Imidazoles 2 + 2 + 2 cycloaddition reactions

Azirine, trans-2-methyl-3-phenyl-racemization, 7, 33, 34 1-Azirine, 2-phenyl-reactions, 7, 69 with carbon disulfide, S, 153 1-Azirine, 3-vinyl-rearrangements, 7, 67 Azirines, 7, 47-93 cycloaddition reactions, 7, 26 fused ring derivatives, 7, 47-93 imidazole synthesis from, 5, 487-488 photochemical addition reactions to carbonyl compounds, 7, 56 photolysis, 5, 780, 7, 28 protonated... 

Similarly, /V-sulfonyl-protected vinylimidazole 597 reacts with PTAD to provide the cycloaddition reaction product 598 which easily undergoes the retro-Diels-Alder reaction upon heating or with acid treatment. The primary product is easily isomerized using a base to the aromatized condensed imidazole 599 (Scheme 95) <1998TL4561>. 

Pyranopyrroloimidazoles have been prepared stereospecifically by an intramolecular 1,3-dipolar cycloaddition reaction. Either enantiomer of the imidazoline derivative 176 (the -enantiomer is shown) may react with the bromoacetyl-containing acrylate dipolarophile 177, in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to give the diastereomerically pure tricyclic product 178 in moderate yield (Equation 15). This reaction involves quaternization of the imidazole N, reaction of the quaternary salt with base to give the 1,3-dipole, which can then react, intramolecularly and stereospecifically, with the tethered dipolarophile <1997TL1647>. 

Imidazole nitrones 127 reacted with dimethyl acetylenedicarboxylate to yield imidazo[l,5-fc]isoxazoles 128, which in the presence of base afforded imidazoles 129 <00TL5407>. Chiral imidazoline nitrone 130 participated in a [3+2] cycloaddition reaction with various dienophiles to furnish imidazoisoxazoles 131 <00SL967>. A convenient synthesis of AyvyV -trisubstituted ethylenediamine derivatives from 2-methyl-2-imidazoline has been reported <00SC3307>. Dehydrogenation of 1,3-di- and 1,2,3-trisubstituted imidazolidines afforded l//-4,5-dihydroimidazolium salts <00SC3369>... 

Both 3-diazO 1,2,4-triazoles and 4-diazo-l,2,3-triazoles easily give cycloaddition reactions with ynamine leading to 4-aminotriazolo-triazine 284 and the yields are generally higher than in the pyrazole and imidazole series (77S556) (Scheme 85). 

Cycloaddition reactions of A -(phenylmethylene)benzenesulfonamide with meso-ionic oxazolones 311 produces 2,5-disubstituted imidazoles 313 in a highly regio-selective process via cycloreversion of cycloadduct 312 and subsequent loss of benzenesulhnic acid. 

Syntheses of fused heterocycles by l,3 dipolar cycloaddition reactions to imidazole ylids have been described by several research groups. Boekelheide and Fedoruk150 quatemized the imidazoles 183 with phenacyl bromide, generated the corresponding ylids 184 and then added excess EP. The anticipated product (186) was apparently formed but was dehydrogenated to pyridoimidazole (185), which was isolated in 14% overall yield. 

Anomalous cycloaddition reactions from benzocinnoline A-alkyli-mides and acetylenic esters were also described, in 1974, by Rees et al. 59 Benzocinnoline Af-alkylimides (487 and 488) gave adducts 492 via the sequence shown in Scheme 10 with acid, they rearranged to the imidazoles 493 and 494. 

Azirene + cation radicals (81) have proven useful as 1,3-dipole equivalents for cycloaddition reactions. Several heterocycles, such as pyrrolines, imidazoles, pyrroles and porphyrins, have been synthesized from azirenes in low to moderate yields, via PIET using DCN or DCA as electron acceptors (Scheme 76)163. 

The use of cycloaddition reactions for the synthesis of partially reduced heterocyclic systems was shown to be an attractive approach to dihydrobenzimidazoles, dihydroquinazolines, and dihydro-//n-benzopurines (Scheme 14) <86JOC6i6>. The dihydroxylation of the Diels-Alder adduct dimethyl 3,6-dihydrophthalate (128) with 0s04 and NMO followed by protection of the diol as the iso-propylidene derivative afforded compound (129). Saponification, dehydration with ethoxyethyne, and rearrangement with TMS—N3 effected conversion to the substituted tetrahydroisatoic anhydride (130), and subsequent treatment with formamidine acetate yielded compound (131). The substituents at the 6,7-positions of compound (131) were not amenable, however, for annelation of an imidazole. 

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). 

An interesting application of PET mediated bond cleavage reaction from azirine 63 has been reported by Mattay et al. [67] for synthesizing N-substituted imidazoles (65) via the (3 + 2) cycloaddition reaction of resultant 2-azaallenyl radical cations with imines 64. Synthesis of pyrrolophane 3,4-dimethyl ester (68) has been reported recently [68] by the ring opening of 66 followed by inter-molecular cycloaddition with dimethyl acetylene dicarboxylate (67) as shown in Scheme 13. 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

Samanta et al. [23] conveniently synthesized the 1,5-disubstituted imidazoles (xxv) on a polymeric support using base-promoted 1,3-dipolar cycloaddition reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines under microwave irradiation. 

Oxazoles represent the most widely recognized heteroaromatic azadiene capable of [4 + 2] cycloaddition reactions. The course of the oxazole Diels-Alder reaction and the facility with which it proceeds are dependent upon the dienophile structure (alkene, alkyne), the oxazole and dienophile substitution, and the reaction conditions. Alkene dienophiles provide pyridine products derived from fragmentation of the [4 + 2] cycloadducts which subsequently aromatize through a variety of reaction pathways to provide the substituted pyridines (Scheme 14). In comparison, alkyne dienophiles provide substituted fiirans that arise from the retro Diels-Alder reaction with loss of R CN from the initial [4 + 2] cycloadduct (Scheme 15,206 Representative applications of the [4 + 2] cycloaddition reactions of oxazoles are summarized in Table 14. Selected examples of additional five-membered heteroaromatic azadienes participatiitg in [4 + 2] cycloaddition reactions have been detailed and include the Diels-Alder reactions of thiazoles, - 1,3,4-oxadiazoles, isoxazoles, pyrroles and imidazoles. ... 

The [4 + 2] cycloaddition reactions of 7V-sulfinylphosphoramidates,(prepared from the corresponding phosphoramidates by treatment with A-(chlorosulfinyl)imidazole) with 1,3-cyclohexadiene occur diastereoselectively in the presence of SnCU (Eq. 71) [109]. 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

As was mentioned in the earlier review, considerable difficulties arise in the classification of imidazole syntheses. There is a great variety of methods, few of which have wide general application, and in many instances the mechanism is poorly understood. For example, some syntheses almost certainly involve concerted cycloaddition reactions, but sound evidence for this process is lacking. In addition, numerous examples have appeared of conversions of other heterocyclic compounds into imidazoles. While the... 

Similar cycloaddition reactions of C=C bonds have been described starting from substituted pyrrole and imidazole derivatives (eq. (18)) [49]. 

---