Diazomethane, 1,3-dipolar cycloaddition reaction

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. 

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. 

Mechanistically the 1,3-dipolar cycloaddition reaction very likely is a concerted one-step process via a cyclic transition state. The transition state is less symmetric and more polar as for a Diels-Alder reaction however the symmetry of the frontier orbitals is similar. In order to describe the bonding of the 1,3-dipolar compound, e.g. diazomethane 4, several Lewis structures can be drawn that are resonance structures ... 

The first [3S+2C] cycloaddition reaction using a Fischer carbene complex was accomplished by Fischer et al. in 1973 when they reported the reaction of the pentacarbonyl(ethoxy)(phenylethynyl)carbene complex of tungsten and diazomethane to give a pyrazole derivative [45]. But it was 13 years later when Chan and Wulff demonstrated that in fact this was the first example of a 1,3-dipolar cycloaddition reaction [46,47a]. The introduction of a bulky trime-thylsilyl group on the diazomethane in order to prevent carbene-carbon olefi-nation leads to the corresponding pyrazole carbene complexes in better yields (Scheme 15). 

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 second well-known dipolar cycloaddition reaction which is useful for the synthesis of thia-diazoles utilizes diazomethane and its derivatives. 

Reactions of aliphatic thiones (139) with diazomethane yields a mixture of isomers via a 1,3-dipolar cycloaddition reaction. Larger R groups lead to the formation of 1,3,4-thiadiazolines... 

The 1,3-dipolar cycloaddition reaction of diazoalkanes with alkenes has also been reported (395). Kanemasa and Kanai (395) used the chiral DBFOX-Ph ligand with various metals such as Ni, Zn, and Mg for the preparation of 255a-c. The reaction of TMS-diazomethane 171 with alkene 241 was catalyzed by 10 mol% of 255b to afford the 1,3-dipolar cycloaddition product 296 in good yields and enantioselectivities of up to 99% ee (Scheme 12.96). Also, the Ni-catalyst 255a and the Mg-catalyst 255c were excellent catalysts for the reaction, resulting in >90% ee in both cases. 

The exocyclic double bond of 4-arylidene-5(47/)oxazolones 383 reacts with diazomethane in a 1,3-dipolar cycloaddition reaction to give the corresponding... 

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... 

TABLE 7.47. OXAZOLONE SPIROCYCLOPROPANES FROM 1,3-DIPOLAR CYCLOADDITION REACTION OF UNSATURATED 5(4/7)-OXAZOLONES WITH DIAZOMETHANE... 

Substituted l,2,4-triazoline-3,5-diones are excellent dienophiles which react rapidly at room temperature with oxepins, but particularly with the arene oxide valence tautomer. A similar [4+2] cycloaddition reaction between the episulfide tautomer of thiepin (44) and 4-phenyl-l,2,4-triazoline-3,5-dione has been reported (74AG(E)736>. Benzene episulfide (the valence tautomer of thiepin 44) was generated in situ by thermal decomposition of the diepisulfide (151) at 20 °C and trapped as a cycloadduct at the same temperature (equation 34). A 1,3-dipolar cycloaddition reaction between thiepin (152) and diazomethane has been reported (56CB2608). Two possible cycloadduct products are shown since the final structure has not been unequivocally established (equation 35). 

Although it has been established that the HOMO (diazoalkane)-LUMO (alkene) controlled concerted cycloaddition occurs without intervention of any intermediate for the reactions of simple diazoalkanes with alkenes, Huisgen once proposed a mechanistic alternative 4 namely an initial hypothetical nitrene-type 1,1-cycloaddition reaction of phenyldiazomethane to styrene followed by a vinylcyclopropane-cy-clopentene-type 1,3-sigmatropic rearrangement Control experiments, however, excluded this hypothesis for the bimolecular 1,3-dipolar cycloaddition reaction of diazomethane (Scheme 60).204... 

The combination of the spin-coupled formulation of modem valence bond theory with intrinsic reaction coordinate calculations provides easy-to-interpret models for the electronic rearrangements that occur along reaction pathways. We survey here the information revealed by such studies of the mechanisms of various gas-phase six-electron pericyclic reactions the Diels-Alder reaction between butadiene and ethene, the electrocyclization of cis-l,3,5-hexatriene, the 1,3-dipolar cycloaddition between fulminic acid and ethyne, and the 1,3-dipolar cycloaddition of diazomethane. The fully-variational CASVB strategy proves particularly efficient for such studies. 

Dichloroacetamido)-l-methyl-5-nitroimidazole undergoes a 1,3-dipolar cycloaddition reaction with diazomethane to give (dichloroacetimino)tetrahydroimidazo[4,5-c]pyrazoles in about 10% each (Scheme 5). The failure to observe cycloaddition with l,2-dimethyl-5-nitroimidazole underlines the role of the N- methylated imidazole intermediate (184), a typical non-aromatic a, j6-unsaturated nitro compound acting as a dipolarophile (80TL4757). 

Dipolar cycloaddition reactions are most commonly applied for the synthesis of five-membered heterocyclic compounds.86 87 [3+2] cycloaddition reactions of transition-metal propargyl complexes have been reviewed.88 Addition of diazomethane to carbene complexes (CO)5Cr= C(OEt)R results in cleavage of the M = C bond with formation of enol ethers H2C = C(OEt)R,3 89 but (l-alkynyl)carbene complexes undergo 1,3-dipolar cycloaddition reactions at the M = C as well as at the C=C bond. Compound lb (M = W, R = Ph) affords a mixture of pyrazole derivatives 61 and 62 with 1 eq diazomethane,90 but compound 62 is obtained as sole... 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

Some examples are known of 1,3-dipolar cycloaddition reactions of trifluoromethyl-substituted alkenes and alkynes with other dipoles (see Table 12), such as diazomethane.nitrile imines, " " nitronates," and munchones." Depending on reaction conditions, cycloadditions may occur via a two-step process. 

The reaction of 27/-azirine-3-carboxylates unsubstituted at C2 with diazomethane occurs to produce a 4,5-dihydro-3/f-pyrazole derivative 185. This reaction represents an interesting example of the imino group acting as a 27t-component in a 1,3-dipolar cycloaddition reaction <03TL6313>. The process seemingly involves the reaction of 2//-azirine 182 with... 

Due to the electrophilic character of carbenes, they are not expected to easily react with electron-poor alkenes, and the only reported examples concern reactions with diazo compounds (i.e., diazomethane, 56 157 diazofluorenc.158 ethyl diazoacetate,159 and phenyldiazomethane160). However, depending on the reaction conditions, carbenes arc not always the reactive species. Cyclopropanes are often obtained by decomposition of pyrazolines which arise from 1,3-dipolar cycloaddition reactions (see Section 2.1.1.6.2.3.1.). Even when reactions are performed under irradiation, pyrazolines can be obtained as the result of a diradical addition.156... 

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