Nitrogen compounds carbene insertion

The photoelimination of nitrogen from diazo compounds provides a simple and versatile route for the generation of carbenes, and in certain instances, insertion reactions of carbenes can be employed in the synthesis of heterocycles. Carbenes are believed to be involved at least in part in the photochemically induced conversion of N,N-diethyldiazoacetamide (439) into the y-lactam 440 and the /Mactam 441,365 and a similar approach has been successfully employed in the synthesis of a carbapen-2-em366 and of 7-methylcephalosporin analogues.367 Carbene insertion of a different type has been observed on irradiation of the 6-anilino-5-diazouracils 442 to give the indolo[2,3-d]pyrimidines 443.368 Ring contractions in heterocycles... 

Carbene complexes, generated by the reaction between metal salts and diazo compounds can insert into C-H bonds in a form of CH activation (see Chapter 3 for other CH activation reactions). While early reactions involved the use of copper salts as catalysts (Schemes 8.143 and 8.144), rhodium complexes are now more widely used. In molecules such as cyclohexane, there is no issue of regioselectivity, but this issue is critical for the use of the reaction in synthesis. Both steric and electronic factors influence selectivity. Carbon atoms where a build up of some positive charge can be stabilized are favoured. Hence, allylic positions and positions a- to a heteroatom such as oxygen or nitrogen, are favoured. The reaction at tertiary C-H bonds, rather than primary C-H bonds is also favoured for the same reason, but, in this case, are also disfavoured by steric effects. Reactivity and selectivity are also influenced by both the structure of the catalyst, and the... 

The properties of 5-azido and 5-diazomethyl-l,4-diphenyltriazole are unusual in that both compounds lose nitrogen under very mild conditions. The products derived from the azide are mainly those of ring cleavage (Section IV, G), but the diazoalkane gives a carbene which undergoes addition and insertion reactions with several solvents. These reactions are illustrated in Scheme 49. 

One of the key steps in building the fused ring involves the reaction of the activated acetoacetate methylene group in that compound with toluenesulfonyl azide to give the diazo intemediate (12-1). Treatment of that product with rhodium acetate leads to a loss of nitrogen with the consequent formation of carbene (12-2) this inserts into the adjacent amide N—H bond to form a five-membered ring and thus the carbapenem (12-3) [15]. The first step in the incorporation of the thioenol function consists in the conversion of the ketone to the enol phosphate derivative... 

The reaction of a nitrogen-substituted silylene (88) with a 2H-azaphosphirene (87) gave a bicyclic compound (89), which contains an Si-Si bond and a tungsten-bound carbene.96 Compound (89) was isolated in 62% yield and its crystal structure was described. However, when an extra phosphorus atom was inserted into the ring as in (90), the monocyclic (91) was isolated in 90% yield. A crystal structure for (91) was also reported. 

Recently, Schulze and coworkers synthesised a group of (2-aryl-4,5-diphenyl)isothiazol-3-ylidenes (see Figure 6.11) by deprotonation of the respective isothiazolium perchlorates with Bu OK as base [37], The compounds are yellow solids that dimerise readily and show typical carbene reactions like insertion into NH bonds. The tendency to dimerise follows the known electronic properties of substituents on the phenyl ring on nitrogen (< -methyl [Pg.317]

Carbenes are known intermediates in the photodecomposition of diazo-compounds. Insertions of singlet methylene, generated by photoelimination of nitrogen from diazomethane, into 2,3-dimethyl-2,3-epoxybutane and into acetonitrile have been described. Methylene and other photochemically generated carbenes (43) add efficiently to 2-acetoxyacrylonitrile to give the corresponding 1-acetoxy-l-cyanocyclopropanes (44). The formation of methylidyne radicals by irradiation of diazomethane in the presence of hydrogen, however, does not seem to involve an intermediate carbene. ... 

Many substituted carbenes have been prepared in situ by heating the tolyl hydrazones of aldehydes and ketones with alkali in aprotic solvents. Intermediates are diazo compounds which then decompose thermally to give nitrogen and a carbene. In the carbene, a-H or a-R migration readily occurs to give an olefin product and some intramolecular cyclization is observed. If no a-H or a-R are available, possible fates of the carbene include dimerization, insertion, and addition to the substrate. Some examples are... 

The time-resolved method was applied to another photodissociation reaction [124], Upon the photoexcitation of diazo compounds (Fig. 16), nitrogen is dissociated to yield the singlet carbenes. In alcoholic solvents such as methanol, the O—H bond is inserted into the carbene part quickly (within 40 ps for diphenylcarbene), and an ether is formed. The AH and AV values for the ether formation from DPDM in methanol were measured by the time-resolved method. A similar TG signal to the DPCP case was observed after the excitation of DPDM in methanol. The signal rises within 50 ns after the excitation and decays monotonously. The time profile of the signal was found to be expressed well with a tri-exponential function... 

The diazo compound decomposes to gaseous nitrogen and a carbene under catalysis by Cu(Il). Insertion into the exposed alkene gives the three-membered ring. The stereochemistry partly comes from the tether —the hnkage between the carbene and the rest of the molecule that delivers the carbene to the bottom face of the alkene. The rest comes from the inevitable cis fusion between the five- and three-membered rings. 

---