Thermolysis diazirines

Thermal conversion of diazirines to linear diazo compounds was postulated occasionally and proved by indirect methods. The existence of a diazo compound isomeric to diazirine (197) was proved spectroscopically on short thermolysis in DMSO (76JA6416). An intermediate diazoalkane was trapped by reaction with acetic acid, yielding the ester (198) (77JCS(P2)1214). 

Formation of azines on thermolysis of diazirines was reported repeatedly (B-67MI50800), e.g. with perfluorodimethyldiazirine (204), with chloromethoxydiazirine and with chloro-phenyldiazirine. 

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). 

As shown in Table 1, however, the product distribution depends on the method of carbene generation. Whereas thermolysis of either tosylhydrazone salt (7) or methylethyldiazirine (8) affords essentially the same product distribution (in which 95% of the products are the 2-butenes), photolysis of diazirine 8 is quite different. 

In pentane, the distribution of 1,3-insertion product 25 to 1,2-Me shift product 26 is 91 9. Upon addition of 2-methyl-1-butene, the yield of 25 smoothly decreases (to 19% with 4 M alkene), but the yield of 26 is unaffected 1 Moreover, correlation of addn/l,3-CH insertion (to 25) for 18 is nicely linear. The simplest interpretation is that 25 comes directly from carbene 18, whereas the 1,2-Me shift product 26 comes from the excited diazirine.27 Interestingly, thermolysis of 24 at 79°C produces 90% of 25 and 10% of 26, but now the yields of both products smoothly decrease in the presence of an alkene. In thermolysis the (electronically) excited diazirine is unavailable, both 25 and 26 stem from the carbene, and their formation is suppressed by the alkene s interception of the carbene. A pyridine ylide kinetic study gave the 1,3-CH insertion rate constant (18 - 25) as 9.3 x 10s s"1.27-47... 

It is suggested that the real carbene, generated by thermolysis of the diazo or diazirine precursors or photolysis of 40, gives mostly 1,3-insertion, whereas photolysis of either the diazoalkane or diazirine yields much 1,2-Me migration directly from precursor excited states.15 1 An analogous intervention of 1,2-Me migration via RIES was also observed in the photolytic decomposition of f-butylchlorodiazirine (24) to f-butylchlorocarbene (18) cf. Eq. 14.27... 

Generation of 78 by thermolysis or photolysis of a diazoalkane or diazirine precursor, however, affords the singlet carbene, whose 1,2-H shift to ethene is opposed by a barrier of only 0.678 to 1.298 kcal/mol. Consequently, even in cryogenic matrices, singlet 78 rearranges more rapidly than it intersystem crosses to the triplet, which has therefore not been detected by UV or ESR in either an Ar matrix at 8 K or a Xe matrix at 15 K." The lifetime of singlet 78 at ambient temperature has been estimated at <0.5 ns.89,98b (Note the enormous spectator substituent effect of Cl the lifetime of MeCCl is 740 ns,60 at least 1500 times longer than that of MeCH.)... 

Thermolysis of aryl chloro diazirine (18) in the presence of acetone and a trapping agent such as A -phenylmaleimide gave rise to cycloadducts such as 41. The unstable adduct hydrolyzed during purification resulting in synthesis of bicyclic hemiacetals 42 and 43 as a mixture of endo and exo adducts in 37 and 8% yield, respectively. The exclusive generation of the singlet carbene was confirmed by low-temperature electron spin resonance (ESR) study of the irradiated diazirine. 

Data are at 25 °C except for CCI2 (80 °C). AU carbenes were generated from diazirines except CCI2 which was produced by thermolysis of CgHsHgCClBr. 

Kinetic analysis of the rearrangement of benzylfluorocarbene, generated by laser flash photolysis of the corresponding diazirine, gave a rate constant of 9.2 x 106 s 1 at 26 °C with activation entropy —17.2 eu and activation energy 3.25 0.34 kcal mol-1, very similar to the values for the chlorocarbene.80 A product analysis study of the thermolysis and photolysis of the diazirine (73) in the presence of tetramethylethylene showed tiiat die ring-expanded cyclobutene and the cyclopropanation products do not arise via a common intermediate.81 The ring expansion was proposed to occur by loss of N2 from the diradical intermediate (74). 

C6o reacts with diazomethane to yield fulleroids [97,99,100,234], Carbene generated from the thermolysis of precursors such as diazirines, sodium trichloroac-etate, cyclopropene, oxadiazole, and tosylhydrazone [60,235] adds onto C6o leading to methanofullerenes [12,15,236], Recently, Akasaka et al. described the photochemical reaction of diazirine with C6o [237], Irradiation of a benzene solution of 2-adamantane-2,3 -[3H]-diazirine 58 and C6o with a high pressure mercury lamp (cutoff <300 nm) at 15°C in a Pyrex tube resulted in the formation of mixture of the isomers 59a and 59b in a ratio of 51/49 (Scheme 24). 

Depending on the mode of generation, a carbene may be initially formed in either the singlet or triplet state, irrespective of its stability. Common methods used for the generation of carbenes include photolytic, thermal, or metal catalyzed decomposition of diazocompounds, elimination of halogenfrom gem-dihalides, elimination of Hx from CHX3, decomposition of ketenes, thermolysis of a-halo-mercury compounds and cycloelimination of shelf stable substrates such as cyclopropanes, epoxides, aziridines and diazirines. 

Diaziridines and diazirines were first prepared by Abendroth and Henrich <1959AGE283>, Schmitz <1959AGE127>, and Paulsen <1960AGE781> at the turn of the 1960s. Nearly 50 years later, both diaziridines and diazirines have seen tremendous utility in synthetic chemistry and biochemistry. In particular, diazirines have been widely used as photochemical and thermal precursors of carbenes in their primary role as photoaffinity tags. Unlike diazo compounds, diazirines are reasonably stable and have been used extensively in both photolysis and thermolysis. 

The stereoselectivity of the addition of ammonia has been studied <2003HCA1488>, along with the thermolysis of the diazirine products <1994HCA2335>. The addition of the corresponding carhenes to, among others species, alcohols and buckminsterfullerene (Cso) has been fully investigated <1993HCA2847>. 

Diazirines (isomeric with diazoaUcanes) give carbenes/ but aryhnethyl radicals have also been generated from diazirines. In a different study, thermolysis of diaryloxydiazirines gave the anticipated carbene products, but photolysis gave both carbenes and aryloxy radicals by a-scission. ... 

Chloro(methoxy)- and chloro(phenoxy)carbenes, which are generated from the diazirine precursors, behave as ambiphiles in additions to alkenes, exhibiting high reactivities toward both electron-poor and electron-rich olefins. Methoxy(phenyl)- and ferrocenyl(methoxy)methylenes have been transferred in a stereospecific manner from transition metal complexes of these species to electron-deficient alkenes. Irradiation of benzocyclobutanedione with UV light induces a rearrangement of the cyclic a-diketone to 17, which has been trapped by alkenes in good yields " . Thermolysis of 18 gives rise to nucleophilic dimethoxycarbene, which has been intercepted by electron-deficient olefins or by styrene derivatives. 

Diazirines 179 and 181, the cyclic structural isomers of diazo compounds, are often employed as entry to carbenes. By thermolysis of diazirines methoxychloro- , cyanophenyl- and chlorophenyl carbenes are generated and are able to undergo addition across olefinic derivatives (equation 44). 

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