Diazirine derivatives

The stabilization reactions of alkylcarbenes were used preparatively in some cases. The diazirine derived from adamantanone gave the dehydroadamantane (2l7) thermally in 96% yield 73ZOR430). Alkene formation was reported for a steroid with its C-3 atom part of a diazirine ring. At 140 °C a A-2-unsaturated steroid was formed 65JA2665). 

Further examples and a mechanistic discussion may be found in reference 7. Borrevang10 has reported a closely related fragmentation involving diazirine derivatives of cyclic a,/ epoxyketones. 

The mechanism of Scheme 5 accounts for these observations. Both excited diazirine 29 and carbene 20 are regarded as product precursors. A strict partition is postulated, whereby cyclobutene 30 comes only from 29, while the carbene reacts only intermolecularly, either with the freon solvent or added alkene. In Scheme 5, the excited diazirine pathway is expanded by interposition of the opened diazirine biradical, 29, as the proximate partitioning intermediate.46-48 Of course either an excited diazirine or a diazirine-derived biradical, would satisfy the need for a second intermediate in cases where curved correlation of addn/rearr vs. [alkene] require expansion of the kinetic scheme. 

As illustrated in Section 4.1.1, the addition of nonstabihzed carbenes to the oxygen atom of a carbonyl derivative can lead to the production of carbonyl yhdes. However, these methods are not always practical for preparative scale since many side reactions can accompany the decomposition of alkyl diazo and diazirine derivatives. Landgrebe and co-worker (8) extensively studied the thermal decomposition of organomercurials in the presence of carbonyl compounds for the preparative generation of carbonyl yhdes (Scheme 4.6). 

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. 

Patent Diazirine Derivatives of Aromatic Heterocyclic Compounds... 

An interesting subject is the influence of substituents on the relative stability of the corresponding diazomethane and diazirine derivatives, because there is a qualitative indication that difluorodiazirine is more stable than difluorodiazomethane. 

The carbene-generating biotinylated 2-acetamido-2-deoxy-D-glucopyranosyl-amide diazirine derivative 54 and the lactoside 55 have been synthesized for photoaffinity labelling of P-(l ->4)-galactosyl transferase and GMj synthase. ... 

Carba disaccharide 97 has been prepared by insertion of a sugar glycosylidene carbene (made in situ from a glycosyl diazirine derivative) into OH groups of protected deoxy m o-inositoI orthoformate derivatives. ... 

The D-gluco-diazirine derivative (45) and its D-manno- and D-galacto-analogues have been prepared from the corresponding hexono-1,5-lactone oximes, and shown to be stable at low temperatures (Scheme 9). They are precursors of... 

The p-triphosphate derivatives of ATP and AZT were synthesised and shown to inhibit DNA polymerase activity even using NRTI and NRTII resistant strains. dNTPs have been labelled at the y-phosphate by fluorophores for use in real-time PCR ° and as a method for the labelling of microtubules.Using a method known as compartmentalised selfreplication (CSR), the DNA polymerase from Pyrococcus furiosus has been evolved such that dNTPs bearing a fluorophore attached at the y-phosphate are better substrates.Ferrocene, attached via a linker as a y-phosphor-amidate has been used in an electrochemical assay to study kinase-catalysed phosphorylation reactions.The photoactivatable diazirine derivative (37) also attached to the y-phosphate was shown to be a specific label for tropomysin even in the presence of other actinomysin components. 

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