Diazocarbonyls

Stereoselective asymmetric synthesis with participation of diazocarbonyl intermediates in the presence of catalysts possessing chiral heterocyclic ligands 97CC983. 

Synthesis of oxazoles from diazocarbonyl compounds 97PHC1. 

Diazoester aziridinations may be carried out in ionic liquids [39]. Other carbene equivalents have been investigated in aziridination reactions, though not to the same extent as diazocarbonyl compounds. Dibromo(tert-butyldimethylsilyl)me-thyllithium, for example, aziridinates N-arylimines to give l-bromo-2-aryl-3-silyla-ziridines these compounds function as useful synthetic intermediates, reacting... 

A special method involves the carbenoid displacement reaction with diazocarbonyl compounds75, which is also used in an intramolecular fashion76. 

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]. 

Although 2-acyl-2//-azirines are known to give oxazoles upon irradiation, the reaction is wavelength dependent, and isoxazoles are formed at some wavelengths, as they are in the thermal rearrangement of 2-acyl-2//-azirines.<74TL29,75JA4682> Since the thermal reaction of diazocarbonyl compounds with nitriles leads to oxazole formation, it would seem that mechanistic path C is unlikely in these reactions. 

The role of Lewis acids in the formation of oxazoles from diazocarbonyl compounds and nitriles has primarily been studied independently by two groups. Doyle et al. first reported the use of aluminium(III) chloride as a catalyst for the decomposition of diazoketones.<78TL2247> In a more detailed study, a range of Lewis acids was screened for catalytic activity, using diazoacetophenone la and acetonitrile as the test reaction.<80JOC3657> Of the catalysts employed, boron trifluoride etherate was found to be the catalyst of choice, due to the low yield of the 1-halogenated side-product 17 (X = Cl or F) compared to 2-methyI-5-phenyloxazole 18. Unfortunately, it was found that in the case of boron trifluoride etherate, the nitrile had to be used in a ten-fold excess, however the use of antimony(V) fluoride allowed the use of the nitrile in only a three fold excess (Table 1). 

Many of the early workers who studied the thermal decomposition reactions of diazocarbonyl compounds found that the addition of copper metal or copper salts allowed the reaction to be achieved at a lower temperature,<63AG(E)565, 64CB2628, 73JOU431> although no detailed study of this catalytic effect was undertaken. Alonso and Jano studied the copper-salt reaction of ethyl diazopyruvate 26 with acetonitrile and benzonitrile. The... 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

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). 

The role of the rhodium is probably two-fold. Initially due to its Lewis acidity it reversibly forms a complex with the nitrile nitriles are known to complex to the free axial coordination sites in rhodium(II) carboxylates as evidenced by the change of colour upon addition of a nitrile to a solution of rhodium(II) acetate, and by X-ray crystallography. Secondly the metal catalyses the decomposition of the diazocarbonyl compound to give a transient metallocarbene which reacts with the nitrile to give a nitrile ylide intermediate. Whether the nitrile ylide is metal bound or not is unclear. 

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>... 

To date most of the nitriles studied have been simple alkyl or aromatic derivatives with little other functionality. We recently attempted to extend the reaction to iV-protected a-aminonitriles, derived by dehydration of a-aminoacid amides (Path A, Scheme 25), but this proved unsatisfactory, and therefore we investigated an alternative diazocarbonyl based route in which the order of steps was reversed, i.e. a rhodium catalysed N-H insertion reaction on the amide followed by cyclodehydration to the oxazole (Path B, Scheme 25). 

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 ... 

In the same area, good levels of enantioselectivity have been achieved in intramolecular C H insertion reactions of a-diazocarbonyl compounds... 

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