Diazoketone preparation

A solution of the diazoketone prepared above (1.39 g, 3.52 mmol) in MeOH (60 ml) was placed in a 100 ml pyrex test tube, and irradiated by a Hanovia 30620 type medium pressure UV arc under constant cooling by running H20 for 48 h. The reaction mixture was concentrated in vacuo to give a yellow oil, which was purified by column chromatography over silica gel (hexane-Et20, 3 2) to afford 0.96 g (68%) of methyl (methyl 2,3-di-0-benzyl-4-deoxy-a-D-glucoheptopyranosiduronate as a colorless viscous oil. 

One method for the synthesis of hydroxyalkyl-substituted P-lactams is by the Staudinger reaction, the most frequently used method for the synthesis of P-lactams.86 This method for the preparation of 4-acetoxy- and 4-formyl-substituted P-lactams involves the use of diazoketones prepared from amino acids. These diazoketones are precursors for ketenes, in a diastereoselective, photochemically induced reaction to produce exclusively tram-substituted P-lactams. The use of cinnamaldimines 96, considered as vinylogous benzaldimines, resulted in the formation of styryl-substituted P-lactams. Ozonolysis, followed by reductive workup with dimethyl sulfide, led to the formation of the aldehyde 97, whereas addition of trimethyl orthoformate permitted the production of the dimethyl acetal 98 (Scheme 11.26). 

Esters of a-hydroxymethyl ketones are formed by heating diazoketones with organic acids. The crude diazoketones prepared from acyl halides and diazomethane may be used. The over-all yields of acetoxy ketones, ArCOCHjO,CCHj, from benzoyl and /3-naphthoyl chlorides are 55% and 72%, respectively. ... 

A total synthesis of a mixture of diastereoisomers having the constitution of magnolamine was reported recently by Kametani and Yagi 26). Arndt-Eistert reaction of 3-methoxy-4-benzyloxyphenethylamine with the diazoketone prepared from the acid chloride XLVII furnished the diamide LI. Bischler-Napieralski cyclization of the latter afforded the dihydroisoquinoline derivative XLIX, whose methiodide was reduced with sodium borohydride to the stereoisomers of constitution XLV. Debenzylation of the latter mixture gave a noncrystalline product which behaved similarly on paper chromatography to magnolamine and had IR- and UV-spectra which were superimposable on those of the alkaloid. 

Full details are also available of the structure elucidation of elaeokanines A-E, and elaeokanidines A-C, the leaf alkaloids of E. kaniensis Schltr. further, the structures of elaeokanines A-C have been confirmed by synthesis. The reaction of the diazoketone prepared from butyroyl chloride and diazomethane with pyrrole in the presence of copper powder gave the ketone (9), which was hydrogenated to the basic pyrrolidine ketone (10). Michael addition of ethyl acrylate... 

A nice example of photochemical synthesis has been reported for the case of p-lactams. Thus, a-diazoketones prepared from aminoacids by diazotransfer are decomposed under irradiation and undergo an intramolecular Wolff rearrangement to give a p-lactam. This occurs with complete retention of the configuration and indeed the enantiomerically pure diazoketones prepared from natural aminoacids give likewise pure p-lactams (see... 

A synthesis of papaverine-l- C in 11 % yield was performed starting from veratric acid labeled at the carboxyl group (CXII). The diazoketone prepared from the aeid chloride was eondensed with homoveratrylamine and the resulting amide (CXIII) cyclized to 3,4-dihydropapaverine (CXIV). Dehydrogenation of the latter with palladium-charcoal in tetralin afforded papaverine. The loealization of the labeled carbon atom, indicative of an Amdt-Eistert rearrangement, was confirmed because the base, on oxidation with neutral 5% potassium permanganate, afforded 6,7-dimethoxyisoquinoline-l-i C-l-carboxylic acid (CXV) (183). 

A variation of Hantzsch s synthesis, using thioureas in conjunction with a-diazoketones in place of a-halogenoketones, has proved to be generally applicable. In this manner, King and MUler (310) obtained 2-amino-4-phenylthiazole in 67% yield. A wide range of 4-substituted 2-aIkyl (or aryl) aminothiazoles and 2-arylimino-3,4-diarylthiazolines have been prepared by Hampel and Muller (627, 665, 666). 

The diazoketohe synthesis for the preparation of 21-methyl-20-keto steroids has been discussed earlier. 21-Oxygenated derivatives can also be prepared by this route simply by reacting the diazoketone with an appropriate acid-nucleophile combination. For example, reaction of a diazoketone with acetic acid leads to the 21-acetate and boron trifluoride in the presence of methanol affords the 21-methyl ether. 

The photolytic decomposition of a-diazoketones, accompanied by rearrangement to ketene (photolytic Wolff rearrangement), has been used successfully in the preparation of A-nor- and C-norsteroids. The method is reviewed in chapter 15 by R. M. Scribner. ... 

Photolysis of a-diazoketones has also been used to prepare A-norsteroids. Results in the A-nor series support the ketene intermediate invoked for the assignment of the 16) -configuration to the D-nor acids. Thus, irradiation of 2-diazo-5a-cholestan-3-one (99) gives 2/ -carboxy-A-nor-cholestane (100, R = H) in 45 % yield. ... 

Diazoketones that are readily prepared from acyl chlorides and diazomethane [92] also undergo a variety of fluorination reactions... 

Preparation of the sulfur analogue involves as the first step cyclization of the terephthalic acid derivative 92. The acid is then converted to the acid chloride and this is allowed to react with diazomethane. Rearrangement of the resulting diazoketone (95) under the conditions of the Arndt-Eistert reaction leads to the homologated acid. 

The Arndt-Eistert reaction (Scheme 2.1) which involves the Wolff rearrangement of diazoketones 13 (prepared from the corresponding commercially available N-protected-a-amino acids 12 by reaction of their mixed anhydrides with diazomethane a cautionary note is warranted here the generation and handling of diazomethane require special precautions) has been used extensively by Seebach and coworkers for the preparation of N-protected /9 -amino acids 14 and /9 -amino acid esters 15 and 16. 

Diazoalkanes are u.seful is precursors to ruthenium and osmium alkylidene porphyrin complexes, and have also been investigated in iron porphyrin chemistry. In an attempt to prepare iron porphyrin carbene complexes containing an oxygen atom on the /(-carbon atom of the carbene, the reaction of the diazoketone PhC(0)C(Ni)CH3 with Fe(TpCIPP) was undertaken. A low spin, diamagnetic carbene complex formulated as Fe(TpCIPP)(=C(CH3)C(0)Ph) was identified by U V-visible and fI NMR spectroscopy and elemental analysis. Addition of CF3CO2H to this rapidly produced the protonated N-alkyl porphyrin, and Bit oxidation in the presence of sodium dithionitc gave the iron(II) N-alkyl porphyrin, both reactions evidence for Fe-to-N migration processes. ... 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

One of the most common approaches to pyrazine ring construction is the condensation of diaminoethane and 1,2-dicarbonyI compounds such as 206 to provide pyrazines 207 after aromatization. Aromatization was accomplished by treating the dihydropyrazines with manganese dioxide in the presence of potassium hydroxide <00JCS(P1)381>. The N-protected 1,2-dicarbonyl compounds 206 were prepared from L-amino acids by initial conversion into diazoketones followed by oxidation to the glyoxal. 

Diazotized 2- and 4-aminophenols as well as corresponding diazotized aminonaphthols and hydroxy derivatives of higher condensed aminoaromatic systems exist in neutral aqueous solutions as zwitterions (23b) which are mesomeric with the corresponding quinone diazides (23a). They can therefore be classified either as diazonium ions or as diazoketones. Indeed, preparative methods for these compounds include those typical for diazonium ions and those used for diazoketones. 

As the preparative methods related to the syntheses used for diazoketones are no di-azotizations and, in part, do not start from amines, they are not within the scope of this book. They are reviewed in Zollinger s books on diazo chemistry3b,7c. 

In addition to the methods sketched in Figure 4.2, diazoketones are frequently prepared from acyl halides and diazomethane. Because this methodology requires the use of distilled diazomethane, it is hazardous and not well suited to large-scale preparations. 

The ring closure of a-diazoimines (Scheme 22) is a well-established route to w-triazoles and to 1//-triazoles. The a-diazoimines may be prepared in situ from a-diazoketones and amines, or by diazo... 

The HC1 generated in this reaction destroys one equivalent of diazomethane. This can be avoided by including a base, such as triethylamine, to neutralize the acid.74 Cyclic z-diazoketones, which are not available from acyl chlorides, can be prepared by reaction of an enolate equivalent with a sulfonyl azide. This reaction is called diazo transfer 5 Various arenesulfonyl azides76 and methanesulfonyl azide77 are used most frequently. Several types of compounds can act as the carbon nucleophile. These include the anion of the hydroxymethylene derivative of the ketone78 or the dialkylaminomethylene derivative of... 

Decomposition of diazoketone 113 with rhodium acetate led to the formation of a tethered cyclic carbonyl ylide 114 that was poised to undergo an intramolecular cycloaddition, preparing 115 in 60% yield. Interestingly, if DMAD was added to the reaction mixture, the only product arose from intermolecular cycloaddition. 

The 3//-l,2,4-diazaphospholes formed from the reaction of diazomethane and its monosubstituted derivatives (R CH=N2 R = H, alkyl, aryl, acyl, phosphoryl) could not be isolated due to a rapid 1,5-H shift leading to 27/-l,2,4-diazaphospholes 227. When diazo(trimethylsilyl)methane or [bis(diisopropylamino)phosphino]dia-zomethane was used, the l,5-SiMe3 [or PR2, R = N(/-Pr)2] shift completely dominates over the H shift (289,290). In the case of open-chain or cyclic a-diazoketones, cycloadducts 228 cannot be isolated due to rapid acyl shifts giving 229 and ultimately 230 (289). This transformation offers a versatile method to prepare [h]-fused 1,2,4-diazaphospholes from cyclic a-diazoketones and phos-phaalkynes (289). 

---