Dipolar addition, 1,3, diazomethane

The interaction of diazomethane with 1-azirines was the first example of a 1,3-dipolar cycloaddition with this ring system (64JOC3049, 68JOC4316). 1,3-Dipolar addition produces the triazoline adduct (87). This material can exist in equilibrium with its valence tautomer (88), and allylic azides (89) and (90) can be produced from these triazolines by ring cleavage. 

The stereochemistry of the 1,3-dipolar cycloaddition reaction is analogous to that of the Diels-Alder reaction and is a stereospecific syn addition. Diazomethane, for example, adds stereospecifically to the diesters 43 and 44 to yield the pyrazolines 45 and 46, respectively. 

Dipolar additions of diazomethane to acetylenes under mild conditions are restricted to monosubstituted acetylenes thus the formation of pyrazole derivatives 1 (1,3-dipolar addition, C=C isomerization, then methylation) confirms the existence of a terminal acetylene in caryoynencins (87TL3981) (Scheme 5). 

While Kakisawa et al. (87TL3981) reported formation of Wmethylpyrazole 1, Yamaguchi et al. obtained the NH derivative 2 by reaction of caryoynencins with diazomethane in ethyl acetate at 0°C (94BSJ1717 95JMC5015). The 1,3-dipolar addition was quite sensitive to the solvent employed, and a very low yield of pyrazole derivative 2 was obtained in ether or methanol (Scheme 5). 

The 1,3-dipolar reagent diazomethane reacts with oxepin and substituted derivatives to afford 1 1 or 2 1 adducts 13 or 14 across the C-C double bonds of the isomeric benzene oxides.238 239 In the 1 1 addition product 13, the two heterocycles adopt a cis orientation.238 The nitrogen can be extruded by irradiation of the dihydropyrazole. 

For corresponding reactions with 2-furyl- and 2-thienyldiazomethylketone see reference [131]. An obvious mechanism for the reaction of WJV -thiocarbonyldiimidazole with diazomethane is a 1,3-dipolar addition [13°3... 

The 4ne component in a (4tc + 2n) cycloaddition need be neither a four-atom system (as in 1,3-dienes), nor involve carbon atoms only, so long as the HOMO/LUMO symmetry requirements for a concerted pathway can be fulfilled. The most common of these non-dienic 4ne systems involve three atoms, and have one or more dipolar canonical structures, e.g. (34a), hence the term—1,3-dipolar addition. They need not, however, possess a large permanent, i.e. residual, dipole, cf. diazomethane (34a 34f>) ... 

Further studies on 1,3-dipolar addition reactions of diazophosphonates have been recorded,122 and work on 2-diazo-l-hydroxyalkylphosphonates also continues.123 The ester (155 R = H) reacts with esters of acetylenedicarboxylic acid without liberation of nitrogen to give stereoisomeric C-phosphorylated pyrazolines, which can be decomposed with both phosphorus-carbon and carbon-carbon bond fission, affording mixtures containing dimethyl acetylphosphonate, dimethyl hydrogen phosphonate, and tri(alkoxycarbonyl)pyrazolines. In the reaction between the same diazophosphonate and diazomethane, the latter conceivably acts as a basic catalyst for proton transfer in a series of steps which includes phosphonate-phosphate isomerization. The importance of a labile proton is demonstrated by the fact that the ester (155 R = Me) does not react in the manner described above. 

A -1,3,4-Thiadiazoline-1 -oxides (146) (Equation (18)) are formed by addition of diazo compounds (R2C=N2) to sulfines (R R C =S=0). The adducts from diazomethane and aryl substituted sulfines are unstable and give the thiadiazole (147) via a Pummerer-type aromatization <84CHEC-I(4)545>. The A -thiadiazoline-1,1-dioxide (149) has been produced by oxidation of the hydrazone (148) (Equation (19)) and treatment with sulfur dioxide <84CHEC-i(4)545>. 2-Alkylidenethiadiazolines can be obtained from the dipolar addition of diazo compounds to thioketenes <83CB66, 90TL3571, 92HCA1825>. 

The product (6-4) from that sequence, which is of course simply 6-methyldios-genin, is then subjected to a series of degradation reactions as those used for the parent compound to give the 6-methyl derivative (7-1) of dehydropregnenolone. Reaction of the enone function of that product with diazomethane leads to 1,3-dipolar addition and the formation of the pyrrazoline (7-2). That intermediate loses... 

The perfluorinated cyclopropenes (292, X = C(CF3)NH) may be prepared from (293) by 1,3-dipolar addition of diazomethane followed by desulphurisation with, triphenylphosphine to produce, (294), and then thermolysis. Addition of (292, X = C(CF3)0) to 2,3-dimethylbutadiene occurs predominantly in an endo-manner, the intermediate undergoing an intramolecular ene-reaction to produce (295). In the same way reaction with pyrrole leads to (296), in this case presumably by an intramolecular nucleophilic attack in the initially formed endo-adduct 237). 

Addition of diazomethane to 3,3-dimethylcyclopropene leads to the pyrazolines (303, R = H) but methyl diazoacetate leads to (304) and (305) the former is apparently derived by base induced reaction of the pyrazoline, while the latter may be explained in terms of rearrangement to the diazocompound (306) followed by dipolar addition to the cyclopropene 242). 

R = Ph) is also formed in the reaction between diazomethane and thiobenzoyl chloride, probably via a 1,3-dipolar addition of diazomethane to the thiocarbonyl group. Similar additions have been observed by Huisgen et The reaction between thioacyl chlorides and diazo compounds was first studied by Staudinger and Siegwart.i 3 (R = Ph) has been prepared by cyclization of 11 with triethylortho-formate, and also from 2-phenyl-1,3,4-oxadiazole and phosphorus pentasulfide. ... 

Lemal et al. studies the 1,3-dipolar addition reaction of the Dewar thiophene with trifluoromethyl diazomethane. The cycloadduct shows reactions which are similar to those of the azide adducts (122) 126). 

Dipolar Additions. Low regioselectivity but high stereoselectivity have been observed in the 1,3-dipolar addition of phenyl azide, diazomethane, and... 

Many enone systems readily undergo 1,3-dipolar addition reactions. This applies to steroids, as illustrated by the formation of the fused pyrazole 16-4 from reaction of the enone 16-2 with diazomethane. Pyrolysis of that pyrazole results in extrusion of nitrogen to leave behind a methyl group at position 1 (16-5). 

Fig. 10.17. Transition structures for 1,3-dipolar addition of methoxyethene and diazomethane. Structures A1 and B1 correspond to the syn conformation of methoxyethene, whereas A2 and B2 correspond to the anti conformation. The TS with the lowest energy corresponds to the observed product. From J. Chem. Soc., Faraday Trans., 90, 1077 (1994).

Pyrazolinyltriphenylphosphonium salts (88) can be prepared by 1,3-dipolar addition of excess diazomethane to triphenylvinylphosphonium salts. Thermolysis of (88) gave phosphonium salts (89) by elimination... 

For a discussion of the orbital interactions that control dipolar additions of diazomethane, see Fleming, I. Frontier Molecular Orbitals and Organic Chemical Reactions, Wiley New York, 1976 p 148. 

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