Mesoionic compounds cycloadditions

The mesoionic compound 3-phenylsydnone (10) (see Houben-Weyl, Vol. E8c, p 398ff) reacts with benzocyclobutadiene (9), generated by the action of zinc on /ra x-l, 2-dibrotno-l, 2-dihy-drobenzocyclobutadiene(8), to give 3-phenyl-3//-2,3-benzodiazepine(13). The process involves sequential 1,3-dipolar cycloaddition to give 11, decarboxylation to 12 and, finally, valence... 

Tetrazolium ylides are quite reactive and are easily alkylated.168 The mesoionic tetrazolium thiolate 117 readily adds bromine to yield 174 which can then react with a number of active methylene compounds to give mesoionic compounds, e.g., 175.293,294 They also undergo 1,3-dipolar cycloaddition with olefins and acetylenes to yield bicyclic tetrazolo-thiazolines... 

Thiolactams 622 treated with carbon suboxide provide mesoionic compounds 623. Their 1,4-dipolar cycloaddition reaction with highly reactive PTAD gives compounds 624, formed by the cycloaddition followed by extrusion of COS, in quantitative yield (Scheme 100) <1995T6651, 1995H(41)1631>. 

In the course of investigation of reactivity of the mesoionic compound 44 (Scheme 2) the question arose if this bicyclic system participates in Diels-Alder reactions as an electron-rich or an electron-poor component <1999T13703>. The energy level of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were calculated by PM3 method. Comparison of these values with those of two different dienophiles (dimethyl acetylenedicarboxylate (DMAD) and 1,1-diethylamino-l-propyne) suggested that a faster cycloaddition can be expected with the electron-rich ynamine, that is, the Diels-Alder reaction of inverse electron demand is preferred. The experimental results seemed to support this assumption. 

Some mesoionic compounds have also been found to engage in cycloadditions to cydoproparenes. Benzocyclopropene (1) forms a 1 1 adduct 333 with 332. 

An attractive approach toward the preparation of polycyclic systems containing a thiophene ring involves the intramolecular [3 - - 2] cycloaddition of thiocarbonyl ylides. A number of representative examples were reported using mesoionic compounds. Gotthardt et al. (151) used l,3-dithiolium-4-olates such as 89 bearing an olefinic side chain. Upon heating to 120 °C in xylene, the polycyclic tetrahy-drothiophene 90 was formed (Scheme 5.33). 

Kato et al. (151,152) explored the chemistry of 2-ferf-butylMvenes with isomiinchnones, as well as with several other mesoionic compounds, in a novel approach to pseudo-hetero-azulenes. Thus, isomtinchnone 51a, generated as before in situ from A-benzoylphenylglyoxyanilide 253 with triethylphosphite, reacts with 2-ferf-butyl-6-(dimethylamino)fulvene to give the [47i+6ti] adduct diphenylcyclo-penta[c]pyran in low yield. Likewise, reaction of 51a with dimethylfulvene gave a mixture of two adducts, one of which arises from a [47i+2ti] cycloaddition. 

Of the mesoionic systems, (40) and its aza derivatives (43), (44) and (49) have been designated as Class B by Ollis (76AHC(l9)l), including compounds with X = CRR there are 88 total systems. Class A mesoionic compounds include (41), (42) and their aza derivatives (45)-(48), (50) and (51), giving a total of 144 systems. Members of the latter group contain 1,3-dipoles, often reflected in their pronounced ability to undergo cycloaddition reactions. 

Dehydrodithizone (252) adds directly to DMAD to give the thiazolo-tetrazole 253 with no loss of fragments that are usually extruded during cycloadditions to mesoionic compounds.124... 

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-... 

The synthesis of various heterocyclic systems via 1,3-dipolar cycloaddition reactions of 1,3-oxazolium-5-oxides (32) with different dipolarophiles was reported. The cycloaddition reactions of mesoionic 5H,7H-thiazolo[3,4-c]oxazolium-l-oxides (32), which were prepared from in situ N-acyl-(/J)-thiazolidine-4-carboxyIic acids and N,N -dicyclohexylcarbodiimide, with imines, such as N-(phenylmethylene)aniline and N-(phenylmethylene)benzenesulfonamide, gave 7-thia-2,5-diazaspiro[3,4]octan-l-one derivatives (33) and lH,3H-imidazo[ 1,5-cJthiazole derivative (35). The nature of substituents on imines and on mesoionic compounds influenced the reaction. A spirocyclic p-lactam (33) may be derived from a two-step addition reaction. Alternatively, an imidazothiazole (35) may be obtained from a typical 1,3-dipolar cycloaddition via a tricyclic adduct (34) which loses carbon dioxide and benzenesulfinic acid. [95T9385]... 

Mesoionic compounds of this series may participate in 1,3-dipolar cycloaddition reactions they may also undergo photochemical rearrangements. 

Mesoionic compounds may undergo 1,3-dipolar cycloaddition reactions. Thus anhydro-1 -hydroxythiazolo[3,2-a]guinolinium hydroxide (396) is a substrate for the reaction with DMAD. The formation of the pyrrolo[l,2-a]quinoline (397) from this reaction involves COS elimination from the initial adduct. Ethyl propiolate also reacts in the same fashion. The orientation in the cycloadduct can be arrived at from the ylide form (396a). With fumaronitrile, however, the fused pyridinone (398) is formed by loss of sulfur from the primary cycloadduct (78JOC2700). 

An example of an intramolecular cycloaddition reaction was offered by the mesoionic compound (129) which contains in the same molecule both a non-activated alkenic function and a cyclic thiocarbonyl ylide system. In an intramolecular [3 + 2] cycloaddition, (129) yields at 120 °C the tetracyclic primary adduct (130 90%) (81LA347). 

Only a few examples of a Diels-Alder type reaction of the valence tautomeric ketene of mesoionic 1,3-dithiolones are known. Thus the reactions of differently substituted mesoionic compounds (2) with o-chloranil give the unusual adducts (142), derived via [4 + 2] cycloaddition to the non-detectable valence tautomeric ketene (141) which is in equilibrium with (2). The reaction rate depends upon the nature of the substituents, for example substituents with —I and/or —M effects lower the reaction rates (81ZN(B)609). 

There are two common forms of mesoionic compound that belong to the oxazole ring system mlinchnones (1,3-oxazolium-5-olates) 86, named by Huisgen for the city Miinchen, and isomilnchnones (l,3-oxazolium-4-olates) 87 (Figure 4). These are highly versatile compounds which are often used as 1,3-dipoles in cycloaddition chemistry <2002HC(59)681>. 

When a similar mesoionic compound 180 was used in the cycloaddition reaction with l,2,3-triphenyl-l/7-phosphir-ene 181, the cycloadduct 182 was obtained. Irradiation of the latter afforded exclusively the thiophene 183 (Scheme 19) <1995H(40)311>. 

As early as 1963, interesting cycloadditions of 3,4-dihydroisoquinolinium methylides 76 (R = H, EWG = P-NO2C6H4 or PhCO) with carbon disulfide were reported (63TL1441). A spontaneous dehydrogenation of the initial cycloadducts gives rise to red-colored thiazole-type mesoionic compounds 224. 

Cycloaddition reactions of heterocyclic ylides and mesoionic compounds containing a... 

Cycloaddition reactions of the C(3)=N bond of azirines are common (Scheme 45) <71AHC(13)45, B-83MI 101-03,84CHEC-I(7)47>. Azirines can participate in [4 + 2] cycloadditions with dienes including cyclopentadienones, isobenzofurans, triazines, and tetrazines. They also participate in 1,3-dipolar cycloadditions with azomethine ylides, nitrile oxides, mesoionic compounds, and diazomethane. Cycloadditions with heterocumulenes, benzyne, and carbenes are known. Azirines also participate in other pericyclic reactions, such as ene reactions. 

A new approach to 4,5-dihydro-9//-pyrido[l,2-a]thieno(3,2-c]pyrimidine-4,9-di-ones 198 is based on 1,3-dipolar cycloaddition of the above-mentioned mesoionic compounds with dimethyl acetylenedicarboxylate (2001JCR(S)304). 

Intermediates of type 42 may be generated by cycloaddition reactions. Thus, when the thiirene 1,1-dioxide 45 was treated with the mesoionic compound 46 at ambient temperature, the sulfone 44b was produced in high yield the thiazine dioxide 44a was prepared in a similar manner. It is noteworthy that the intermediate cycloadducts 47a and 47b lost carbon dioxide in preference to sulfur dioxide. 

There have been few applications of theoretical methods in this area, but attempts have been made to rationalize the structure and reactivity toward cycloaddition of the mesoionic compounds (45) using MNDO and FMO (frontier molecular orbital) methods <86CB2308,86CB2317>. 

Recent developments in the chemistry of mesoionic compounds85 include cycloaddition-elimination reactions, which afford novel synthetic routes to a variety of heterocyclic systems. These reactions may be seen as involving 1,3-dipolar cycloadditions, following Huisgen,86 or alternatively as 1,4-cycloadditions to heterodiene systems,87 depending on the choice of canonical structure to represent the mesoionic compound. Benzyne has been employed in such reactions less frequently than more stable acetylenic or ethylenic dipolarophiles. 

If there is any one feature that characterises mesoionic compounds it is that their dipolar structures lead to reactions in which they serve as 1,3-dipoles in cycloadditions. 

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