Reaction with diazoketones

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-... 

Whereas metal-catalyzed decomposition of simple diazoketones in the presence of ketene acetals yields dihydrofurans 121,124,134), cyclopropanes usually result from reaction with enol ethers, enol acetates and silyl enol ethers, just as with unactivated alkenes 13). l-Acyl-2-alkoxycyclopropanes were thus obtained by copper-catalyzed reactions between diazoacetone and enol ethers 79 105,135), enol acetates 79,135 and... 

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

From (S)-l-acetylpyroglutamic acid via its chloride and subsequent reaction with diazoketone, the homologous ester was obtained. Hydrolysis gave the acid, which reacted with DPPA and afforded the optically active product (Scheme 48) [92H(33)619]. In a similar manner, compound 78 was obtained from N-protected L-Hys with N,N -diisopropylcarbodiimide (59JA6086). 

A closely related reaction employs a-diazoesters or y-diazoketones.23 With these compounds, molecular nitrogen acts as the leaving group in the migration step. The best results are achieved using dialkylchloroboranes or monoalkyldichloroboranes. 

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. 

At the present time, most of the positive photoresists used in the manufacture of microcircuits consist of a low molecular weight phenolic resin and a photoactive dissolution inhibitor. This composite system is not readily soluble in aqueous base but becomes so upon irradiation with ultraviolet light. When this resist is exposed, the dissolution inhibitor, a diazoketone, undergoes a Wolff rearrangement followed by reaction with ambient water to produce a substituted indene carboxylic acid. This photoinduced transformation of the photoactive compound from a hydrophobic molecule to a hydrophillic carboxylic acid allows the resin to be rapidly dissolved by the developer. (L2,3)... 

Beyond these systems, challenges in stereocontrol remain for both inter- and intramolecular cyclopropanation reactions with diazoketones, diazoketoesters (18), diazomalonates, and diazomethane. Although some progress has been made in intramolecular reactions of diazoketones, with selected examples having high % ee values,enantiocontrol is generally low to moderate for these systems. 

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

The reaction of an acid chloride with diazomethane illustrates a general method of preparing diazoketones. The acid chloride is slowly added to at least two equivalents of diazomethane the hydrogen chloride liberated (eq. 1) is then consumed according to eq. 2. When the order of addition is reversed (e.g., acid chloride is in excess) and only 1 mole of diazomethane is employed, the diazoketone reacts with hydrogen chloride (eq. 3) to form the a-chloroketone. 

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. 

Diacidic phosphonates (Vla-VId), i.e., those with two protons available for substitution, had a tendency to yield significant a-mounts of bis-substituted phosphonates [(RiC0CH20)2P0(R2) ] upon reaction with IV. However, it was found that careful addition (Table I) of the a-diazoketone to the phosphonate at reaction temperature minimized the formation of this by-product moreover, the bis-substituted phosphonates could be converted to the corresponding monoacids by refluxing the former with sodium iodide in methyl ethyl ketone. In this manner higher yields of phosphonates (e.g., Vllla-VIIId) could be obtained. 

The reaction of diazoketone 621 with either silver benzoate in methanol or with rhodium acetate in dichloromethane led to the formation of the stable azetinium salt 622, which was isolated as yellow crystals (Equation 236) <1998AGE2229>. 

Hydantocidin, which bears a spiro skeleton, is a natural product and a herbicide. Eq. 3.113 shows the typical preparation method of spiro-diketone (277) from the reaction of a-diazoketone (276) with Rh2(OAc)4 via a carbenoide species. However, this spiro skeleton can be also constructed by radical reactions. Treatment of (3-keto ester (278) with Mn(OAc)3 in the presence of electron-rich olefin generates spiro-cyclic thioketal (279) through the formation of a (3-keto ester radical, intermolecular radical addition to... 

In the dipole cascade reaction, a proton must be removed from the a-carbon atom in order to generate the azomethine ylide. When the a-position of the pyrrolidine ring was blocked by a benzyl group, formation of the azomethine ylide dipole could not occur. In fact, treatment of diazoketone 186 with rhodium(II) acetate in the presence of dimethyl acetylenedicarboxylate afforded only the carbonyl ylide-derived cycloadduct 187 in 95% yield [117]. 

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