Cycloaddition of diazomethane

Since 1,3-dipolar cycloadditions of diazomethane are HOMO (diazomethane)-LUMO (dipolarophile) controlled, enamines and ynamines with their high LUMO energies do not react (79JA3647). However, introduction of carbonyl functions into diazomethane makes the reaction feasible in these cases. Thus methyl diazoacetate and 1-diethylaminopropyne furnished the aminopyrazole (620) in high yield. 

Using dioxolane as a substituent in the 1,3-dipolar cycloaddition of diazomethane with olefinic double bonds, it was found that the bulky dioxolane ring plays a major role in the diastereoselection [OOJOC388]. 

Dihydro-2(l,3-dimethyluracil-5-yl)-l,3,4-oxadiazole was obtained in 53% yield by the [3+2] cycloaddition of diazomethane to the formyl group of l,3-dimethyl-5-formyluracil <1997T7045>. The reaction of l-acetyl-2-benzyl-hydrazine with methyl glyoxalate in toluene afforded an oxadiazolidine derivative <1996TL4323>. 

Dipolar cycloaddition of diazomethane to aldehydes can successfully be used for the preparation of tetrahy-drooxadiazole derivatives. Photochemical interconversion of 3-acylamino-l,2,5-oxadiazole derivatives leads to 1,3,4-oxadiazoles, though the method suffers from lack of selectivity. Many reports concentrate only on the synthesis and applications of new 1,3,4-oxadiazoles substituted with a wide variety of groups without introducing much of new chemistry. 

Apparently, the synthesis of 3-cyanoisoxazoline-2 N-oxide from diazomethane and cyanodinitromethane derivatives also occurs through cycloaddition of diazomethane to intermediate 1-cyano-l-nitroethylene (84). 

The 1,3-dipolar cycloaddition of diazomethane to MFA (24) occurred exclusively at the C2-C3 Jt-bond to give 4-(fluoromethylene)pyrazolines. The methylene group of diazomethane was regioselectively attached to the C2 carbon atom of 24 with a syw.anti ratio of 88 12 [72b], DFA (25) similarly reacted with diazomethane to give 4-(difluoromethylene)pyrazoline 89 selectively [72b, 86], The cycloaddition reaction of bulkier 2-diazopropane with DFA was less regioselective. 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

Figure 9. Preparation of some carbohydrate pyrazolines by cycloaddition of diazomethane to nitroalkenic sugars.

In the context of stereoselective organic synthesis, diastereofacial-selective cycloadditions of diazoalkanes and diazoacetates with functionalized alkenes has attracted some attention. 3,4-Disubstituted cyclobutenes were studied as dipolar-ophiles by the groups of Gandolfi and co-workers (113) and Martin and co-workers (114). The transition state structures of the cycloaddition of diazomethane with cis-3,4-dimethylcyclobutene was investigated theoretically by DPT methods (113a). 

Dipolar Cycloaddition Reactions. Dehydroamino acid derivatives behave as dipolarophiles in 1,3-dipolar cycloaddition reactions that leads to a variety of interesting compounds. For example, 1,3-dipolar cycloaddition of diazomethane to dehydroamino acid esters 475 and 481 gives the corresponding pyrazolines 476 and... 

The 3-benzylidenepiperazine-2,5-dione (97) derived from L-proline and (Z)-2-methyI-4-benzyIideneoxazolone has been converted to a pyrazo-line by cycloaddition of diazomethane and then photolyzed to yield a... 

The 1-pyrazolines, e.g. (52), formed by the cycloaddition of diazomethane to 1,2-disubstituted cyclobutenes are converted quantitatively to 4,5-dihydro-lH-l,2-diazepines (53) on treatment with hydrogen chloride (76H(4)1509). 

The cycloaddition of diazomethane to benzalanilines does not show any pronounced solvent effect with increasing dielectric constant of the solvent, there is hardly any increase in reaction rate with the exception of protic (e.g., water, alcohols) and dipolar aprotic solvents (e.g., DMF) that produce a significant acceleration in the reaction rate.182 The protic-dipolar aprotic solvent effects are found to be dependent on the electron-withdrawing or... 

The cycloaddition of diazomethane to SchifT bases from heterocyclic aldehydes and anilines provides a useful route to heterocyclic substituted triazolines. Unlike olefins bearing heterocyclic substituents, the heterocyclic imines can be obtained readily by reaction of the appropriate aldehyde and amine thus the diazomethane-imine addition has greater scope than the olefin-azide reaction. NMR spectroscopic studies of the orientation of addition are in accord with previously reported mechanistic considerations (see, e.g., Scheme 93).329 In addition to the influence of the N-aryl group, the electron-withdrawing power of the heterocyclic substituent on the Schiff-base carbon also has a substantial effect on imine reactivity, in the order 2-quinolyl 2-, 3-, or 4-pyridyl > phenyl > 2-thienyl as 2-furyl.329... 

The possibility of cycloaddition of diazomethane to the imine bond in azirines has been investigated365,366,366 the products comprise a mixture of isomeric allyl azides, and it is possible that bicyclic triazolines are intermediates in this reaction (Scheme 103).366... 

The first recorded cyclopropyl acyl silane (69) was generated by vapour phase pyrolysis of a pyrazoline derived from a,/)-unsaturated acyl silane by 1,3-dipolar cycloaddition of diazomethane (vide supra, Section DTE)141. Exposure of 69 to titanium tetrachloride induced ring expansion to give the cyclobutanone in 75% yield (Scheme 113). 

The cycloaddition of diazomethanes under different conditions leads to 3-silyl-l-pyrazoline derivatives in yields variable according to the conditions employed and the substituents on the reactants.106-108... 

The 1,3-dipolar cycloaddition of diazomethane with tert-butyl 4-oxo-6-phenyl-4//-pyran-3-carboxylate 411 has been reported to give 412 (Scheme 68) <1991JOC4963>. Further development of simple 7-pyrones as the 2rt-component in 1,3-dipolar cycloadditions of stabilized and nonstabilized azomethine ylides has provided some interesting polycyclic heterocycles such as 413-415 (Scheme 68) <1999J(P1)1167>. 

Fig. 15.37. Frontier orbital interactions in the transition state of the 1,3-dipolar cycloaddition of diazomethane to ethene.

The simplest 1,3-dipolar cycloadditions of diazomethane were presented in Figure 15.36. Diazomethane is generated from sulfonamides or alkyl carbamates of A-nitrosomethylamine. The preparation shown in Figure 15.40 is based on the commercially available />ara-toluene-sulfonylmethylnitrosamide (Diazald ). In a basic medium, this amide forms a sulfonylated... 

Fig. 15.41. Orientation-selective and stereoselective 1,3-dipolar cycloaddition of diazomethane. The trans-configured 2-methyl-2-butenoic acid is converted to the trans-configured cycloadduct with a diastereoselectivity of better than 99.997 0.003.

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