Diazomethane diazoketone from

Illustrating the versatility of C-cyanoglycoside nitrile derivatives, Myers, et ai.,15 formed a diazoketone from the peracetylated C-cyanoglucoside shown. The reaction sequence, illustrated in Scheme 2.2.20, involved the initial hydrolysis of the nitrile to the corresponding primary amide. Subsequent hydrolysis afforded the carboxylic acid. On conversion of the acid to a mixed carbonic anhydride followed by treatment with diazomethane, the desired diazoketone was obtained. 

Diazomethane is a valuable and useful agent in organic synthesis that can be employed as a Ci building block in many single-step chemical reactions, for example, the methylation of alcohols or phenols, esteriflcations of carbonic adds, cyclopropanation reactions with alkenes, the synthesis of heterocycles, and the synthesis of a-diazoketones from acid chlorides or anhydrides. In general, the reactions proceed with release of nitrogen. Usually, diazomethane is freshly prepared from N-methyl-nitroso compounds and aqueous KOH solution and can be stored as a cooled solution for a couple of days. However, its low boiling point... 

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

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. 

DIAZOCYCLOHEXANONE, 51, 86 a-Diazoketones, reaction with trialkylborane, 53, 82 rearrangement, 52, 53 synthesis, 52, 53 >°-Diazoketones, aromatic, from acid chlorides, 53, 37 -Diazoketones, cyclic, alkylation of, 53, 82, 83 Diazomethane, in modified Arndt-... 

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 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... 

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). 

Diazomethane is generated by the reaction of aqueous NaOH with N-methyl-N-nitroso-p-toluenesulfonamide (Diazald ) in DMSO. The diazomethane is generated quantitatively and is removed by a stream of N2 into a packed column containing a stream of mixed anhydride formed from an N-protected (BOC or CBZ) amino acid and ethyl chloroformate. The diazoketone is converted to the chloroketone using HCI, as shown in Scheme 11.10. The chiral epoxide can then be formed via diastereoselective reduction with NaBH4 and treatment with base. 

Benzo[6]thiophene-2-carboxamides have been prepared by treatment of 2-benzo[6]thienyllithium with isocyanates,564 but are more conveniently obtained from the appropriate acid chloride by the conventional procedure.334,481,548,556,564,686-688 The acid chlorides react with diazomethane to give the diazoketone,218,689 and with dimethylcadmium 76,90 or diethyl ethoxymagnesium malonate218,336... 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

Carbenes have divalent carbon with a lone pair and hence only six electrons in the outer shell of the carbon atom. They are normally electrophilic and can form two bonds at once with a re-system.7 One way to make carbenes is by loss of nitrogen from diazocompounds such as diazoketones 33. The formation of very stable nitrogen is initiated by heat or light and compensates for the formation of the unstable carbene 30. Diazoketones are easily made by acylation of diazomethane with an acid chloride 31. Loss of a very acidic proton from the diazonium salt 32 gives 33. Normally the diazoketone and the alkene are combined and treated with heat or light.8... 

An enamine is ideal for the conjugate addition. We could have used diazomethane for the ring expansion but a better idea is to make it intramolecular by using a diazoketone 28 easily made from the free acid 27 with diazomethane. This time the rearrangement was initiated with Meerwein s salt and only the more substituted carbon atom migrates.4... 

A synthesis of L-sorbose by the diazomethane reaction on 2,4 3,5-diethylidene-L-xylonyl chloride (XXX) was performed by Gatzi and Reichstein.54 Oxidation of 3,5 4,6-diethylidene-L-gulitol (l,3 2,4-dieth-ylidene-D-glucitol) (XXVIII) gave the diethylidene-L-xylonic acid (XXIX). Addition of diazomethane to the acid chloride (XXX) yielded a sirupy diazoketone (XXXI) from which L-sorbose (XXXII) was obtained by acid hydrolysis with dilute sulfuric acid. 

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. ... 

In contrast, 4-benzylidenetetronic acid exists as only a single tautomer.152 Simple tetronic acids are always written as 4-hydroxyfuran-2(5//)-ones even when there is little doubt that 2-hydroxyfuran-4(4//)-one tautomers are also present. Diazomethane affords the methyl ethers of both,15 1 and 2-alkoxyfuranones are readily available from the copper-catalyzed decomposition of malonate ester diazoketones.152 154... 

Aromatic a-diazoketones can be prepared from 1 equivalent of CH N2, instead of the 2 equivalents usually used, by addition of triethyl-amine. The results with aliphatic compounds were less encouraging. —E A soln. of p-methoxybenzoyl chloride in ether added to a well stirred, ice-salt cooled soln. of diazomethane and triethylamine in ether during 20 min., and stirring continued in the cold for 12 hrs. —y p-methoxy-a-diazoacetophenone. Y 73%. (M. S. Newman and P. Beal, 3rd., Am. Soc. 71, 1506 (1949) s. a. M. Berenbom and W. S. Fones, Am. Soc. 71, 1629 (1949).)... 

A similar disconnection on cyclopropyl ketones (18) requires a reagent for carbene (19). This can be supplied as the diazoketone (20), made from acid chloride (21) and CH2N2, diazomethane. Carbene (19) is probably an intermediate in this reaction when (20) is either photolysed or heated with Ag(I) salts. 

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