Amination diazirines

The sequence carbon radical —> imine —> amine is illustrated in equation 30. Irradiation of the pyridinethione 64 (R = cyclohexyl) with the light of a tungsten lamp generates the cyclohexyl radical 65, which was trapped as the imine 67 in the presence of the diazirine 66. The imine was finally hydrolysed to cyclohexylamine80. 

Diazirine ring formation from oxime 0-tosylates or 0-sulfonates ° and NH3 or primary amines has been described. Recently, it was found that this reaction was catalyzed... 

Scheme 15 Loading the e-Amine in [l4C Lvsyl-tRNALys with Succinimidyl 4-[3-(Trifluoromethyl)-3//-diazirin-3-yl]benzoatel141142l...

One example has been reported in which fluorine is replaced by an N-nuclcophilc with the intermediacy of a carbene species. Thus, when 3-fluoro-3-phenyl-3//-diazirine (2) is irradiated in the presence of a secondary amine, a diaminophenylmcthanc derivative 3 is formed.19... 

Difluoroamine reacts with primary and secondary amines to give alkanes (32). With imines, a variety of products are obtained depending on the structure of the imine. The three types of compounds obtained are diazirines (I), a-haloazo compounds (II), and a-fluoroalkylidine-hydrazines (III) (138, 139). The reaction of HNF2 with formaldehyde imines or negatively substituted aromatic imines yields diazirines in fair yield as the principal product, whereas with imines derived from aliphatic aldehydes the reaction gives a mixture of the corresponding diazirine derivative and a-fluoroazo compound. 

E14b, 976 (aus N-NO—amin) Cyclobutan Diazo- X/4, 540 3H-Diazirin 3-Ethenyl-3-methyl-E16c, 722 (R3N-Abspaltung) Diazomethan Cyclopropyl- X/4 535 (aus N-NO —amid) E14b, 976 (aus N-NO —amin)... 

In a usually less favorable procedure formamide acetals (437 equation 204) are accessible from chloroform or trichloroacetic acid esters and mixtures of secondary amines and alkoxides - dichlorocar-bene is thought to be an intermediate. Chloromethoxycarbene, generated from the diazirine (438 equation 205) inserts into the NH bond of diethylamine to yield the amide acetal (439). The undissociated a,a-difluorotrialkylamines (440 Scheme 80) react with the alkali metal salts of diols to afford 1,3-dioxanes or l,3-dioxolMes7 - Noncyclic amide acetals can be prepared in the same manner. 

Besides the dehydrogenation agents silver oxide and bichromate, described in the first papers on diazirine synthesis, there has been application of bromine, iodine, and t-butyl hypochlorite. Chloramine, which is used as aminating agent in diaziridine synthesis, may act as a dehydrogenating agent when applied in excess, e.g., in reactions of simple aliphatic ketones or steroid ketones. ... 

Diazirines fluorinated at the ring carbon were first described by Mitsch, °° and shortly afterward by Rebertus and co-workers. They are obtained from suitable perfluorinated amines by reduction with ferrocene or iodide, as well as by reduction with diphenylamine, semicarbazide hydrochloride and by electrolytic reduction. ... 

O-acyl thiohydroxamates was initially thwarted by competing ionic reactions but eventually culminated in the introduction of 3-bromo or 3-(trifluoromethyl)-3-phenyl diazirine as extremely effective reagents [27]. In contrast to almost all of the other reactions of Barton esters described in this chapter, however, the reaction sequence does not involve a chain process. Thus, as outlined in Scheme 25, capture of the alkyl radical by the diazirine is followed by dimerization and subsequent loss of nitrogen to give the product imine from which the desired amide or amine is easily liberated by mild hydrolysis. Some typical yields are shown in the Scheme 26. 

Scheme 26. Representative examples of decarboxylalive amination using diazirine traps [27]...

Monoalkylhydrazines can also be prepared by hydrolysis of diaziridines that are obtained from diazirines and Grignard reagents.287 Pentamethylenedi-azirine (2,3-diazaspiro[2.5]oct-2-ene)288 is a particularly suitable starting material for this synthetic route, which is of special value when the alkyl halide is more accessible than the amine. 

Prepared by lead tetraacetate oxidation of the corresponding diaziridine, bis(trifluoromethyl)diazirine (263) has also been made by hypochlorite oxidation of hexafluoroacetone aminal 262. Instead of by oxidation, ring formation in the case of difluorodiazirine (265) has been achieved by mild reduction of bis(difluor-... 

Barton, D.H.R. Jaszberenyi, J.Cs. Theodorakis, E.A. Reibenspies, J.H. The invention of radical reactions. 30. Diazirines as carbon radical traps. Mechanistic aspects and synthetic applications ofa novel and efficient amination process. 7. Am. Chem. Soc. 1993,115, 8050. 

Finally, the ferrocenyl complexes were decomposed photochemically and thermally. Thermolyses can be performed in this case because the decomposition temperature of the azide (96) (80 °C) is much lower than those employed for other diazirines and azides. The results obtained from photolyses and thermolyses do not differ significantly. Here again, a-CD causes the most drastic changes because of the complete encapsulation of the guest in a 1 2 complex (Scheme 10.27). In accord with the other reactions performed in a-CD, the main reaction pathway is hydrogen abstraction from the host. Upon thermolysis ferrocenyl amine (112) is obtained in a yield up to 60%. More remailcably, ferrocenyl nitrene (111) seems to react in very low yields with a-CD. However, the structure of the reaction product 113 has not been fully established yet and is quite unexpected because 113 is the result of a glucopyranose-furanose conversion. In contrast, the products obtained by thermolysis of ferrocenyl nitrene in the soUd state, namely... 

RCOOH - RHNi. Acyl derivatives (2) of N-hydroxy-2-thiopyridone (12,417 14,268) when photolyzed in the presence of this diazirine (1) transfer the alkyl group to 1 to form the imine 3. These imines are hydrolyzed by boric acid in refluxing ethanol to primary amines (4). 

Radical amination. - A radical reaction has been developed to effect the replacement of a hydroxy-group by an amino-group. For example, the carbon radicals generated fnim either the xanthate 13 or anisyltelluride 14 can be trapped by the diazirine 15 (Scheme 5). The resulting imine 16 was hydrolysed to the amine 17. ... 

The PAL probe can be prepared efficiently by coupling a small molecule of interest containing a terminal amine group with an activated fluorous diazirine reagent [23, 25] such as Rf-diazirine-NHS (Scheme 1). A general procedure is described below when PIP2 is the small molecule of interest. 

---