Diazoketones from acid chlorides

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... 

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-... 

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. 

Diazoketones such as 307 can be formed from acid chlorides by reaction with diazomethane. Subsequent treatment with aqueous Ag20 leads to the Wolff rearrangement and formation of a carboxylic acid of one carbon more than the starting acid chloride. This sequence is known as the Arndt-Eistert synthesis.252 a synthetic example using this is taken from Weinreb s studies toward the synthesis of cylindrospermopsin,253 iu which 315 was treated with (1) oxalyl chloride, (2) CH2N2 and (3) Ag20, MeOH to give a mixture of products 22% of 316 and 39% of 317. 

Under the usual conditions one equivalent of the diazoalkane is consumed by the liberated acid but this can be avoided by use of an added base such as triethylamine/ Cyclic a-diazoketones, which are not available from acid chloride, can be prepared by reaction of a nucleophilic derivative such as the a-hydroxymethylene enolate with arylsulfonyl azides. Several combinations of carbon nucleophile and sulfonyl... 

Acid chlorides, reduction to aldehydes, 53, 55 Acid chlorides, aromatic, diazoketones from, 53, 37... 

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... 

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... 

The formation of a-diazoketones from carboxylic acids (via the acyl chloride or an anhydride) and the subsequent Wolff Rearrangement in the presence of nucleophiles results in a one-carbon homologation of carboxylic acids. This reaction sequence. 

The total syntheses of clivonine (114) and clividine (138) have been achieved from the anhydride 75 already used in the syntheses of dihydrolycorine (85), y-lycorane (87), and S-lycorane (92). Treatment of 75 with MeOH mainly gave the half ester 127 which was converted into the urethane 131 via the acid chloride 128, the azide 129, and the isocyanate 130. The desired methyl ester 132 was obtained from 131 through the corresponding chloride and diazoketone. The... 

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... 

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. 

Trimethylsilyldiazomethane (96), prepared in excellent yield from chloromethyltrimethylsilane, is now commercially available (Petrarch). Trimethylsilyldiazomethane is readily lithiated and alkylated (equation 40).Synthetic applications of the resultant silyldiazoalkanes (97) have not yet been extensively explored. These might, for instance, react smoothly with acid chlorides to give diazoketones (see Section 1.4.6.1). 

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. 

Doering et al." extended this application to the synthesis of tricyclic ketones from monocyclic diazoketones, using as catalyst copper powder, cupric sulfate, or cuprous iodide with apparently equal success. A sketchy advance report,12 claims the synthesis of 8,9-dehydroadamantane-2-one (5, m.p. 206.5-207.5°) via the acid chlorides (3) and (4) and the derived diazoketones. 

Starting from 6-methoxynaphth-2-oic acid (64), the 1,2,3,4,5,8-hexahydro-derivative (65) was prepared by reduction with excess lithium and t-butyl alcohol in liquid ammonia. Compound (65) was converted into the keto-acid (66) by hydrolysis. Reduction of (66) with lithium tri-t-butoxyaluminium hydride gave the hydroxy-acid (67). The acetate derivative (68) was converted into the acid chloride (69) by reaction with oxalyl chloride in pyridine. Treatment of this compound with diazomethane afforded the diazoketone (70). Decomposition of the latter with copper powder in cyclohexane gave the cyclopropyl ketone (71) in yields of 70—80%. The acetate function was then hydrolysed, and the resulting hydroxy-ketone (72) was oxidized to the cyclopropyl diketone (73) with Jones reagent. Treatment of (73) with a weakly acidic acetone solution or adsorption on to basic alumina produced the enedione (74) via a retrograde... 

In another procedure a diazoketone (48) (derived from the corresponding acid chloride by treatment with diazomethane) was coupled with an a-free pyrrole... 

Diazoketones derived from acids whose acid chlorides are inaccessible may be prepared by the action of diazomethane on... 

---