Diazo reaction with carbonyl compounds

Reactions of Phosphonium Ylides. - 2.3.1 Reactions with Carbonyl Compounds. This year we are able to report several variations of the traditional Wittig olefination which employ the addition of catalysts to effect the reaction. For example, Lebel et al. have reported a new salt-free process for the methyl-enation of aldehydes, in which the phosphorane is generated in situ from triphenylphosphine and a diazo precursor with either a rhodium- or rhenium-based catalyst (Scheme 6). It was found that the most effective combination of catalyst and diazo-compound were Wilkinson s catalyst [RhCl(PPh3)3] and... 

Ohira, S. Methanolysis of dimethyl (1 -diazo-2-oxopropyl)phosphonate generation of dimethyl (diazomethyl)phosphonate and reaction with carbonyl compounds. Synth. Common. 1989, 19, 561-564. 

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. ... 

Reactions with Carbonyl Compounds and Utilization of 2-Diazo-2-(trimethyIsiIyI)ethanoIs. Diazo(trimethylsilyl)-methyllithium (TMSC(Li)N2) reacts with aldehydes and ketones to give lithium 2-diazo-2-(trimethylsilyl)ethoxides by nucleophilic addition, which produce alkylidene carbenes by expulsion of TMSOLi and nitrogen (eq 12). 

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

Reaction of carbonyl compounds with aliphatic diazo compounds to deliver homologated ketones. 

In the catalytic cycle itself, ylides A are generated in situ in the presence of carbonyl compounds in a reaction between a sulfide and a carbenoid B, which in turn is generated from a diazo compound C and a metal catalyst D. At the same time, ylides A react with carbonyl compounds to give trans-(S,S)-epoxides and are simultaneously regenerated to... 

Triorganylbismuthines can mediate such C-C bond forming reactions as shown in Scheme 5.38 in the presence or absence of a transition metal salt. Tributylbismuthine promotes the allylation of carbonyl compounds with allylic bromide [91HAC297] and the olefination of diazo compounds with carbonyl compounds in the presence of catalytic amounts of a copper(I) halide [90TL5897]. A combination of triphenylbismuthine and WCle promotes the metathesis of olefins, while a similar combination with TiC facilitates the stereoselective Diels-Alder reaction of unsaturated esters [76TMC183, 93JOC4783]. 

Alternatively, Homer-Wittig reaction of diazomethylphosphonate (11) with carbonyl compounds gives, presumably, the diazoalkenes (12). Replacement of the diazo group in situ by an alkoxy group gives the enol ethers (13 Scheme 3). ... 

A-Phthaloyl-protected (S)-phenylalanine has been used as a ligand for rhodium in the formation of metallocarbenes from diazo compounds for C-H insertion reactions (Section D.1.2.2.3.2.). Ar-Sulfonyl-protected (S)-alanine and (S)-valine are efficient ligands for chiral Lewis acids used in the Diels-Alder reaction (Section D.1.6.1.1.1.3.). A -Sulfonyl-pro-tected (S)-phenylalanine methyl ester has been used for the enantioselective protonation of lactone enolates (Section D.2.I.). The terf-butyl ester of (S)-valine readily forms imines with carbonyl compounds which are used for the highly efficient alkylations of their azaenolates (Sections D.1.1.1.4.1D.1.5.2.4.). All these derivatives can be obtained by the standard methods described in Houben-Weyl3. 

We add an investigation of Chinese chemists to this section, although it is not related to carbenoid reagents that we have discussed above. Zhou et al. (1993) studied reactions of dimethyl diazomalonate and ethyl diazoacetate with carbonyl compounds mediated by diorganyl tellurides and catalytic amounts of cuprous iodide (8-69). Dibutyl telluride (8.155) yields the dimethyl l-arylethene-2,2-dicarboxylate 8.157 with 4-chlorobenzaldehyde in 95<7b yield at 100 °C. It is assumed that the reaction passes the telluronium ylide 8.156 as intermediate. If so, the process is clearly different from the carbenoid transformations discussed in this section. The originally diazo-substituted C-atom has nucleophilic character in 8.156 and is not electrophilic, as in 8.104. 

Trimethylsilylstyrenes are formed by reaction of alka-nesulfonyl chlorides with TMSCHN2 in the presence of triethyl-amine (eq 13). TMSC(Li)N2 reacts with carbonyl compounds to give a-diazo- -hydroxy silanes which readily decompose to give O, /3-epoxy silanes (eq 14). However, benzophenone gives diphenylacetylene under similar reaction conditions (eq 15). ... 

The 5-7V-tosylamino substituted a-diazo-P-keto carbonyl compounds 101 were obtained from the reaction between diazo ketone 100 and the tosylimine 99 in the presence of TiCU in dichloromethane. The diazo ketone 101 underwent Wolff rearrangement in benzene upon irradiation with a high-pressure Hg lamp to afford 102, which subsequently cyclized to give the expected y-lactam derivatives. ... 

The diazo reaction with olefins as shown previously is still the fastest method to get hold of mixtures of diastereomers, often, however, with moderate yields due to the lack of reactivity of the olefins. Several nor-chrysanthemic esters [479], alkoxycyclopro-pane carboxylic esters [480,481], which are interesting because of their photostabihty and insecticidal activity [482], and 2,2,3,3-tetramethylcarboxyhc ester [483] were prepared by this route. Asymmetric synthesis using optically active iron carbonyl-olefin complexes afforded 1-R-configurated esters, i.e. precursors for caronaldehyde [484]. The addition of diazopropane across the double bond of olefinic esters via pyrazolines [485, 486] also provides a rapid access to sometimes more complex cyclopropane carboxylic esters with questionable purity, from which the pure compounds can be separated. 

Two main obstacles were well-known (a) diazo compounds can react directly with carbonyl compounds generating homologated products (Amdt-Eistert reaction, Scheme 7.59a), (b) diazo compounds can dimerize in the presence of metal salts and form alkenes (Scheme 7.59b) [204]. Other reactions involve carbene insertions or acid/water addition. 

Carbonyl oxides (formed by the reaction of diazo compounds with singlet oxygen) may also be used to oxidize sulphoxides74. The corresponding sulphone is formed in reasonable yields and the reaction may be carried out in the presence of the sulphide functionality. The reaction proceeds as shown in equation (21) and involves initial nucleophilic attack by the carbonyl oxide on the sulphoxide sulphur atom followed by the facile departure of the carbonyl compound yielding the required sulphone. 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

Diazo compounds are photoreduced to hydrazines in the presence of silanes and stannanes in a process that apparently involves initial H-atom transfer to an excited state of the diazo compound.105 LFP studies of reactions of Bu3SnH with excited states of diazo compounds 40 and 41 found fast reactions. The singlet diazo species reacted with Bu3SnH about as fast as singlet carbonyl compounds, whereas the triplet diazo species reacted with tin hydride somewhat slower than triplet excited states of carbonyl compounds.100,105... 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

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