Carbenes intramolecular rearrangements

Cydizations and Other Intramolecular Rearrangements of Carbene Complexes... 

In contrast to carbenes of the AX2 type, which contain three atoms, generation of carbenes with a more complex structure under photolysis or vacuum pyrolysis conditions may be accompanied by intramolecular rearrangements. Thus, the matrix isolation study of the vacuum pyrolysis... 

The identification of unknown chemical compounds isolated in inert gas matrices is nowadays facilitated by comparison of the measured IR spectra with those computed at reliable levels of ab initio or density functional theory (DFT). Furthermore, the observed reactivity of matrix isolated species can in some instances be explained with the help of computed reaction energies and barriers for intramolecular rearrangements. Hence, electronic structure methods developed into a useful tool for the matrix isolation community. In this chapter, we will give an overview of the various theoretical methods and their limitations when employed in carbene chemistry. For a more detailed qualitative description of the merits and drawbacks of commonly used electronic structure methods, especially for open-shell systems, the reader is referred to the introductory guide of Bally and Borden.29... 

Electrophilic carbene complexes generated from diazoalkanes and rhodium or copper salts can undergo 0-H insertion reactions and S-alkylations. These highly electrophilic carbene complexes can, moreover, also undergo intramolecular rearrangements. These reactions are characteristic of acceptor-substituted carbene complexes and will be treated in Section 4.2. 

Note that despite the death of the carbene-alkene complex in the study of benzylchlorocarbene (53) (see above), benzene is able to modulate the intramolecular reactivity of ferf-butylcarbene. ° Some sort of complex must be involved here. Benzene complexes with carbenes have been proposed before. Kahn and Goodman found a transient species on photolysis of diazomethane in benzene, and attributed it to a complex. Moss et al. found that benzene modulated the ratio of intramolecular rearrangement to intermolecular addition for three different carbenes (53), chloropropylcarbene, and chlorocyclopropylcarbene, and proposed that a carbene-benzene complex 70 favored the intramolecular rearrangement (Scheme 7.31). Their proposal was bolstered by ab initio calculations that found such stable complexes for CCI2 and CH3CCI. 

Phenyl azides (azidoarenes), introduced by Knowles and co-workers,[8 9] are the most abundantly used class of photophores. Examples include 4-azidophenylalanine (1) and 4-azido-3-nitrophenylalanine (4) (Scheme 1). Irradiation (<300 nm) of phenyl azide (13) generates nitrene 14, electrophilic in nature, which prefers insertion into O—H and N—H bonds over C—H bonds. Nitrenes are considerably less reactive and, therefore, more selective than carbenes. Nevertheless, due to their short life span (0.1-1 ms) they react indiscriminately with virtually any amino add residue in the target protein.1101 Intramolecular rearrangements do not compete effectively with intermolecular proton abstraction and insertion reactions (Scheme 4). 

The thermal decompositions of diazirines appear to be homogeneous, uni-molecular processes " . Cyclic diazirines decompose with a slightly smaller activation energy (Table 14) due to ring strain. Product distributions presumably result from intramolecular rearrangement of carbene intermediates, and the fact that the product ratios differ from those obtained on photolysis supports the hypothesis that the carbenes generated photolytically contain considerable excess vibrational energy. 

Photolysis of diazirine 63 included within the cavities of CyDs presumably formed carbene 64 CyD ICs, i.e., 64 CyD (Equation (7)). The lifetime (t) of carbene 64 was expected to be prolonged due to the preclusion of intermolecular reactions (Scheme 14), such as azine 70 formation and solvent insertion, i.e., 64->72. However, interfering innermolecular reactions21 between the host and guest were indicated (vide infra). Therefore, the latent intramolecular rearrangement of carbene 64 to cyclic allene 65, a rare transformation seen under the forbidding, low-temperature... 

Like diazoketones, acyl azides lose nitrogen when heated or irradiated. The end result is an isocyanate, formed either directly from the acyl aade, in a reaction called the Curtius rearrangement after Theodore Curtius (1857-1928), or by intramolecular rearrangement of a nitrene, which is the nitrogen analogue of a carbene (Fig. 18.70). For most acyl azides, it is known that the isocyanate is formed by direct rearrangement of the acyl compound and that the nitrene, though also formed from the azide, is not involved in isocyanate production. 

The above—considered reactions of singlet carbenes involving cycloaddition and bond insertion processes by no means represent all the reaction diversity they are capable of At the same time, precisely these reactions exhibit all the principal steps of the most important intramolecular rearrangements of carbenes, such as the reactions of 1,2-shift, of cycle extension, etc. [82-84]. 

The generation of carbenes by reaction of metastable singlet carbon atoms with aldehydes and ketones has been described in detail the distribution of intramolecular rearrangement products is identical with that observed from toluene-p-sulphonylhydrazone-derived carbenes. Suitably substituted carbenes generated in this manner, e.g. that prepared from (4), can be trapped by olefins, when the cyclopropane (5) produced retains the original olefin geometry, indicative of a singlet species. 

Phenylcarbene (12). Aromatic carbenes have received considerable attention as they undergo fascinating intramolecular rearrangements. Recently, theoretical investigations by... 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

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