Munchnones, cycloaddition

Pinho e Melo and co-workers heated a diastereomeric mixture of (2R,4R)- and (25,4/ )-2-phenylthiazolidine-2-carboxylic acids 114 with acetic anhydride in the presence of DMAD to afford pyrrolothiazole 115 in good yield and 99% ee (Fig. 4.40). Robba and co-workers synthesized the 2-azapyrrolo[l,2-a]indole ring system via a munchnone cycloaddition strategy. Trapping the munchnone derived from proline derivative 116 gave pyrrole 117 in 75% yield (Fig. 4.41). Further elaboration yielded the desired 118 and subsequent target compounds. 

Pinho e Melo and co-workers employed an intramolecular munchnone cycloaddition to construct several l//-pyrrolo[l,2-c]thiazole derivatives. Thus the Al-acylthiazolidines 189 on heating in acetic anhydride yielded 190 (Fig. 4.67). The structure of 190a was confirmed by X-ray crystallography. Analog 191 was also synthesized in this study. 

Martinelli and co-workers employed an intramolecular munchnone cycloaddition to craft a series of 4-keto-4,5,6,7-tetrahydroindoles 192-195 in two steps (Fig. 4.68). The requisite acetylenic precursors were prepared from glutaric... 

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

Dipolar cycloaddition reactions of thioisoraunchnones (l,3-thiazolium-4-olates) have not been as extensively studied as those of munchnones (l,3-oxazolium-5-olates) despite offering rapid access to novel heterocyclic compounds. The cycloaddition of the thioisomunchnone (52) with trans-P-nitrostyrene results in the formation of two diastereoisomeric 4,5-dihydrothiophenes (53) and (54) via transient cycloadducts. These cycloadducts then undergo rearrangement under the reaction conditions <96JOC3738>. 

Other 1,3-dipolar reagents show the same mode of reactivity towards cyclopropenones. Thus, the Munchnones 412 serving as potential azomethine ylides259-261 or the nitrile ylids 41 3262 effect expansion of the three-membered ring to the 4-pyridone systems 411/414 as a result of (2 + 3) cycloaddition to the C /C2 bond. 

Merlic demonstrated the direct, non-photochemical insertion of carbon monoxide from acylamino chromium carbene complexes 14 to afford a presumed chromium-complexed ketene 15 <00JA7398>. This presumed metal-complexed ketene leads to a munchnone 16 or munchnone complex which undergo dipolar cycloaddition with alkynes to yield the pyrroles 17 upon loss of carbon dioxide. 

Cyclic amino acids 139, when heated in acetic anhydride, probably form initially mesoionic oxazolium 5-oxides (munchnones) subsequent 1,3-dip olar cycloaddition of 1,2-dicyanocyclobutene, loss of carbon dioxide, and opening of the cyclobutane ring lead to dinitriles 140 (80JHC1593). Pyridone 141 is the by-product (together with an indolizine) of the mono-cyclic pyridone dicarboxylate and acrylic ester (73JHC77). 

TABLE 10.1. 1,3-DIPOLAR CYCLOADDITION REACTIONS OF IN SITU GENERATED MUNCHNONES AND METHYL PROPIOLATE AND METHYL 3-PHENYLPROPIOLATE"... 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

Munchnones 298 obtained in situ by N-alkylation of 5(4/f)-oxazolones undergo 1,3-dipolar cycloaddition with dimethyl acetylenedicarboxylate to give Al-alkylpyr-roles 299. 1,3-Dipolar cycloaddition of munchnones with triphenylvinylphos-phonium bromides affords tri- and tetrasubstituted pyrroles 300. In this case, the interaction of the phosphonium group with the carbonyl group leads to high levels of regioselectivity (Scheme 7.99 Table 7.27, Fig. 7.29). ... 

TABLE 7.27. SUBSTITUTED PYRROLES VIA CYCLOADDITION OF DIPOLAROPHILES WITH MUNCHNONES PREPARED FROM SATURATED 5(4/ )-OXAZOLONES... 

The cycloaddition reactions of isoquinolinium species produce fused isoquinoline products. The Af-ylide of 53, formed with base addition, couples with alkenes <99S51> or imines <99T7279> to afford tricyclic products, such as 54. Pyrrole-fused isoquinolines result from the reaction between mUnchnone imine intermediates and a,yff-ethylenic esters <99EJOC297>. N-Arylimides undergo 1,3-dipolar cycloaddition with strained frani-cyclooctenes, as opposed to common cycloalkenes, to tdford the pyrazolidine-fused ring system <99H(50)353>. 

The munchnone (66) reacts by [3+2] cycloaddition with dimethyl acetylenedicarboxylate to give an intermediate which spontaneously loses carbon dioxide (Scheme 21) (72JOC3111). 

Mesoionic compounds have been known for many years and have been extensively utilized as substrates in 1,3-dipolar cycloadditions.158-160 Of the known mesoionic heterocycles, munchnones and sydnones have generated the most interest in recent years. These heterocyclic dipoles contain a mesoionic aromatic system i.e. 206) which can only be depicted with polar resonance structures.158 Although sydnones were extensively investigated after their initial discoveiy in 1935,160 their 1,3-dipolar character was not recognized until the azomethine imine system was spotted in the middle structure of (206). C-Methyl-N-phenylsydnone (206) combines with ethyl phenylpropiolate to give the tetrasub-... 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

The mesoionic heterocycles called munchnones function as cyclic azomethine ylides in cycloaddition reactions.63 The alkenyl moiety can be attached at carbon or at nitrogen. 

Acetylation of the amide (128) produced a fused tricyclic pyrrole in 17% yield (Scheme 39).64 A munchnone intermediate was postulated and could be trapped via intermolecular cycloaddition with diethyl acetylenedicarboxylate. Presumably the direct cyclization product lost carbon dioxide, a known reaction of munchnone cycloadducts.65 An homologous munchnone with an o-(propenyl)phenyl group, rather than o-(butenyl)phenyl group, failed to cyclize, although it could again be trapped with diethyl acetylenedicarboxylate. 

A number of appropriate diazo precursors have been subjected to tandem carbene cyclization-iso-munchnone intramolecular cycloaddition.129 Thus, (232a) was cyclized with rhodium acetate to provide a tricyclic tetrahydrofuran (232b) cyclized similarly and produced just one stereoisomer. 

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