Diazocarbonyl compounds synthesis

In contrast to the aforementioned diazoalkanes and aryldiazomethanes, whose instability and high explosiveness have diminished their general utility as a monomer for polymer synthesis, diazocarbonyl compounds have been known to be rather stable and frequently used as a reagent for organic synthesis [35, 36], In particular, transition metal catalyzed cyclopropanation of diazocarbonyl compounds with C=C double bonds has been extensively investigated and established as a very useful method for the formation of cyclopropane frameworks, where application for asymmetric synthesis using various optically active ligands has been successfully achieved. 

Synthesis of oxazoles from diazocarbonyl compounds 97PHC1. 

Diazocarbonyl compounds are especially useful in these reactions because of their ease of formation, relative stability, and controlled reactivity in catalytic reactions [ 1,11 ]. As outlined in Scheme 1, a wide diversity of methodologies are available for this synthesis, with access dependent on the nature of Z. Vinyl- and aryldiazoacetates are accessible by other pathways [2]. The order of reactivity toward diazo decomposition has diazoketones and diazoacetates much more reactive than diazoacetoacetates or diazomalonates. However, the influence of electronic effects on reactivities is more pronounced with phenyl- and vinyl-diazoacetates than with diazoacetoacetates and, especially, diazoacetates [12]. 

Helquist s work on the use of diazomalonate in the synthesis of oxazoles has been extended to other diazocarbonyl compounds in our own laboratory.<92TL7769, 94T3761> Thus it was found that sulfonyl-, phosphonyl- and cyano-substituted diazoesters gave the corresponding 4-functionalised oxazoles 30 in acceptable yield (Scheme 20). In many cases the yield of oxazole was significantly improved by the use of rhodium(II) trifluoroacetamide as catalyst. The 4-cyano-oxazole 30 (R = Me, Z = CN) proved interesting in that it allowed the formation of a bis-oxazole 31 by a second rhodium catalysed reaction (Scheme 20). 

Whatever the exact mechanism, the rhodium(II) catalysed reaction of diazocarbonyl compounds with nitriles is a useful route to oxazoles. A further example from our own laboratory illustrates the use of the reaction in the synthesis of the oxazolylindole alkaloids pimprinine 43a, pimprinethine 43b, and WS-30581A 43c. Diazoacetylindole 42 reacted with simple nitriles in the presence of rhodium(ll) trifluoroacetamide to give the corresponding oxazoles, deprotection of which gave the natural products 43 (Scheme 24).<94S1021>... 

Progress in Heterocyclic Chemistiy (PHC) Volume 9 reviews critically the heterocyclic literature published mainly in 1996. The first two chapters are review articles. Chapter 1 by C.J. Moody and K.J. Doyle deals with "The Synthesis of Oxazoles from Diazocarbonyl Compounds," and Chapter 2 by J.A. Sikorski provides a detailed account of the heterocyclic chemistry suiTounding the remarkable herbicide glyphosate ("Roundup" ). This latter chapter illustrates the role that heterocyclic chemistry plays in other areas of modem chemistry, since glyphosate is a far cry from being heterocyclic ... 

Synthesis of a-alkoxyketones from a-diazocarbonyl compounds and alcohols under the influence of copper or rhodium catalysts is well established as an alternative to the Lewis or proton acid catalyzed variant of this synthetic transformation. The sole recent contribution to the aspect of general reactivity deals with the competition between O/H insertion and cyclopropanation of unsaturated alcohols 162). The results... 

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

Carbonyl ylides can be viewed as an adduct between a carbonyl group and a carbene and, in fact, some ylides have been prepared this way (see above). The application of carbonyl ylides to the synthesis of complex natural products has been greatly advanced by the finding that stabilized carbenoids can be generated by the decomposition of ot-diazocarbonyl compounds with copper and rhodium complexes. The metallocarbenoids formed by this method are highly electrophilic on carbon and readily add nucleophiles such as the oxygen of many carbonyl derivatives to form carbonyl ylides. This type of reaction is in fact quite old with the first report being the addition of diazomalonate and benzaldehyde (33,34). 

The (ri" -diene tricarbonyliron)-substituted diazocarbonyl compounds 25 have been found to undergo 1,3-dipolar cycloaddition with methyl acrylate in high yield, but with little or no diastereoselectivity (56). Nevertheless, the facile chromatographic separation of the diastereomeric products 26a,b and 27a,b (Scheme 8.8), permits the synthesis of pure enantiomers when optically active diazo compounds (25) [enantiomeric excess (ee) >96%] are employed. When the reaction of 25 (R = C02Et) with methyl acrylate was carried out at 70 °C, cyclopropanes instead of A -pyrazolines were formed. The enantiomerically pure... 

TABLE 8.3. SYNTHESIS OE 1,3-OXAZOEES EROM a-DIAZOCARBONYL COMPOUNDS AND NITRIDES... 

TABLE 8.3. SYNTHESIS OF 1,3-OX AZOLES FROM a-DIAZOCARBONYL COMPOUNDS AND NITRILES... 

Cainelli and coworkers have reported the synthesis of a class of 4-(2-oxoethy-lidene)azetidin-2-ones (IV, Fig. 14) that could be carried out by a novel Lewis acid mediated reactions of 4-acetoxyazetidin-2-ones with a-diazocarbonyl compounds [277]. 

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