Nitrenes cyclohexane

In 1982, Breslow and coworkers reported the first example of iron-catalyzed nitrene C-H bond insertion [29]. They used [Fe(TTP)] as catalyst and PhINTs as nitrene precursor to achieve C-H bond amination of cyclohexane. However, the product yield was low (around 10%). Subsequently, the same authors found that iminoio-dane 7 derived from 2,5-diisopropylbenzenesuIfonamide underwent intramolecular C-H amination efficiently with [Fe(TPP)Cl] as catalyst at room temperature, giving the insertion product in 77% yield (Scheme 29) [85]. 

Upon irradiation of (dimesityl)(trimethylsilyl)silylazide at 254 nm in a cyclohexane/t-butanol or a cyclohexane/ethanol solution, migration of the trimethylsilyl group to the nitrene center is observed (Eq. 2). The products are equivalent to the addition products mentioned above. 

Photolysis of bis(dimethylamino)phosphoryl azide 2071401 represents an entirely different entry to a metaphosphorimidate. If the reaction is performed in cyclohexane, it gives only 7 % of the amide 209 which can be rationalized as the insertion product of the intermediate nitrene 208 into a CH bond of cyclohexane. The major product component is a polymer. The assumption that it is polymeric aminometa-phosphorimidate 212 is substantiated indirectly by the nature of the principal product of photolysis of 207 in methanol. A 1,2-shift of a NMe2 moiety which... 

Arylsulphonyl nitrenes usually give better yields of hydrogen-abstraction products from aliphatic hydrocarbons. -Toluenesulphonyl azide gave a 5% yield of -toluenesulphonamide on thermolysis in cyclohexane... 

On the other hand, thermolysis of ferrocenylsulpkonyl azide (14) in aliphatic solvents may lead to the predominant formation of the amide (16) 17>. A 48.4% yield of (16) was obtained from the thermolysis in cyclohexane while an 85.45% yield of 16 was formed in cyclohexene. Photolysis of 14 in these solvents led to lower yields of sulphonamide 32.2% in cyclohexane, 28.2% in cyclohexene. This suggests again that a metal-nitrene complex is an intermediate in the thermolysis of 14 since hydrogen-abstraction appears to be an important made of reaction for such sulphonyl nitrene-metal complexes. Thus, benzenesulphonamide was the main product (37%) in the copper-catalyzed decomposition of the azide in cyclohexane, and the yield was not decreased (in fact, it increased to 49%) in the presence of hydroquinone 34>. On the other hand, no toluene-sulphonamide was reported from the reaction of dichloramine-T and zinc in cyclohexane. 

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... 

No insertion product was observed on photolysis of ferrocenylsul-phonyl azide in cyclohexane or in cyclohexene 25>, suggesting that the reactive intermediate formed is the triplet sulphonyl nitrene. The fact that addition to the olefinic bond of cyclohexene takes place under these conditions 25> does not necessarily argue against this conclusion (vide infra). 

Sulphonyl nitrene-metal complexes also undergo insertion into aliphatic C—H bonds as witnessed by the insertion into dioxan on treatment with chloramine-T and copper 45> and into cyclohexane with di-chloramine-T and zinc 44> and into cyclohexene with benzenesulphonyl azide and copper 34> and with ferrocenylsulphonyl azide 25>. 

Xylene was found to be twice as reactive as benzene towards tosyl azide, and a benzene double bond eight times more reactive towards singlet sulphonyl nitrene than a carbon-hydrogen bond in cyclohexane 8>12>. 

Perez and co-workers reported the electron-deficient copper homoscorpionate catalyst TpBr3Cu(NCMe)-catalyzed nitrene insertion into C-H bonds of toluene, mesitylene, and cyclohexane, which are very unreactive substrates (Equations (100)—(102)). In contrast to the former reports, they obtained very high yields for these products. 

Both compounds 190 and 193 are reduced to 9,10-diphenylanthracene (205) by zinc and acetic acid. However, more interest attaches to the formation of anthracenes from anthracen-9,10-imines in nonreducing conditions. The iV-ethoxycarbonyl derivative (192) decomposed at 215° in cyclohexane to 33% of 205, although curiously this product was not obtained if the solvent was previously degassed. Whether or not the reaction involves simple extrusion of ethoxycarbonyl nitrene could not be established, since the expected iV-cyclohexylurethane was not detected. The 9,10-epithioanthracene (194) loses sulfur thermally to give 205. ... 

Polyfluorination does seem to suppress rearrangements of alkyl azides and to extend the lifetimes of the corresponding singlet nitrenes. Photolysis of 5 in cyclohexane produces insertion adduct 6." ... 

However, Lwowski and co-workers demonstrated that photolysis of 7 in cyclohexane, cyclohexene- or 2-methylbutane does lead to the formation of adducts. Therefore, the acylnitrene 8 is a trappable intermediate. The thermal Curtius rearrangement does not involve free nitrenes and it must be a concerted process. 

In the absence of amine, the ketenimine-azirine singlet nitrene species can equilibrate and, eventually, the singlet nitrene can cychze to form carbazole. Berry and co-workers independently monitored the growth of carbazole ( max = 289.4 nm) by this process. In cyclohexane, some carbazole was formed this way with an observed rate constant of 2.2 x 10 at 300 K over a barrier of 11.5 kcal/mol. Tsao and co-workers recently used TRIR spectroscopy to show that ketenimine decay equals the rate of carbazole formation. 

Efficient nitrene generation and insertion into the CHf bonds of the solvent (cyclohexane) was observed for a series of perfluoroarylazides linked to metal-ligating systems (63).70... 

More importantly, this silver system catalyzes the intermolecular amination of hydrocarbons, as shown in Table 6.3. In addition to animating weaker benzylic C-H bonds, stronger aliphatic C-H bonds such as those in cyclohexane were also reactive. Although yields with more inert hydrocarbons were modest with the bathophenan-throline system, the discovery of the first silver-catalyzed intermolecular amination opens opportunities for further developments. This reaction favored tertiary cyclic sp3 C-H bonds over secondary cyclic sp3 C-H bonds, and showed limited success with simple linear alkanes. No conversion was observed with any aromatic C-H bonds. The compound NsNH2 was tested as the nitrene precursor with different oxidants. The use of PhI(OAc)2 as oxidant gave the expected amination product with a lower yield, while persulfate and peroxides showed no reactivity. 

Such metal-complexed nitrenes were also generated by the reaction of (tosyliminoio-do)benzene (106) with Mn(m)- or Fe(n)-tetraphenylporphyrin, 107, in a mimic of cytochrome P-450 but with a tosylimino group instead of an oxygen atom on the metals (108) [179]. It was able to functionalize cyclohexane solvent, by nitrogen insertion into a C-H bond to form 109. Furthermore, the metalloporphyrins also catalyzed an intramolecular nitrogen insertion converting 110 into 111 [180]. 

The C—H insertion reaction of nitrenes is a potentially useful way of functionalizing unactivated C—H bonds, converting hydrocarbons into amine derivatives. In its intermolecular form the synthetic utility of the reaction is highly dependent on the substituents on the nitrene, and on the manner in which it is generated. To exemplify these effects, the results for the functionalization of cyclohexane by insertion of various nitrenes (equation 1) are summarized in Table 1. 

Table 1 Functionalization of Cyclohexane by Nitrene htsertion (equation 1)...

The insertion reactions into cyclohexane C H bonds (Table 1) give some idea of which nitteties give synthetically useful yields. However, since most other substrates will contain more than one sort of C—bond, it is important to know the selectivity of nitrenes for different types of C—bond. Several snidies of nitrene selectivity towards tertiary, secondary and primary unactivated C—H bonds have been made, although attempts to study allylic C—insertion reactions are complicated by the competing nitrene addition to the double bond. In cyclohexene it has been estimated that the allylic C—bond is only about three times more reactive than the homoallylic C—H bond towards insertion of ethoxycarbo-nylnitrene. However, the reaction is totally unsatisfactory as a means of allylic fhnctionalization since, as shown in Scheme 3, the yields are so low. 

The stereochemistry of nitrene insertion into unactivated C—bonds has been studied using substituted cyclohexanes as substrates. For arylnitrenes which usually exhibit triplet reactivity, the reaction is nonspecific, but most other nitrenes undergo stereospecific C—insertion. For example, benzqylni-trene inserts selectively into the tertiary C—bond of toth cis and tra/u-1,4-dimethylcyclohexane with retention of configuration. Similarly with cis- and rra/is-l,2-dimethylcyclohexane as substrate, ethoxycarbonyl-, methatiesulfonyl- and cyano-nitrenes all insert with retention of configuration at the tertiary C—bond. 

Although the functionalization of unactivated C—H bonds by intramolecular nitrene insertion has been aj Iied to the synthesis of diterpene alkaloids and in the modification of steroids as described below, it has also been used to good effect in simpler systems. For example, 1-adamantyl azidoformate, readily prepared from 1-adamantanol, gives the oxazolidinone (17) on irradiation in cyclohexane by in-... 

The intramolecular aziridination of 2-(alkenyl)phenyl azides was best performed under pho-tolytic conditions116-117, generating the nitrene (ca. 0.001 M solution in cyclohexane, 350 nra, Rayonet Photoreactor)118. The nitrene addition reaction proceeded with complete diastereose-lectivity, the double bond geometry was retained in the aziridine thus produced. The alkaloid ( )-virantmycin was synthesized from the aziridine 2117. 

Experimental observations of the aziridination of styrene-type alkenes, catalyzed by CuPF6 in the presence of chiral diimine ligands (such as (lR,2R,A i4A i4)-A A -bis(2,6-dichlorobenzylidene)cyclohexane-l,2-diamine 425), have been taken as evidence of the intermediacy of a discrete, monomeric Cu(lll)-nitrene complex, (diimine)Cu=NTs 423. Variation of the steric properties of the aryl group in the oxidant TsN=IAr (Ar = Ph, 2-/-Bu, 5,6-Me3C6H) has no effect on the enantioselectivities in forming the aziridination products 424 (Scheme 108) <1995JA5889>. 

The cyclohexylpyrazole (376) and the azirine (377) are formed by irradiation of 3-diazo-4-methyl-5-phenylpyrazolenine (378) in cyclohexane (Scheme 35) (77JA633). The former is the result of carbene insertion into cyclohexane followed by a [1,5] hydrogen shift, whereas the latter arises by ring cleavage of nitrene (379) or by a concerted pathway. 

In contrast with these ring expansion processes, photoelimination of nitrogen from ethyl o-azidobenzimidate (114) is followed by cyclization with the formation of 3-ethoxy-IH-indazole (115), and irradiation of the 2-azidopyrazines (116) yields the ring-contracted 1-cyanoimidazoles (117), presumably via the nitrenes (118). Products derived by insertion of (p-toluenesulphonyl)nitrene are obtained on irradiation of p-toluenesulphonyl azide in p-xylene or cyclohexane. "... 

Other aminoferrocene precursors are Af-ferrocenyl phthalimide, which can be converted to FC-NH2 by N2H4 H2O in boiling ethanol (82% yield) [16, 44], and ferrocenyl azide, FC-N3, which has been reduced with LiAlH4 (72% yield) (cf. Scheme 5-6) [45]. Ferrocenyl amine, FC-NH2, is generally formed among other products in the thermal or photochemical decomposition of FC-N3 [56] and in the thermolysis of ferrocenyl isocyanate, Fc-NCO [57], in solvents such as cyclohexane, cyclohexene and benzene, probably by reaction of the intermediate nitrene, [Fc-N], with the solvent [56, 57]. The reduction of nitroferrocene, FC-NO2, provides another route to aminoferrocene, FC-NH2 [58 — 61] however, FC-NO2 is not an easily accessible starting material. 

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