric acid and the corresponding methyl ester (Table 2).By contrast, esters 5b,c proved to be much more stable to hydrolysis on SiO 2 and in the presence of nucleophilic reagents.For example, when heating in boiling MeOH for 2 h no hydrolysis of ketoester 5с occurs according to 1 H NMR spectra.
The assumed ways for light-induced reactions of diazodiketones 1 can be represented as follows.The direct irradiation (λ > 210 nm) of diazodiketones 1 gives rise to accumulation of one of their upper singlet excited states On the other hand, the sensitized photoexcitation of diazodiketones 1 gives rise to generation of triplet excited states of diazo compounds 3 (1) 1 which interact with the H-donor (tetrahydrofuran) producing N-alkyl-substituted hydrazones 2 (Scheme 2, reaction II).Based on the comparison study of the sensitizers' efficiency in this reaction (Table 2) one can conclude [41,52], that the energy of the triplet excited states 3 T 1 of diazodiketones 1 are about 68 kcal/mol.This provides a possible explanation why the use of Michler's ketone was found to be ineffective as a photosensitizer in the process.The energy of the triplet excited state 3 T 1 of this sensitizer (64 kcal/mol) is somewhat lower than the corresponding energy of the diazodiketones 1 making it inadequate to initiate the C-H insertion reaction.
On the other hand, the triplet excited state energy of benzophenone (69 kcal/mol) renders it a suitable sensitizer for this reaction.
In the case of tricyclic diazodiketones 1d,f (with annulated furan and 2-methylfuran-motifs in their structures), a tandem photochemical process of C-H-insertion followed by cycloelimination of furan from the initially generated hydrazones 2d,f apparently occurs, giving rise to the formation of hydrazone 3 as the final reaction product (Scheme 1).

Conclusion
The sensitized photoexcitation of carbocyclic diazodiketones proceeds without elimination of dinitrogen.Instead, the reaction leads to the insertion of the terminal N-atom of the diazo group into the C-H bond of THF giving rise to the appropriate N-alkyl-substituted hydrazones in yields of up to 63-71%.The most powerful sensitizer for this light-induced process in the series of acetophenone, benzophenone and Michler's ketone was found to be benzophenone.Hence, the diazodicarbonyl compounds can be successfully used for a photochemical N-functionalization of C-H-bonds of organic compounds.In contrast to this, the direct photolysis of carbocyclic diazoketones produces exclusively Wolff rearrangement products in yields of 90-97%.

Experimental General methods
All reactions were carried out under argon atmosphere in solvents that were purified and dried before use by common methods.Monitoring of the reaction course was accomplished by thin layer chromatography (TLC) on silica gel SIL G/UV254 plates (Marcherey, Nagel & Co.).Chromatography was performed using Merck silica gel 60, 230-400 mesh. 1 H and 13 C NMR spectra were recorded using a Bruker-400 Avance NMR spectrometer.All HRMS spectra were recorded on a «MaXis» (Bruker Daltonik GmbH), the HPLC system (UHPLC) with the combined high-resolution quadrupole-timeof-flight mass spectrometer with electrospray ionization (ESI-QTOF).Chemical shifts are reported in ppm, and coupling constants are given in hertz (Hz).All signals in NMR spectra were normalized relative to signals of CНCl 3 (δ = 7.26 ppm in 1 H NMR) and CDCl 3 (δ = 77.0 in 13 C NMR spectra).
For single crystal X-ray diffraction experiments of 1c (CCDC 1584937) and 2b (CCDC 1584938) an Agilent Technologies «Xcalibur» diffractometer with monochromated MoKα radiation was used.All samples were measured at 100 K.The unit cell parameters were refined by least square techniques in CrysAlisPro (Agilent Technologies, 2012) program complex.Empirical absorption correction was applied using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.The structures were solved by the Superflip [56][57][58] and ShelXS [59] structure solution programs using Charge Flipping and Direct Methods, respectively, then refined by means of the ShelXL [60] program, incorporated in the Olex2 program package [61].

Sensitized reactions of diazodiketones 1a-g
General procedure.The solution of diazodiketone 1a-g (1 equiv) and benzophenone (up to 10 equiv) in THF (10-30 ml) was irradiated in a quartz reactor (λ > 210 nm) under an argon atmosphere for up to 6.5 h (control of the reacted diazodiketone 1 by TLC).Thereupon the reaction mixture was dried over magnesium sulfate, the solvent completely distilled off in vacuum and the residue separated by column chromatography (SiO 2 , eluent: petroleum ether → petroleum ether/acetone 8:1) to give the hydrazones 2 and 3.

Photolysis of diazodiketone 1a (with MeOH).
A solution of sublimated diazodiketone 1а (2.48 g, 0.02 mol) in 80 ml of anhydrous THF and pure CH 3 OH (4 ml, 0.10 mol) was irradiated in a quartz reactor (λ > 210 nm) for 55 min and worked up similarly as described in the previous experiment.The resulting reaction mixture after removal of THF and methanol in vacuum was distilled to give methyl ester 5а.

Figure 1 :
Figure 1:The structures of carbocyclic diazodiketones 1a-g and C-H-donating tetrahydrofuran used in the project.

Figure 2 :
Figure 2: Molecular structure of hydrazone 2b as determined by X-ray analysis data (Olex2 plot with 50% probability level of ellipsoids).

Table 2 :
Direct photolysis of diazodiketones 1a-с by UV light with λ > 210 nm.a Yield determined by 1 H NMR spectroscopy is given in parenthesis.