Secondary -diazo ketones

A neutral diazo compound can be considered as both a nucleophile and an electrophile. Thus, it can be substituted by the combination of an electrophilic moiety and a nucleophilic moiety (X+ Nu ") (Scheme 8). In practice, the diazomethyl group is transformed to the fluoromethyl group by treatment with hydrogen fluoride/pyridine mixture (70 30 w/w) (X = H Nu = F), or to the halofluoromethyl group by addition of A-halosuccinimide in the same medium (X = Cl, Br, I Nu = F), e.g. formation of l.16 The reaction can be performed on secondary diazo alkanes, diazo ketones or diazo esters.16 90 316... 

Wolff rearrangement of /)-diazenyl-a -diazo ketone 83 in the presence of water, methanol (or even with primary and secondary amines) under varied reaction conditions comes with surprise Instead of the expected homologous acid 89, methyl ester 90 (or the respective amide), 2-phenylcinnolin-3(2E0-one (91) is the only product indicative of the anticipated in situ formation of ketene intermediate 88 (Scheme 22). Obviously, the apparent 67r-electrocyclization reaction prevails forming the isolated heterocyclic product 91, a so far unknown compound. 

Maas and co-workers have elaborated the approach to l-oxa-2-silacyclo-pentene derivatives based on cyclization of a siloxyalkylidenecarbene. Thus, as a result of intramolecular aliphatic C — H insertion of the carbene derived from diazo ketone 576, l-oxa-2-sila-4-cyclopentenes 577 were obtained in high yields. Here, the insertion may occur in primary, secondary, and tertiary C—H bonds (87CB635 94JOM115). When no C—H bond is adjacent to the Si atom, as in substrate 578, the cyclopropanation of a benzene ring with concomitant ring expansion may result in oxasilacyclopentene 579 (86CC1782). Photolysis or catalytic decomposition of bissilanes 580 furnishes fused bicyclic heterocycles 581 in moderate yields (90JOM229). 

The Dakin-West reaction provides a source of V-acyl-a-amino ketones (e.g. 1), which Franzen has exploited for the synthesis of secondary diazo ketones, thereby avoiding the need to use the higher homologs of diazomethane (Scheme 2). The ketoamide (1) is first nitrosated using N2O3 in glacial acetic acid. The oily Af-nitroso derivative is separated and then decomposed with sodium methoxide in methanol to give the diazo ketone (2) yields are about 50-60%. 

Since 0i refers to a proton in flight , which is loosely bound, it will be considerably less than unity, leading to k - /kP- > 1, although the factor P (with / = 0.69) will produce a solvent isotope effect which is smaller than that commonly found for pure primary effects. This is in fact what is found for a number of reactions in which the rate-determining step is believed to involve proton-transfer from hydronium ion to carbon, typical values being 1.7 for the reaction of the enolate ion of 2-acetylcyclohexanone with hydronium ion, 1.7-3.0 for the hydrolysis of vinyl ethers by strong aqueous acids,1.7-3.2 for the acid-catalysed cleavage of alkyl-mercuric iodides, and 1.7-2.5 for the hydrolysis of a number of secondary diazo-ketones. " ... 

An attractive alternative to the direct preparation of enamines from mono-substituted phosphonate reagents is the use of dimethyl diazomethylphosphonate (Me0)2P(0)CH= N2. Treatment of this diazo compound with t-BuOK (or with LiOH or K2C03), followed by various ketones in the presence of secondary amines, delivered the corresponding enamines251-253 (equation 17). In the presence of amines, (MeO)2P(0)CH= N2 and RCHO afforded the terminal acetylenes RC=CH. 

In addition, manganese oxide oxidizes benzylic methyl or methylene to carbonyl [814] and cleaves the carbon bonds of vicinal diols [577, 522]. It converts amines into imines [577, 525] tertiary amines into secondary amines [572], formamides [526, 527, 525], or ketones aromatic primary amines [575, 525] and hydrazo compounds [525] into azo compounds hy-droxylamines into nitroso [576] or nitro compounds [525] hydrazones into diazo compounds [520] phosphines into phosphine oxides [575] thiols into disulfides [576] and sulfides into sulfoxides [541]. 

The Regitz reaction provides a gateway for the synthesis of the following diazo derivatives cyclopentadienes, cyclohexadienes, ketones, 1,2-, and 1,3-diketones and their derivatives, (3-keto esters, a-iminoketones, a-ketohydrazones, amino-1,3-diketones, nitro-1,3-diketones and 1,3,5-triketones. Secondary reactions of diazo compounds lead to heterocycles such as 1,3,5-triazoles, 1,2,3-thiadiiazoles, and pyrazolines. 

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