Diazo imide

These results show for the first time, the reactivity of the double bond C = N with the 2 diazopropane that constitutes an efficient route for the preparation of new heterocyclic systems. In all cases, the reaction is peris-elective only the double bond C = N is affected diazo carbon attacks the quaternary carbon of the imidate 60 and not the double bond C = O (substrates 60b and 60c). Indeed, diazopropane reacts with ketones with inverse regioselectivity (with regards to imidates 60) to yield oxadiazoUnes [32,33] (Scheme 14). 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

The perfluoroacetamide catalysts, rhodium(II) trifluoroacetamidate [Rh2(tfm)4] and rhodium(II) perfluorobutyramidate [Rh2(pfbm)4], are interesting hybrid molecules that combine the features of the amidate and perfluorinated ligands. In early studies, these catalysts were shown to prefer insertion over cycloaddition [30]. They also demonstrated a preference for oxindole formation via aromatic C-H insertion [31], even over other potential reactions [86]. In still another example, rhodium(II) perfluorobutyramidate showed a preference for aromatic C-H insertion over pyridinium ylide formation, in the synthesis of an indole nucleus [32]. Despite this demonstrated propensity for aromatic insertion, the perfluorobutyramidate was shown to be an efficient catalyst for the generation of isomtinchnones [33]. The chemoselectivity of this catalyst was further demonstrated in the cycloaddition with ethyl vinyl ethers [87] and its application to diversity-oriented synthesis [88]. However, it was demonstrated that while diazo imides do form isomtinchnones under these conditions, the selectivity was completely reversed from that observed with rhodium(II) acetate [89, 90]. 

Doyle et al. (34) were the first group to generate isomiinchnones from diazo imides using Rh(II) catalysis. For example, isomiinchnone 60 was produced from diazo imide 59, but attempts to trap this species with ethyl acrylate were unsuccessful. The only material identified was the isomiinchnone hydrolysis product. This use of Rh(II) to generate a rhodium-carbenoid species from an a-diazo carbonyl compound is reminiscent of the first successful synthesis of... 

The first successful generation and trapping of isomiinchnones using this strategy was described independently by Maier et al. (36,37) and Padwa et al. (38,39). Maier and Evertz (36) were the first workers to report the intramolecular dipolar cycloaddition of isomiinchnones to alkenes, the reaction that Padwa would later exploit so spectacularly. Thus, diazo imide 62 was readily prepared from... 

Padwa et al. (38) also explored the rhodium-catalyzed reaction of diazo imides to form isomtinchnones (Scheme 10.10). Thus, 70 smoothly forms isomtinchnones 71 that can be intercepted in high yield with DM AD to give furans 73, following loss of methyl isocyanate from the cycloadducts 72. 

Kappe et al. (166) employed an isomilnchnone generation-trapping sequence to access conformationally restricted dihydropyrimidine derivatives as novel calcium channel modulators. For example, the conformationally restricted analogues 269 were prepared via intramolecular cycloadditions from the isomiinchnones generated from a-diazo imides 268. The structures of these cycloadducts were established by X-ray crystallography. 

Gowravaram and Gallop (169) adapted the rhodium-catalyzed generation of isomiinchnones from diazo imides to the solid-phase synthesis of furans, following a 1,3-dipolar cycloaddition reaction with alkynes. A variety of furans were prepared in this fashion. With unsymmetrical electron-deficient alkynes (e.g., methyl... 

Other cycloadditions were reported. The intramolecular cycloaddition of alkenylnitrones was 2q>phed to the synthesis of piperidines <99TL1397, 99JCS(P1)185>. Cycloaddition of an alkenyl azide afforded piperidines after reduction of the bicyclo triazole <99T1043, 99EJOC1407>. Similar to the cyclization of the diazo imide 2 in section 6.1.2.1, isomiinchnone intermediates can rearrange to functionalized piperidines <99JOCS56>. 

The isomunchnone dipole approach has been successfully applied to the synthesis of alkaloids ( )-lycopodine. As outlined in Scheme 9, 5-methylcyclohexenone 73 was converted to a-diazo imide 74 in seven steps. The diazo decomposition of 74 with Rh2(pfb)4 in CH2CI2 at 25 °C gives expected tandem ylide cycloaddition products 76 and... 

The para-diamines cannot be estimated by means of the diazo reaction. The following estimation is based on the formation of benzoquinone dichloro-imide when p-phenylenediamine in hydrochloric acid solution is added to a solution containing excess of sodium hypochlorite and sodium carbonate. 

The modification of carboxyl groups has been carried out (1) by esterification with dry methanol and HC1, (2) by esterification with aliphatic diazo compounds, (3) by the formation of adducts with carbodi-imides, or (4) by the formation of amides through activation with carbodiimides. Both complete and, apparently specific, partial modification of the 11 free carboxyl groups have been obtained. In general, the first method suffers from the denaturing medium, the second from incomplete reaction, and the third from the uncertain nature of the products. The fourth procedure is perhaps subject to the least question. There are a total of 11 free carboxyl groups in native RNase-A l (Val), 5/ (Asp), 5y(Glu). A summary of the derivatives is given in Table V. 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

Photolysis of the diazo compound 27 results in the formation of a P, Si substituted carbodi-imide 28. ... 

Essigsaure Diazo- -(benzolsulfonyl-imid)-ethylester E14b, 1160 (In-ether + R —S02 —N3)... 

The best results are obtained with trisyl azide, which again leads to high yields of the azide transfer product 2, especially if the enolate 1 is added to trisyl azide (see entries 1 and 2). Interestingly, the best chemoselectivity and, in addition, identical yields of azide (73%) result from the reaction of the lithium enolate with trisyl azide (entry 3). The reaction of the ester enolate 1 with trisyl azide is less sensitive to the nature of the enolate metal than is the corresponding imide enolate reaction (see Section 7.1.1.). Acetic acid quench, on the other hand, again proved to be useful. Unfortunately, bis-azidation to 3 and diazo transfer to 4 are also observed. 

When the chiral, cyclic imide 1 is subjected to the azidation procedure outlined in detail in Section 7.1.1., only modest levels of asymmetric induction are observed for 2 2 (determined by H NMR). Moreover, 10% of diazo transfer occurs (not shown). 

Failure to use 2,4,6-Triisopropylbenzenesulfonyl Azide results in substantial diazo imide formation. However, optimization for the formation of the a-diazo imide compounds can be achieved with NaHMDS and p-nitrobenzenesulfonyl azide, followed by a neutral quench (eq 27). These diazo compounds, however, have failed to demonstrate utility in asymmetric carbenoid chemistry. ... 

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