Insertion reactions of carbenes

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... 

The intramolecular C-H insertion reaction of carbene species has been used in a number of studies for the synthesis of strained molecules and cage com-... 

The transition metal-catalyzed C-H insertion reaction of carbenes to organic compounds is a well-established synthetic method, as shown in the first two sections in this chapter. However, nitrene C-H insertion, the corresponding reaction of carbene analog, is much less known. In the past decade, considerable advances have been made in the development of this chemistry into a generally useful C-H amination process by using improved catalysts and protocols, in which readily available amines or amides are used as the starting substrates. Moreover,... 

Here we will briefly consider the kinetics and activation parameters of several representative intramolecular insertion reactions of carbenes, the role of bystander substituents, and the possible intervention of tunnehng. 

Excellent reviews of early research on C—H insertion reactions of carbenes may be found in Refs. 5 and 6. 

It would appear from the foregoing that the reactions of recombination and disproportionation of radicals fall into a reasonable relation with each other and with abstraction reactions if in the approach of the radical pair, either head-to-head as in recombination or head-to-tail as in disproportionation, there occurs an appreciable contribution of ionic structures to the attractive potential of the radical pair. These then also fall into a consistent relation with the insertion reactions of carbenes and the snap-out reactions of stable molecules from which latter, the present experimental evidence requires a large charge separation in the transition state. 

Several silver complexes have been investigated in C-H insertion reactions of carbenes. One of the earliest reports by Sulikowski and Burgess describes an intramolecular C-H insertion of a chiral aryl diazoacetate 80 as part of a study on the total synthesis of mitomycin family of natural products (Scheme 8.15).41 Among several catalysts that were screened was AgSbly, in the presence of bis(isoxazoline)-type ligands, which led to the formation of the desired insertion product 81 in moderate yield and modest diastereoselectivity. 

In an exciting new challenge the Bristol-Myers-Squibb group carried out an ACP on a 100-kg scale with a chiral Ru Pybox catalyst, especially in two-phase media of water and ferf-butyl methyl ether (Scheme 5) [35]. The operations produced good yields and enantioselectivity,but separation was difficult. Similarly, Wurz and Charette [36] demonstrated ACP in aqueous media by using Ru, Rh, and Co catalysts including an O-H insertion reaction of carbenes. 

The intramolecular cycloaddition and insertion reactions of carbene are described in Scheme 2.57. 

Intermolecular reactions between coordinatively unsaturated metal atoms and the C-H groups of relatively unreactive hydrocarbons such as cyclohexane and even methane have been reported (Scheme 1.4). ° Insertion reactions of carbenes R R C into C-H or other bonds are clearly of the same type, the carbene carbon atom playing the role of the coordinatively unsaturated metal... 

Miller, D. J., Moody, C. J., Synthetic Applications of the O H Insertion Reactions of Carbenes and Carbenoids Derived from Diazocarbonyl and Related Diazocompounds, Tetrahedron 1995, 51, 10811 10843. 

Scheme 7. General method for the preparation of PAHs by insertion reactions of carbenes generated by the thermal acetylene to vinylidene-carbene rearrangement [53b, 54a]...

However, within the confined environment, the 1,3 C—H insertion reaction of carbene 75 is not favored the yield of didehydroadamantane (76) remains low (9%) and CH-insertions into the host do not occur as well. Instead, the production of adamantane (77) is strongly enhanced and reaches 31%. The formation of 77 is particularly facilitated by the fact that the singlet-triplet gap in adamantanylidene 75 is low (3.1 to 4.8kcalmor ). Although... 

C-H insertion reactions of carbenes and nitrenes assisted by transition metals have been overviewed. Transition-metal-catalysed carbenoid insertions as a tool for C-H functionalization have been detailed. The intermolecular versions of these C-H insertions have been discussed from the point of view of their mechanisms and stereochemical outcomes. ... 

Miller DJ, Moody CJ (1995) Synthetic applications of the O-H insertion reactions of carbenes and carbenoids derived from diazocarbonyl and related diazo compounds. Tetrahedron 51 10811-10843... 

Table 8.4. Ab initio calculation data on activation barriers of insertion reactions of carbenes and silylenes into the tr-bonds...

A review on the CH insertion reactions of carbenes and nitrenes with alkanes has appeared developing the current state of the art of this valuable synthetic method. ... 

Lactams, and /S-lactams in particular, are interesting owing to their occurrence in biologically active compounds such as antibiotics related to penicillines. Insertion reactions of carbenes offer useful access to poly heterocyclic systems contain a -lactam nucleus, particularly when using rhodium and copper catalysis. Moreover, palladium catalyzed carbonyla-tion of azirines affords )S-lactam derivatives [93] in one step. 

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