Carbenes, from hydrazones

Among the many reaction products obtained from hydrazones and osazones that offer promise to synthetic chemists are the carbenes generated from azirines and sulfonylhydrazono-1,5-lactones by irradiation.299 300... 

This section deals with the photochemical loss of nitrogen from compounds containing a diazo group. As a result of the scale of the work some material has had to be excluded. Within this section paths to the synthesis of diazo compounds from hydrazones have been omitted. Much of the use of diazo compounds and the photochemical (and thermal) elimination of nitrogen is in the generation of carbenes, from which a variety of reactions of synthetic value can occur. This short section is aimed mainly at that area, although some reference will be made to the elegant low-temperature studies that have been carried out. 

Acylation of 2- -octylthiochroman by AczO is quantitative at the 6-position (Equation 23) <2003PS(178)993> and benzoylation of thioxanthene occurs at the 2- and 7-positions and both ketone functions have been converted into the hydrazones and thence the diazo compound 277. The bis-carbene derived from 277 by cryogenic photolysis has been used to study magnetic coupling interactions through the sulfur atom (Scheme 32) <1997JA8058>. 

The Shapiro reaction has been used as a method for the initiation of anionic cyclisations, as described in section 7.2. Hydrazones derived from 23 are particularly valuable in this area, not only as the source of vinyllithiums but also as carbene equivalents. Nucleophilic addition to 26 promotes the collapse of the product lithioamine to give the organolithium 27. 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

Diazo-compounds can in turn be generated photochemically from sodium salts of toluenesulphonyl hydrazones. Irradiation of the cyclobutane tosylhydrazone (44) gave trans-tricyclo[5.1.0.0 ]-octane (45 R=Me) by the pathway shown in Scheme 4 44 the tricycle (45 R=H) can also be obtained by photoelimination of nitrogen from the diazatricyclo[ 5.2.1.0 4]decene (46). The unexpected conversion of the anthracenocycloheptatriene derivative (47) into triptycene with loss of one carbon atom was observed on irradiation in tetrahydrofuran 4 the mechanism of this unusual reaction remains obscure and merits further investigation, but neither 1-triptycenyl nor 2-triptycenyl carbene appears to be an intermediate in this transformation. 

Photodecomposition of sodium salts of toluene-p-sulphonylhydrazones is a well-established route for the generation of carbenes. Irradiation of the lithium salt of the hydrazone (150) or the diazoalkenyl ether (151) derived from it afforded... 

Diazo compounds, precursors to carbenes, were prepared by the oxidation with active manganese(IV) oxide (or mercury(II) oxide) of the corresponding hydrazones which in turn were obtained from the corresponding ketones by the reaction with anhydrous hydrazine (or hydrazine monohydrate). This method was employed for the introduction of the diazo groups in most of our compounds... 

Semi-empirical INDO calculations have been carried out on cycloheptatrienyli-dene, cycloheptatetraene, and related systems. The most stable structure for cyclo-heptatetraene was found to be non-planar with a C2 axis of symmetry, and should be more stable than the carbene form. Even though most of the chemistry of cyclo-heptatrienylidene is consistent with carbene behaviour, the allene and carbene forms may be in equilibrium, and the position of equilibrium solvent-dependent. In fact decomposition of the sodium salt of the toluene-p-sulphonyl-hydrazone (163) gives dimeric products formed from allene (164), and addition of cycloheptatrienylidene to tetracyclones gives products derived from the adduct (165). ... 

The generation of carbenes by the thermolysis of lithium or sodium salts of tosyl-hydrazones continues to provide interesting chemistry. The selectivity exhibited by 7-bicyclo[2,2,l]hept-2-enylidene (generated from the corresponding tosylhydrazone) is quite the opposite to that expected from theoretical predictions and earlier studies. Addition to 3,3-dimethylbut-l-ene affords the syn-isomer (118) as the major adduct and consequently any carbene-7i interaction resulting in bridge bending cannot of itself dominate the stereoselectivity of addition. Furthermore, the intramolecular insertion products of 2-methylbicyclo[2,2,l]hept-2-en-7-ylidene have been characterized and, from the product ratios, the species behaves as a true carbene. A 3-furyl-... 

Bamford-Stevens and Shapiro Reactions. The Bamford-Stevens reaction is used to obtain unsaturated compounds from tosylhydrazones. A base is required to generate its monoanion, which thermally decomposes to yield the corresponding di-azo derivatives. These reactive species evolve to give an aUcene through carbenium ions in protic solvents or carbenes in aprotic solvents. The thermal decomposition of the monoanions of trisyl-hydrazones is commonly used to obtain diazoalkanes for different applications such as functionalization of solid supports, epox-idation and alkenylation of aldehydes, or the study of radicals and carbenes The functionalization of a Merrifield resin with... 

A novel method related to the insertion of carbenes into N-H bonds has been reported. It involves the reductive coupling of A-tosylhydrazones under mild basic conditions to afford the corresponding A-alkylated hydrazones in moderate to good yields The procedure benefits from the well-known ability of A-tosylhydrazones to generate carbenes in situ, the so-formed carbene finally undergoing insertion into the N-H bond of the second equivalent of A-tosylhydrazones. 

Extension of this work to the diastereoselective synthesis of y-lactams from N-sulfonyl aldimines [93] and ketimines [94] was subsequently reported. Scheldt and coworkers disclosed an enantioselective version (up to 98% ee) from reactive hydrazones in the initial demonstration of cooperative NHC/Lewis acid catalysis using a bulky, chiral triazolium salt and catalytic Mg(OBu )2 [95]. Rovis and coworkers synthesized y-lactams 109 enantioselectively using a chiral N-C Fs triazolium salt (Scheme 18.19). A weak carboxylate base was sufficient to partially deprotonate the precatalyst 108 in situ, and the carboxylic acid formed could activate the N-Ar imine acceptor 107 via protonation [lib]. In all these cases, a fine balance must exist between sufficient electrophilicity vis-a-vis the competing enal and reversible addition of the carbene to the imine/hydrazone/iminium or to the Lewis acid. 

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