1.3- Dipolar cycloadditions-cycloreversion

Three new syntheses of fro-condensed heteroaromatic pyrroles and their derivatives were described <1995T193, 2003T1477> using retro-malonate addition and/or 1,3-dipolar cycloaddition-cycloreversion methods. 

Treating a solution of 15 in CH2CI2 with ozone leads, via 1,3-dipolar cycloaddition, cycloreversion, and again 1,3-dipolar cycloaddition, to the formation of the secondary ozonide, which is then transformed to the aldehyde 16 when the solution is worked up with dimethylsulfide. 

Dipolar cycloaddition—cycloreversion reactions involving iso-miinchnones sometimes lead to the formation of substituted 3-pyrrolin-2-ones as minor by-products (1994JOC2447, 1994TL7159, 1996T3247, 1998BMC1273). 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

In addition there are certain other methods for the preparation such compounds. Upon heating of the thionocarbonate 2 with a trivalent phosphorus compound e.g. trimethyl phosphite, a -elimination reaction takes place to yield the olefin 3. A nucleophilic addition of the phosphorus to sulfur leads to the zwitterionic species 6, which is likely to react to the phosphorus ylide 7 via cyclization and subsequent desulfurization. An alternative pathway for the formation of 7 via a 2-carbena-l,3-dioxolane 8 has been formulated. From the ylide 7 the olefin 3 is formed stereospecifically by a concerted 1,3-dipolar cycloreversion (see 1,3-dipolar cycloaddition), together with the unstable phosphorus compound 9, which decomposes into carbon dioxide and R3P. The latter is finally obtained as R3PS ... 

The three-component reaction between isatin 432a, a-aminoacids 433 (proline and thioproline) and dipolarophiles in methanol/water medium was carried out by heating at 90 °C to afford the pyrrolidine-2-spiro-3 -(2-oxindoles) 51. The first step of the reaction is the formation of oxazlidinones 448. Loss of carbon dioxide from oxazolidinone proceeds via a stereospecific 1,3-cycloreversion to produce the formation of oxazolidinones almost exclusively with /razw-stereoselectivity. This /f-azomethine ylide undergo 1,3-dipolar cycloaddition with dipolarophiles to yield the pyrrohdinc-2-r/ V -3-(2-oxindolcs) 51. (Scheme 101) <2004EJ0413>. 

Pyrazoles can be synthesized by thermal cycloreversion of adducts formed in the 1,3-dipolar cycloaddition of alkyldiazoacetates with norbornadiene. The rate of the primary process of cycloaddition is accelerated by iron pentacarbonyl (Scheme 88)155 a similar catalytic effect has been observed during the formation of ethyl 5-phenyl-A2-pyrazoline-3-carboxylate from cycloaddition of ethyl diazoacetate and styrene.155 Reactions of this type are catalyzed presumably because of coordination of one or both reactants to the transition metal, and a wider study of the effect of a variety of complexes on 1,3-dipolar cycloaddition processes would be valuable. 

Dimethyl-3-methylenepyrrolidine-2-thione, which reacts with nitrones regio- and stereoselectively at its exocyclic C=C bond to give only spirocy-cloadducts 116, behaves more complicatedly with nitrile oxides. The latter undergo 1,3-dipolar cycloaddition both to the exocyclic C=C and C=S double bonds with subsequent cycloreversion and formation of spiro-lactams 117 (281). 

In 1984, a facile synthesis of pyrrolo[3,4-/7]indole (5) as a stable indole-2,3-quinodimethane analogue using an intramolecular azide-alkene cycloaddition-cycloreversion strategy was reported (Scheme 9.2) (3). Treatment of bromo compound 3 with NaNs in aqueous tetrahydrofuran (THF) produced the triazoline 4 via an intramolecular 1,3-dipolar cycloaddition of an intermediate azide. Treatment of the triazoline 4 with p-toluenesulfonic acid (p-TSA) effected 1,3-dipolar cycloreversion of 4 to give pyrroloindole 5 in 82% yield along with diethyl diazomalonate. 

This method was also applied to preparation of thieno[3,4-c]pyrroles, including the first preparation of the parent compound (Scheme 9.4) (5a,b). When treated with NaNs, the bromo compounds (12) underwent 1,3-dipolar cycloaddition to yield the triazolines 13. 1,3-Dipolar cycloreversion gave the salts of the thieno[3,4-c]pyrroles... 

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... 

Dipolar cycloadditions are another important family, with the impressive sequence of reactions involved when ozone reacts with an alkene as an example here. At -78°, ozone adds 1.3 (arrows) to give the molozonide 1.4. On warming, this undergoes a 1,3-dipolar cycloreversion (1.4 arrows),... 

The Criegee mechanism for ozonolysis a dramatic sequence with successively a 1,3-dipolar cycloaddition, a 1,3-dipolar cycloreversion and another 1,3-dipolar cycloaddition, all taking place below room temperature. 

Tandem intramolecular 1,3-dipolar cycloadditions and cycloreversion, phosphinimine alkylidenemalonate cyclization, and retro-malonate additions have been reviewed.52 The origins of the stereoselection in the 1,3-dipolar cycloadditions to chiral alkenes53 and the 3 + 2-cycloadditions of fullerene, Cea, have been reviewed.54 The selectivity of the double 3 + 2-cycloaddition of tethered double vinyl carbene species in die presence of C6o varies witii the nature of the tether.55... 

The mechanism proposed by Criegee for the ozonolysis of alkenes <1975AGE745> considers an initial it-complex between the alkene and ozone which decays via a 1,3-dipolar cycloaddition into a 1,2,3-trioxolane or primary ozonide, known also as the molozonide . These compounds are unstable, even at low temperatures, and due to cycloreversion decompose into a carbonyl fragment and a CO, which may recombine by another 1,3-dipolar cycloaddition step to form the more stable 1,2,4-trioxolane ( secondary ozonide or final ozonide (see also Section 6.06.2). 

Dipolar Cycloadditions and 1,3-Dipolar Cycloreversions as Steps in the Ozonolysis of Alkenes... 

Phenyl azide is formed from phenyldiazonium chloride and sodium azide by way of two competing reactions (Figure 12.46). The reaction path to the right begins with a 1,3-dipolar cycloaddition. At low temperature, this cycloaddition affords phenylpentazole, which decays above 0°C via a 1,3-dipolar cycloreversion. This cycloreversion produces the 1,3-dipole phenyl azide as the desired product, and molecular nitrogen as a side product. 

An interesting example of the solvent-dependent cycloreversion of a substituted 3/f-A -pyrazoline (formed by the 1,3-dipolar cycloaddition of diazomethane to an allylic bromide) has been given by Kolsaker et al. [675]. 

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