Pyrazolines, synthesis, diazomethane

Synthesis of pyrazolines in reactions of a,(3-enones with diazomethane and hydrazines 97KGS747. 

Extension of the 1,3-DC approach to the synthesis of novel pyrazoline-fused chlorin 78 by the reaction of P-nitro-meso-tetraphenylporphyrin le with diazomethane has also been explored by Cavaleiro and co-workers (Scheme 27) <02S 1155>. The resulting chlorin 78 could be further converted into the pyrazole-fused porphyrin 79 by treatment with DBU or into the methanochlorin 80 by refluxing in toluene. 

The pyrazoline derivative 260 was also the precursor for the synthesis (252) of the naturally occurring umbelactone. Reaction of butenolide 159c with diazomethane gave the pyrazoline 260, which was subjected to pyrolysis to give (—)-(5 )-umbelactone (261). As the natural umbelactone was described as being dextrorotatory, the synthesis of (+)-(R)-umbelactone from 159c was also performed. 

Unfortunately, several important classes of a-diazo ketones cannot be prepared in good yield via these standard methods. a -Diazo derivatives of a.p-unsaturated ketones, for example, have previously proved to be particularly difficult to prepare.1113 12 The acylation of diazomethane with a.p-unsaturated acid chlorides and anhydrides is generally not a successful reaction because of the facility of dipolar cycloaddition to conjugated double bonds, which leads in this case to the formation of mixtures of isomeric pyrazolines. Also problematic are diazo transfer reactions involving base-sensitive substrates such as certain a,p-enones and heteroaryl ketones. Finally, the relatively harsh conditions and lack of regioselectivity associated with the thermodynamically controlled Claisen formylation step in the "deformylative" diazo transfer procedure limit the utility of this method when applied to the synthesis of diazo derivatives of many enones and unsymmetrical saturated ketones. 

The synthesis and relative stability of 3,5-diacyl-4,5-dihydro-l//-pyrazoles prepared by dipolar cycloaddition of enones and a-diazoketones has been published <2004JOC9085>. 3-Acyl-4-aryl-2-pyrazolines have been synthesized by the reaction of a,/3-unsaturated ketones with diazomethane <1996IJB1091>. Ethyl diazoacetate added to 1,3-diarylpropenones in a regioselective fashion to give the intermediate 4,5-dihydto-3//-pyrazole derivative 1,3-hydride shift in the latter led to the formation of the isomeric ethyl 4-aryl-5-aroyl-4,5-dihydro-l//-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-l/7-pyrazole-5-carboxylate in a ratio of 5 1 <2001RJ01517>. 1,3-Dipolar cycloaddition of 2-diazopropane with diarylideneacetones afforded diastereomeric bis-A -pyrazolines <1999T449>. 

Thermolysis of pyrazolines was also used for aminocyclopropane synthesis. The corresponding starting materials were obtained from diazomethane and an alkene bearing a suitable nitrogen functional group, e.g. an amido or azido moiety. 

The reaction of nitro alkenes attached to sugar residues with diazomethane gave 3-methyl-3-nitro-4-gly-A -pyrazolines <88JOC5648>. In a similar way was prepared an intermediate for the synthesis of 2, 3 -dideoxyformycin B (a pyrazolopyrimidine) <92TL2921>. 

Three-membered carbocycles 1,1,2,2-Tetracycanocyclopropane was prepared in a one-pot synthesis from TCNE and diazomethane. First pyrazoline 364 is formed by cycload-... 

The dienophilicity of thiet 1,1-dioxide was utilized to synthesize (73) from tetracyclone, whilst it acted also as a good dipolarophile towards diazoalkanes, giving mixtures of 1-pyrazoline derivatives (74) and (75) in which the isomers (74) predominated, except in the cases of diazomethane and diazoethane, where (75) was the major isomer. Ethyl diazoacetate on the other hand gave the 2-pyrazoline (76). These compounds arc potentially useful for the synthesis of bicyclobutanes by sequential expulsion of nitrogen and sulphur, and thermolysis or photol3rsis of (74 = R =... 

General Methods.— The cyclopropanation of alkenes with diazocarbonyl compounds is one of the most widely used procedures for the synthesis of functionalized cyclopropanes. This year has seen the introduction of molybdenum hexacarbonyl/ palladium(ii) carboxylate, and iodorhodium(lll) mesotetraphenylporphrin as useful catalysts for this method of cyclopropanation. Reactions between diazomethane and alkenes often lead to pyrazolines [e.g, (1)] by 1,3-dipolar cycloaddition. Whereas thermolyses of these pyrazolines lead mostly to olefinic products [e.g, (3)], Martelli and Gree have now shown that Ce ions in acetone at 0 °C catalyses their decomposition to give largely cyclopropanes [e.g. (2)]. ... 

Aminocyclopropanecarboxylic acids often exhibit interesting biological activity and the azides (47) are logical precursors to such molecules. The synthesis of (47) has been described, and makes use of the readily available 2,3-dibromoalkanoates (44), which react with sodium azide to give high yields of the 2-azido-alk-2-enoates (45). Transformation to pyrazolines (46) with diazomethane and subsequent pyrolysis yields (47) (Scheme 57). Alternatively, the azide (45) reacts with nucleophiles to provide a convenient route to (Z)-2-aminopropenoates. 

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