Insertion nitrenes into hydrogen-carbon

The chemical reactions of sulphonyl nitrenes include hydrogen abstraction, insertion into aliphatic C—H bonds, aromatic substitution , addition to olefinic double bonds, trapping reactions with suitable nucleophiles, and Wolff-type rearrangement. Hydrogen-abstraction from saturated carbon atoms is usually considered to be a reaction typical of triplet... 

Examples of such reactions are well known. Sloan, Breslow, and Renfrow found that both alkane and arenesulphonyl azides insert into the carbon-hydrogen bonds of saturated hydrocarbons 12>. Thus, 1-pentane,- 2-propane- and -toluene-sulphonyl nitrene inserted into cyclohexane to give 54, 60, and 58% yields of the corresponding IV-cyclohexylamide derivatives 8>. Similarly, 2-phenoxybenzene-, diphenyl sulphide-2-, and... 

Only limited success was achieved in determining the relative reactivity of primary, secondary, and tertiary carbon-hydrogen bonds to sulphonyl nitrenes 8>. Insertion of p-toluenesulphonyl nitrene into 2-methylbutane gave a mixture of products which could not be completely resolved. The ratio of (primary) (secondary + tertiary) = [38 + 39 40 + 41] was 1.53, compared to a ratio of 5.6 for carbethoxynitrene58>, indicating the lowered selectivity of the sulphonyl nitrene relative to the carbethoxynitrene, as might be expected from the possible resonance stabilization of the latter species. 

Figure 5.16 Photoactivation of a phenyl azide group with UV light results in the formation of a short-lived nitrene. Nitrenes may undergo a number of reactions, including insertion into active carbon-hydrogen or nitrogen-hydrogen bonds and addition to points of unsaturation in carbon chains. The most likely route of reaction, however, is to ring-expand to a dehydroazepine intermediate. This group is highly reactive toward nucleophiles, especially amines.

The deoxygenation of o-nitrobiphenyls followed by the insertion of nitrene into the o -carbon-hydrogen bond is a useful and versatile method for the synthesis of... 

The efficient light-initiated decomposition of azides has been the basis for commercially important photoresist formulations for the semiconductor industry. A common approach is to mix a diazide, such as diazadibenzylidenecyclohexanone (I), with an unsaturated hydrocarbon polymer. Excitation of the difunction-al sensitizer produces highly reactive nitrenes which crosslink the polymer by a variety of paths including insertion into both carbon-carbon double bonds and carbon-hydrogen bonds, and by generation of radicals. The polymer component in the most widely used resists is polyisoprene which has been partially eye Iized by reaction with p-toluenesulfonic acid G). Other polymers used include polycyclopentadiene and the copolymer of cyclopentadiene and a-methyI styrene ( ). 

Both alkane and arene sulfonyl nitrenes insert into the carbon-hydrogen bonds of saturated hydrocarbons although not as efficiently as carbenes (10). 

The importance of this rearrangement pathway for nitrenes generated in a biological receptor site is not known, however, and in model systems an aryl nitrene will insert into a carbon-hydrogen bond if tiiere is one in the near neighborhood. Thus irradiation of 2-azidobiphenyl results, via both the singlet and the triplet nitrene, in the formation of carbazole ... 

The reactive nitrene is covalently inserted into exposed carbon-hydrogen bonds of the protein in about 2 msec. This method was applied to RNase A. From the amino acid analysis of labeled protein, only the exposed residues were shown to react with the nitrene those buried at the interior of the molecule (according to the X-ray data) do not react. 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

Further applications of nitrene cyclizations have also been reported in which the intermediate nitrene inserts into a 7r-deficient heterocycle or a nitrene on a -deficient nucleus inserts into a proximal carbon-hydrogen bond. In general, the preferred source of the nitrene is the photolysis or thermolysis of an azide. The versatility of this approach is shown in two syntheses of pyrrolo[3,2-J]thiazoles (selenazoles) (177), (178), (180) (Equations (52) and (53)). Thermolysis of the / -thiazolyl (selenazolyl)-a-azido-esters (176) or the / -(4-azido-5-thiazolyl)-x,/J-enones (179) affords these bicyclic heterocycles in excellent yields (79JHC1563, 92JCS(Pi)973>. The same strategy has also been... 

The electron-deficient sulfonyl nitrene (88) can insert into electron-rich carbon-hydrogen bonds, abstract hydrogen atoms, and add to double bonds and aromatic rings. These reactions may be initiated by acids, heat, light and transition metals. The reactions are illustrated by heating methanesulfonyl azide (89) with bezene (23) (Scheme 59). Here, the electrophilic sulfonyl nitrene (90) adds to the electron-rich aromatic double bond, but the kinetically favoured azepine(91) rearranges to give the thermodynamically favoured N-phenyl sulfonamide (92) (Scheme 59). 

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