Hydrolysis of diazo ketones

Reduction of N-nitro compounds 0-5 Hydrolysis of diazo ketones... 

Hydrolysis of enol esters 0-76 Reduction of halo ketones 0-78 Reduction of hydroxy ketones 0-82 Reduction of diazo ketones or nitro ketones... 

In order to prepare an acid, a dioxan solution of the diazo ketone is added slowly to a suspension of silver oxide in a dilute solution of sodium thiosulphate Iftheco)iversion to the acid yields unsatisfactory results, it is usually advisable to prepare the ester or amide, which are generally obtained in good yields hydrolysis of the derivative gives the free acid. 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

Following Scheme 4, L-a-aminosuberic acid can be obtained from iV-tosyI -L-gl utamic acid (5, n=2), upon protection of the a-carboxy and tosylamino groups as an oxazolidone 6, by extension of the side chain with the Amdt-Eistert method via the diazo ketone 7 by one methylene moiety in each cycle to produce in subsequent steps the L-a-aminoadipic acid [(5)-2-aminohexanedioic acid, 8, n = 2], L-a-aminopimelic acid [(5)-2-aminoheptanedioic acid, 8, n = 3] and finally L-a-aminosuberic acid [(5)-2-aminooctanedioic acid, 8, n = 4]J22 Treatment with HBr in AcOH was the method of choice for the acidolytic hydrolysis of the tosyl group. 23 ... 

GRUNDMANN ALDEHYDE SYNTHESIS. Transformation of an acid into an aldehyde of the same chain length by conversion of the acid chloride via the diazo ketone to the acetoxy ketone, reduction with aluminum isopropoxide and hydrolysis to the glycol, and cleavage with lead tetraacetate. 

Extension of the C-tether to m = 2 can be achieved by subjecting diazo ketone 58 to the Wolff rearrangement using silver benzoate, triethyl-amine and methanol. Hydrolysis of the resulting methyl 4-methyl-4-[(E)-phenyldiazenyllpentanoate (74) (94%) yields the acid 75 (84%). Conversion of 75 into the mixed anhydride 76 followed by treatment with diazomethane gives 1 -diazo-5-methyl-5-[(E)-phenyldiazenyl]hexan-2-one (77) in low yield (19%) and methyl ester 74 (78%) (Scheme 18). 

Thietanones also have been obtained by treatment of aliphatic ketones with an a-methylene group with thionyl chloride, usually in the presence of a base as shown for the synthesis of 359. A 3-thietanone was suggested as a possible structure for the product obtained by the acid-catalyzed hydrolysis of the bis-thioglycolic thioacetal of substituted benzaldehydes, but an elemental analysis was the only evidence. Treatment of l-diazo-3-phenylthio-2-propanone with acid gives the -phenyl salt of 3-thietanone (Section VII.1.). Similar 5-alkyl salts may be intermediates, but they readily decompose either by loss of the 5-alkyl group or... 

Bestmann and co-workers developed a synthesis of o-ketoaldehydes which involves in the first step reaction of a diazo ketone with triphenylphosphine to form a phosphorazane (3). This can be converted into the a-ketoaldehyde (6) by hydrolysis o o... 

Dihydrothebainone [ix], obtained by the catalytic reduction of thebainone-A [v] [1] and thebainone-B [xm] [13], can be most conveniently prepared by the catalytic reduction of thebaine in acid solution [9-12, 25], and it can also be obtained by the hydrolysis of its two enol ethers (see below). It is a phenolic, ketonic, base, that shows the diazo-reaction in dilutions up to 1 in 2,000,000 [26-27], gives a methyl ether [28], oxime [9], semicarbazone [29], and a benzylidene [30] and piperonylidene [25] derivative. The optical antipode is produced by the sodium amalgam reduction of sinomenine [xxvi] and is known as desmethoxydihydrosinomenine [31]. 

As reported by Thomas and Fritzen, a-diazo ketones react with preformed iminium salts with loss of N2 to a ord vinylogous amides. An example is shown in Scheme 6 involving an a-diazo ketone derivative (42) of spectinomycin, which upon treatment with salt (31) affords enamide (44) via the diazo-nium adduct (43). Triethylamine must be present in the reaction to prevent hydrolysis of the enamide. If the iodide salt (30) is used instead of the chloride salt (31), multiple products are obtained due to the higher reactivity of the counterion. This example elegandy portrays the degree of complex functionality which can be tolerated in Mannich reactions using preformed iminium salts. 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

Hydroxymethyl ketones. Preparation of ketones of this type by reaction of acid chlorides and diazomethane followed by hydrolysis of the diazo ketone is not practical for large scale work. The desired transformation can be carried out with the new reagent 1, a derivative of ketene. A typical example is formulated in equation (I). Aromatic acid chlorides react more slowly with 1 than aliphatic acid... 

It should be noted that there are several other means by which the key a-aminocarbonyl intermediates of the Gutknecht synthesis may be prepared besides by the reduction of a-oximino ketones. The oxidation of a-aminoalcohols, reduction of a-amino acids and their derivatives, hydrolysis of a-acetamido ketones formed from a-amino acids and acetic anhydride by the Dakin-West reaction, and the reduction of a-azido, a-diazo, and a-nitro ketones all lead to dihydropyrazines by way of a-amino ketones. The Gastaldi synthesis provides an alternate use of a-oximino ketones, to afford dicyano pyrazines. ... 

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. " ... 

Since Theodor Curtius reported the synthesis of ethyl diazoacetate in 1883, Buchner had investigated its reactions with carbonyl compounds, alkenes, alkynes, and aromatic compounds for more than 30 years.His extensive contributions in this area resulted in two reactions named in his honor the Buchner-Curtius-Schlotterbeck reaction (formation of ketones from aldehydes and aliphatic diazo compounds) and the Buchner reaction. The prototypical example of the latter involves the thermal or photochemical reaction of ethyl diazoacetate with benzene to give (via norcaradiene 7) a mixture of four isomeric cycloheptatrienes 8-11. Initially, Buchner believed that a single norcaradiene product 7 was generated from this reaction, but later, he realized that the hydrolysis of the product afforded a mixture of four isomeric carboxylix acids. The norcaradiene formulation persisted until 1956 when Doering reinvestigated this reaction. ... 

The same group also reports an alternative method of generating the intermediate ( )-vinyloxyboranes from diazo-ketones and trialkylboranes. Isomerization of (E) - to (Z) -intermediates can be effected simply, and both isomers are again used in stereoselective aldol syntheses. Interestingly, hydrolysis of the intermediates leads directly to ketones, and hence constitutes a synthesis of ketones from carboxylic acid derivatives (Scheme 77). Evans etal. have reported similar results from the use of boron enolates in the stereochemical control of aldol reactions. ... 

ArCH=NPhO to bis-(trifluoromethyl)-acetylene rearrange to the oxazolines (318), which, on hydrolysis and subsequent cyclisation, yield the indole (319). Indole-3-carboxamides (322 R R = H, alkyl, or Ar) are produced by irradiating the diazo-ketones (320) in the presence of amines HNR R the Wolff rearrangement product (321) is a likely intermediate in this reaction. Crossover experiments show that the thermal rearrangement of the 3if-indole (323) to... 

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