Insertion reaction, intramolecular

There are numerous examples of metal carbene insertion reactions, usually requiring a catalyst. " The C—H insertion reactions of metal carbenes can be highly selective. Intramolecular insertion reactions are very versatile and tolerate a... 

There is some increase in selectivity with functionally substituted carbenes, but it is still not high enough to prevent formation of mixtures. Phenylchlorocarbene gives a relative reactivity ratio of 2.1 1 0.09 in insertion reactions with i-propylbenzene, ethylbenzene, and toluene.212 For cycloalkanes, tertiary positions are about 15 times more reactive than secondary positions toward phenylchlorocarbene.213 Carbethoxycarbene inserts at tertiary C—H bonds about three times as fast as at primary C—H bonds in simple alkanes.214 Owing to low selectivity, intermolecular insertion reactions are seldom useful in syntheses. Intramolecular insertion reactions are of considerably more value. Intramolecular insertion reactions usually occur at the C—H bond that is closest to the carbene and good yields can frequently be achieved. Intramolecular insertion reactions can provide routes to highly strained structures that would be difficult to obtain in other ways. 

Intramolecular insertion reactions show a strong preference for formation of five-membered rings.219 This was seen in a series of a-diazomethyl ketones of increasing chain length. With only one exception, all of the products were five-membered lactones.220 In the case of n = 3, the cyclization occurs in the side chain, again forming a five-membered ring. 

The most common rearrangement reaction of alkyl carbenes is the shift of hydrogen, generating an alkene. This mode of stabilization predominates to the exclusion of most intermolecular reactions of aliphatic carbenes and often competes with intramolecular insertion reactions. For example, the carbene generated by decomposition of the tosylhydrazone of 2-methylcyclohexanone gives mainly 1- and 3-methylcyclohexene rather than the intramolecular insertion product. 

A few intramolecular insertion reactions, especially in aromatic systems, go in good yield.253... 

Under the influence of nickel catalysts, 1,5- and 1,6-dienes undergo isomerization and cyclization, preferably to five-membered ring compounds. The cyclization takes place probably via an intramolecular insertion reaction ( , ) involving a ir-5-alken-l-ylnickel complex such as 33, Table III, and 34, Table IV formed by Ni — C, and Ni — C2 additions... 

Photolysis of nitrile oxide 377 (R = CNO) gives acylnitrene 377 (R = CON), which undergoes intramolecular insertion reactions to give products 378 and 379 (428). 

The intramolecular insertion reactions of nitrenoids into G-H bonds as described above provide an attractive alternative to conventional methods of amine formation. Both carbamate and sulfamate C-H insertions have been applied successfully to the total syntheses of natural products. - The first application of carbamate G-H insertion was reported by Trost in the total synthesis of methyl-L-callipeltose 118 (Equation (92)).230 Intermolecular G-H insertion of carbamate 117 using 10mol% Rh2(OAc)4, PhI(OAc)4, and DTBMP (2,6-di-/ / -butyl-4-methylpyridine) in dichloromethane (40 °C) furnished methyl-L-callipeltose 118 in 63% yield. In an another independent total synthesis of 118, Panek performed this step in refluxing benzene and improved the yield to 93%.231... 

In recent years, several attempts have been made to prepare the first disilynes, compounds having Si-Si triple bonds,791 792 until Sekiguchi et al. in 2004 succeeded in the isolation and full characterization of the first member of this compound class.793 West et al. have studied the dehalogenation of 2,6-Mes2C6H3SiF3 761 with sodium, which has afforded the bis(silafluorene) derivative 762, whose formation may be rationalized in terms of two intramolecular insertion reactions of a bis(silylenoid) 763 into two C(.r/>z)-C(.r/>3) bonds (Scheme 99). 794... 

Scheme 10.7 gives some additional examples of intramolecular insertion reactions. 

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. 

The preparation of azulene (Expt 6.16) provides an interesting series of rearrangements.9 The key step in the synthesis is the intramolecular insertion reaction, carried out under conditions of high dilution, of the ketocarbene (22) into the 1,2-position of the benzene ring. The unstable norcaradiene (23) which is formed then ring-opens to the bicyclic trienone (24), which isomerises to the more stable cross-conjugated trienone (25) during isolation. Dehydration of the trienone with a mixture of phosphorus pentoxide and methanesulphonic acid yields azulene. 

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