Nitrogen-containing carbenes

In some cases, nitrogen-containing carbenes, generated by thermolysis, give five-mem bered heterocycles as a result of a formal 1,3-dipolar cycloaddition (Scheme 23) [81AG(E)113 85CB634],... 

Reviews of nitrogen-containing carbenes are available.Although only a few stable yhdes have been made fi"om keto- or carbalkoxycarbenes, 269 and 272 form a stable yhdes with alkyl sulfides and isoquinoline,such as 270 and 273, respectively (Scheme 52). 

Table 2.21. Preparation of five-membered, nitrogen-containing heterocycles by rearrangement of chromium-carbene-derived ammonium ylides.

Photolysis or thermolysis of heteroatom-substituted chromium carbene complexes can lead to the formation of ketene-like intermediates (cf. Sections 2.2.3 and 2.2.5). The reaction of these intermediates with tertiary amines can yield ammonium ylides, which can undergo Stevens rearrangement [294,365,366] (see also Entry 6, Table 2.14 and Experimental Procedure 2.2.1). This reaction sequence has been used to prepare pyrrolidones and other nitrogen-containing heterocycles. Examples of such reactions are given in Figure 2.31 and Table 2.21. 

Table 4.11. Preparation of nitrogen-containing heterocycles by intramolecular N-H insertion of electrophilic carbene complexes.

A nitrene is a nitrogen-containing compound in which the nitrogen has only a sextet of electrons. Such a species is neutral but electron-deficient cf. carbenes (Section 5.6). 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Carbene reactions provide a versatile approach to the synthesis of five-membered nitrogen-containing rings. Of particular importance here are intramolecular insertion of a carbene into C — H and N — H bonds, addition onto multiple carbon-carbon bonds, intermediate formation of ylides as a result of carbene addition onto the heteroatom followed by rearrangement, cycloaddition, and cyclization. 

A number of nitrogen-containing five-membered heterocycles were synthesized through ring contraction accompanied by diverse carbene reactions whose mechanisms are not always well established. 

Diazirines were detected when there was broad activity in the carbene field. From their structure, cleavage to nitrogen and carbene was foreseeable, and this was shown to occur on photolysis as well as on thermolysis. As early as 1962, Frey and Stevens in a series of papers reported on photolysis of simple diazirines. According to these authors, diazirines are especially fit for the study of excited intermediates and their stabilization products. Products of isomerization of carbenes, i.e., olefins and cyclopropanes, are formed containing more energy than is necessary for their further decomposition. Their stabilization by loss of energy to partners competes with stabilization by subsequent reactions. 

With lithiated imidazoles, only bis(carbene) complexes are formed, although careful adjustment of the conditions can lead to a compound which contains carbene ligands resulting from both alkylation and protonation411. A similar methodology is applicable with isothiazolyl lithium. In the product the nitrogen atom occupies a position remote from the coordinated carbon (equation 93)412. 

The observation that hetarylcarbenes alwa3rs rearrange to nitrenes, when possible, suggests that nitrenes are thermodynamically more stable than carbenes (cf. Section V.2). That this is so can be seen by comparing the heats of formation of CH2 and NH (triplet ground states) with those of some "normal molecules (Table 26). Normal nitrogen containing compounds have heats of formation... 

The reactions to be described in this chapter have in common the formal involvement of even-electron intermediates having unfilled orbitals of low energy. The most familiar of these intermediates are carbonium ions. Sections 8.4 and 8.5 contain examples of fragmentation and rearrangement reactions of carbonium ions that are of synthetic value the discussion of these reactions supplements the mechanistically oriented discussion presented in Part A, Chapter 5. Also important are the neutral divalent carbon and monovalent nitrogen species, carbenes and nitrenes, respectively. 

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